CANADA HEALTH Drinking-Water-Quality-Guideline-Lead

Guidelines for
Canadian Drinking
Water Quality
Guideline Technical Document
Lead
Health Canada is the federal department responsible for helping the people of Canada
maintain and improve their health. Health Canada is committed to improving the lives of
all of Canada's people and to making this country's population among the healthiest in the
world as measured by longevity, lifestyle and effective use of the public health care system.
Guidelines for Canadian Drinking Water Quality: Guideline Technical Document – Lead
is available on the internet at the following address:
www.canada.ca/en/health-canada/services/environmental-workplace-health/reports-
publications/water-quality.html
Également disponible en français sous le titre :
Recommandations pour la qualité de l’eau potable au Canada : Document technique –Le

plomb.
To obtain additional information, please contact:
Health Canada
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© Her Majesty the Queen in Right of Canada, as represented by the Minister of Health,
2019
Published: March 2019
This publication may be reproduced for personal or internal use only without permission
provided the source is fully acknowledged.
Cat.: H144-13/11-2018E-PDF
ISBN: 978-0-660-27191-0
Pub.: 180137
Guidelines for
Canadian Drinking
Water Quality
Guideline Technical Document
Lead
Health Canada
Ottawa, Ontario
March, 2019
This document may be cited as follows:
Health Canada (2019). Guidelines for Canadian Drinking Water Quality: Guideline Technical
Document — Lead. Water and Air Quality Bureau, Healthy Environments and Consumer Safety
Branch, Health Canada, Ottawa, Ontario. (Catalogue No H144-13/11-2018E-PDF).
The document was prepared in collaboration with the Federal-Provincial-Territorial Committee

on Drinking Water of the Federal-Provincial-Territorial Committee on Health and the
Environment.
Any questions or comments on this document may be directed to:
Water and Air Quality Bureau

Healthy Environments and Consumer Safety Branch
Health Canada
269 Laurier Avenue West, Address Locator 4903D
Ottawa, Ontario
Canada K1A 0K9
Tel.: 613-948-2566
Fax: 613-952-2574
E-mail: [email protected]
Other Guideline Technical Documents for the Guidelines for Canadian Drinking Water Quality
can be found on the following web page: www.canada.ca/en/health-
canada/services/environmental-workplace-health/reports-publications/water-quality.html
Table of Contents
Part I. Overview and Application ................................................................................................... 1
1.0 Guideline ............................................................................................................................. 1
2.0 Executive summary............................................................................................................. 1

2.1 Health effects .......................................................................................................... 1
2.2 Exposure ................................................................................................................. 1
2.3 Analysis and treatment ............................................................................................ 2
2.4 International considerations .................................................................................... 2
3.0 Application of the guideline................................................................................................ 2

3.1 Monitoring .............................................................................................................. 3
3.1.1 Monitoring in residential dwellings ........................................................... 4
3.1.2 Monitoring for schools, multi-dwelling residences and large buildings .... 4
Part II. Science and Technical Considerations ............................................................................... 6
4.0 Identity, use and sources in the environment ...................................................................... 6

4.1 Environmental fate .................................................................................................. 7
4.2 Sources of lead in drinking water ........................................................................... 8
5.0 Exposure ............................................................................................................................. 9

5.1 Water ....................................................................................................................... 9
5.1.1 Canadian exposure to lead from drinking water ...................................... 11
5.1.2 Sampling to assess exposure to lead from drinking water ....................... 14
5.2 Food ...................................................................................................................... 17
5.3 Air ......................................................................................................................... 18
5.3.1 Ambient air............................................................................................... 18
5.3.2 Indoor air and dust.................................................................................... 19
5.4 Consumer products ............................................................................................... 19
5.5 Soil ........................................................................................................................ 20
5.6 Blood lead levels in Canada .................................................................................. 20
5.7 Multi-route exposure through drinking water ....................................................... 22
6.0 Analytical methods ........................................................................................................... 22

6.1 Sample preparation ............................................................................................... 23
7.0 Treatment technology and distribution system considerations ......................................... 24

7.1 Municipal scale ..................................................................................................... 25
7.1.1 Treatment considerations ......................................................................... 26
7.1.2 Distribution system considerations .......................................................... 26
7.1.2.1 Lead service lines ....................................................................... 26
7.1.2.2 Correlation between particulate lead and iron ........................... 28
7.1.2.3 Brass alloys ................................................................................ 28
7.1.2.4 Mitigation strategy for lead service lines ................................... 29
7.1.2.5 Mitigation strategy for distribution and plumbing systems ....... 30
Lead (March 2019)
7.1.2.6 Mitigation strategy for impacts resulting from treatment .......... 30

7.2 Residential scale.................................................................................................... 31
8.0 Kinetics and metabolism ................................................................................................... 33

8.1 Absorption............................................................................................................. 33
8.2 Distribution ........................................................................................................... 35
8.3 Metabolism ........................................................................................................... 36
8.4 Excretion ............................................................................................................... 36
8.5 PBPK models ........................................................................................................ 37
8.5.1 O’Flaherty model ..................................................................................... 37
8.5.2 Leggett model ........................................................................................... 38
8.5.3 IEUBK model ........................................................................................... 39
9.0 Health effects .................................................................................................................... 40

9.1 Effects in humans .................................................................................................. 40
9.1.1 Acute toxicity ........................................................................................... 40
9.1.2 Subchronic and chronic toxicity and carcinogenicity .............................. 41
9.1.2.1 Neurological effects ................................................................... 41
9.1.2.2 Cardiovascular effects ................................................................ 43
9.1.2.3 Renal effects............................................................................... 45
9.1.2.4 Cancer ........................................................................................ 46
9.1.3 Developmental and reproductive toxicity ................................................ 48
9.1.3.1 Reproductive effects .................................................................. 48
9.1.3.2 Neurodevelopmental effects ...................................................... 49
9.2 Effects on experimental animals ........................................................................... 52
9.2.1 Acute toxicity ........................................................................................... 52
9.2.2 Short-term exposure ................................................................................. 52
9.2.2.1 Neurological effects ................................................................... 52
9.2.2.2 Cardiovascular effects ................................................................ 53
9.2.2.3 Renal effects............................................................................... 54
9.2.3 Long-term exposure and carcinogenicity ................................................. 54
9.2.4 Genotoxicity ............................................................................................. 55
9.2.4.1 In vitro findings.......................................................................... 55
9.2.4.2 In vivo findings .......................................................................... 56
9.2.5 Reproductive and developmental toxicity ................................................ 56
9.2.5.1 Reproductive effects .................................................................. 56
9.2.5.2 Neurodevelopmental effects ...................................................... 57
9.3 Mode of action ...................................................................................................... 58
9.3.1 Neurodevelopmental effects ..................................................................... 59
9.3.2 Cancer....................................................................................................... 60
9.3.3 Increases in blood pressure ...................................................................... 61
10.0 Classification and assessment ........................................................................................... 62

10.1 Cancer risk assessment ......................................................................................... 63
10.2 Non-cancer risk assessment .................................................................................. 64
10.3 Comparison of cancer and non-cancer risk assessments ...................................... 68
10.4 International considerations .................................................................................. 68
Guidelines for Canadian Drinking Water Quality: Guideline Technical Document

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Lead (March 2019)
11.0 Rationale ........................................................................................................................... 69
12.0 References ......................................................................................................................... 70
Appendix A: List of acronyms .................................................................................................... 105

v
March 2019
Lead in Drinking Water

Part I. Overview and Application
1.0 Guideline
The maximum acceptable concentration (MAC) for total lead in drinking water is
0.005 mg/L (5 µg/L), based on a sample of water taken at the tap and using the appropriate
protocol for the type of building being sampled. Every effort should be made to maintain lead
levels in drinking water as low as reasonably achievable (or ALARA).
2.0 Executive summary

Lead is usually found in drinking water as a result of leaching from distribution and
plumbing system components, particularly in aggressive (corrosive) waters. Historically, lead
has been used extensively in service lines, solders and fittings, making its presence in drinking
water more likely in older homes and neighbourhoods.
This guideline technical document reviews and assesses all identified health risks
associated with lead in drinking water. It assesses new studies and approaches and takes into
consideration the availability and limitations of appropriate treatment and analytical
technologies. The information contained in this document is complementary to that found in
Guidance on Controlling Corrosion in Drinking Water Distribution Systems.
2.1 Health effects

Inorganic lead compounds have been classified as probably carcinogenic to humans,
based on findings in experimental animals. However, the cancer effects are not the main health
effects of concern in humans.
The toxicity of lead has been extensively documented in humans, based on blood lead
levels (BLLs). Effects that have been studied include increased blood pressure and renal
dysfunction in adults, as well as adverse cognitive and behavioural effects in children. The
strongest association observed to date is between increased BLLs in children and reductions in
intelligence quotient (IQ) scores, which is the key health endpoint of concern. The threshold
below which lead is no longer associated with adverse neurodevelopmental effects has not been
identified. As the MAC exceeds the drinking water concentration associated with
neurodevelopmental effects in children, every effort should be made to maintain lead levels in
drinking water as low as reasonably achievable (or ALARA)
2.2 Exposure
Lead is commonly found in the environment, both naturally and as a result of human
activities. Canadians are exposed to small amounts of lead in water, food, air, soil and consumer
products. Lead has historically been used in drinking water distribution and plumbing systems,
as well as in paints and as an additive in gasoline. Significant reductions of lead in products such
as gasoline and paints mean that food and drinking water have become more important sources
of lead exposure for average adult populations. Inhalation can also be an important source for
individuals residing in the vicinity of point sources, such as racetracks and airports where leaded
gasoline may still be used.
Lead (March 2019)
2.3 Analysis and treatment

The establishment of a drinking water guideline must take into consideration the ability
to measure the contaminant. There are several methods available for the analysis of total lead in
drinking water. Based on the capacity of commercial laboratories in Canada, analytical methods
are available to reliably measure total lead in drinking water below the MAC. These methods
require sample preparation steps to ensure that they are able to detect both dissolved and
particulate lead.
The guideline development process also considers the ability to remove the contaminant
from drinking water supplies to meet the MAC. Although there are treatment technologies that
can remove lead efficiently at the treatment plant, municipal treatment alone is may not be an
effective strategy to reduce lead to concentrations at the tap below the MAC. This is because
materials used in the distribution and plumbing systems, such as service lines, solder and fittings,
may contain lead, which may leach into the water and be found at the tap as a result of corrosion
in these systems. Consequently, the best approach to minimize exposure to lead from drinking
water at the municipal level is to remove the full service line and to control corrosion in the
distribution and treatment systems.
As the primary source of lead in drinking water is the leaching from distribution and
plumbing system components, drinking water treatment devices offer an effective option to
lower exposure to lead from drinking water at the residential level. However, their use should not
be considered to be a permanent solution because filters must be replaced regularly and the
systems require ongoing maintenance. There are a number of certified residential treatment
devices available that can remove lead from drinking water.
2.4 International considerations

Drinking water guidelines, standards and/or guidance from other national and
international organizations may vary due to the age of the assessments as well as differing
policies and approaches, including the choice of key study and the use of different consumption
rates, body weights and allocation factors.
Various organizations have established values for lead in drinking water. The U.S. EPA
has not established a maximum contaminant level for lead in drinking water, but has a maximum
contaminant level goal of zero, and has established an action level of 0.015 mg/L (15 µg/L ) in
its treatment-based Lead and Copper Rule, though a revision of this rule is currently underway.
The World Health Organization has established a provisional drinking-water quality guideline of
0.01 mg/L (10 µg/L), the European Union directive includes a parametric value of 0.01 mg/L (10
µg/L), and the Australian National Health and Medical Research Council has established a
guideline value of 0.01 mg/L (10 µg/L) for lead in drinking water.
3.0 Application of the guideline

Note: Specific guidance related to the implementation of drinking water guidelines
should be obtained from the appropriate drinking water authority in the affected jurisdiction.
The MAC for lead is established based on feasibility rather than only health protection.
This is because lead is introduced in drinking water in the distribution and plumbing systems,
after the treated water leaves the treatment plant. As current science cannot identify a level
under which lead is no longer associated with adverse health effects, lead concentrations in
drinking water should be kept as low as reasonably achievable (ALARA). Since formula
reconstituted with tap water can represent a major source of exposure to lead in infants,
alternate sources should be used if the tap water contains lead.

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Lead (March 2019)
Considering that lead levels at the consumer’s tap may be significantly higher than levels
at the treatment plant or in the distribution system, strategies to reduce exposure to lead will
need to focus on controlling corrosion within the distribution and plumbing systems and on
removing lead-containing components, such as lead service lines, from these systems. Although
it is recognized that a utility’s responsibility does not generally include residential plumbing
systems, most of the established guidelines are intended to apply at the consumer’s tap. Lead
monitoring should focus on areas known or likely to have lead service lines or that have older
buildings and should include zones supplied by potentially corrosive water (e.g., dead ends in a
chloraminated system) and consecutive systems (i.e., public water systems whose drinking
water supply is from another public water system).
An exceedance of the MAC should be investigated and followed by the appropriate
corrective actions. These actions include, but are not limited to, resampling, public education,
removal of lead service lines and corrosion control measures. It should be kept in mind that
flushing the cold water tap has not been found to sufficiently reduce lead exposure in schools,
multi-dwelling residences and large buildings in a consistent fashion. These actions should be
based on an assessment of the cause of the exceedance using appropriate protocols, such as
those found in the Health Canada publication Guidance on Controlling Corrosion in Drinking
Water Distribution Systems.
Discoloration (red water) episodes are likely to be accompanied by the release of
accumulated contaminants, including lead because dissolved lead is adsorbed onto iron deposits
in the lead service line. Therefore, discolored water events should not be considered only as an
aesthetic issue, but should trigger sampling for metals and possibly distribution system
maintenance.
3.1 Monitoring
Sampling protocols will differ, depending on the desired objective (i.e., identifying
sources of lead, controlling corrosion, assessing compliance, estimating exposure to lead). As
monitoring of lead at the tap can be done using different sampling protocols, it is important that
the selected protocol be appropriate to meet the desired objective.
The objective of sampling protocols in this document is to monitor for typical community
exposure to total lead to determine whether there are concerns related to effects on human health.
Compliance monitoring should be conducted at the consumer’s tap, with priority given to
identifying homes with lead service lines, as these are likely to have the highest lead
concentrations. If the objective is to characterize whether distributed water is corrosive to the
materials found in the distribution system and household plumbing, the Guidance on Controlling
Corrosion in Drinking Water Distribution Systems should be used.
In order to identify zones with lead issues, sampling protocols should initially capture the
entire distribution system. However, utilities that have already identified zones/areas of concern
can focus on further characterization of these zones. The determination of the source of the lead
issues can help select the most appropriate mitigation measures within identified zones. For
example, the province of Québec currently uses a full flush protocol in areas with homes
suspected of having lead service lines. The protocol compares the results from a fully flushed
sample against a specified lead threshold, validated through studies, to confirm homes with lead
service lines and subsequently prioritize for mitigation measures. A list of sample types,
protocols and the objective of each of these protocols can be found in section 5.1 of this
document.
Schools and daycare facilities should also be prioritized for monitoring to ensure that the
most sensitive population (i.e., young children) is captured. However, a different sampling

3
Lead (March 2019)
protocol may need to be considered for schools, daycare facilities and larger buildings or
dwellings. It is difficult to assess exposure in these buildings because of their unique and
complex plumbing configurations and the large number of pipes and plumbing components.
Sampling should be conducted at least once per year, with the number of sites to be monitored
determined based on the size of the drinking water system and the type of building, as discussed
below.
3.1.1 Monitoring in residential dwellings

Random daytime (RDT) and 30 minute stagnation (30MS) sampling protocols can both
be used for residential sites, as they capture typical exposures, including potential exposure to
particulate lead. They are considered appropriate for identifying priority areas for actions to
reduce lead concentrations and assessing compliance. Although both RDT and 30MS are suitable
for evaluating the effectiveness of corrosion control strategies, RDT sampling is used system-
wide and 30 MS sampling is typically used at sentinel sites. Due to its random nature, RDT
sampling requires 2-5 times more samples than 30MS to be statistically robust. Whereas RDT
sampling is relatively inexpensive, more practical to implement and generally more acceptable to
the consumer than 30MS sampling, the 30MS sampling protocol can also be used for
investigating the cause of exceedances and identifying appropriate mitigation measures.
Sampling programs should be conducted throughout the year to take into account
seasonal effects on lead variability. Sampling should be conducted at the cold water tap in the
kitchen or other appropriate location where water is used for drinking or food preparation.
Regardless of the protocol used, all samples should be collected in wide-mouth sample bottles,
and without removing the aerator. The samples need to be acidified using a 2% nitric acid
solution (by volume) and held for a minimum of 16 hours after preservation with nitric acid
before analysis. Each sample should be thoroughly mixed prior to analysis using an appropriate
method (see Section 6.0).
For RDT sampling, the establishment of a lead service line inventory will help identify
water supply zones (geographical areas within which the quality of drinking water is considered
approximately uniform) that are more likely to have high lead concentrations. Monitoring
programs are conducted within defined water supply zones, which can vary in size but generally
should not exceed 50,000 residents each. It is recommended that total lead be monitored, at least
once per year, at the tap of a minimum of 20 randomly selected residences in each water supply
zone.
RDT sampling: A 1 L sample should be collected randomly during the day from a drinking water
tap in each of the residences. Samples should be collected without prior flushing; no stagnation
period is prescribed, to better reflect consumer use.
30MS sampling: The tap should be flushed for 5 minutes, allowed to stand for a 30-minute
stagnation period, during which time no water should be drawn from any outlet within the
residence (including flushing of toilets). Two 1 L samples should then be collected at a medium
to high flow rate (greater than 5 L/minute). The lead concentration is determined by averaging
the results from the two samples.
3.1.2 Monitoring for schools, multi-dwelling residences and large buildings

In schools and daycares, it is recommended that total lead be monitored, at least once per
year, at each of the drinking water fountains or cold water taps where water is used for drinking
or food preparation. Sampling should be conducted between the months of June and October, but

4
Lead (March 2019)
when the buildings are fully occupied and functional, to capture typical exposure levels –
recommended to be in either June or October for schools. Jurisdictions may choose to reduce
monitoring if they have established that the lead issues have been identified and addressed.
In multi-dwelling (i.e., more than six residences) buildings or large buildings, it is
recommended that total lead be monitored in a manner such that each of the drinking water
fountains and a proportion of cold water taps where water is used for drinking or food
preparation is sampled within a specified period. When sampling multi-dwelling buildings,
priority should be given to sites suspected or known to have full or partial lead service lines. A
RDT sampling protocol is recommended for these sites to capture typical exposures, including
potential exposure to particulate lead.
RDT sampling should be conducted by collecting a sample at drinking water fountains or
at cold water taps where water is used for drinking or food preparation, without a stagnation
period and without prior flushing. Two 125 mL samples should be collected, preferably in wide-
mouth sample bottles, at a medium to high flow rate without removing the aerator. The samples
need to be held for a minimum of 16 hours after they are acidified using a 2% nitric acid solution
(by volume) and prior to analysis. Each sample should be thoroughly mixed prior to being
analyzed using an appropriate method (see Section 6.0). The lead concentration is determined by
averaging the results from the two samples.
The sampling plan for schools and child care centres/facilities must consider that many
occupants in these buildings are the most susceptible to the adverse health effects from lead
exposure. Consequently, sampling plans for these facilities should prioritize every drinking water
fountain and cold water outlet used for drinking or food preparation over infrequently used
outlets. In other building types, sampling plans should also target drinking water fountains and
cold water outlets used for drinking or food preparation, but with the number of sites sampled
based on the size and population of the building.

5
Lead (March 2019)
Part II. Science and Technical Considerations
4.0 Identity, use and sources in the environment
Lead (Pb) is a dense, odourless, bluish-grey, lustrous metal that is malleable and
insoluble. Lead (Chemical Abstracts Service No. 7439-92-1) has a molecular weight of 207.2
g/mole, a melting point of 327.4°C, a boiling point of 1740°C and a density of 11.34 g/cm3 at
room temperature. There are no data pertaining to partition coefficients or Henry’s Law
constants for lead. Lead is a post-transition metal of Group IVA (14) of the periodic table. It can
be found in three oxidation states: Pb0 (elemental lead), Pb2+ (as part of plumbous lead
compounds) and Pb4+ (as part of plumbic lead compounds). Pb2+ and, to a lesser extent, Pb4+ are
the dominant forms of lead found in the environment. Although elemental lead is insoluble, lead
salts of the plumbous form can be highly water soluble (e.g., lead(II) nitrate) (ATSDR, 2007).
Lead is highly reactive and readily alloys with other metals, such as tin, antimony, copper and
zinc, to form more stable products. Assessment of lead levels in the environment generally
focuses not on the form of the metal, but rather on the lead moiety contained within an
unspecified substance.
Canada is an important producer and supplier of lead. In 2009, Canada ranked sixth in the
world in terms of refined lead production (estimated production of 101 484 tonnes) (Panagapko,
2009). Owing to its low melting point and excellent corrosion resistance, lead has been used
extensively in a variety of applications. When exposed to air and water, lead forms a protective
film composed of lead sulphate, lead oxides and lead carbonates, thus making it an ideal building
material for cable sheathing, circuit boards, chemical storage vessel linings, chemical
transmission pipes, electrical components and radiation shielding.
Soluble and insoluble lead compounds can be used as flame retardants (lead chloride),
heat stabilizers in nylon (lead nitrate), pigments in paints, plastics and rubber (lead chromate)
and catalysts for various chemical reactions (lead carbonate, lead fluoride and lead fluoborate),
among various other uses. They are also used in the manufacturing of varnishes and chrome
pigments (lead acetate trihydrate), asbestos clutch and brake linings (lead chloride), matches and
explosives (lead nitrate), munitions (lead azide and lead styphnate) and galvanic batteries (lead
sulphate), as well as numerous other manufacturing processes (Health Canada, 2013c).
Lead service connections (lines) were installed in drinking water systems in many
countries, including Canada. Widespread installation of lead service lines occurred in Canada
until 1975. Additionally, the use of solder containing lead for new plumbing and in repairs to
plumbing continued until 1986. As a result, plumbing and distribution system materials can be an
important source of lead in tap water of homes built prior to the 1990s (Health Canada, 2009b).
Lead may be found in brass and bronze fittings, such as faucets and valves, and fixtures, such as
refrigerated water coolers and drinking water fountains commonly used in schools and other
non-residential buildings. Selected components of water coolers, such as soldered joints within
the fixtures or the lining of the tank, may contain lead alloys (U.S. EPA, 2006, 2018). Until
recently, most brasses contained between 2% and 8% lead (Health Canada, 2009b). In the United
States, legislation limiting the weighted average lead content of pipes, pipe fittings and plumbing
fittings to 0.25% became effective in January 2014 (U.S. EPA, 2011b). The National Plumbing
Code of Canada (NPC) was amended in November 2013 to reference plumbing standards with
requirements for the 0.25% lead limit (NRCC, 2013).
Lead (lead(II) chromate) was also added in significant quantities (ranging from 10% to
50%) to household and industrial paints until the 1960s, as a pigment and drying agent. Although
the lead content in indoor paint and paints used to coat furniture or products designed for

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Lead (March 2019)
children was further reduced to 90 mg/kg (0.009%) in 2010 (Government of Canada, 2010a;
Health Canada, 2010a, 2010b), opportunities for lead exposure still exist in older homes and
buildings.
Organic lead compounds (e.g., tetraethyl lead, tetramethyl lead) were also added to motor
vehicle fuel until 1993, when this use of lead was prohibited in Canada, other than for piston
engine aircraft and racing fuels for competition vehicles. Worldwide reductions of lead in fuels
started in the early 1970s and were followed by a complete phasing out of leaded fuels for use in
on-road vehicles for many countries in the 1990s (OECD/UNEP, 1999). Lead can also be present
in some products used in recreational activities, including weights for fishing and diving, lead
shot for hunting, artist-grade paints and glazes for pottery, as well as glass blowing and screen
printing supplies. However, there are no permissible uses of lead in food or cosmetics in Canada
(Health Canada, 2012a).
Since the prohibition of leaded fuels, the primary source of lead in the environment has
been the mining and smelting of lead ores and ores in which lead is a by-product or contaminant
(ATSDR, 2007). Release of lead also occurs from factories that use lead, lead alloys and other
lead compounds. Other significant sources include air travel, owing to the use of leaded fuels in
smaller aircraft, and electrical utilities that release lead as a result of burning coal and other lead-
contaminated fuels. The release of lead in the environment has been monitored by Environment
Canada’s National Pollutant Release Inventory (NPRI). In 2009, lead release was estimated to be
260 000 kg in air, 16 000 kg in water and 160 000 kg on land, for a total of 436 000 kg (Health
Canada, 2013a). However, these numbers are assumed to be underestimates of total release
because of the number of facilities that are not required to report to the NPRI, as well as
additional lead sources. Despite lead reduction measures, lead exposure remains a concern
because of the presence of older lead-containing materials in the environment and ongoing uses
of lead.
4.1 Environmental fate

Lead released in the atmosphere exists primarily in the form of particles. Small lead
particles can travel considerable distances, whereas larger particles (i.e., > 2.5 μm) tend to settle
out of the atmosphere rapidly and deposit relatively close to the emission source. Lead is
removed from air primarily through rain, but it can also precipitate via dry deposition. Various
compounds of lead are released in the atmosphere as a result of the many emission sources. The
primary forms are lead(II) sulphate and lead(II) carbonate (ATSDR, 2007).
Additional lead can deposit onto soil from chipping and weathering of lead-based paints
from housing, buildings and other structures. The association of lead with soil particles is very
strong. For this reason, past uses of lead, including its addition to gasoline, represent an
important contribution to lead levels measured in soils today (ATSDR, 2007). The mobility of
lead in soil is generally limited; thus, deposited lead will tend to remain in the upper layer of the
soil, with limited leaching to groundwater. However, the fate of lead will depend on many
factors, including soil pH, soil type, organic matter content in soil and the concentration of lead
within the soil (NSF, 1977; Reddy et al., 1995). Acidity greatly increases the solubility of lead
and is considered the most important factor in determining lead mobilization. Solubilisation can
occur at pH levels below 6 and increases substantially in more acidic conditions (U.S. EPA,
1986). In addition to acidic conditions, decreased organic matter onto which lead can be
adsorbed and the presence of lead at concentrations that exceed or approach the cation exchange
capacity of soil will also increase the mobility of lead, leading to potential runoff to surface
water, leaching to groundwater or uptake by plants. Such environmental conditions are more
likely to occur near lead smelting sites.

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Lead (March 2019)
Lead can be found in surface water, but generally at low concentrations. Soluble lead
concentrations will generally increase with acidic conditions (i.e., low pH). The dissolved salt
content is another important factor in determining lead solubility and, thus, the concentration of
lead in surface water. Above pH 5.4, the solubility of lead is approximately 500 μg/L in soft
water, whereas it is only 30 μg/L in hard water (ATSDR, 2007). However, a significant portion
of lead found in surface water consists of insoluble particles of lead compounds or lead-
containing soil particulate resulting from erosion. The concentrations of lead in mountain
drainage water were shown to be similar to levels from the weathering of bedrock and soil. Lead
particles were shown to coprecipitate and adsorb onto surfaces of iron-rich particles, such as iron
oxides. The resulting iron/lead ratio was found to be relatively constant in the bedrock, the soil,
soil and rock leachates, unfiltered and filtered groundwater and filtered and unfiltered stream
water (Erel et al., 1991; Erel and Morgan, 1992).
Lead compounds can be degraded or chemically transformed within air, soil and water.
However, the elemental lead within these compounds cannot be broken down.
Lead does not biomagnify in aquatic or terrestrial food chains. However,
bioconcentration can occur in plants and animals, especially in areas that are contaminated by
lead. Older organisms tend to contain the greatest body burdens of lead. Organisms that are in
contact with soil and sediment, such as aquatic benthic invertebrates and algae, tend to contain
the highest levels of lead.
4.2 Sources of lead in drinking water

Lead is present in tap water principally as a result of dissolution (corrosion) from
components of distribution and household plumbing systems that contain lead, such as pipes,
fittings, solder or service connections to homes. Corrosion can be caused by several factors,
including the type of materials used, the age of the piping and fittings, the stagnation time of the
water in pipes and the water quality (e.g., pH and alkalinity) in the system (Health Canada,
2009b).
Lead service lines have been shown to be a consistently high source of lead for many
years after being installed under various conditions (Britton and Richards, 1981; Schock et al.,
1996; Sandvig et al., 2008; Cartier et al., 2011, 2012a; Xie and Giammar, 2011). Lead service
lines can contribute 50–75% of the total lead at the tap after extended stagnation times (Sandvig
et al., 2008). Lead concentrations at the tap originating from lead solders and brass fittings were
thought to decline with age, with the highest lead concentrations appearing in the first year
following installation (Birden et al., 1985; Boffardi, 1988, 1990; Schock and Neff, 1988; Boyd et
al., 2008a). Studies, conducted under continuous flow conditions, have shown that when lead is
released in the dissolved form from solder and fittings, concentrations diminish over time
(Kirmeyer et al., 2007; Zhang and Edwards, 2011; Boyd et al., 2012). A number of studies have
identified several factors that can result in the release of high levels of lead into the water long
after installation of lead service lines, solders and brass fittings, including water quality
characteristics (e.g., temperature, pH, alkalinity, chloride levels), stagnation time, water flow,
lead content and surface area of lead and brass fittings (Lee et al., 1989; Maas et al., 1991;
Dodrill and Edwards, 1995; Lytle and Schock, 1996, 2000; Oliphant and Schock, 1996; Schock
et al., 1996; Reiber et al., 1997; Kimbrough, 2001, 2007, 2009; Sandvig et al., 2007, 2008;
Elfland et al., 2010; Schock and Lytle, 2011; Deshommes et al., 2012b; Clark et al., 2014).
Lead release can be significant when particulate material is present in the water or is
subsequently trapped in the tap aerator. The sources of these particulates include lead solder
particles, pipe deposit solids, dezincification of brasses and adsorption onto iron or manganese
particles originating from the distribution system (Hulsmann, 1990; Lytle et al., 1993;

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Lead (March 2019)
Triantafyllidou et al., 2007; Deshommes et al., 2010a; Zhang and Edwards, 2011; Cartier et al.,
2012c; Schock et al., 2014).
The relative contribution of lead in dissolved lead and particulate forms is not clearly
understood and likely varies with water chemistry, plumbing configuration, stagnation time, flow
regime, age of the plumbing materials containing the lead and use patterns (Hulsmann, 1990;
Deshommes et al., 2010a, 2012b; Schock and Lytle, 2011; Xie and Giammar, 2011; Cartier et
al., 2012a, 2013; Wang et al., 2012; Welter et al., 2013; Clark et al., 2014). The presence of
particulate lead in drinking water is sporadic, unpredictable and often associated with mechanical
disturbances to the system; it has been shown to also result from galvanic corrosion (Sandvig et
al., 2008; Deshommes et al., 2010, 2012b; Triantafyllidou and Edwards, 2010; Schock and Lytle,
2011; Cartier et al., 2012a, 2013; Wang et al., 2012, 2013; Clark et al., 2014).
Galvanic solder corrosion resulting from disinfectant or coagulant changes has been
identified as an important factor leading to elevated lead levels (Edwards and Dudi, 2004;
Edwards and Triantafyllidou, 2007; Nguyen et al., 2010). Several studies have identified changes
in the chloride to sulphate mass ratio (CSMR) resulting from a coagulant change as the driver of
lead release from brass due to galvanic corrosion (Edwards and Triantafyllidou, 2007; Nguyen et
al., 2010; Triantafyllidou and Edwards, 2010; Cartier et al., 2012c, 2013). Galvanic corrosion
resulting from partial lead service line replacement has also been shown to increase
concentrations of both dissolved and particulate lead (Sandvig et al., 2008; Deshommes et al.,
2010a, 2012b; Triantafyllidou and Edwards, 2010; Schock and Lytle, 2011; Cartier et al., 2012a,
2013; Wang et al., 2012, 2013; Clark et al., 2014).
Lead has also occasionally been found in drinking water as a result of the weathering of
certain rock formations into the groundwater (Hamilton Health and Social Services, 2006). In
2006, a public health advisory was issued to all rural City of Hamilton residents located above
the Niagara Escarpment whose drinking water supply was obtained from a drilled well.
Residents were advised that there was a potential for high lead levels in some wells due to
naturally occurring lead in the bedrock (Richardson, 2006). Sweeney et al. (2017) analysed lead
from 2,750 fully flushed drinking water samples obtained from private wells (dug and drilled),
municipal supplies and unknown sources. The authors found that drinking water obtained from
dug wells had 4.4% of samples exceeding 10 µg/L compared to 1.8% for drilled wells and 0.7%
for municipal water supplies. The authors did not determine if the source of lead was the water
supply or the result of leaching lead from materials in the plumbing system.
5.0 Exposure
Lead is found ubiquitously in the environment as a result of its extensive anthropogenic
use over a substantial period of time as well as its natural occurrence. Canadians are exposed to
small amounts of lead through various environmental media, including water, food, air and soil,
as well as consumer products. Water was historically assumed to account for 14–20% of lead
exposures (U.S. EPA, 1991, 2005). However, food and drinking water have now become more
important sources of lead exposure for average adult populations, because of significant
reductions of lead in products such as gasoline and paints. Inhalation can also be an important
route of exposure for individuals residing in the vicinity of point sources.
5.1 Water
Exposure to lead in drinking water can be properly assessed only by monitoring lead
levels at the tap. This is because lead is present in tap water principally as a result of dissolution

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Lead (March 2019)
(corrosion) from components of distribution and household plumbing systems that contain lead.
However, as discussed below, the concentration of lead can vary significantly both across a
system and within an individual site as water use, flow rate and stagnation time between use vary
(Karalekas et al., 1978; Bailey and Russell, 1981; AwwaRF, 1990; Schock, 1990; U.S. EPA,
1991; Triantafyllidou et al, 2007; Schock and Lemieux, 2010; Deshommes, 2010a; Cartier et al.,
2011, 2012a; Schock and Lytle, 2011; Wang et al., 2012, 2013; Del Toral et al., 2013; Clark et
al., 2014 ). This variability makes the assessment of lead exposure from drinking water
challenging. Monitoring of lead at the tap (as discussed in Section 3) can be done using different
sampling protocols; the selection of an appropriate protocol must take into consideration the
desired objective, such as identifying sources of lead, effectively controlling corrosion or
estimating exposure to lead. Table 1 provides a list of objectives and the type of sampling to
undertake as well as a description of the protocols to achieve those objectives.
Sampling volumes vary in order to accommodate plumbing configurations as well as
ensure the representativeness of the exposure. For example, in a single family home, typically a
1 L volume is drawn. However, for a 30MS sample, a 1 L sample would underestimate the lead
concentration due to the limited contact time (stagnation). Therefore, it was determined two
consecutive 1 L samples should be taken for this protocol (European Commission, 1999), which
would permit the identification of the source of lead. Volumes ingested at a drinking water
fountain in a school environment are typically much smaller. Collection of a sample volume that
is smaller (250 mL) than those typically used in residential buildings (1 L) is considered
important for sampling in non-residential buildings as it is more representative of potential
exposure. In addition, these smaller samples represent the water from the fitting (fountain or
faucet) and a smaller section of plumbing and has the added benefit of being more effective at
identifying the source of lead at an outlet (U.S. EPA, 1994a, 2006a). For this reason, breaking
down the smaller volume into smaller samples (two 125 mL samples, multiple smaller volumes,
etc.) during the sampling event has the benefit of not having to return to the location to re-sample
to identify the source of lead. However, the disadvantage is the added burden and cost of
analyzing multiple samples that make up the 250 mL samples.

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Lead (March 2019)
Table 1: Sampling types, protocols and objectives of sampling
Objective Sampling type Protocol
6+ hr stagnation
Regulatory First draw (U.S. EPA)
Collect 1 L
compliance
for lead Random sample collection without prior flushing
RDT (UK/EU) Captures variable stagnation
and/or Collect 1 L
Corrosion 2–5 min. flush

control efficacy 30MS (Ontario) 30 min. stagnation
Collect first two liters
Profile (or sequential) Defined stagnation time
Determination of
sampling 10–20 sequential samples of a defined volume
lead sources
–traditional (125 mL, 250 mL, 1 L, etc.)
(plumbing/lead
service line)
Profile sampling that Traditional profile sampling at increasingly
and/or stimulates particle release higher water flow rate (low, medium and high)
5 min. flush
Identification of Fully flushed sampling Collect 1 L and compare to validated threshold
type of lead for presence of LSL
Overnight stagnation
3T’s for schools and Collect first 250 mL from all taps and fountains
Sample results from each facility should be
childcare facilities: revised
compared to prioritize follow-up sampling and
manual, U.S. EPA
remediation (done in consultation with the
drinking water authority at the State level)
Captures actual water use (and variability)
Composite proportional Device collects 5% of every draw from the tap
for consumption during 1 week
Exposure 5 min. flush
assessment 30MS 30 min. stagnation; captures inter-use time
Collect first two liters and average results
Random sample collection without prior flushing
RDT Captures variable stagnation and inter-use time
Collect 1 L
5.1.1 Canadian exposure to lead from drinking water

Lead concentrations were sampled at 65 sites in all provinces and territories in the
summer and winter seasons during 2009–2010 for the National Survey of Disinfection By-
Products and Selected Drinking Water Contaminants in Canadian Drinking Water (2009–2010)
(Health Canada, 2014). However, the results are not statistically representative of Canadian

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Lead (March 2019)
population exposure. Samples were collected from the distribution system after 10 minutes of
flushing, representing treated and distributed water, and analyzed after hot acid digestion by
inductively coupled plasma–mass spectrometry (ICP-MS), with a method detection limit (MDL)
of 0.5 µg/L. The average concentration in winter was 0.9 μg/L, with concentrations ranging from
< 0.5 to 8.2 μg/L. The average concentration for summer samples was 1.27 μg/L, with
concentrations ranging from < 0.5 to 24 μg/L.
Provincial, territorial and municipal databases that include lead concentrations in
drinking water supplies are available. These compliance databases contain the results of water
quality analyses, including the concentrations of lead. It must be recognized that many provinces
and territories currently assess compliance for lead based on a flushed sample, which is not
representative of exposure (European Commission, 1999).
The Ontario Drinking Water Surveillance Program database includes concentrations of
lead in raw and treated water as well as concentrations of lead at the tap (OMOE, 2014).
Between 2000 and 2007, the annual median lead concentrations measured in 5947 samples of
treated and distributed water ranged from < 0.01 to 0.32 μg/L (OMOE, 2014). The lead
concentrations ranged from below 0.01 to 359 μg/L. However, when the single sample site with
the lead concentration of 359 μg/L was resampled three times, lead concentrations were all found
to be below 1.68 μg/L. The Province of Ontario changed its regulatory requirements for
sampling of lead in June 2007 and now requires that samples be collected after 30 minutes of
stagnation from homes known or suspected to have lead service lines (Government of Ontario,
2014). In a Community Lead Testing Program conducted in 2007–2008, lead concentrations
were analyzed in more than 37 000 samples collected in two sampling campaigns. During these
sampling campaigns, it was determined that ≤ 3.1% of the samples exceeded the regulated level
of 10 µg/L. Subsequent to these campaigns, eight communities were identified for another
sampling round in 2009. The concentrations of lead in 3159 samples collected were reported to
range from < 0.02 to 1320 μg/L (OMOE, 2014).
In Prince Edward Island, over 10,000 samples were collected from private wells between
2005 and 2010. Samples for this period had lead concentrations ranging from < 2 to 335 μg/L
with 88% of all samples containing lead at concentrations below the MDL of 2 μg/L (Prince
Edward Island Department of Environment, Energy and Forestry, 2011).
In Edmonton, Alberta, the reported median concentration of lead was < 0.5 μg/L (Alberta
Department of Environment and Sustainable Resource Development, 2011). In Portage la
Prairie, Manitoba, 159 samples were collected between 2008 and 2009, and lead concentrations
ranged from 0.1 to 36 µg/L, with an average concentration of 0.7 µg/L (Manitoba Conservation
and Water Stewardship, 2013). In Saskatchewan, the median lead concentration for 176 samples
analyzed was reported to be 6.7 μg/L, with the concentrations ranging from < 0.1 to 60 μg/L
(Saskatchewan Ministry of the Environment, 2011). Data from Quebec in 2013 and 2014
indicates that the annual median lead concentration from more than 23,000 samples was 1 μg/L
(concentrations of lead in tap water ranged from 0,01 to 977 μg/L) (Ministère du Développement
durable, de l’Environnement et de la Lutte contre les changements climatiques, 2017). In
Newfoundland and Labrador, 5331 tap water samples were collected between 2005 and 2010 and
reported to have lead concentrations ranging from < 0.1 to 60 μg/L (Newfoundland and Labrador
Department of Environment and Conservation, 2011). In Yukon, lead concentrations ranging
from < 0.1 to 7.6 μg/L were detected in 125 tap water samples collected between 2005 and 2010
(Yukon Environmental Health Services, 2011).
A number of corrosion studies have been undertaken since 2007. The studies used a
variety of sampling protocols with highly variable results for lead in drinking water (Hayes and
Croft, 2012; Health Canada, 2013c; Hayes et al., 2014).

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Lead (March 2019)
In Alberta, a corrosion optimization study analyzed lead levels in 12 sequential 1 L
samples from 12 homes supplied by a lead service line in Edmonton and Calgary (six homes in
each city) after 30 minutes and 6 hours of stagnation. The peak lead concentrations for
Edmonton ranged from 1.3 to 31.8 µg/L and from 3.0 to 62.7 µg/L after 30 minutes and 6 hours
of stagnation, respectively. The peak lead concentrations for Calgary ranged from 5.7 to 39.6
µg/L and from 9.1 to 96.5 µg/L after 30 minutes and 6 hours of stagnation, respectively (Hayes
et al., 2014).
In Manitoba, a study was conducted to assess worst case lead levels in water from homes
and schools in the cities of Brandon and Portage la Prairie. Samples from homes supplied with a
lead service line were collected after 6 hours of stagnation in four consecutive 1 L samples and
subsequently after flushing for 5 minutes. For Brandon, the average lead concentrations were
39.2 µg/L (ranging from non-detect to 280 µg/L, n = 80) for the four 1 L stagnant samples and
21.62 µg/L (ranging from non-detect to 79 µg/L, n = 20) for the flushed samples. For Portage la
Prairie, the average lead concentrations were 19.3 µg/L (ranging from 0.61 to 140 µg/L, n = 72)
for the four 1 L stagnant samples and 3.62 µg/L (ranging from 0.55 to 21 µg/L, n = 14) for the
flushed samples (Manitoba Conservation and Water Stewardship, 2013). This study also
included the collection of first-draw, 30-second flushed and 5-minute flushed samples from
schools in Brandon and Portage la Prairie (five schools in each city). For schools in Brandon, the
average lead concentrations were 11 µg/L (range: 2.7–27 µg/L), 3.4 µg/L (range: 0.54–13 µg/L)
and 1.33 µg/L (range: 0.59–2 µg/L) for first-draw, 30-second flushed and 5-minute flushed
samples, respectively. For schools in Portage la Prairie, the average lead concentrations were
9.14 µg/L (range: 0.5–36 µg/L), 0.93 µg/L (range: 0.5–2.2 µg/L) and 0.55 µg/L (0.5–0.75 µg/L)
for first-draw, 30-second flushed and 5-minute flushed samples, respectively. Total lead
concentrations were decreased after 30 seconds of flushing in 9 of 10 schools and greatly
decreased after 5 minutes of flushing in all schools (Manitoba Conservation and Water
Stewardship, 2013).
Seven Canadian elementary schools and one high school built before 1970 were sampled
to assess human exposure to lead and to develop a sampling protocol in large buildings (Doré et
al., 2014). Samples were taken at drinking water fountains and classroom taps (6–10 sites per
building) after 30 seconds and 5 minutes of flushing and 30 minutes and 8 hours of stagnation.
The study found that 72.7% of the 356 samples had lead concentrations below 5 µg/L and that
lead concentrations ranged from < 0.15 to 851 µg/L (average 11 µg/L). A large contribution of
particulate lead to the total lead concentration was seen when water was left to stagnate for as
little as 30 minutes. However, the authors also found that allowing the water to run for as little as
30 seconds before drinking significantly decreased the total lead concentration. Deshommes et
al. (2016) gathered lead results from 78,971 water samples from 8,530 non residential buildings
in four Canadian provinces, which included elementary schools and daycares, as well as
universities, hospitals and penitentiaries. The data were gathered from samples taken from cold
water taps used for consumption and using a variety of sampling protocols and volumes (6 h
stagnation; 30 sec. flush; 5 min flush or 30MS). Maximum concentrations reached 13,200 and
3,890 µg/L, respectively, following long and short stagnation periods. High lead levels were
persistent at all taps in some large buildings and at only a few taps in other buildings. The
authors found that lead concentrations were generally low and, based on biokinetic modelling
using the extensive database, anticipated that lead at the tap would not contribute to elevated
BLLs in young children and adults at the majority of the taps monitored. However, the data also
revealed some daycares and elementary schools presented system-wide lead release with extreme
lead concentrations that had the potential to cause acute lead exposure (i.e., BLL far exceeding 5
µg/dL) in young children.

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Lead (March 2019)
5.1.2 Sampling to assess exposure to lead from drinking water

Monitoring of lead at the tap can be done using different sampling protocols, but the
selected protocol must take into consideration the desired objective. Sampling protocols can be
used to identify sources of lead, effectively control corrosion, assess compliance and estimate
exposure to lead. They will vary based on factors such as desired stagnation time, sample
volume, sampling sites and sampling frequency (Schock, 1990; van den Hoven and Slaats, 2006;
Schock and Lemieux, 2010). The variability of lead concentrations across a system and within an
individual site represents the range of exposures that can occur in the population and must be
captured in the design of a monitoring scheme that provides reliable information with which to
evaluate exposure (Schock and Lytle, 2011).
For the purposes of this document, the objective of the sampling protocol is to represent
the average or typical exposure to lead in drinking water for a population (i.e., within the water
supply zone). It is important to note that a sampling protocol that assesses the average intake of
lead will not capture the highest concentrations of lead or the full contribution of lead from the
lead service line but will capture the variability of lead exposure. Currently, sampling protocols
in the United States under the Lead and Copper Rule are treatment based, with the objective of
using long stagnation times to capture the highest levels of lead (U.S. EPA, 1991). A similar
protocol is suggested in the guidance for corrosion control document published by Health
Canada
(2009b). These high levels permit a system-wide assessment of the efficacy of corrosion control
treatment before and after implementation, with the objective to minimize lead levels in drinking
water and, thus, indirectly reduce exposure to lead. The United Kingdom (UK) has documented
the effectiveness of system-wide RDT sampling for compliance monitoring and to assess the
performance and optimization of corrosion control (Cardew, 2000, 2003; Hayes and Croft, 2012;
Hayes et al., 2014).
The average intake of lead by an individual varies considerably as a result of several
factors, including consumer behaviour, configuration of the plumbing system (e.g., single-family
dwelling, apartment building, office building, school), water usage patterns (e.g., flow regime),
contact time of the water with the plumbing, seasonal effects and water chemistry (Cardew,
2000, 2003; van den Hoven and Slaats, 2006; Schock and Lytle, 2011; Deshommes et al., 2016).
Sampling methods used to assess exposure should ideally take these variations into account.
Studies have demonstrated that composite proportional sampling captures the inherent variability
of lead exposure from drinking water and is representative of this exposure (Anjou Recherche,
1994; van den Hoven and Slaats, 2006; Schock and Lytle, 2011). Composite proportional
sampling is achieved with a consumer-operated device fitted to the drinking water tap that splits
off a small, constant proportion of every volume of water drawn, typically over a period of 1
week. Composite proportional sampling requires equipment that is impractical for routine
monitoring and is better suited for long-term sampling.
A number of studies evaluated RDT, fully flushed (FF) and 30MS sampling protocols to
identify methods to estimate the average weekly concentration of lead at a consumer’s tap (i.e.,
composite proportional sampling) (Baron, 1997, 2001; European Commission, 1999; van den
Hoven and Slaats, 2006). In these studies, the RDT sampling consisted of the collection of a 1 L
sample from a drinking water tap without any prior flushing; the FF protocol involved the
flushing of approximately three plumbing (pipe) volumes of water (i.e., 5 minutes) before
collecting a 1 L sample; and the 30MS protocol involved collecting two 1 L samples after
flushing of three plumbing volumes of water and letting the water stagnate for 30 minutes prior
to sampling.

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Lead (March 2019)
The objective of the European Commission (1999) study was to determine which of these
three common sampling protocols was the most representative of a weekly average amount of
lead ingested by consumers. The performance of the tested protocols was evaluated in terms of
representativeness (i.e., estimating the average lead concentration at a consumer’s tap), cost,
reproducibility, practicality and consumer acceptability. The study was conducted in five
member countries and included a variety of water qualities (classified as low, medium and high
corrosivity). Each country undertook sampling at a minimum of two areas, selecting sampling
sites with at least 50% of the sites in each area/district being served by lead service lines.
The study determined that RDT sampling was representative and enabled the detection of
a large proportion of sites with lead issues. It also found that RDT was relatively inexpensive,
practical to implement and acceptable to consumers. RDT sampling was determined to have a
stagnation time close to or higher than the actual average inter-use stagnation time (i.e., accounts
for the water consumption pattern of the consumer) and to overestimate lead exposure. 30MS
sampling was found to be representative, to enable the detection of almost as many problem sites
as RDT sampling and to be more reproducible than RDT. However, 30MS sampling was found
to be relatively expensive, less practical to implement and more inconvenient for consumers. FF
sampling was not found to be representative and did not enable detection of sufficient problem
sites (European Commission, 1999). In other studies (Bailey et al., 1986; van den Hoven and
Slaats, 2006), RDT sampling was also found to be representative of the average inter-use
stagnation time of water in a residential setting.
Baron (2001) confirmed these findings during a study in France comparing the same
three types of sampling, but without undertaking composite proportional sampling. The author
found that at the zonal level, RDT and 30MS samples have very similar results when sampled for
a sufficient number of households. It was determined that random selection of properties
appeared to be a good solution for assessing the situation in a zone and helping to prioritize and
determine the types of actions to implement. RDT sampling was considered more practical and
acceptable to consumers, whereas 30MS sampling was found to be more reproducible and
equally representative. FF sampling was deemed to be unrepresentative of average
concentrations and provided only an indication of the minimum lead levels at the tap (Baron,
2001; van den Hoven and Slaats, 2006). As such, sampling protocols using a fully flushed
sample are not appropriate for assessing average exposure to lead in drinking water, although
they may be suitable for other objectives, such as identifying the location or presence of lead
service lines (Cartier et al., 2012b).The European Commission (1999) recommended that either
RDT or 30MS sampling be used for compliance monitoring purposes and zone assessment and
that corrosion control treatment be assessed using RDT sampling. Cardew (2003) concluded that
RDT was better correlated to true exposure than 30MS and that RDT sampling had a tendency to
give false positive (i.e., more conservative) lead exposure results. The study also found that
corrosion control effectiveness could be assessed using the RDT compliance data, making it a
useful tool for monitoring changes in lead levels over time and assessing the efficacy of
corrective treatment system-wide. In addition, it established that optimization could be modeled
to evaluate the point of diminishing returns for phosphate concentration on lead levels.
For the 30MS protocol, typical exposure is best reflected by taking the average lead
concentration of two 1 L samples collected. The reproducibility of the 30MS sample also makes
it a useful tool for monitoring changes in lead levels over time and assessing the efficacy of
corrective treatment at sentinel sites (Jackson, 2000). However, 30MS has a tendency to
underestimate lead exposure. When combined with profile sampling, 30MS can be used for
investigative purposes at individual homes (Cartier et al., 2011) and is representative of
household level exposure (Cardew, 2000). Results from RDT sampling are more variable than

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Lead (March 2019)
those from 30MS. Flushing prior to stagnation has been shown to eliminate accumulated
particles (van den Hoven and Slaats, 2006; Deshommes et al., 2010a, 2012b). However,
increased turbulent flow seen at higher flow rates has been associated with the presence of
particulate lead (Cartier et al., 2012a; Clark et al., 2014). In consideration of this, sampling
should be conducted at medium to high flow rates (> 5 L/minute) to capture particulate lead
release for the sampling protocol.
Many factors contribute to the variability of lead concentrations, including the sampling
method used and fluctuations in water quality (e.g., pH, NOM, temperature). Cardew (2003)
assessed water quality fluctuations and their impact on the overall variability of lead levels using
a Monte Carlo simulation and found that the coefficient of variation increased for both 30MS
and RDT sampling because of water quality fluctuations. Generally, the number of samples
needed for the RDT sampling protocol is higher than for the 30 MS protocol. However, it was
determined that water quality fluctuations dramatically increase the number of samples needed to
detect a change for 30MS sampling, thereby reducing the relative sample size needed for RDT by
a factor of two. However, in the absence of water quality fluctuations, the number of samples
required to detect a change with RDT sampling is ten times greater than for 30MS. Jackson
(2000) determined that a RDT protocol would require 3–5 times the number of samples to
provide equivalent information if used as an alternative to stagnation samples. Consequently, the
perceived advantage of sampling at the same properties using 30MS is less significant in reality.
Compliance sampling requires the collection of a set frequency and number of samples which
will depend on the population served in a water supply zone. The frequency may be reduced if
no failures have occurred in a defined period as determined by the regulator. The number of
samples required depends on the actual level of non-compliance in the water supply zone and the
variation in lead concentrations observed. There is a need to increase the number of samples
when the level of compliance is high (i.e., 90%) to ensure that the zone is actually well
characterized (European Commission, 1999; Baron, 2001).
Typically, a minimum of 20 samples is required in a water supply zone, regardless of
sampling methodology. However, for small water systems, fewer samples may be appropriate,
depending on local circumstances. Hayes et al. (2012) found that results from RDT sampling
were adequately representative if at least 100 samples were taken per year and aggregated over
several years.
Schools present particularly difficult sampling challenges for the following reasons: the
complexity of use patterns, the variability in age of the plumbing, the variability in plumbing
configuration between rooms and the lack of a detailed inventory of the plumbing products
installed in the buildings. In a study in four Canadian provinces, water samples were collected in
elementary schools, daycares, and other large buildings using different sampling protocols and
analyzed for lead (Deshommes et al., 2016). The authors found high lead levels were highly
variable (lead concentrations varied by a factor of 10–2000 between taps) within large buildings
and system- wide. They also confirmed that concentrations of lead at a specific tap cannot
predict the lead concentrations for other taps in a building and further support the need to sample
every tap in schools and daycares. The study authors also stated that basing the estimation of
exposure on concentrations after extensive flushing was not appropriate.
No representative sampling site can be established for most schools, thereby requiring
the sampling of every drinking water location to assess exposure of children in the schools.
Depending on the type of sampling site (i.e., school vs. multi dwelling building), smaller sample
and smaller total volumes may be necessary ( Health Canada, 2009b; Schock and Lytle, 2011;
U.S. EPA, 2018).

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Lead (March 2019)
Maintaining stagnation in larger buildings can be very difficult. Studies have found that
lead concentrations at the tap varied significantly even after carefully controlling for water use
by all units connected to the service line, regardless of the type of multiple‐family dwelling—
row, duplex, triplex or large building (Deshommes et al., 2013; Ngueta et al., 2014). Lead
concentrations in drinking water from these dwellings were as high as those seen in single-family
homes with similar lead service line configurations. These studies clearly demonstrate the
challenges in assessing exposure using stagnant samples and provide support for using the RDT
sampling protocol when multiple-family dwellings or large buildings are included in the
sampling pool.
5.2 Food
The use of lead in food products is prohibited in Canada. However, small quantities of
lead can be detected in food as a result of the trace amounts found in plants and animals, lead
incorporation during food transport, past use of lead arsenate as a pesticide, processing and
preparation, as well as the use of lead bullets to shoot wild game. Health Canada’s Total Diet
Study estimated the levels of various chemicals, including lead, in food in six studies that took
place between 1969 and 1973, 1976 and 1978, 1985 and 1988, 1992 and 1999, 2000 and 2004
and 2005 and the present day (ongoing; data up to 2007 are available) (Health Canada, 2009a).
The results of these studies show a significant decrease of lead concentrations in food since
1981. The current estimated dietary intake of lead from food for all ages of the general Canadian
population is approximately 0.1 μg/kg body weight (bw) per day. Exposure is generally higher in
children and decreases with age (Health Canada, 2011a). For the period 2003–2007, lead
concentrations were highest in herbs and spices (i.e., 292–392 μg/kg), although the most
significant contributions of lead to the diet were from beverages, such as beer, wine, coffee, tea
and soft drinks, as well as cereal-based foods and vegetables. Traditional foods consumed by
First Nations people residing on reserves in British Columbia contained only background levels
of lead, except for beaver heart, Canada geese, deer and grouse meat, which contained higher
lead concentrations (up to 61 μg/kg) (Chan et al., 2011). Lead levels in Canadian food have also
been measured through the Canadian Food Inspection Agency’s Children’s Food Project and
National Chemical Residue Monitoring Program (NCRMP). Data from the 2007–2008
Children’s Food Project, in which 836 various processed foods were tested for lead content,
indicate that grain-based products contained the most lead. Of the 365 grain-based products
tested, 162 had detectable levels of lead, with a mean concentration of 25 μg/kg in these samples.
In the previous assessment in 2006–2007, only 11 samples of the 350 foods tested had detectable
levels of lead. The highest lead concentration was reported in organic vegetable baby food (140
μg/kg). The NCRMP detected lead concentrations of up to 2040 μg/kg in chicken muscle
samples, although lead was not present at detectable levels in an additional 80 samples of
chicken muscle (CFIA, 2010). Other foods with detectable levels of lead included fruits and
vegetables as well as honey.
Breast milk can be a significant source of exposure to lead in infants. In a 1981 survey of
chemicals found in the breast milk of 210 mothers across Canada, lead concentrations were
shown to range from non-detectable to 15.8 μg/L, with a geometric mean concentration of 0.566
μg/L (Dabeka et al., 1986). Concentrations of lead in breast milk from 25 Cree mothers ranged
from 0.41 to 8.33 μg/L, with an average concentration of 2.08 μg/L (Hanning et al., 2003). More
up-to-date data on lead levels in breast milk are expected to be available upon final publication
of the Maternal–Infant Research on Environmental Chemicals study, a national 5-year study that
recruited approximately 2000 women across 10 Canadian cities. Formula reconstituted with tap
water also represents a major source of exposure to lead in infants, as up to 90% of their diet by

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Lead (March 2019)
weight can be tap water, depending on how the formula is reconstituted (Shannon and Graef,
1989; Edwards et al., 2009; Triantafyllidou and Edwards, 2012). It has been estimated that
feeding with formula can represent over 50% of total lead exposure in infants (Triantafyllidou
and Edwards, 2012).
Additionally, foods prepared with water containing high concentrations of lead have been
shown to significantly impact blood lead levels (BLLs). In Greenville, North Carolina, a study
was initiated to investigate the source of lead poisoning of children where there was no apparent
source of lead in the home. It was determined that pasta prepared with water from a tap that had
lead particles trapped in the aerator was the most likely source of lead. During the investigative
study, the authors measured a lead concentration of 535 µg/L in the water used to cook pasta.
Subsequently, they demonstrated that 95% of the small, insoluble lead particles remained on the
pasta after the water was poured off, resulting in a mass of 381 µg of lead in a single serving of
pasta (Triantafyllidou et al., 2007). It is of interest to note that this mass is well above the U.S.
Consumer Product Safety Commission’s (CPSC) threshold for acute exposure health concerns of
175 µg of lead in children’s jewellery, which is used by the CPSC as the basis for product recalls
or other corrective measures (CPSC, 2005). Deshommes et al. (2012a) studied the impact of tap
water as a source of lead in prepared foods consumed by children, including prepared beverages,
rice or pasta. Sources of lead in the tap water included solder, lead(II) and lead(IV) pipe scales as
well as lead originating from yellow and red brass. It was determined that both particulate and
soluble lead from tap water can contribute to increased lead levels in beverages and food
prepared in the home. The authors found that the tap water contributed 0.01–1 mg/L and 4–40
mg/L of soluble and particulate lead, respectively, resulting in an average load of 25 µg of lead
per 100 g of cooked pasta or rice. The bioaccessibility of lead from food cooked with water was
dependent on the form of lead. Lead particles from tap water did not dissolve to a great extent
during cooking, but lead emitted from particles (dissolved) as well as dissolved lead from the
lead sources were concentrated in the food. In addition, the authors found that small particles of
lead would likely be ingested and become bioaccessible once in the stomach.
Certain sub-populations may receive additional exposure of lead through the
consumption of wild game. For example, mean lead content in samples of white-tailed deer
(n=35) and moose (n=37) harvested using lead ammunition were 0.28 and 0.17 mg/kg,
respectively, as measured in a study conducted in Quebec (Fachehoun et al., 2015).
5.3 Air
5.3.1 Ambient air
Ambient air concentrations of lead on filter-collected particulate matter having an
aerodynamic diameter of less than 2.5 μm (PM2.5) have been measured annually at 26 sites
within Canada. This is part of Environment Canada’s National Air Pollution Surveillance
program, established in 1969. As a result of major restrictions in the use of leaded fuels
worldwide that started in the 1970s, the concentrations of lead in air have been reduced
considerably. In Canada, average concentrations of lead in ambient air declined by more than
99% from 1984 (0.1600 μg/m3) to 2008 (< 0.0015 μg/m3) (Environment Canada, 2010b).
Measurements done from 2000 to 2009 indicate that lead concentrations in ambient air have been
fairly consistent, with 5th to 95th percentile concentrations of PM2.5 lead ranging from 0.0004 to
0.014 μg/m3 (Environment Canada, 2010a). Aviation gasoline used in small aircraft continues to
be an important source of lead in ambient air. Children 9 months to 7 years of age living within
1000 m of airports in North Carolina were shown to have statistically higher BLLs compared
with children residing farther from the airports, with the largest impact occurring in children

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Lead (March 2019)
residing within 500 m of an airport (mean BLL of 3.88 μg/dL in the study population) (Miranda
et al., 2011).
5.3.2 Indoor air and dust

Ingestion of settled household dust can be a major source of exposure to lead for children,
especially in older homes where lead-based paints have been applied (Lanphear et al., 1998).
Behaviours observed in children, including crawling and frequent hand-to-mouth contact, can
increase lead exposure through ingestion of paint chips and house dust. There is a significant
relationship between exposure to household dust and BLLs in children (Dixon et al., 2009).
Other sources of indoor lead include contamination from exterior soil, exposure to tobacco
smoke and hobbies such as welding, pottery and stained glass making (HUD, 2001). In 2002,
median PM2.5 lead concentrations in the indoor air of Ottawa homes with non-smoking residents
were 0.0023 μg/m3 (0.0004–0.0027 μg/m3, n = 10) and 0.0015 μg/m3 (0.0010–0.0051 μg/m3, n =
10) for rural and urban residences, respectively (Rasmussen et al., 2006). In Windsor, Ontario,
the median PM2.5 lead concentration in matched personal, indoor and outdoor air samples was in
the range of 0.001–0.010 μg/m3 (n = 8 in 2004 and n = 37 in 2005–2006); the highest
concentrations of lead were measured in outdoor air in this study (Rasmussen et al., 2007, 2009).
Several studies have examined lead levels in household dust by examining samples collected in
vacuum cleaner bags. Median lead concentrations in household dust were 63 mg/kg (7.9–3916
mg/kg from 2007 to 2010) and 93 mg/kg (2.9–6898 mg/kg from 2010 to 2011) in 1025 homes
across Canada and in 201 homes in four boroughs of Montréal, Quebec, respectively (Gauvin et
al., 2011; Rasmussen et al., 2011). Other Canadian studies have investigated lead concentrations
in household dust using wipe sampling over various areas within homes. Overall, median
concentrations of lead found using the wipe sampling technique ranged from undetectable to 190
µg/m2 (McDonald et al., 2010; Bell et al., 2011; INSPQ, 2011; Richardson et al., 2011).
Older homes may have lead-based paint on the walls. Disturbing this paint through
normal wear-and-tear (such as paint on doors, windows, stairs and railings) or through removal
or repairing can contribute to indoor air and dust lead levels. The amount and type of lead will
vary based on paint type (Health Canada, 2013c). Beauchemin et al. (2011) and Walker et al.
(2011) investigated the speciation of lead in household dust samples from one 65-year-old two-
storey home and one two-storey home of unidentified age in Ottawa, Ontario. Walker et al.
(2011) reported that lead levels from dust in the upstairs bedrooms, where recent renovations had
been completed, were substantially higher than in the living room (adult bedroom 14,000 mg/kg
versus living room 240 mg/kg); lead particles in dust from the main floor living room were
consistent with lead particles found in garden soil, whereas dust particles in the upstairs
bedrooms were primarily consistent with the components of paint (including white lead and
lithopone) (Walker et al. 2011). Beauchemin et al. (2011) analyzed samples of paint, plaster, and
household dust in the same 65-year-old home and reported that paint was a major contributor to
the lead content of household dust.
5.4 Consumer products

Lead-containing consumer products can include inexpensive jewellery, professional art
supplies, leaded crystal and glazes on ceramics and pottery. The concentration of lead in
consumer products is heavily restricted through regulations under the Canada Consumer Product
Safety Act (CCPSA), especially in products intended for children. As of November 2010, the
lead content of applied surface coatings on toys, jewellery, furniture and other products intended
for children and on pencils and artists’ brushes was restricted to 90 mg/kg total lead, although
applied surface coatings on older products sold between 2005 and 2010 may have contained up

19
Lead (March 2019)
to 600 mg/kg total lead, and those sold between 1976 and 2005 may have contained up to
5000 mg/kg lead. In addition, there is a 90 mg/kg total lead limit for all toys intended for
children under 3 years of age and all products whose normal pattern of use involves mouth
contact. The lead content of all jewellery items intended for children under 15 years of age is
limited to 600 mg/kg total lead and 90 mg/kg migratable lead (Health Canada, 2010b, 2012b).
There are also stringent leachable lead limits for glazed ceramics and glass foodware and for
kettles (Government of Canada, 2010a). The Hazardous Products (Kettles) Regulations, which
fall under the CCPSA, limit the amount of lead that may be released when water is boiled, in
kettles or similar products, to 0.010 mg/L (Government of Canada, 2010b).
Health Canada issued a public advisory in September 2005 informing consumers about
the potential exposure to lead through kohl, a traditional eye cosmetic of Middle Eastern, Asian
and North African societies (Health Canada, 2011b). Kohl is also used in ways similar to a
natural health product for general eye health, treatments to cuts, and is regarded as a general
antibacterial substance. Health Canada has taken action to remove known lead-containing kohl
from the market, however it is suspected that there may be more kohl products currently being
sold in Canada which contain lead.
Codes of practice are in place for various other categories of products. The National
Plumbing Code (NPC), established by the National Research Council of Canada, permitted the
use of lead as an acceptable material for drinking water service pipes until 1975 and the use of
lead solders in plumbing and distribution systems until 1986. The use of solder containing lead in
new plumbing and in repairs to plumbing for drinking water supplies has been prohibited under
the code since 1990 (NRCC, 2010). Changes to the NPC now include a requirement for
plumbing fittings to meet the low lead requirement of 0.25% lead as a weighted average (NRCC,
2013).
5.5 Soil
Lead levels in soils tend to be higher in cities and in proximity to roads, industrial point
sources, weapon firing ranges and buildings with deteriorating leaded paints. The levels of lead
in residential and parkland soils across Canada were examined in several studies from 2003 to
2010. Mean lead concentrations were shown to range from 35.6 to 766 mg/kg (Rasmussen et al.,
2001; Bowman and Bobrowsky, 2003; Ndzangou et al., 2006; Bell et al., 2010, 2011; Heidary-
Monfard, 2011; Richardson et al., 2011), although most samples contained lead at concentrations
below the current Canadian Council of Ministers of the Environment (CCME) soil quality
guideline for human health (140 mg/kg; CCME, 1999). Mean lead concentrations in soil near
point sources across Canada ranged from 13 to 750 mg/kg, although samples generally contained
more lead than those collected from residential and parkland soils (OMOE, 2001; Hilts, 2003;
Centre for Environmental Monitoring, 2004; Defence Research and Development Canada, 2004;
Lambert and Lane, 2004; Manitoba Conservation, 2007; Aqua Terre Solutions Inc., 2009;
Conestoga-Rovers and Associates, 2010; Fisher Environmental Ltd., 2010; Laird, 2010; Saint-
Laurent et al., 2010). Of the 106 sites tested in Flin Flon and Creighton, Manitoba (influenced by
mining), 41% contained lead at concentrations that exceeded the soil quality guideline
established by the CCME (Manitoba Conservation, 2007). The background concentration of lead
in soil is estimated to be 9.65 mg/kg, which is based on the mean concentration in 7398 glacial
till samples collected throughout Canada (Rencz et al., 2006).
5.6 Blood lead levels in Canada

Biomonitoring of exposure to lead throughout the population is predominantly assessed
by measurements of lead in blood samples. BLLs in the Canadian population have been assessed

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Lead (March 2019)
as part of the Canadian Health Measures Survey (CHMS), which consisted of 5319 participants
aged 6–79 years in cycle 1 (2007–2009), 6070 participants aged 3–79 years in cycle 2 (2009–
2011) and 5538 participants aged 3-79 years in cycle 3 (2012-2013). The CHMS is a nationally
representative survey representing 96% of the Canadian population providing national baseline
BLLs for many chemicals, including lead. Geometric mean BLLs of total participants were 1.3,
1.2 and 1.1 µg/dL for cycles 1, 2 and 3, respectively. In general, BLLs decreased slightly from 3
to 19 years, then increased with age, with the highest BLLs detected in the 60–79 years age
group. For cycles 1, 2 and 3, respectively, geometric mean BLLs for each age group were as
follows: not available, 0.93 and 0.77 µg/dL for 3–5 years; 0.90, 0.79 and 0.71 µg/dL for 6–11
years; 0.80, 0.71 and 0.64 µg/dL for 12–19 years; 1.1, 0.98 and 0.90 µg/dL for 20–39 years; 1.6,
1.4 and 1.3 µg/dL for 40–59 years; and 2.1,1.9 and 1.6 µg/dL for 60–79 years. For the most part,
BLLs were slightly higher in males than in females (Health Canada 2015).
Higher BLLs can be measured in individuals residing in communities with atypical
exposure sources, such as smelter communities or rural communities where significant amounts
of game killed with lead shot are consumed. In these atypical circumstances, geometric mean
BLLs have been shown to range from 1 to 5.6 µg/dL in children (2000–2010) and from 1.7 to
3.9 µg/dL in adults (2001–2005). Maximum BLLs of approximately 40 and 50 µg/dL have been
observed in children and adults, respectively (SENES Consultants Ltd., 201 2).
The ingestion of lead in drinking water is known to have a direct impact on BLLs.
However, data from studies investigating this effect can be difficult to interpret as a result of
different water sampling protocols used, variability in individual consumption of tap water,
different practices followed, such as using filtered water or flushing tap water before use, and
individual susceptibility factors that affect the bioavailability of lead, such as age, diet and
genetics. Factors such as seasonal fluctuations in lead concentrations in water (e.g., higher lead
concentrations in summer months) or significant decreases in lead concentrations in water have
been associated with concomitant changes in BLLs (Sherlock et al., 1984; Deshommes et al.,
2013; Ngueta et al., 2014). Triantafyllidou and Edwards (2012) noted the need for additional
research on the associations between lead concentrations in water and BLLs to better
characterize the health risks associated with this exposure to lead. Simulations using the
Integrated Exposure Uptake Biokinetic Model for Lead in Children or IEUBK model (see
Section 8.5.3) were done to assess the impact of different concentrations of lead in drinking
water on BLLs for children 0–7 years of age. Data from previous studies were input into the
model, and the resulting geometric mean percentages (percentage range) of children with BLLs
exceeding 5 µg/dL were estimated to be 33.8% (6.8–55.1%), 9.4% (1.9–24.5%) and 2.2% (0.4–
9.3%) when concentrations of lead in drinking water were 20, 10 and 5 µg/L, respectively
(Deshommes et al., 2013). Children residing in homes with lead service lines were shown to
have higher BLLs than those residing in housing with service lines not made of lead (Brown et
al., 2011). There is evidence that even very low levels of lead in drinking water can significantly
influence BLLs. In a group of 306 children aged 1–5 years, Levallois et al. (2014) demonstrated
an association between elevated BLLs and lead concentrations in tap water after adjusting for
risk factors associated with elevated BLL, including ethnicity, season and water consumption, as
well as the other studied lead exposure variables (i.e., floor dust, windowsill dust and paint). The
authors found that BLLs were elevated (> 1.78 µg/dL; corresponding to the 75th percentile)
when lead concentrations in drinking water exceeded 3.3 µg/L.
It is important to note that BLLs have declined significantly over time. BLL reductions of
over 70% have been observed since 1978–1979, when the mean BLL was
approximately 4.79 µg/dL in people 6–79 years of age (Bushnik et al., 2010). Declines are due to

21
Lead (March 2019)
significant reductions of lead in gasoline, paints, solder and food cans, as well as additional
measures taken to reduce exposure to lead.
5.7 Multi-route exposure through drinking water

As the required physical/chemical properties (e.g., octanol–water partition coefficient,
Henry’s Law constant) are not available for lead, a multi-route exposure assessment as outlined
by Krishnan and Carrier (2008) could not be performed.
As lead compounds are not volatile, inhalation of lead is limited to particle-bound lead,
an exposure scenario that is not applicable to drinking water. Furthermore, lead is predominantly
found in its inorganic form in drinking water, and inorganic lead is not readily absorbed by the
skin. As such, the dermal and inhalation routes of exposure to lead in drinking water were not
considered significant in this assessment.
6.0 Analytical methods

The U.S. Environmental Protection Agency (EPA) has two approved analytical methods
(Method 200.8 Rev. 5.4 and Method 200.9 Rev. 2.2) for the analysis of total lead in drinking
water. The following methods, developed by consensus by standards organizations and a
commercial manufacturer, are also approved by the U.S. EPA for the analysis of lead: Standard
Method (SM) 3113B (APHA et al., 2005); D3559-96 and D3559-03 (ASTM, 1996, 2003); and
Palintest method 1001 (U.S. EPA, 1994c, 2009a, 2014). These methods are general methods for
the determination of metals and use ICP followed by mass spectrometry (MS), graphite furnace
atomic absorption spectroscopy (GFAAS) or differential pulse anodic stripping voltammetry
(ASV) to analyze lead. Both U.S. EPA methods 200.8 Rev. 5.4 and 200.9 Rev. 2.2 provide
procedures for the determination of dissolved and total recoverable lead. The methods applied
use the same preservation and/or pretreatment steps, including acid pretreatment with nitric
and/or hydrochloric acid. Hot digestion may be required, depending on the characteristics of the
samples collected. The differences between these methods are the equipment used for the
analysis.
Method 200.8 Rev. 5.4 (U.S. EPA, 2009a) uses ICP-MS and has MDL values ranging
from 0.02 to 0.6 µg/L. The sample is atomized and ionized into radio-frequency plasma. The
ions are extracted from the plasma by a vacuum interface and separated on the basis of their
mass-to-charge ratio by a mass spectrometer. Separated ions are detected by an electron
multiplier or Faraday detector (U.S. EPA, 1994).
Method 200.9 Rev. 2.2 (U.S. EPA, 2009a) uses stabilized temperature platform GFAAS
and has an MDL of 0.7 µg/L. The technique includes a series of three heating steps to dry, char
(to reduce interferences by other ions) and atomize lead from the pyrolytic graphite surface. The
atomization raises lead into an atmosphere of high-purity argon, and light of a specific
wavelength is passed through the atomic cloud. The attenuation of the intensity of light is
measured (U.S. EPA, 1994).
The two ASTM International methods approved by the U.S. EPA for the analysis of lead
in drinking water are the 1996 and 2003 versions of ASTM D3559 (U.S. EPA, 2014a). Both
methods utilize atomic absorption spectrophotometry and differential pulse ASV. These ASTM
methods (D3559-96 and D3559-03) are proprietary methods, and no MDLs were available
(ASTM, 1996, 2003; U.S. EPA, 2014a).
SM 3113B has also been approved for the analysis of lead using GFAAS and has an
MDL of 1 µg/L (APHA et al., 2005); the optimum lead concentration range reported for this

22
Lead (March 2019)
method is 5–100 µg/L. The most recent version of this method has an estimated detection level
of 0.7 µg/L (APHA et al., 2012).
Palintest method 1001 is a proprietary method for the analysis of lead in drinking water
based on differential pulse ASV. This electrochemical technique electroplates metals when the
electrode is immersed in the sample and a voltage is applied to the electrode. This step induces a
small electric current to pass through the sample, and the dissolved metal ions (e.g., lead) are
deposited onto the electrode surface. Once the plating phase is complete, an increasing reverse
voltage is applied to the electrode to strip off the deposited metals. Each metal is stripped from
the electrode in a defined order and at a precisely known voltage and is thus identified. The
signal readings are captured by a scanning analyzer, and a processor interprets them to identify
and quantify the metal of interest. An MDL of 2 µg/L was established for lead during U.S. EPA
validation testing done by three laboratories (U.S. EPA, 1996) and confirmed in recent product
literature (Palintest, 2014).
The practical quantitation limit (PQL) for the U.S. EPA-approved methods is 0.005 mg/L
(5 µg/L), based on the capability of laboratories to measure lead within reasonable limits of
precision and accuracy at the time of regulation (U.S. EPA, 1991). Current PQL assessments are
based on two approaches: (1) the lowest value for which 75% of laboratories can quantitate
within prescribed accuracy limits based on actual performance data, if the data are sufficient; or
(2) multiplying the upper levels of the MDLs to account for the variability inherent to test
methods and instruments used for analyses, when data are insufficient. In establishing the PQL,
the U.S. EPA considers and prefers the laboratory performance data for methods approved at the
time of the review over the MDL approach.
In the second six-year review of existing National Primary Drinking Water Regulations,
the U.S. EPA determined that it could not lower the PQL for lead. Although data were collected
for lead in the first six-year review, they were not analyzed at that time. The data sets for both
six-year reviews were analyzed, which determined that there was a lack of data and a downward
trend in laboratory passing rates below the current PQL for both six-year reviews and a lack of
data below the current PQL for the second six-year review’s proficiency testing results. It was
concluded that it was not appropriate to recommend reducing the PQL (U.S. EPA, 2009b). There
is no equivalent centralized program for the collection and rigorous statistical analysis of
analytical data in Canada. As such, establishing a PQL for Canadian laboratories is not possible.
However, currently available Canadian data support the ability of Canadian laboratories
to achieve detection limits well below this PQL. It is important that analyses are undertaken by
an accredited laboratory to ensure accurate results and appropriate quality assurance and quality
control.
6.1 Sample preparation

Analysis of total lead requires sample preparation to ensure that both the particulate and
dissolved fractions of lead are capable of being detected. Generally, all methods listed above
follow the same preservation steps, including the use of 0.15% nitric acid, a 16-hour holding
time and the addition of hydrochloric acid for hot digestion when the sample turbidity is above 1
nephelometric turbidity unit (NTU). The standard acid preservation (pH < 2) has been shown to
quantify total lead in water samples where lead was predominantly in dissolved form or from
very fine lead solder (Lytle et al., 1993; Deshommes et al., 2012b; Haas et al., 2013;
Triantafyllidou et al., 2013). However, when particles of lead are present in a sample, they may
not be well dispersed and may settle to the bottom of the sampling bottle, resulting in turbidity
below 1 NTU. As such, the current protocol may underestimate total lead in drinking water when
particulate lead is present, and a different approach for the preservation step should be used

23
Lead (March 2019)
(Triantafyllidou et al., 2007, 2013; Deshommes et al., 2010a; Haas et al., 2013; Clark et al.,
2014). Increasing the nitric acid strength to 2% for the preservation step resulted in substantially
better recovery for most forms of particulate lead (Haas et al., 2013; Triantafyllidou et al., 2013;
Clark et al., 2014). However, Haas et al. (2013) found that when particulate tetravalent lead was
present, a more rigorous preservation step (i.e., hot digestion with both 2% nitric acid and 1%
hydrochloric acid) was needed. Clark et al. (2014), on the other hand, found that the addition of
2% nitric acid by volume in the original bottle, followed by a holding time of 16 hrs and
thorough shaking prior to taking an aliquot for analysis provided over 80% recovery of total
lead. This recovery improved to almost 100% when the holding time increased to 48hrs.
Since the use of 0.15% nitric acid for preservation does not adequately capture particulate
lead, it is recommended that 2% nitric acid by volume be used for the preservation step. Heated
digestion, as outlined in EPA Method 200.8, could also be used when analyzing lead in drinking
water samples. However, this method requires that only an aliquot of the original sample be
digested and this would likely not capture particulate lead. This method also includes the
criterion of 1 NTU which is insufficient for capturing colloidal or particulate lead, even if those
particles are visible in the sample bottle or if the presence of particulates is suspected but they
are not visible (e.g., presence of particles in the aerator, disturbance of lead service line). For this
reason, if hot acid digestion is to be conducted, preservation with 2% nitric acid by volume (after
the 16 hour holding time) and thorough sample mixing should be done prior to taking an aliquot
for analysis.
Best practices leading to a better estimation of total lead include ensuring that no aliquot
or volume transfers occur prior to preservation or analysis; in situ sample preservation to pH < 2
with 2% by volume; maintaining a minimum holding time of 16 hours after preservation;
thoroughly mixing the sample prior to analysis and; taking the aliquot directly from the original
sample bottle (Cartier et al., 2013; Haas et al., 2013; Triantafyllidou et al., 2013; Clark et al.,
2014).
As noted above, it has been demonstrated that 2% nitric acid by volume greatly improves
the recovery of particulate lead. It is important to note that the addition of 2% nitric acid should
be undertaken by qualified personnel and using appropriate precautions. To this end, if sampling
is conducted by homeowners, the sample should only be acidified and held upon arrival at the
laboratory.
7.0 Treatment technology and distribution system considerations

Corrosion tends to increase the concentrations of many metals, including lead, in tap
water. Lead in drinking water results primarily from the release of lead through corrosion of
lead-bearing materials in plumbing and distribution systems. Corrosion control is the most
effective treatment approach for minimizing lead concentrations at the point of consumption
(Health Canada, 2009b). Although water treatment can reduce lead concentrations in tap water
substantially, treatment alone may not be sufficient to reduce lead to concentrations below the
MAC if water is supplied through a lead service line (Sandvig et al., 2008). As such, the removal
of the full lead service line is likely the most effective and most permanent solution.
Additionally, where lead-bearing fittings contribute significantly to lead in drinking water, the
replacement of older fittings (faucets, etc.) with ones that meet low-lead content requirements
can reduce lead concentrations in drinking water (Sandvig et al., 2007, 2009; Boyd et al., 2008a;
Turković et al., 2014). Generally, strategies to reduce exposure to lead will need to focus on
controlling corrosion within the distribution and plumbing systems and on removing lead-

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Lead (March 2019)
containing components. As some treatment technologies can increase lead in drinking water by
changing water quality parameters that impact lead release, corrosion control and/or mitigation
measures selected may also depend on the treatment processes in place.
7.1 Municipal scale

Lead levels in source water are typically very low. As lead is generally introduced into
the drinking water after it leaves the treatment plant, the treatment approach for lead in drinking
water is primarily focused on corrosion control (Health Canada, 2009b).The approaches used for
corrosion control include water quality adjustments (pH, alkalinity, etc.) and the use of an
orthophosphate corrosion inhibitor. Another strategy to reduce exposure to lead is the removal of
the full lead service line.
It is important to characterize the sources of lead in order to select the appropriate
approach for minimizing corrosion and, thus, lead exposure. The selection of an appropriate
strategy for minimizing lead at the tap will depend on many factors, including the characteristics
of the raw water supply and the source and concentration of lead, as well as the type of corrosion
(Health Canada, 2009b).
Changes in a water system, either in the treatment processes or the quality of the source
water, must be taken into consideration. In April 2014, the city of Flint, Michigan, changed its
water supply from Detroit-supplied Lake Huron water to the Flint River to save money and as an
interim solution while awaiting the completion of a new pipeline. The change in source water
resulted in a significantly different treated water quality being supplied to residents with
concomitant discolouration episodes; microbiological contamination issues due to lack of
disinfection residual; and high disinfection by-products. These issues were further compounded
by a more corrosive water — having higher chloride levels and chloride-to-sulfate mass ratio
and no orthophosphate inhibitor — causing high lead levels. The Flint water distribution system
was estimated to have anywhere from 10% to 80% lead service lines. Between February and
September 2015, 252 homes were sampled and the 90th percentile for lead was determined to be
25 µg/L, well above the U.S. EPA lead action level of 15 µg/L, with several first draw sample
samples having lead levels over 100 µg/L (Torrice, 2016). Subsequent to these results, Hanna-
Attisha et al. (2016) analyzed differences in pediatric BLLs for children younger than 5 years
before (2013) and after (2015) the source water change in Flint. The percentage of elevated
BLLs during both time periods were assessed and geographical locations were identified through
spatial analysis. The authors found the incidence of elevated BLLs increased from 2.4% to 4.9%
(P < .05) after the source water change, and neighborhoods with the highest water lead levels
experienced a 6.6% increase. No significant change was seen outside the city.
Natural organic matter (NOM) can contain organic ligands that form soluble complexes
with lead (Schock et al., 1996). NOM may also complex calcium ions and keep them from
forming a protective CaCO3 coating (Schock and Lytle, 2011). The presence of NOM has been
shown to: increase dissolved lead concentrations (Schock et al., 1996; Burlingame et al., 2006);
increase total lead solubility and disperse colloidal lead (Korshin et al., 2005); reductively
dissolve lead (IV) oxides (Lin and Valentine, 2008); and accelerate lead release via ligand-
promoted dissolution (Korshin et al., 1999). In the United Kingdom, NOM is considered to be a
challenge to controlling plumbosolvency (lead release) with orthophosphate (Colling et al., 1987;
Hayes et al., 2008). Optimizing water treatment processes (i.e., coagulation and adsorption) to
remove NOM is expected to result in the removal of the complexing ligands thus limiting the
release of lead. Although research on this phenomenon is limited, the removal of NOM may play
an important role in strategies to minimize the release of lead.

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Lead (March 2019)
As noted above, corrosion control treatment can substantially reduce lead concentrations
at the tap, but treatment alone may not be sufficient to reduce lead to concentrations below the
MAC when water is supplied through a lead service line (Sandvig et al., 2008; Camara et al.,
2013). In this instance, the removal of the full lead service line may be necessary to achieve lead
reduction.
7.1.1 Treatment considerations

Conventional water treatment, including settling, aluminum sulphate (alum) or ferric
sulphate coagulation and filtration, is reasonably effective at removing lead from drinking water.
Lime softening at elevated pH is also effective for the removal of lead. For public water systems,
the U.S. EPA has identified point-of-use (POU) ion exchange (using cationic resins) and reverse
osmosis (RO) as small systems (i.e., serving fewer than 10 000 people) compliance technologies
for lead removal (U.S. EPA, 1998). These technologies are also relevant for residential-scale
treatment (see Section 7.2). Orthophosphate and zinc orthophosphate are generally the most
successful corrosion inhibitors for reducing lead levels in drinking water (Dodrill and Edwards,
1995; Schock et al., 1995).
7.1.2 Distribution system considerations

Lead may leach into drinking water from lead service lines, lead compounds used to join
pipe and solder joints, lead in brass plumbing fittings and lead in goosenecks, valve parts or
gaskets used in water treatment plants or distribution mains. Lead was commonly used in brass
components of distribution and plumbing systems for many decades, including the use of lead
service lines to supply water to homes. The NPC allowed lead as an acceptable material for
service lines until 1975 (NRCC, 2010), although their installation continued until 1980 in some
provinces and territories. Galvanized pipes can also be a source of lead, as lead is present as an
impurity (Leroy et al., 1996). The NPC permitted the use of galvanized steel for pipes in
plumbing systems until 1980 (NRCC, 2010). All provinces and territories use the NPC as the
basis for their plumbing regulations.
7.1.2.1 Lead service lines

Lead service lines have been shown for many years to be a consistently high source of
lead and to contribute 50–75% of the total lead at the tap after extended stagnation times. As
such, the removal of the full lead service line is likely the most effective and most permanent
solution to reducing lead at the tap.
Although the majority of lead released under stagnant conditions is dissolved lead (van
den Hoven and Slaats, 2006; Sandvig et al., 2008; Xie and Giammar, 2011; Cartier et al., 2012a),
water flow can increase the release of both dissolved and particulate lead through the mass
transfer of lead out of pipe scales and by physically dislodging the pipe scales (Xie and
Giammar, 2011).
The full replacement of a lead service line (i.e., utility and homeowner portions) can
significantly reduce lead concentrations at a consumer’s tap. Although partial lead service line
replacement (i.e., replacing only the utility or consumer’s portion) can also reduce lead
concentrations, it does not result in a proportional decrease in lead levels when compared with
full service line replacement (U.S. EPA, 2011; Camara et al., 2013; Cartier et al., 2013).
Replacing the lead service line can disturb or dislodge existing lead scales or sediments
containing lead, resulting in a significant increase in lead levels at the tap. This increase has been
shown to continue for 3 or more months after the lead service line replacement (Renner, 2007;
Sandvig et al., 2008; U.S. EPA, 2011; Cartier et al., 2013; Del Toral et al., 2013). A study in

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Lead (March 2019)
Providence, Rhode Island, showed a consistently large decline in the total mass of lead released
(concentration adjusted for actual volume) after partial lead service line replacement. The
average reduction of the total mass of lead was 62% (210 μg). The study also showed the
expected spike immediately following partial replacement of the lead service line, but lead levels
declined after 3 days and 2 weeks. After 4 months, first-draw and flushed samples showed a
large, consistent reduction in the lead concentrations and the time needed to flush the lead-
bearing water out of the internal plumbing (Commons, 2011). Del Toral et al. (2013) found that
disturbances to the lead service line increased lead concentrations in the water in 11 of 13 sites.
These disturbances included meter installation or replacement, automated meter installation,
service line leak or external service shut-off valve repair, and significant street excavation in
proximity to the home.
Stagnation times, flow regime and water chemistry have been shown to influence the
release of particulate lead from lead service line scales. Particulate lead has been observed to
increase under flowing (Kim et al., 2011; McFadden et al., 2011; Xie and Giammar, 2011) and
stagnant water conditions (Triantafyllidou and Edwards, 2010; Cartier et al., 2013) as well as
low-flow conditions (Del Toral et al., 2013; Welter et al., 2013); in the presence of
orthophosphate (McFadden et al., 2011); in the presence of orthophosphate with increasing
stagnation time (Xie and Giammar, 2011); and at higher pH under flowing water conditions
(Kim et al., 2011). Of particular interest is that studies have consistently shown that moderate to
high flow rates typical of turbulent flow or flow disturbances can increase the mobilization of
lead and result in significant contributions of particulate lead to the total lead concentration
(Triantafyllidou et al, 2007; Deshommes, 2010a; Cartier et al., 2011, 2012a; Schock and Lytle,
2011; Wang et al., 2012, 2013; Del Toral et al., 2013; Clark et al., 2014). This is an important
consideration when sampling, as low flow rates are not considered to be common homeowner
behaviour and therefore not representative of typical use patterns.
Studies have also correlated increased lead concentrations with galvanic corrosion
resulting from partial lead service line replacement where new copper piping is connected to the
remaining lead pipe (Triantafyllidou and Edwards, 2010; Schock and Lytle, 2011; Xie and
Giammar, 2011; Cartier et al., 2012a, 2013; Wang et al., 2012; Welter et al., 2013; Clark et al.,
2014). However, when the galvanic connection was removed (i.e., no contact between metals,
use of non-metallic coupling to connect pipes), lower lead levels were observed (Triantafyllidou
and Edwards, 2010; Wang et al., 2013; Welter et al., 2013). Increased lead levels were also noted
when a galvanic connection between lead and copper pipes occurred under conditions of high
CSMR (i.e., greater than 0.58) (Edwards and Triantafyllidou, 2007).
Galvanic corrosion can result in increased concentrations of both dissolved and
particulate lead (Sandvig et al., 2008; Deshommes et al., 2010a, 2012b; Triantafyllidou and
Edwards, 2010; Schock and Lytle, 2011; Xie and Giammar, 2011; Cartier et al., 2012a, 2012c;
Wang et al., 2012; Welter et al., 2013; Clark et al., 2014). Research shows that under continuous
flow conditions, dissolved lead predominates (Welter et al., 2013), but that particulate lead is
more prevalent under stagnant conditions, with particulate lead levels increasing by greater than
50% after 6 hours of stagnation (Triantafyllidou and Edwards, 2010; Wang et al., 2012, 2013).
There is evidence that low water usage resulting from water efficiency and conservation
initiatives is causing increased concentrations of lead in drinking water (Elfland et al., 2010).
Lower water use is related to increased stagnation time of the water in pipes and correlated with
increased lead concentrations.

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Lead (March 2019)
7.1.2.2 Correlation between particulate lead and iron
Contaminants may accumulate within or on top of iron and lead corrosion products and
scale deposits in distribution systems (Lytle et al., 2004; Schock, 2005; Schock et al., 2008,
2014; Friedman et al., 2009). Subsequently, scales can be dislodged and released back to the
water in the distribution system with these accumulated contaminants (Schock, 2005; U.S. EPA,
2006). Studies have shown that both iron and manganese scales can act as a sink for, and
persistent source of, lead in drinking water (Friedman et al., 2009; Schock et al., 2014). Iron
release was seen after both full and partial lead service line replacement (Deshommes et al.,
2010a; McFadden et al., 2011; Camara et al., 2013). These studies established a correlation
between particulate lead at the tap and metals such as iron, zinc, tin and copper.
Schock et al. (2014) were able to elucidate, through scale analysis and historical data, the
mechanism for the release of high levels of lead after full lead service line replacement in
Madison, Wisconsin. It was postulated that manganese and iron accumulation onto pipe walls of
premise plumbing provided a sink for lead. The scale analysis provided a plausible explanation
for historical observations relating to particulate lead, which continued to be released for 4 years
after complete lead service lines were removed. These findings were also consistent with the
subsequent reduction in lead release once better control of manganese (particulate and dissolved)
entering the household plumbing was achieved. Deshommes et al. (2010a) found that particulate
lead was highly correlated with iron owing to the adsorption of dissolved lead onto iron deposits
in the lead service line and premise plumbing. Spikes in particulate lead concentrations occurred
simultaneously with spikes in concentrations of particulate zinc, tin, iron or copper, alone or in
combination. An investigation of sustained lead release after full lead service line replacement
found that the lead release could be attributed to the adsorption of lead onto iron corrosion scales
from old galvanized iron plumbing. The extent of the release was found to vary based on the
home’s unique history, but factors included flow velocity and stagnation (McFadden et al.,
2011). A case study found that cast iron water mains exacerbated the release of lead when lead
service lines were replaced. Camara et al. (2013) found that lead service lines connected to
tuberculated (i.e., corroded) iron pipes increased lead concentrations after both partial and full
service line replacement. The authors determined that iron scales detached from the cast iron
water main and adsorbed lead from the service line and lead-containing components of the
plumbing system. Ultimately, lead was released in the consumer’s drinking water through
desorption or dissolution from iron scales. It was shown that full replacement of the service line
consistently produced lower lead release compared with partial replacement.
It is important to note that discoloration (red water) episodes are likely to be accompanied
by the release of accumulated contaminants, including lead. Therefore, such events should not be
considered only as an aesthetic issue, but should trigger sampling for metals and potentially
additional distribution system maintenance.
7.1.2.3 Brass alloys

In Canada, copper plumbing with lead–tin solders (widely used until 1989) as well as
brass faucets and fittings are prevalent in domestic plumbing systems (Churchill et al., 2000).
The NPC officially prohibited lead solders from being used in new plumbing or in repairs to
plumbing for drinking water supplies in the 1990 version (NRCC, 2010). Under the NPC, all
fittings must comply with the American Society of Mechanical Engineers (ASME) 112.18.1 /
Canadian Standards Association (CSA) B125.1 standard for plumbing supply fittings. This
standard requires that fittings meet the low lead requirement of 0.25% lead as a weighted
average.

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Lead (March 2019)
Typically, non-leaded brass alloys contain lead in the range of 0.1–0.25% by weight as an
incidental impurity from the recycled materials or ores used as source metals. Bismuth or a
combination of bismuth and selenium replaces lead in these alloys to improve mechanical
characteristics (Sandvig et al., 2007). Brass alloys that contain as little as 0.25% lead are now
available for plumbing fittings and in-line devices.
Laboratory experiments were conducted to quantify the levels of lead leached from seven
commercially available low-lead brass alloys containing lead at 0.25% or less. The tests were
conducted with two different waters, including an NSF International (NSF) / American National
Standards Institute (ANSI) Standard 61 section 9 test water and a low-pH, low-alkalinity,
chloraminated water expected to be aggressive with respect to lead leaching. The concentrations
of lead leached from all low-lead alloys were below 1 µg/L under both leaching conditions for
the 4-week duration of the experiment (Triantafyllidou and Edwards, 2010).
A study was undertaken to assess the effect of various water quality parameters (i.e., pH,
alkalinity, chlorine, chloramine) on the performance of these low-lead brasses, including their
potential to leach metals. Normalized lead levels obtained under NSF/ANSI Standard 61 section
8 test waters indicated very low lead concentrations for the devices with a lead content of 0.25%
or less (Sandvig et al., 2012).
Another study evaluated the effect of changes in key water quality parameters (i.e., hard
and soft water; high chloride; low, medium and high pH; low, moderate and high alkalinity) on
the performance and leaching of non-leaded brasses (lead content of 0.25% or less). Low
concentrations of lead were observed for all of the non-leaded brasses, under all test water
conditions, for both the short-term and long-term leaching tests. The measured lead
concentrations were all below 1 μg/L, with the majority of results less than the MDL of 0.16
μg/L (Turković et al., 2014).
7.1.2.4 Mitigation strategy for lead service lines

Generally, utilities should encourage consumers to replace their portion of the lead
service line when the utility is undertaking to replace the public portion.This ensures a full
replacement of the lead service line and minimizes the consumer’s exposure to lead (Renner,
2007; Sandvig et al., 2008; U.S. EPA, 2011; Camara et al., 2013; Cartier et al., 2013). Mitigation
measures that include partial or full replacement of the lead service line should ensure that
appropriate flushing is conducted after the replacement and that debris is subsequently cleaned
from the screens or aerators of outlets (Triantafyllidou et al., 2007; Sandvig et al., 2008;
Deshommes et al., 2010a; Cartier et al., 2013; Del Toral et al., 2013). Extensive initial flushing
by the consumer should be encouraged and other mitigation measures, such as point-of-use
filtration, public education and/or weekly or biweekly sampling until lead levels stabilize, should
be considered by the utility. The water quality at the consumer’s tap should be monitored closely
following both full and partial lead service line replacement for several months after
replacement. The importance of regularly cleaning outlet aerators should be communicated to
consumers to ensure that any lead-containing particles are removed as part of ongoing
maintenance (Triantafyllidou et al., 2007; Sandvig et al., 2008; Deshommes et al., 2010a; Cartier
et al., 2013; Del Toral et al., 2013). Seasonal variations in lead concentrations have been
observed, with increased lead concentrations frequently associated with the summer months
(Britton and Richards, 1981; Karalekas et al., 1983; Colling et al., 1987, 1992; Douglas et al.,
2004). Douglas et al. (2004) reported a strong seasonal variation in lead concentration, with the
highest lead levels seen during the months of May to November. However, more recent
information indicates that routine sampling should be conducted during the same period every
year from June to October, especially for monitoring of homes with lead service lines, as levels

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Lead (March 2019)
of lead are expected to be highest in those months, (INSPQ, 2011; Del Toral et al., 2013; Ngueta
et al., 2014 ).
Galvanic corrosion caused by partial lead service line replacement can be mitigated by
the use of plastic couplings to connect the old lead service line with new copper pipe (Wang et
al., 2013; Clark et al., 2014). Similarly, it is expected that connecting polyvinyl chloride piping
to the lead service line in a partial replacement scenario would also prevent galvanic corrosion.
Reducing exposure to lead can also be achieved, as an interim measure, by the use of
drinking water treatment devices. It must be noted that in situations where high levels of lead are
possible after replacement of lead service lines, drinking water treatment devices may have
reduced capacity and require more frequent replacement.
7.1.2.5 Mitigation strategy for distribution and plumbing systems

As discoloration (red water) episodes can be accompanied by the release of accumulated
contaminants, including lead, they should trigger maintenance actions, such as systematic
unidirectional flushing of the distribution system, to ensure that all particles are flushed out
before the water reaches the consumer (Vreeburg, 2010).
The level of trace metals increases upon stagnation of the water. Flushing the water
present in the plumbing system can significantly reduce the levels of lead and is therefore
considered a mitigation strategy. However, flushing the cold water tap in buildings may not be
sufficient to reduce the levels of lead (Singh and Mavinic, 1991; Murphy, 1993). It has been
shown that lead concentrations in samples from school drinking fountains and faucets increased
significantly a few hours after a 10-minute flush. The study found that periodic flushing
throughout the day would be necessary to adequately reduce lead concentrations (Murphy,
1993).
A number of studies found that drinking water fountains, chillers and faucets were the
sources of lead in drinking water (Gnaedinger, 1993; Bryant, 2004; Sathyanarayana et al., 2006;
Boyd et al., 2008a, b). Fountains or faucet and plumbing components can be major contributors
to elevated lead concentrations at outlets in non-residential buildings (Bryant, 2004; Boyd et al.,
2008b). As such, identifying and replacing the problematic components with non-leaded ones
can be the most effective mitigation strategy in schools and buildings as well as residences.
7.1.2.6 Mitigation strategy for impacts resulting from treatment

Some treatment technologies can increase lead in drinking water by changing water
quality parameters that impact lead release. In the anion exchange process, used for removal of
contaminants such as uranium, freshly regenerated ion exchange resin removes bicarbonate ions,
causing reductions in pH and total alkalinity during the initial 100 bed volumes (BVs) of a run.
Raising the pH of the treated water may be required at the beginning of a run (100–400 BVs) to
avoid corrosion (Clifford, 1999; Wang et al., 2010; Clifford et al., 2011). Similarly, frequent
regeneration of an ion exchange resin can have an impact on corrosion. In a case study in Maine,
frequent regeneration of the ion exchange resin was instituted to reduce the levels of uranium in
the waste stream (residuals). This resulted in a significant and continual decrease of pH and
subsequent leaching of copper and lead into the drinking water (Lowry, 2009, 2010). Since
reverse osmosis (RO) continually and completely removes alkalinity in water, it will continually
lower the pH of treated water and increase its corrosivity. Therefore, the product water pH must
be adjusted to avoid corrosion issues in the distribution system such as the leaching of lead and
copper (Schock and Lytle, 2011; U.S. EPA, 2012).

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Lead (March 2019)
7.2 Residential scale
It is not generally recommended that drinking water treatment devices be used to provide
additional treatment to municipally treated water. However, as the primary source of lead in
drinking water is the leaching from plumbing and distribution system components, a private
residential drinking water treatment device is the best option for reducing lead concentrations in
drinking water at the tap. However, the use of such devices should not be considered to be
apermanent solution since these systems require ongoing maintenance and filters must regularly
be replaced, in accordance with the manufacturer’s instructions.
Before a treatment device is installed, consumers should have the water tested to
determine general water chemistry and to verify the concentration of lead. Periodic testing by an
accredited laboratory should be conducted on both the water entering the treatment device and
the finished water to verify that the treatment device is effective. Products that use adsorption
technology can lose removal capacity through usage and time and need to be maintained and/or
replaced. Consumers should verify the expected longevity of the adsorption media in their
treatment device as per the manufacturer’s recommendations and service the device when
required. They may also wish to consult a qualified treatment specialist to help in selecting the
system best suited for their needs and water quality.
Health Canada does not recommend specific brands of drinking water treatment devices,
but it strongly recommends that consumers use devices that have been certified by an accredited
certification body as meeting the appropriate NSF/ANSI drinking water treatment unit
standard(s). These standards have been designed to safeguard drinking water by helping to
ensure the material safety and performance of products that come into contact with drinking
water. Certification organizations provide assurance that a product conforms to applicable
standards and must be accredited by the Standards Council of Canada (SCC). In Canada, the
following organizations have been accredited by the SCC to certify drinking water devices and
materials as meeting NSF/ANSI standards (SCC, 2018):
• CSA Group (www.csagroup.org);
• NSF International (www.nsf.org);
• Water Quality Association (www.wqa.org);
• UL LLC (www.ul.com);
• Bureau de normalisation du Québec (www.bnq.qc.ca – available in French only);
• International Association of Plumbing & Mechanical Officials (www.iapmo.org) and
• Truesdail Laboratories Inc. (www.truesdail.com).
An up-to-date list of accredited certification organizations can be obtained directly from
the SCC (2018).
Drinking water treatment devices can be installed at the faucet (POU) or at the location
where water enters the home (point-of-entry or POE) in residential settings to reduce
contaminant concentrations. POU systems are preferred for the removal of lead, as lead levels
may increase in the plumbing system and because exposure to these contaminants from drinking
water is a concern only if the contaminants are ingested (i.e., inhalation and dermal absorption
are not significant routes of exposure and thus, bathing, showering and similar water uses do not
pose a substantial lead exposure risk). As such, POU treatment devices installed at individual
drinking water taps are considered to be the best approach to reduce concentrations to safe levels
immediately before consumption or for preparation of food or beverages.
A number of certified residential treatment devices are available that can remove lead
from drinking water. Adsorption (i.e., carbon block/resin), RO and distillation technologies are
effective treatment technologies at the residential scale for the removal of lead at the tap.
Certified residential treatment devices using adsorption and RO are currently available for the

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Lead (March 2019)
reduction of lead (dissolved and particulate forms) in drinking water. There are currently no
certified distillation systems.
For a drinking water treatment device to be certified to NSF/ANSI Standard 53 (Drinking
Water Treatment Units—Health Effects) for the removal of lead, the device must be capable of
reducing an influent lead concentration of 150 µg/L to a maximum final (effluent) lead
concentration of less than 10 µg/L (NSF/ANSI, 2017a). Treatment devices that are certified to
remove lead under NSF/ANSI Standard 53 are generally based on activated carbon adsorption
technology.
RO systems certified to NSF/ANSI Standard 58 (Reverse Osmosis Drinking Water
Treatment Systems) may also be certified for the reduction of lead to achieve a final
concentration below 10 µg/L (NSF/ANSI, 2017b). RO systems certified to this standard are
intended for POU installation only. This is because water treated by an RO system may be
corrosive to internal plumbing components. RO requires larger quantities of influent water to
obtain the required volume of drinking water, because these systems reject part of the influent
water. A consumer may need to pretreat the influent water to reduce fouling and extend the
service life of the membrane.
Distillation systems certified to NSF/ANSI Standard 62 (Distillation Drinking Water
Treatment Systems) can also be certified for the reduction of lead to achieve a final
concentration below 10 µg/L (NSF/ANSI, 2017c). Distillation systems that would be certified to
this standard are also intended for POU installation, for the same reasons described above. The
distillation process is effective for the reduction of inorganic contaminants, but requires an
electrical energy input.
Generally, all of the above-listed technologies are expected to be capable of removing
lead to concentrations well below10 µg/L and capable of achieving the MAC. Deshommes et al.
(2012b) studied the removal of lead using POU filtration devices certified to NSF/ANSI
Standard 53 in a large building. The authors found that the devices removed both particulate and
dissolved lead to well below the concentration of lead for which they were certified. All devices
reduced total lead concentrations to 2.2 µg/L or less, even with an influent total lead
concentration as high as 270 µg/L (median concentration 111 µg/L) in the field, and under
different use patterns.
As noted previously, lead may leach from materials used in drinking water systems, such
as plumbing components and fittings. An important consideration for reducing exposure to lead
is to address leaching from these materials by specifying that they meet health-based and
plumbing standards. NSF/ANSI Standard 61 (Drinking Water System Components—Health
Effects) limits the leaching of lead into drinking water. The standard ensures that materials meet
health-based leaching requirements and are safe for use in potable water applications. When
materials are certified to the standard, the total concentration of lead from all materials must not
exceed the total allowable concentration of 5 µg/L (NSF/ANSI, 2017d). NSF/ANSI Standard
372 (Drinking Water System Components—Lead Content) evaluates the lead content of
components such as plumbing fittings (NSF/ANSI, 2016). Components and materials must not
contain more than 0.25% lead, as a weighted average, to comply with this standard. A number of
studies have demonstrated that the use of components such as faucets and other fittings with a
low lead content can result in a reduced concentration of lead at the tap (Sandvig et al., 2007,
2009; Boyd et al., 2008b; Turković et al., 2014).
Pieper et al. (2015) reported on the analysis of 2,146 samples submitted by private system
homeowners. The authors found that close to 20% of first draw samples submitted contained
lead concentrations above the U.S. EPA action level of 15 μg/L, suggesting that corrosion may
be a significant concern for well owners. The correlations between lead, copper and zinc

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Lead (March 2019)
suggested brass components as the most likely source of lead. Similarly to the PATH study
(Sweeney et al., 2017), dug/bored wells had significantly higher lead concentrations as compared
to drilled wells. A random subset of samples selected found that, on average, 47% of lead in the
first draw samples was in particulate form. Whereas flushing the tap reduced lead levels below15
μg/L for most systems, some systems experienced an increase that may have been a result of
either particulate lead or the presence of lead-bearing components (i.e., valves, pumps) upstream
of the faucet (Pieper et al., 2015). A study exposed brass and galvanized steel meeting the low-
lead requirements (i.e., NSF/ANSI Standard 372) to more aggressive waters typically found in
groundwaters. The authors found that low-lead brass released non-detectable concentrations of
lead when exposed to aggressive conditions. Leaching from C36000 brass (non low-lead) was
found to increase with decreasing pH and alkalinity. The study also found that galvanized steel
may still release significant lead in aggressive waters as a result of the sorption of lead to
plumbing. The authors concluded that although lead-free brass products protect private wells,
elevated lead from legacy materials and galvanized steel will remain an issue for systems without
corrosion control. As such, it is important for private well owners to test for lead and to ensure
that replacement parts and components meet the low-lead requirements.
Currently, the NPC requires that components (i.e., fittings) used for potable water
applications meet relevant standards for plumbing fittings (NRCC, 2013). The relevant
standards, namely ASME A112.18.1/CSA B125.1 and CSA B125.3, include requirements to
comply with both NSF/ANSI Standard 61 and NSF/ANSI Standard 372 (CSA, 2018a, 2018b).
8.0 Kinetics and metabolism

8.1 Absorption
The absorption of lead from the gastrointestinal tract following oral exposure will depend
on the physiological state of exposed individuals (e.g., age, fasting, calcium and iron intake) as
well as physicochemical characteristics of the ingested lead (e.g., particle size, solubility and
lead species) (ATSDR, 2007). Two studies have investigated lead uptake from drinking water. In
one study, 0.37 MBq of 203Pb-labelled lead chloride in 100 mL water was administered to 10
healthy male volunteers, aged 25–35 years, who had eaten a light breakfast 2 hours prior to
exposure. Average whole-body retention at 96 hours after exposure was approximately 21% and
ranged from 10% to 65% (the highest percentage represents an average of two samples, as the
measurement was repeated) (Blake, 1976). In a second study, three individuals from the Blake
(1976) study were administered 0.37 MBq of 203Pb-labelled lead chloride with 300 μg of
unlabelled lead chloride in 100 mL distilled water after 18 hours of fasting and with 6 additional
hours of fasting after exposure (Blake et al., 1983). Whole-body lead retention at 96 hours post-
exposure demonstrated that fasting significantly increased lead uptake, as shown by mean
absorption levels of approximately 70% (67–76%) and 15% (11–23%) for fasted and non-fasted
individuals, respectively (Blake, 1976; Blake et al., 1983). In two subjects who were
administered 203Pb and carrier in a control meal prepared with distilled water with and without
minerals (also with fasting 18 hours prior to and 6 hours after exposure), mineral content was
shown to significantly affect absorption. With minerals, whole-body lead retention after 96 hours
in the two individuals was 0.94% and 1.5%, whereas it was 65.4% and 71.6% without minerals
(Blake et al., 1983). Additional experiments indicated that decreasing dietary consumption of
calcium and phosphorus increased lead retention (Blake and Mann, 1983). In a study of exposure
to lead through sherry stored in a lead crystal container, 70% of the dose was shown to be
absorbed in fasted individuals (Graziano et al., 1996). The absorption of lead from food has been
evaluated according to age. In adults, levels of absorbed lead varied widely (from 9.7% and up to

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Lead (March 2019)
61%) and increased with fasting and low dietary intake of calcium and phosphate (Rabinowitz et
al., 1976, 1980; James et al., 1985). Some data suggest that lead is more readily absorbed by
infants and children than by adults. Without any fasting, lead absorption in infants and children
aged 3 months to 8 years and 14–746 days was 41.5% and 53%, with an estimated retention of
31.7% and 18%, respectively (Alexander, 1974; Ziegler et al., 1978).
An in vitro test was developed to determine the bioaccessibility of lead particles from tap
water, based on a Relative Bioaccessibility Leaching Procedure used for soils, to assess the
hazard associated with the ingestion of various types of particulate lead. Bioaccessibility was
evaluated for particles representative of those found in drinking water distribution systems.
Particles were either laboratory‐generated or collected from the aerators of taps during field
sampling. Particles from field-sampled taps contained significant amounts of lead (0.003–71%,
median 4.7%). The bioaccessibility of the laboratory‐generated particles ranged from 2% to
96%, depending on the type of particle (lead(II) > brass > lead(IV) > solder), whereas that of the
field-collected particles was homogeneously distributed between 1.5% and 100% (median 41%).
The hazard of particulate ingestion was found to depend on the amount and concentration
ingested as well as the bioaccessibility of the particulate forms of lead. The impact of particulate
lead on the exposure of children aged 0.5–7 years was estimated using the IEUBK model. The
model found that the exposure was most significant for lead particles originating from large
buildings in the distribution system under study (Deshommes et al., 2012c). In another study,
Deshommes et al. (2012a) assessed the impact of tap water as a source of lead in prepared foods
consumed by children, including prepared beverages, rice or pasta. The authors found that the
range of bioaccessibility of lead from food cooked with water varied with the lead form.
Although lead particles did not dissolve during cooking, the dissolved lead from the lead sources
and emitted from these particles was found to concentrate in the food. It was also determined that
small particles of lead would likely be ingested and become bioaccessible once in the stomach.
Data on absorption following oral exposure in humans are further supported by
observations in experimental animals. Absorption of 210Pb-labelled lead acetate administered by
oral gavage (6.37 mg/kg bw) was approximately 38% in juvenile rhesus monkeys, whereas it
was only 26% in adult females (Pounds et al., 1978; ATSDR, 2007). Rat pups also absorbed
more lead via diet than their adult counterparts (Forbes and Reina, 1972; Kostial et al., 1978).
Gastrointestinal absorption of lead following oral uptake from soil is generally less than
absorption of dissolved lead due to factors in addition to fasting and nutritional status, including
those that affect lead’s mobility in soil (e.g. pH, organic carbon content and cation exchange
capacity) (ATSDR, 2007).
Particle-bound lead can be inhaled at various respiratory depths, and thus absorption will
depend on the lead deposition within the lung. Lead associated with larger particles will be
deposited in the upper respiratory tract, resulting in mucociliary clearance and leading to
swallowing and thus gastrointestinal absorption of lead. Small particles (i.e., < 1 μm in diameter)
can reach the lower respiratory tract, where they can enter the circulation or be engulfed by
phagocytic macrophages. Virtually all particulate lead reaching the deeper lung is absorbed. In
adults, deposition within the deeper lung was shown to range from 14% to 40%, with near
complete retention of the deposited dose in blood (Chamberlain et al., 1975; Wells et al., 1975).
Dermal absorption of lead is significantly less than absorption through the oral and
inhalation exposure routes. Application of 203Pb-labelled lead acetate in a cosmetic preparation to
the skin of eight male volunteers over 12 hours demonstrated that absorption was less than 0.3%,
based on whole-body counts and urinary radioactivity normalized to 203Pb-labelled lead chloride
administered in blood (Moore et al., 1980). Another study indicated that soluble forms of lead,

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Lead (March 2019)
such as lead nitrate and lead acetate, can be absorbed superficially into skin and potentially
through the skin upon dermal application of lead filter paper for 6 hours on the forearm at levels
of up to 29.5% (Stauber et al., 1994). In vitro experiments using human skin indicate that
absorption of organic lead depends on the lead compound. Tetrabutyl lead was the most readily
absorbed, followed by lead nuolate, lead naphthenate and lead acetate. Organic lead compounds
appear to be more readily absorbed than inorganic lead compounds. Similar observations were
made in in vitro experiments with guinea pig skin tissue (Bress and Bidanset, 1991). Application
of inorganic and organic lead (i.e., lead naphthenate, lead nitrate, lead stearate, lead sulphate,
lead oxide and lead metal powder) to the shaved backs of rats resulted in absorption at rates
ranging from 0.002% to 0.17%, as based on dose recovered in urine. Although absorption was
low for all compounds, it was especially low for inorganic lead compounds (Sun et al., 2002;
ATSDR, 2007).
8.2 Distribution
The distribution of lead is very similar to the distribution of calcium, owing to the
molecular similarities of the two substances. Lead distribution is essentially the same regardless
of the route of exposure. Once in the body, lead will primarily partition to blood, soft tissues and
bone. The half-life of lead in blood is approximately 35 days (Rabinowitz et al., 1976). However,
bones act as a reservoir for lead, with a biological half-life of approximately 20–30 years
(Patrick, 2006). Thus, bone represents 80–95% of the total retained lead in adults and
approximately 70% of the total retained lead in children (Patrick, 2006). For this reason,
measurement of lead in bone, which can be done using a non-invasive procedure (i.e., X-ray), is
an excellent method for determining lead body burdens. Uptake and release of lead from bone
can significantly affect BLLs.
Under normal conditions, most lead (> 98%) is bound to cellular proteins within red
blood cells. Thus, this lead is not available for crossover to other tissues (Schütz et al., 1996;
Bergdahl et al., 1997, 1999; Hernández-Avila et al., 1998; Manton et al., 2001; Smith et al.,
2002). The remaining lead can be found as complexes with low molecular weight sulphydryl
compounds (e.g., cysteine and homocysteine) within serum and as protein-bound lead (e.g., to
albumin and γ-globulins) within plasma. Although present in only small quantities, the lead in
plasma is the most biologically available for uptake by other tissues (Ambrose et al., 2000).
Small amounts of lead have been found to permeate several tissues, including liver, kidney,
skeletal muscle, pancreas, ovary, spleen, prostate, adrenal gland, brain, fat, testis and heart, with
higher levels observed in bone, hair and nails. Of the soft tissues, aorta, liver and kidney retained
the most lead, as shown in human cadavers (Barry and Mossman, 1970; Barry, 1975; Gross et
al., 1975). Levels of lead in soft tissues are relatively constant in adults, with no accumulation
over time (Gross et al., 1975).
Lead accumulation will occur in bone, generally in regions undergoing active
calcification at the time of exposure. As a result of lead’s accumulation in bone, bone biokinetics
will play an important role in determining BLLs. Bone resorption that occurs with aging can
significantly affect BLLs, as suggested by significant associations between the blood lead index
(time-weighted average BLL corresponding to total exposure) and bone lead levels (Fleming et
al., 1997; Chettle, 2005). It is estimated that lead stored in bones can contribute up to 70% of
total BLLs in adults (Smith et al., 1996; Gulson et al., 1997). Endogenous bone lead can also be
a significant source of blood lead in children. Estimated contributions of endogenous bone lead
to BLLs in children were shown to range from 12% to 66% (Gulson et al., 1997), and
contributions up to 96% were found in one 46-month-old child (Gwiazda et al., 2005). There is

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Lead (March 2019)
also evidence that exposure to lead in early childhood can lead to elevated BLLs at the ages of 19
and 29 years (McNeill et al., 2000).
Two life stages in women, menopause and pregnancy, can significantly affect BLLs. This
is due to increased bone resorption in menopausal women and increased calcium demands in
pregnant and nursing women, leading to the release of lead stored within the skeleton.
Postmenopausal women who were former smelter employees have shown significantly higher
BLLs than premenopausal smelter workers (Popovic et al., 2005). Mean BLLs have been shown
to increase by 20% in pregnant and postpartum women (Gulson et al., 2003). It is estimated that
79–90% of the mobilized lead in pregnant women can reach the fetus via cord blood (Mahaffey,
1991; Gulson et al., 2003). In pregnant women, BLLs have been shown to follow a nonlinear “U-
shaped” pattern during pregnancy (Hertz-Picciotto et al., 2000; Schell et al., 2000, 2003; Sowers
et al., 2002; Gulson et al., 2004a). In a study of 105 healthy women in Mexico City, maternal
BLLs were measured at 12, 20, 28, 36 months and at delivery; throughout pregnancy, BLLs
averaged 7.0 μg/dL with an observed decline of about 1 μg/dL between weeks 12 and 20 and an
increase of 1.6 μg/dL observed between week 20 and delivery (Rothenberg et al., 1994). Lead
will accumulate mostly in fetal bone, but can also be distributed to fetal soft tissues, including
liver, heart and brain, later during the gestational period (Mahaffey, 1991). Postpartum BLLs can
be particularly elevated. These were shown to increase by 30–95% (mean 65%) in postpartum
women in comparison with the minimum value observed during late pregnancy (Gulson et al.,
2004b). The levels of lead in breast milk and blood of mothers are significantly correlated to
infant BLLs (Ettinger et al., 2004; Koyashiki et al., 2010). Concentrations of lead in breast milk
will significantly impact infant BLLs; thus, long-term maternal exposure prior to pregnancy and
breastfeeding can increase lead exposure in children (Gulson et al., 1998; Ettinger et al., 2004).
8.3 Metabolism
Inorganic lead primarily forms complexes with proteins and non-protein ligands. The
majority of lead partitions to serum, where the primary ligand formed is γ-aminolevulinic acid
dehydratase (ALAD), followed by low molecular weight sulphydryl compounds, such as
cysteine and homocysteine (Gonick, 2011). Of the remaining lead found in plasma, 90% is
bound to the albumin fraction (Gonick, 2011). Proteins with high affinity for lead have been
identified in soft tissues (high-affinity cytosolic lead-binding proteins). These include acyl-
coenzyme A binding protein in brain in addition to thymosin β4 in kidney of exposed humans
(Quintanilla-Vega et al., 1995; Smith et al., 1998), as well as a cleavage product of
microglobulin in kidney of male rats (Fowler and DuVal, 1991).
The metabolism of organic lead compounds has been less studied. Alkyl lead compounds
are metabolized by oxidative dealkylation via cytochrome P450 enzymes in liver (ATSDR,
2007). Several metabolites have been detected in the urine of workers exposed to tetraethyl lead,
including triethyl lead, diethyl lead, ethyl lead and inorganic lead (Turlakiewicz and
Chmielnicka, 1985; Zhang et al., 1994; Vural and Duydu, 1995). Increased levels of the
metabolite triethyl lead were measured in liver, kidney, pancreas, brain and heart in three
individuals who died of acute tetraethyl lead poisoning (Bolanowska et al., 1967).
8.4 Excretion
Lead is primarily excreted through urine and feces; other minor pathways include hair,
nails and breast milk. The proportions of lead excreted through each of these pathways will vary
according to the exposure route.
Intravenous injection of lead in humans, as a representation of internalized lead,
demonstrates that approximately one third and two thirds of circulating lead are excreted via the

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Lead (March 2019)
fecal and urinary routes, respectively (Chamberlain et al., 1978). Minor pathways of excretion
included sweat, saliva, hair, nails and breast milk (Hursh and Suomela, 1968; Hursh et al., 1969;
Griffin et al., 1975; Rabinowitz et al., 1976; Chamberlain et al., 1978, 1979; Kehoe, 1987;
Stauber et al., 1994; ATSDR, 2007).
Following oral exposure, most lead is eliminated via the fecal route. Excretion of lead
following daily oral exposure of five men to stable isotope–labelled lead at approximately 210–
360 μg/day (for up to 210 days) was 12% in urine (7–17%) and 90% in feces (87–94%)
(Rabinowitz et al., 1976; ATSDR,2007). Ingestion of 1–3 mg lead per day over 208 weeks was
associated with urinary lead excretion, representing 5% of the total ingested dose (Kehoe, 1987;
ATSDR, 2007).
The ratio of fecal to urinary excretion of inhaled lead particles depends largely on the size
of the particles. Approximately two thirds of submicrometre particles that reach the bronchiolar
and alveolar regions of the respiratory tract are excreted in urine, whereas an estimated one third
are excreted in feces (Hursh et al., 1969; Chamberlain et al., 1978; ATSDR, 2007). The
proportion of lead excreted in feces is expected to increase with particle size as a result of
ingestion of lead-containing phlegm. Lead that is associated with tetraethyl and tetramethyl lead
can be excreted through exhaled air, urine and feces. Inhalation of 203Pb-labelled tetraethyl and
tetramethyl lead resulted in 37% and 51% deposition in the respiratory tract, respectively, of
which 20% and 40% were exhaled in the following 48 hours (ATSDR, 2007). The remaining
lead was excreted in urine and feces. Dermal exposure to lead acetate and lead nitrate has been
associated with detectable levels of lead in sweat and urine (Kehoe, 1987), although dermal
absorption of lead is generally negligible.
8.5 PBPK models

The majority of studies that have investigated the toxicity of lead in humans have used
BLL as a metric of exposure. However, oral doses provide a more flexible toxicological
reference value for setting environmental quality guidelines for drinking water. Three established
and validated physiologically based pharmacokinetic (PBPK) models are available to estimate
the chronic oral dose of lead that would result in specific BLLs (i.e., O’Flaherty, Leggett and
IEUBK models). All three models have been considered in this assessment of lead. Thus, the
three models are described below, along with more specific details pertaining to the
methodologies employed. It should be noted that simpler slope factor models based on linear
epidemiological relationships between BLL and either lead uptake or lead intake are also
available to estimate oral doses from BLLs (JECFA, 2011; EFSA, 2013).
8.5.1 O’Flaherty model

The O’Flaherty model simulates lead absorption and disposition from birth through
adulthood (O’Flaherty, 1993, 1995b). It was originally calibrated to predict blood, bone and
tissue lead concentrations in the rat (O’Flaherty, 1991) and was subsequently modified to reflect
the anatomical and physiological characteristics of children (O’Flaherty, 1995b) and adults
(O’Flaherty, 1993, 1998). The models relevant to adults and children were shown to accurately
reproduce BLL observations, except in cases where lead was ingested at very high
concentrations (O’Flaherty, 1993, 1995b). Uptake of lead by the gastrointestinal tract following
ingestion and uptake from the respiratory tract following inhalation are considered in the model,
along with exchanges of lead between various compartments, including blood plasma, well-
perfused tissues (e.g., tissues of the gastrointestinal tract), poorly perfused tissues (i.e., muscle,
fat), bone (i.e., cortical and trabecular bone), liver and kidney. Elimination from urine and feces
is also considered. Several components of the model are dependent on age-specific

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Lead (March 2019)
pharmacokinetic differences, including rates of absorption of lead from the gastrointestinal tract,
bone formation and resorption, tissue growth and body weight. Gastrointestinal absorption of
lead from drinking water or diet declines from an ingestion rate of 58% at birth to 8% after 8
years of age. The model can be modified to simulate the pharmacokinetics of lead in the bodies
of sensitive individuals, such as pregnant women and fetuses.
The version of the O’Flaherty model used in this assessment was a 1997 C++ version of
the ACSL source code for the O’Flaherty model for humans (O’Flaherty, 1993, 1995a, 1995b,
2000). Only a limited number of input parameters can be adjusted in the C++ model. Outputs of
the C++ version of the O’Flaherty model are limited to the concentration of lead in blood and
bone and do not include intermediate values, such as the intake or uptake of lead from
environmental exposures. The input parameters for the O’Flaherty model were set to model lead
exposure and kinetics from 0 to 5 years of age. Input parameters to the C++ O’Flaherty model
related to lead exposure are limited to environmental concentrations. In order to determine the
corresponding oral dose to be used as a point of departure for risk assessment purposes, the
concentrations of lead in all environmental exposure media except drinking water were set to
zero. Concentration in drinking water was varied between iterative model runs until the model
output for BLL in a 5-year-old was equal to the target BLL. Separate modelling exercises were
computed using the male and female versions of the O’Flaherty model. Body weights of 18.8 kg
and 18.9 kg, drinking water rates of 0.80 and 0.95 L/day and oral bioavailabilities of 17% and
17% for males and females, respectively, were calculated using the model codes described in
O’Flaherty (2000). Specific input and output parameters as well as calculated intermediate
values using the O’Flaherty C++ model are presented in a supporting technical report (Healey,
2014).
8.5.2 Leggett model

The Leggett model was developed from a biokinetic model put forth by the International
Commission on Radiological Protection for calculating radiation doses from radionuclides
present in the environment, including radioisotopes of lead (ICRP, 1993). Additional parameters
specific to lead were used to adjust the model for lead PBPK modelling applications in children
and adults (Leggett, 1993). The model can simulate lead intakes from ingestion, inhalation and
intravenous injection. It consists of a central compartment for diffusible plasma together with its
interactions with the skeleton (cortical and trabecular bone), liver, kidney, brain and other soft
tissues (intermediate turnover, rapid turnover and tenacious retention). The bone portions of the
model each contain a surface compartment and a non-exchange/exchange compartment. Lead
enters the exchangeable portion of bone volume through bone surface, from which it can either
move to the non-exchangeable portion of bone (stored lead) or return to the surface, where it can
re-enter the bloodstream upon bone resorption. Liver and kidney are also further
compartmentalized to take into account rapid lead uptake and transfer and more gradual transfer
and accumulation. Transfer rate constants between compartments in the Leggett model vary with
age and BLL. Elimination from urine, feces and sweat as well as hair, nails and skin is
considered. In this model, the absorption fraction of ingested lead from drinking water changes
with age, declining from 0.45 at birth to 0.3 at 1 year of age and 0.15 past the age of 25.
Validation of the model appeared to predict BLLs of adults, but there are insufficient data to
assess the model’s accuracy in predicting BLLs of exposed children (ATSDR, 2007). At low
doses, the Leggett model has a tendency to overestimate BLLs (Pounds and Leggett, 1998; U.S.
EPA, 2007). The model allows the simulation of lifetime exposures to lead.
For the purposes of this assessment, an enhanced Leggett model developed by Dr. Joel
Pounds was used. This model is consistent with Leggett (1993), but includes some changes to the

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Lead (March 2019)
FORTRAN source code for the model to facilitate modelling chelation. The Leggett model is
written in FORTRAN and distributed as an executable DOS program. Model inputs are defined
in an ASCII input file and read into the DOS executable program. In contrast to other PBPK
models, the Leggett model does not include environmental lead concentrations as input
parameters. Thus, the ingestion route of exposure was specified in the input parameters. The
uptake of lead from the gastrointestinal tract into blood is determined by input values for the
gastrointestinal absorption fraction. The input rate of chronic lead ingestion was varied between
iterative model runs until the average of model outputs for BLLs in 5-year-old children was equal
to the targeted BLL. The input value for the gastrointestinal absorption fraction was 100% for all
model runs. The Leggett model does not include body weight as a model parameter; thus, the
default body weight for 4- to 5-year-old children from the IEUBK model (18.2 kg) was used.
Specific input and output parameters using the enhanced Leggett model are presented in a
supporting technical report
(Healey, 2014).
8.5.3 IEUBK model

The IEUBK model was developed for children ages 0–7 years and designed to predict the
probability of elevated BLLs in children (U.S. EPA, 1994a, 1994b; White et al., 1998). The
model is divided into four submodels, including an exposure model, an uptake model, a
biokinetic model and a blood lead probability model. The exposure model simulates intake of
lead through drinking water, air, soil-derived dust or diet, whereas the uptake model simulates
absorption through the gastrointestinal and respiratory tracts. It is assumed that the absorption
fraction of lead through drinking water and diet at 30 months of age is 0.5, with subsequent
decreases to 0.11. The biokinetic model includes a central plasma compartment and its
interactions with bone (i.e., trabecular and cortical), red blood cells, kidney, liver and other soft
tissues, as well as three elimination pools (i.e., urine, feces, skin/hair/nails). The model is age
dependent and simulates growth of body tissues, compartment volumes and lead concentrations
in each compartment. The BLL at birth is assumed to be 85% of maternal BLL. The blood lead
probability model is used to estimate BLLs of children exposed under specific conditions.
Because BLLs in children with similar exposure can vary significantly, the model simulates the
combined impact of the sources of variability as a lognormal distribution of BLL from which the
geometric mean is used in the derivation of the blood lead probability model. Alternatively, an
extension of the IEUBK model that includes Monte Carlo simulations can be used to simulate
variability and uncertainty in exposure and absorption (Goodrum et al., 1996). Considerable
effort has gone into validating the IEUBK model. Model predictions of BLLs in children were
compared with observations from epidemiological studies of four hazardous waste sites (Hogan et
al., 1998). Predicted geometric mean BLLs were within 0.7 µg/dL of the observed geometric
mean BLLs for each of the sites. Moreover, the prediction of the percentage of children with
BLLs higher than 10 µg/dL was within 4% of the observed percentage for each site. An
additional study that compared water lead levels with actual BLL data and IEUBK estimations
also confirms the validity of the model, with some degree of overestimation for children who
lived in dwellings with a lead service line (Deshommes et al., 2013). Concordance of model-
predicted BLLs and actual BLLs can be influenced by multiple factors, including the extent to
which exposure and blood lead measurements are adequately matched and site-specific factors
that may affect lead intake or uptake (Bowers and Mattuck, 2001). The computer code for the
IEUBK model (IEUBK version 0.99d) has been shown to accurately implement the conceptual
model, as shown through independent validation and verification (Zaragoza and Hogan, 1998).
The version of the IEUBK model used in this assessment was the IEUBK for Windows version
1.1 build 11. In order to determine the corresponding oral dose to be used as a point of
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Lead (March 2019)
departure for risk assessment purposes, the concentration of lead in all environmental exposure
media except drinking water was set to zero. The concentration of lead in drinking water was
varied between iterative model runs until the model output for the geometric mean BLL in 4- to
5-year-old children and 5- to 6-year-old children was equal to the targeted BLL. The IEUBK
default drinking water consumption rate of 0.55 L/day and default bioavailability of lead in
drinking water of 50% were used. The model’s assumed body weight of 4- to 5-year-old children
was 18.2 kg. The lead uptake values reported in the IEUBK outputs were consistently
approximately 93–97% of the lead uptake values that were calculated as intermediate values
from the model input parameters. It is unclear whether this 3–7% has been accounted for in the
model; thus, it is possible that the oral equivalent dose to reach the targeted BLL may in reality
be slightly higher. Specific input and output parameters as well as calculated intermediate values
using the IEUBK model are presented in a supporting technical report (Healey, 2014).
9.0 Health effects

Lead has long been known to cause a variety of health problems. Thus, many studies
have documented adverse health endpoints in exposed humans and experimental animals. As
environmental lead levels have declined considerably in recent times, more epidemiological data
have become available on the low-dose effects of lead. These have demonstrated that lead-
induced toxicities can occur at much lower exposure levels than previously estimated. In many
cases, lead toxicities can be observed at BLLs below 10 µg/dL (corresponding to intervention
levels currently under revision; Health Canada, 2013a). In light of this new evidence, the
literature overview presented herein focuses on the low-dose effects of lead in humans and
experimental animals. In the case of epidemiological studies, emphasis was placed on
longitudinal studies and meta-analyses when possible, as these studies carry more weight in the
interpretation of lead toxicity. The toxicity of lead in humans and experimental animals has also
been reviewed in detail (IARC, 2006; ATSDR, 2007; Health Canada, 2013c).
9.1 Effects in humans

9.1.1 Acute toxicity
Signs of lead intoxication are mostly neurological and gastrointestinal effects, including
dullness, irritability, poor attention span, headache, dizziness, weakness and memory loss, as
well as epigastric pain, constipation, vomiting, anorexia, paresthesia, anemia and convulsions
(ATSDR, 2007). In severe cases, encephalopathy, coma and death can occur (ATSDR, 2007).
Encephalopathy has been reported at relatively high BLLs of 100–120 μg/dL in adults and 80–
100 μg/dL in children (Smith et al., 1938; NAS, 1972; WHO, 2011). However, acute
neurological, gastrointestinal and musculoskeletal symptoms can occur at BLLs below 40 μg/dL
(Baker et al., 1979; Hänninen et al., 1979; Awad El Karim et al., 1986; Holness and Nethercott,
1988; Marino et al., 1989; Matte et al., 1989; Rosenman et al., 2003). Acute gastrointestinal and
musculoskeletal effects have been shown to occur at BLLs as low as 30–39 μg/dL and possibly
at levels as low as 25–30 μg/dL for neurological effects (Rosenman et al., 2003). Severe acute
lead toxicity is also associated with effects on proximal renal tubules, as demonstrated by
Fanconi syndrome–like symptoms in children and adults, including excretion of amino acids,
glucose and phosphates in urine (Chisolm et al., 1955; Goyer et al., 1972; Loghman-Adham,
1998).

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Lead (March 2019)
9.1.2 Subchronic and chronic toxicity and carcinogenicity
9.1.2.1 Neurological effects
Epidemiological data strongly support an association between lead exposure and various
adverse neurological effects in adults. Adverse neurological effects have been observed in cross-
sectional studies of lead workers with elevated BLLs, ranging from 40 to 80 μg/dL. These effects
include saccadic eye movements (Baloh et al., 1979; Glickman et al., 1984), changes in sensory
evoked potential (Araki et al., 1987; Counter and Buchanan, 2002), signs of decreased cognitive
performance, including loss of memory, delayed reaction time and problems with verbal concept
formation (Haenninen et al., 1978; Arnvig et al., 1980; Mantere et al., 1982; Baker et al., 1983;
Hogstedt et al., 1983; Campara et al., 1984; Stollery et al., 1989, 1991; Stollery, 1996), as well as
altered psychological state, such as depressed mood and fatigue (Baker et al., 1983; Maizlish et
al., 1995). Peripheral nerve function, measured by the conduction velocity of electrically
stimulated nerves, was affected at BLLs as low as 30 μg/dL (Seppalainen et al., 1983; Chia et al.,
1996), whereas other studies found no significant association between nerve function and BLL
(Spivey et al., 1980; Ishida et al., 1996).
The strongest support for lead-induced adverse neurological effects is from prospective
studies that have followed populations over many years, as well as bone lead studies that reflect
lead storage over time. In a study of Canadian lead smelter workers exposed on average for 17.1
years (range of 0.2–26 years) and for which BLLs were assessed several times per year,
cumulative BLL (mean = 728.2 ± 434.36 (μg/dL)·year) and the average BLL over the period of
employment (mean = 39.0 ± 12.32 μg/dL) were associated with alterations in auditory verbal
learning; these included effects on memory storage and retrieval, but not on immediate learning,
attention or memory span (Bleecker et al., 2005). Moreover, it was demonstrated in 54 Finnish
storage battery workers with well-documented long-term exposure to lead (1–30 years of
employment) that BLLs exceeding approximately 50 μg/dL can lead to long-lasting adverse
effects on central nervous system functions (Hänninen et al., 1998). There are some data to
suggest that adverse neurological effects in adults can be reversed to a certain extent when
occupational exposure to lead is reduced. This was shown in lead glaze factory workers, whose
BLLs were reduced from 26.3 to 8.3 μg/dL over a period of 4 years resulting in significant
improvements in neurobehavioural performance (finger tapping, pattern comparison reaction
time, and memory testing), and in lead smelter workers whose verbal memory performance
improved when BLLs that exceeded 40 μg/dL prior to 1980 were reduced thereafter (Lindgren et
al., 2003; Chuang et al., 2005). Studies of tibial lead levels, as an indicator of long-term exposure
to lead, have consistently been associated with adverse neurological effects at levels ranging
from 10.5 to 57.0 μg/g (Khalil-Manesh et al., 1993; Shih et al., 2006; Weuve et al., 2009). Tibia
lead levels were also shown to correlate with decreased cognitive function and reduced volume
of the total brain, the frontal and total grey matter as well as the parietal white matter in lead
workers (Stewart et al., 2006).
Several studies have investigated the effects of lead at very low BLLs (e.g., < 10 μg/dL)
(Muldoon, 1996; Nordberg et al., 2000; Louis et al., 2003; Wright et al., 2003; Krieg et al.,
2005). A modest association between BLL and essential tremor diagnosis was observed in a
case–control study of patients with essential tremor (100 patients, mean BLL = 3.3 ± 2.4 μg/dL,
mean age = 70.7 years) and controls (143 controls, mean BLL = 2.6 ± 1.6 μg/dL, mean age =
66.2 years) (Louis et al., 2003). The lifetime occupational exposure to lead was similar in
patients and control groups, and the association was significant after adjusting for potential
confounding effects (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.03–1.37). Effects
on essential tremor are further supported in two case–control studies in separate environmentally
exposed populations that showed an association between BLLs and incidences of essential

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Lead (March 2019)
tremor (Louis et al., 2005; Dogu et al., 2007). Furthermore, it was shown that individuals
carrying the ALAD-2 allele may be more susceptible to lead-induced essential tremor (Louis et
al., 2005). It was not entirely known whether elevated BLLs preceded or followed diagnosis.
This would require further investigations with regards to lead-induced cerebral damage over time
and the development of essential tremor. However, the prevalence of essential tremor would
likely be higher than 1–6% if a BLL of 3.3 μg/dL alone were associated with this adverse
neurological effect.
Two studies have used a battery of neurobehavioural and neuropsychological tests to
investigate adverse cognitive effects in adults when BLL was below 10 μg/dL (Muldoon, 1996;
Krieg et al., 2005). Muldoon (1996) conducted a wide range of neurological tests to measure
memory, language, visual-spatial ability, intellectual status and sensorimotor action in 325
female rural dwellers (mean age = 71.1 years) and 205 female urban dwellers (mean age = 69.4
years) as part of an osteoporotic fracture study. The rural and urban dwellers had mean BLLs of
4.5 μg/dL and 5.4 μg/dL, respectively. A significant association was found only in the rural
dwellers at levels of 4–7 μg/dL for the trailmaking and digit symbol tests and > 7 μg/dL for
reaction time tests. However, urban dwellers did not exhibit any adverse neurological effects,
even at BLLs of 8 μg/dL and above. The study controlled for important confounding effects,
such as age, education, and tobacco and alcohol consumption, in non-occupationally exposed
individuals. The reasons for negative effects in urban dwellers may be related to other, unknown
factors. In contrast to these findings in female rural dwellers, no significant effects occurred in
simple reaction time, symbol–digit substitution and serial-digit learning in a population aged 20–
59 years and in which BLLs ranged from 0.7 to 41.8 μg/dL (mean BLL = 3.30 μg/dL) (4937
participants, data from the third U.S. National Health and Nutrition Examination Survey
[NHANES III]) (Krieg et al., 2005). It was noted that this was likely related to the lack of low-
dose effects in adults or alternatively that specific tests or sample size did not allow detection of
such subtle low-dose effects.
Two additional studies have examined the performance of elderly populations on the
mini-mental status exam (MMSE). The MMSE assesses various endpoints related to orientation
in place and time, memory, attention, language and reasoning. Low scores, typically 23 or less
on a scale of 30, are associated with reduced cognitive function and increased risk for dementia
(Folstein et al., 1975; Santacruz and Swagerty, 2001). Wright et al. (2003) examined an elderly
population in the Normative Aging Study, in which 1031 individuals were administered the
MMSE with concomitant BLL measurements. A significant association was found between BLL
and MMSE scores below 24 (OR = 1.21, 95% CI = 1.07–1.36), after adjustments for covariates,
in the study group that had a mean BLL of 4.5 μg/dL. Significant interactions between BLL and
age suggest that mean BLLs of 5.9 μg/dL and above can accelerate age-related
neurodegeneration. Bone lead, however, was not significantly associated with poor outcomes in
the MMSE or with age-related neurodegeneration, except for a significant age interaction with
patella lead in the 57.6 μg/g group. In another study, however, no association between BLL and
MMSE score was found in a population of 762 elderly men (average age = 88.4 years) with a
mean BLL of 3.7 μg/dL (Nordberg et al., 2000). Thus, there are some data to suggest that BLLs
below 10 μg/dL may accelerate neurodegeneration and dementia in aging populations.
Nonetheless, it should be noted that any gradual neurodegeneration occurring earlier in life as a
result of past lead exposure has not been fully addressed in these studies.
Thus, there is evidence of adverse neurological effects at BLLs below 10 μg/dL.
Generally, though, the association of low BLLs with adverse neurological endpoints was
equivocal, and there were a significant number of data that did not support lead-induced adverse
neurological effects. Moreover, the analyses were based on single BLL measurements at the time

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of examination. This hampers our understanding of the implications of low BLLs on long-term
adverse neurological effects.
9.1.2.2 Cardiovascular effects

Epidemiological data from blood and bone lead studies suggest an association between
lead exposure and several adverse cardiovascular effects, including increased blood pressure and
risk of hypertension, development of peripheral arterial disease as well as increased risk of
coronary- and cerebrovascular-related morbidity and mortality (Navas-Acien et al., 2007; Vaziri
and Gonick, 2008).
Of the cardiovascular effects examined, increases in systolic blood pressure have been
the most studied endpoint and represent the strongest weight of evidence for a causal
relationship. Statistically significant associations, although generally weak, have been found in
three meta-analyses examining blood lead effects on blood pressure (Staessen et al., 1994a;
Schwartz, 1995; Nawrot et al., 2002) as well as in another meta-analysis of bone lead effects on
blood pressure (Navas-Acien et al., 2008). Five important longitudinal studies have also
examined the association between BLL and systolic blood pressure (Weiss et al., 1986; Moller
and Kristensen, 1992; Staessen et al., 1996; Glenn et al., 2003, 2006). This association was
reported as significantly positive after adjustments for covariates in three of the five studies,
although these studies examined populations with current or previous occupational exposure to
lead. Glenn et al. (2006) examined blood lead and tibia lead in 575 workers with a mean baseline
BLL of 31.4 μg/dL and followed over 3 years. Every 10 μg/dL increase in BLL was associated
with an annual increase in systolic blood pressure of 0.9 mmHg (0.12 kPa), although no
association was found with tibia lead. Another longitudinal study of 70 occupationally exposed
policemen followed over 5 years revealed a significant association with systolic blood pressure,
but only at BLLs exceeding 30 μg/dL (Weiss et al., 1986). The study by Glenn et al. (2003) was
considered the most relevant, because exposure occurred an average of 18 years prior and mean
blood and tibia lead levels in the 496 individuals were considered to be in the normal range of
4.6 μg/dL (baseline) and 14.7 μg/g (year 3), respectively. Measurements were taken 3–4 times
for each participant and corrected for various confounding effects, including age, body mass
index, alcohol consumption, smoking and education. An average annual increase in systolic
blood pressure of 0.64 mmHg (0.085 kPa) was reported for every standard deviation increase in
blood lead (2.6 μg/dL) from baseline BLL. The significant association between baseline BLL
and annual changes in systolic blood pressure was stronger in individuals with lower past peak
tibia lead, suggesting that the relationship observed is less likely to be related to previous
occupational exposure.
The two studies that did not support a significant association between BLL and systolic
blood pressure included one study of an environmentally exposed population (Staessen et al.,
1996). This study examined systolic and diastolic blood pressure as well as hypertension in 339
men and 345 women. BLLs and multiple blood pressure readings were taken at baseline (mean
BLL = 8.7 μg/dL) and after a median follow-up time of 5.2 years, at which time the mean BLL
had declined to 2.9 μg/dL. At follow-up, blood pressure was also measured using a 24-hour
ambulatory monitoring system to collect the most accurate information. It was determined that
BLL had no consistent effect on blood pressure and also did not increase risk of hypertension at
the levels studied (< 30 μg/dL). In an additional longitudinal study of aging males (from the
Normative Aging Study) that examined hypertension (but not blood pressure), higher BLLs were
not associated with an increased incidence of hypertension, although the relationship between
bone lead and hypertension was significant (Cheng et al., 2001). In the second non-occupational
longitudinal study, no significant effects on systolic blood pressure were found in individuals

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with baseline BLLs of 13.6 μg/dL for men and 9.6 μg/dL for women upon follow-up
examinations at 5 and 11 years, respectively, once adjustments for covariates were done (Moller
and Kristensen, 1992).
There is evidence to suggest that specific populations and lifestages, including African
Americans, pregnant and menopausal women as well as children, may be more sensitive to lead-
induced adverse cardiovascular effects. One study examined BLLs and blood pressure in 10 548
Caucasian and 4404 African American individuals (Vupputuri et al., 2003). After adjustments
for various potential confounding effects, an increased OR of 1.39 (95% CI = 1.21–1.61) was
measured in African American females. No effects on blood pressure were attributed to blood
lead in Caucasians. BLLs of ≥ 5 μg/dL were significantly associated with higher systolic and
diastolic blood pressure in African American men and women. Significant effects on systolic
blood pressure in African Americans, but not Caucasians, were also reported in Den Hond et al.
(2002) using the same cohort, as well as in Scinicariello et al. (2011). Lead has also been
associated with pregnancy-related increases in blood pressure. BLLs were significantly higher in
women with pregnancy-induced hypertension than in non-hypertensive pregnant women during
the second and third trimesters of pregnancy (mean BLLs were 2.2 μg/dL in hypertensive
subjects and 1.9 μg/dL in non-hypertensive subjects). Another study showed a significant
association between maternal blood pressure and umbilical BLL at very low levels (mean
maternal BLL was estimated to be 0.86 μg/dL from umbilical cord data) (Wells et al., 2011).
However, definitive conclusions cannot be drawn from these data, because blood pressure
measurements were taken during labour and delivery, a time of significant stress, with expected
impacts on blood pressure. Nash et al. (2003) examined blood pressure and hypertension
prevalence in 2165 premenopausal and postmenopausal women and determined that
hypertension was significantly increased in the women at BLLs ranging from 4.0 to 31.1 μg/dL,
with stronger associations observed in the postmenopausal women. Also, testing of 122 children
(all 9.5 years of age) with cord blood and early childhood BLL data demonstrated that BLLs in
excess of 2.9 μg/dL can increase vascular resistance responses to stress in children (Gump et al.,
2005) and that lead exposure is associated with autonomic and cardiovascular dysregulation in
children (Gump et al., 2011).
Few studies have carefully examined cardiovascular disease–related morbidity and
mortality upon prolonged exposure to lead. Mortality resulting from cardiovascular disease and
stroke, as well as all causes, was significantly increased at BLLs of 3.6 μg/dL and above in a
large prospective study of 13 946 adults in the U.S. NHANES monitored over up to 12 years
(Menke et al., 2006). After multivariable adjustment for age, sex, body mass index, smoking,
alcohol consumption, socioeconomic status and additional indicators of overall health, hazard
ratios were 1.25 (95% CI = 1.04–1.51) and 1.55 (95% CI = 1.08–2.24) for all-cause and
cardiovascular mortality, respectively. In a subset of the same cohort (2125 participants over 40
years of age at baseline), ORs of peripheral artery disease were only marginally increased at a
BLL of 2.9 μg/dL and above (OR = 2.88, 95% CI = 0.87–9.47) after adjustments for
demographic and cardiovascular risk factors (Navas-Acien et al., 2004). Schober et al. (2006)
also demonstrated in 9757 participants of the same cohort that were over 40 years of age that
BLLs exceeding 10 μg/dL were associated with cardiovascular disease–related mortality
(relative risk [RR] = 1.55; 95% CI = 1.16–2.07).
The relationship between stress, lead and blood pressure has been studied by a few
authors. Zota et al. (2013) conducted a cross-sectional study to determine whether allostatic load
(AL), a composite measure of physiologic response to chronic exposure to stress, amplifies the
effect of lead exposure on blood pressure among middle-aged adults. Associations between
BLLs and blood pressure in 8,194 U.S. adults (aged 40-65 years) participating in NHANES

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Lead (March 2019)
between 1999-2008 were analysed using logistic regression models revealing a linear dose-
response relationship for BLLs and elevated systolic blood pressure in the high AL group
(p = 0.03) but not the low AL group (p = 0.24); similarly, the relationship between BLLs and
elevated diastolic blood pressure was stronger among the high AL group compared to the low
AL group. Peters et al. (2007) examined whether psychological stress modified the impact of
cumulative lead exposure (measured as tibia and patella lead levels) on hypertension and blood
pressure in lead exposed men from a Boston community participating in the Normative Aging
Study. Cross-sectional analysis showed positive interactions between stress and tibia lead on
systolic blood pressure, after adjusting for confounders (i.e. age, body mass index, family history
of high blood pressure, education, smoking, alcohol consumption, physical activity, and
nutritional factors); individuals reporting high stress had 2.66 (95% CI, 1.43-4.95) times the risk
of developing hypertension per standard deviation increase in tibia lead and had 2.64 (95% CI,
1.42-4.92) times the risk per standard deviation increase in patella lead.
Although epidemiological data are somewhat inconsistent, there is sufficient evidence to
conclude that lead exposure is related to adverse cardiovascular effects and to support a causal
relationship between BLL and systolic blood pressure. Although the increases in blood pressure
reported were relatively small, they can potentially lead to substantive population-level health
impacts. Using distributions of systolic blood pressure in Canadians, it was estimated that a 1%
increase in systolic blood pressure across the population would result in a sex- and age-adjusted
added risk of coronary heart disease mortality of 1 in 2000 in adults 35–74 years of age
(although males were more susceptible, representing approximately 80% of the deaths) (Healey
et al., 2010). As such, even subtle increases in blood pressure should be considered as a
potentially important lead-related adverse health effect.
9.1.2.3 Renal effects

There is consistent evidence of adverse renal effects from lead exposure. Severe deficits
in function and pathological changes can be observed at BLLs exceeding 50 µg/dL (ATSDR,
2007), although much lower BLLs are associated with renal dysfunction. A review of the
epidemiological literature has concluded that lead contributes to nephrotoxicity even at BLLs
below 5 µg/dL, especially in sensitive populations, such as hypertensive and diabetic individuals
and those already affected by chronic kidney disease (Ekong et al., 2006).
Markers of renal dysfunction, including reduced glomerular filtration rate and creatinine
clearance (estimated from creatinine in serum and in urine collected over 24 hours) as well as
increased serum creatinine, have been reported at environmentally relevant BLLs. Of these
markers, glomerular filtration rate is considered the most reliable and was examined in 820
Swedish women with a median BLL of 2.2 µg/dL (Åkesson et al., 2005). Although the study
actually focused on cadmium exposure, the use of lead as a confounding variable revealed
significant associations of increased BLL with reduced glomerular filtration rate as well as
creatinine clearance. No significant interaction between blood lead and blood cadmium was
observed.
Additional epidemiological studies pertaining to environmentally relevant BLLs have
focused on creatinine levels exclusively. In Kim et al. (1996), frozen blood samples taken from
459 men from the Normative Aging Study every 3–5 years between 1979 and 1994 were used to
determine the association of BLL with serum creatinine over time. A significant association was
found even among subjects whose BLL had never exceeded 9.9 µg/dL throughout the study
period. A 10-fold increase in BLL also predicted a serum creatinine increase of 0.08 mg/dL,
which corresponds to approximately 20 years of aging. Two additional studies have reported
significant reductions in creatinine clearance upon environmental exposure to lead, although

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Lead (March 2019)
creatinine levels were not examined over time (Staessen et al., 1992; Payton et al., 1994). This
was shown in a population of 965 men and 1016 women with mean BLLs of 11.4 µg/dL and
7.5 µg/L, respectively, and for which data were adjusted for co-exposure to cadmium and other
covariates. A 10-fold increase in BLL was associated with a reduction of 10–13 mL/minute in
creatinine clearance (Staessen et al., 1992). The second cohort (same as Kim et al., 1996), in
which a positive association was made, examined 744 men with a mean BLL of 8.1 µg/dL
(Payton et al., 1994).
There is evidence to indicate that sensitive populations may be especially vulnerable to
adverse renal effects. Muntner et al. (2003) studied renal effects in 4813 hypertensive (mean
BLL = 4.21 µg/dL) and 10 398 non-hypertensive (mean BLL = 3.30 µg/dL) adults. Although no
association was made in non-hypertensive individuals, those with hypertension had significantly
or marginally significantly increased ORs for elevated serum creatinine (OR = 1.47, 95% CI =
1.03–2.10) and chronic kidney disease (OR = 1.44, 95% CI = 1.00–2.09) after adjustments for
appropriate confounding effects at BLLs as low as 2.5–3.8 µg/dL. Higher adjusted ORs for both
serum creatinine and chronic kidney disease were reported for two additional groups with higher
BLLs (3.9–5.9 µg/dL and 6.0–56.0 µg/dL) in a dose–response trend. Evidence suggesting that
specific subgroups may be more sensitive to developing adverse renal effects as a result of lead
exposure was also shown in Tsaih et al. (2004) through significant associations between lead
levels (both blood and bone) and serum creatinine in diabetic and hypertensive individuals, but
not in the overall study population. It is not clear whether children are more susceptible than
adult populations to adverse renal effects. Reduced glomerular filtration rate was reported in a
population of 769 healthy adolescents with a median BLL of 1.5 µg/dL (Fadrowski et al., 2010).
Thus, there is consistent evidence of adverse renal effects occurring at low BLLs, with
some evidence that BLLs that are chronically below 10 µg/dL can lead to renal dysfunction.
Sensitive populations, including those with hypertension or diabetes, may be specifically
vulnerable to lead-induced adverse renal effects. The lowest BLL associated with an effect was
2.5–3.8 µg/dL in a hypertensive population, with suggestive evidence of effects occurring at
BLLs as low as 2.2 µg/dL. It should be noted that there is a possibility that reduced kidney
function can result in altered lead clearance, thus leading to higher BLLs. Although this is most
likely to occur only upon substantive renal damage, it cannot be ruled out as a potential
confounder in renal toxicity studies.
9.1.2.4 Cancer
The epidemiological studies that have examined the relationship between long-term
exposure to lead and cancer incidence and mortality have reported both positive and negative
findings. Epidemiological studies provide suggestive evidence that lead may be carcinogenic at
high doses.
A number of studies have examined cancer occurrence in occupationally exposed
populations. Two meta-analyses have been conducted. One of the meta-analyses examined all of
the available cancer studies where occupational exposure to inorganic lead occurred, including
studies where lead exposure was known, but not quantifiable (Fu and Boffetta, 1995). RRs were
1.1 (95% CI = 1.05–1.17), 1.33 (95% CI = 1.18–1.49), 1.29 (95% CI = 1.10–1.50) and 1.41
(95% CI = 1.16–1.71) for overall cancers, stomach cancer, lung cancer and bladder cancer,
respectively. Restricting the meta-analysis to studies with heavy lead exposure (battery and
smelter industry workers only) resulted in an increase in RRs for cancers of the stomach (RR =
1.50, 95% CI = 1.23–1.83) and lung (RR = 1.44, 95% CI = 1.29–1.62). This provides some
evidence of a dose-related increase in cancer for exposure to inorganic lead compounds. The
second meta-analysis considered only eight studies that had reported specific measurements of

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Lead (March 2019)
exposure level or BLL (average BLL range of 26–80 µg/L) (Steenland and Boffetta, 2000).
There was evidence of increased lung cancer (RR = 1.30, 95% CI = 1.15–1.46) and stomach
cancer (RR = 1.34, 95% CI = 1.14–1.57). The association for lung cancer remained significant
after exclusion of one study that may have been confounded by exposure to arsenic (RR = 1.14,
95% CI = 1.04–1.73). Increases in cancer at other sites, including kidney and brain, were not
significant. It must be noted that these studies could not take into account potential confounders,
including smoking, dietary habits and exposure to certain chemicals. Thus, the results of the
studies are unreliable with respect to drawing any conclusions on the risks of cancer following
exposure to lead.
Liao et al. (2016) investigated the relationship between occupational lead exposure and
the incidence of stomach, lung, kidney, brain and meninges cancers in two prospective cohorts in
Shanghai, China. Estimates of cumulative exposure to lead fumes and lead dust were derived by
the statistical modeling of expert lead intensity ratings with inspection measurements, which was
then applied to the lifetime work histories of participants from the Shanghai Women’s Health
Study (SWHS; n = 73,363) and the Shanghai Men’s Health Study (SMHS; n = 61,379); exposure
metrics for men and women were then combined into an overall occupational lead exposure
variable. The proportions of SWHS and SMHS participants with estimated occupational lead
exposure were 8.9% and 6.9%, respectively. Lead exposure was positively associated with
meningioma risk in women (n = 38 unexposed and 9 exposed cases; relative hazard ratio (RR) =
2.4; 95% CI: 1.1, 5.0), particularly in the case of above median cumulative exposure (RR = 3.1;
95% CI: 1.3, 7.4); in men, all 12 observed meningioma cases were not due to lead exposure. In
addition, the authors also observed non-significant associations for kidney (n = 157 unexposed
and 17 ever exposed cases; RR = 1.4; 95% CI: 0.9, 2.3) and brain (n = 67 unexposed and 10 ever
exposed cases; RR = 1.8; 95% CI: 0.7, 4.8) cancers for males and females combined, as well as
elevated risks of lung and stomach cancers with high lead exposure in the male cohort (no
associations were observed in the female cohort). These findings suggest an association between
lead exposure and the risk of several cancers, however, the small numbers of cases, particularly
for kidney and brain cancer, limit the interpretation of these results.
Studies that have examined cancer occurrence following exposure of workers in
industrial settings known to be high in lead or by BLL measurements have reported both positive
and negative associations. Of the studies that have reported positive associations, significant
effects have been found for lung, central nervous system, brain, kidney, stomach and all-sites
cancers (IARC, 2006). Stronger and more consistent evidence for causality were made for lung
(Sheffet et al., 1982; Gerhardsson et al., 1986; Ades and Kazantzis, 1988; Anttila et al., 1995;
Lundström et al., 1997; Wong and Harris, 2000; Englyst et al., 2001), stomach (Sheffet et al.,
1982; Gerhardsson et al., 1986; Wong and Harris, 2000) and all-sites cancers (Jemal et al., 2002;
Lustberg and Silbergeld, 2002; Schober et al., 2006) than for other cancers. However, the
associations made were often equivocal and involved co-exposure to other chemicals, including
zinc chromate, arsenic, cadmium or other potential carcinogens. The lack of information
available in most studies also did not enable appropriate controlling for additional covariates.
Few of the studies cited above demonstrated a strong association between cancer risk and
exposure to lead at environmentally relevant doses. Schober et al. (2006) examined 9757
members of the general public in the U.S. NHANES with single BLL measurements. Taking all
age groups into consideration (≥ 40 years), the RR for all-cancer mortality was 1.44 (95% CI =
1.12–1.86) and 1.69 (95% CI = 1.14–2.52) for those with BLLs of 5–9 µg/dL and ≥ 10 µg/dL,
respectively, in comparison with the referent group (BLL < 5 µg/dL). The study was a large
cohort that adjusted for sex, race/ethnicity, education level and smoking status. Menke et al.
(2006) analysed the same cohort using adults 20 years of age and over instead of 40 years of age

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Lead (March 2019)
and over and observed no significant association between cancer mortality and BLL at BLLs
below 10 µg/dL. As the Schober et al. (2006) study examined a broader BLL range and also as
lead exposure–related cancer mortality is unlikely to occur in lower age groups, this study was
considered more sensitive than the study by Menke et al. (2006). Still, only one BLL
measurement was taken, and this lack of monitoring over time reduces our ability to conclusively
determine that the cancers are related to lead exposure. One study investigated lung cancer
following long-term monitoring of BLL (cumulative BLLs following annual measurements in
smelter workers) (Englyst et al., 2001); although a significant number of lung cancer cases were
observed in the lead-exposed workers, the study is confounded by substantive exposure to
arsenic.
Many of the studies reported negative effects on cancer, and interpretation of the positive
studies was often hampered by co-exposure to other substances and lack of controlling for other
confounding factors. However, cancer mortality was slightly increased in one environmentally
relevant study (Schober et al., 2006) that assessed the dose–response relationship and controlled
for important confounders. In conclusion, the data on cancer in humans is suggestive that lead
exposure may be associated with carcinogenic outcomes, especially at higher exposures, such as
in occupational settings.
9.1.3 Developmental and reproductive toxicity

9.1.3.1 Reproductive effects
Adverse reproductive effects of lead exposure included delays in sexual maturation
among men and women, increases in spontaneous abortions and preterm births, reduced birth
weights as well as decreased sperm concentrations.
There was consistent evidence of delayed puberty in women following environmental
exposure to lead. The effects of environmental lead exposure on sexual maturation were
investigated in 600 Caucasian, 805 African American and 781 Mexican American girls aged 8–
18 years. Significant delays in breast and pubic hair development as well as age at menarche
were observed in African American girls at a mean BLL of 3 µg/dL in comparison with a BLL
of 1 µg/dL. These same BLLs were also associated with delayed breast and pubic hair
development in Mexican American girls, although Caucasian girls were not significantly affected
(Selevan et al., 2003). In another study that examined the same population of girls, BLLs higher
than 2.1 µg/dL were associated with delays in pubic hair development and age to menarche, but
not breast development (Wu et al., 2008). The significance of these delays increased with higher
doses, and both studies were adjusted for important confounding effects. Breast and pubic hair
development as well as attainment of menarche at 13 years of age were all significantly affected
in African girls with BLLs above 5 µg/dL in comparison with those with BLLs below 5 µg/dL
(mean BLL in the 1683 girls was 4.9 µg/dL) (Naicker et al., 2010). In a smaller study that
examined exposure to multiple chemicals, including lead, mercury, hexachlorobenzene and
polychlorinated biphenyls, age at menarche in girls with BLLs above the median of 1.2 µg/dL
was 10.5 months later than that for girls with BLLs below the median (Denham et al., 2005).
Increases in BLL were not associated with delayed breast development in an urban study of 192
9-year-old girls with a mean BLL of 2.4 µg/dL, although the lack of association may be related
to the small study population size (Wolff et al., 2008).
There is additional evidence to suggest that exposure to lead may be associated with
younger age at menopause. Higher BLLs were measured in menopausal women in comparison
with women still menstruating after adjustments for bone turnover, age and other covariates at
levels as low as 1.4–2.1 µg/dL (Mendola et al., 2013). In a study of bone lead, as a measure of
cumulative exposure to lead, tibia lead concentrations exceeding 13 µg/g were associated with a

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Lead (March 2019)
reduction of 1.21 years of age at menopause. No associations were found for patella lead or
blood lead (median BLL was 3 µg/dL) (Eum et al., 2012). The effects reported for puberty and
menopause collectively suggest that exposure to lead may shorten a woman’s reproductive
lifespan.
Increased levels of lead in pregnant women have been associated with increases in
spontaneous abortions and preterm births, as well as decreases in birth weights. However, the
epidemiological evidence for these endpoints is inconsistent. One well-conducted study
investigated spontaneous abortions in 668 pregnant women who enrolled in the study in their
first trimester. After multiple adjustments for covariates, it was found that every increase in BLL
of 5 µg/dL (5–9, 10–14, and ≥15 µg/dL) was associated with an OR for spontaneous abortion of
1.8 (95% CI = 1.1–3.1) (Borja-Aburto et al., 1999). Another study estimated that a 0.1% increase
in plasma to blood lead ratio (plasma containing the toxicologically active fraction of lead) was
associated with a 12% greater incidence of spontaneous abortion (Lamadrid-Figueroa et al.,
2007). However, Vigeh et al. (2010) found that BLLs of women who had a spontaneous abortion
in comparison with BLLs of women with ongoing pregnancies did not differ significantly (3.51
µg/dL and 3.83 µg/dL, respectively). Increases in bone lead have been associated with reduced
birth weight and length (González-Cossío et al., 1997; Hernandez-Avila et al., 2002). Increased
maternal BLLs in the first and second trimesters (means of 7.2 µg/dL and 6.3 µg/dL,
respectively) were associated with premature delivery (Cantonwine et al., 2010).
Reproductive effects, including reduced fertility following paternal exposure and reduced
sperm concentrations, have also been reported for males, but generally at higher BLLs (> 30
µg/dL) (Alexander et al., 1996; Sallmén et al., 2000; Shiau et al., 2004). The dose–response
relationship was examined in all three studies but was demonstrated in only two of the
populations. It should be noted that these studies did not always measure and control for
important confounding effects. One environmental exposure study examined puberty in 489 boys
at 8–9 years of age. BLLs above 5 µg/dL were associated with delayed markers of pubertal
development based on genitalia staging and testicular volume (Hauser et al., 2008; Williams et
al., 2010).
Thus, lead exposure can affect the reproductive system in both men and women. Delayed
puberty in females appears to be the most sensitive endpoint, with evidence suggesting effects at
BLLs as low as 1.2 µg/dL. However, the strength of this association is limited by the few studies
that have investigated the effect. Both studies that reported a significant effect were done in the
same population, and there is an additional negative study in urban girls.
9.1.3.2 Neurodevelopmental effects

Neurodevelopmental effects related to decreased intelligence, attention and performance
have long been reported in infants and children exposed to lead early in life as well as in utero.
There are a significant number of data implicating low levels of exposure (BLLs < 10 µg/dL) in
these adverse effects. The deleterious effects of lead exposure manifested in developing children
can potentially have lifelong health and socioeconomic implications.
Epidemiological studies have associated BLL, tooth/dentin lead level and, in some cases,
cord BLL and maternal BLL with adverse neurodevelopmental effects in infants and children,
including inferior neuromotor function (Dietrich et al., 1993b; Wasserman et al., 2000; Ris et al.,
2004; Després et al., 2005; Fraser et al., 2006; Boucher et al., 2012), poorer academic
achievement and reading or math skills (Needleman and Gatsonis, 1990; Fergusson et al., 1997;
Lanphear et al., 2000; Al-Saleh et al., 2001; Wang et al., 2002; Miranda et al., 2007;
Chandramouli et al., 2009; Huang et al., 2012), abnormal behaviour (Fergusson et al., 1993;
Bellinger et al., 1994a; Needleman et al., 1996; Dietrich et al., 2001; Parajuli et al., 2013, 2014),

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Lead (March 2019)
decreased attention or executive functions (Bellinger et al., 1994b; Canfield et al. 2003b; Chiodo
et al., 2004, 2007; Braun et al., 2006; Nigg et al., 2008; Wang et al., 2008; Bouchard et al., 2009;
Froehlich et al., 2009; Ha et al., 2009; Cho et al., 2010; Kim et al., 2010; Nicolescu et al., 2010)
as well as impairments of auditory and visual function (Schwartz and Otto, 1991; Dietrich et al.,
1992; Fox et al., 1997; Osman et al., 1999; Rothenberg et al., 2002; Canfield et al., 2004; Fox et
al., 2008). In most cases, the associations were reported at BLLs below 10 µg/dL after
controlling for confounding effects (Osman et al., 1999; Lanphear et al., 2000, 2005; Canfield et
al., 2003a; Chiodo et al., 2004, 2007; Després et al., 2005; Fraser et al., 2006; Téllez-Rojo et al.,
2006; Miranda et al., 2007; Chandramouli et al., 2009).
There is evidence to suggest that exposure to lead is associated with alterations in
attention-related behaviour, such as attention deficit hyperactivity disorder (ADHD), in studies
of children 3–18 years of age, at BLLs below 5 µg/dL (Chiodo et al., 2004, 2007; Braun et al.,
2006; Nigg et al., 2008, 2010; Wang et al., 2008; Froehlich et al., 2009; Ha et al., 2009; Cho et
al., 2010; Kim et al., 2010; Boucher et al., 2012). One meta-analysis determined that there was a
small but significant association between lead exposure, as measured by blood, tooth and hair
lead levels, and ADHD symptoms, including inattention and hyperactivity/impulsivity (Goodlad
et al., 2013). Braun et al. (2006) examined ADHD prevalence in 4704 children aged 4–15 years
and determined that BLLs exceeding 2 µg/dL were associated with a 4.1-fold increase in risk of
ADHD (95% CI = 1.2–14.0), with an association that remained significant when the BLLs used
for the analysis were restricted to below 5 µg/dL. In the same cohort of children, but only those
aged 8–15 years, BLLs higher than 1.3 µg/dL were associated with a 2.3-fold increase in the risk
of ADHD (95% CI = 1.5–3.8) (Froehlich et al., 2009). An association between BLL and ADHD
(combined type but not predominantly inattentive type) was found in 236 children aged 6–17
years with very low BLLs (maximum BLL of 2.2 µg/dL) after controlling for confounding
effects (Nigg et al., 2010). It was shown in one cohort study that a 1 µg/dL increase in BLL in
children aged 3–5 years (mean BLL = 6.4 µg/dL) resulted in increases in teacher-reported
behaviour scores of 0.32 in emotional reactivity (95% CI = 0.058–0.587), 0.25 in anxiety
problems (95% CI = 0.016–0.500) and 0.30 in pervasive developmental problems (95% CI =
0.046–0.560) (Liu et al., 2014). It is possible that effects on attention may be the underlying
cause of lead’s effects on intelligence quotient (IQ). Additional longitudinal studies will be
helpful in determining the actual effect of lead on attention.
Performance on psychometric tests of intelligence (i.e., IQ testing) is by far the most
documented neurodevelopmental endpoint with the greatest weight of evidence for effects at low
levels of exposure. Decreases in IQ have been reliably associated with limitations in academic
achievements and earning potential, and thus IQ can serve as a surrogate for the many other
adverse neurological consequences beyond the immediate implications of reduced performance
on intelligence tests. Studies of 12 cohorts have examined the effects of BLL on IQ of children
following multiple BLL measurements from birth to evaluation. Data from four of the cohorts
provide strong evidence of decreased IQ following early-life exposure to lead, although these
were generally in highly exposed individuals or in children who had high and low exposures to
lead throughout their lifetimes (Baghurst et al., 1992; Tong et al., 1996; Factor-Litvak et al.,
1999; Wasserman et al., 2000; Canfield et al., 2003a; Chen et al., 2005; Jusko et al., 2008).
However, one of these cohorts provided strong evidence for effects at BLLs below 10 µg/dL. In
a study of 172 mostly African American children, concurrent, lifetime average, average in
infancy and peak BLLs were significantly associated with reductions in IQ scores after
adjustments for confounding effects and remained significant when the population was restricted
to individuals with peak BLLs that never exceeded 10 µg/dL (Canfield et al., 2003a). In the same
cohort, adverse impacts on IQ were measured at the lowest peak BLL of 2.1 µg/dL (Jusko et al.,

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2008). Six of the other cohorts supported the association between BLL and reduction in IQ in
children, without reaching statistical significance (Bellinger et al., 1992; Dietrich et al., 1993a;
Shen et al., 1998; Schnaas et al., 2000; Gomaa et al., 2002; Ris et al., 2004; Téllez-Rojo et al.,
2006), whereas only two cohorts showed no association (Ernhart et al., 1987, 1989; Cooney et
al., 1989a, 1989b). Nonetheless, the overall evidence for effects on IQ decrements is strong when
considering the persistence of the effect through childhood and early adulthood. Although one
study confirmed that lower IQ scores occur in adults 28–30 years of age following childhood
exposure to lead (Mazumdar et al., 2011), further longitudinal studies that extend into adulthood
would be needed to firmly conclude that IQ decrements persist over a lifetime.
Overall, four meta-analyses have examined the relationship between prenatal and
postnatal BLLs and performance on psychometric tests using data from the above-mentioned
longitudinal studies and additional cross-sectional studies (Needleman and Gatsonis, 1990;
Thacker et al., 1992; Pocock et al., 1994; Schwartz, 1994a). These meta-analyses are unanimous
in their conclusions that the epidemiological evidence supports an association between increases
in BLL and decrements in IQ. One study in particular investigated the effects of lead exposure
on IQ decrements using longitudinal data exclusively (Lanphear et al., 2005). The pooled data
set included 1333 subjects from diverse backgrounds comprising four American cohorts—
Boston, Massachusetts (Bellinger et al., 1992), Cincinnati and Cleveland, Ohio (Ernhart et al.,
1989; Dietrich et al., 1993a), and Rochester, New York (Canfield et al., 2003a)—as well as three
other cohorts from Mexico City (Schnaas et al., 2000), Port Pirie, Australia (Baghurst et al.,
1992), and Kosovo, Yugoslavia (Wasserman et al., 2000). All of the studies measured IQ using
the same approach (i.e., the Wechsler Intelligence Scales for Children), and information on the
same covariates was available (i.e., maternal IQ, marital status, prenatal alcohol and tobacco use,
quality of the home environment as measured by the Home Observation for Measurement of the
Environment [HOME] inventory score, sex, birth order and birth weight). Information on
ethnicity was available for the U.S. data, although socioeconomic status, nutrition and paternal
IQ were not assessed. The analysis included children with BLLs below 10 µg/dL (approximately
18% of the children never exceeded BLLs of 10 µg/dL) and various BLL measurements,
including concurrent BLL (taken closest to IQ testing, median = 9.7 µg/dL), maximum BLL
(median = 12.7 µg/dL), average lifetime BLL (mean from 6 months to concurrent BLL,
median = 12.4 µg/dL) and childhood BLL (mean BLL from 6 to 24 months, median = 12.7
µg/dL). Overall, concurrent BLL was most strongly associated with decreases in IQ, and the
severity of the effect increased at a higher rate at lower BLLs than at higher BLLs. Increases in
BLL from 2.4 to 10 µg/dL and from 10 to 20 µg/dL resulted in IQ point decrements of 3.9 (95%
CI = 2.4–5.3) and 1.9 (95% CI = 1.2–2.6), respectively (changes in IQ from 20 to 30 µg/dL were
not significant). Moreover, IQ was more substantially affected by an increase in BLL in children
with maximal BLLs < 7.5 µg/dL then in those with maximal BLLs ≥ 7.5 µg/dL, indicating that
the dose–response relationship for lead exposure is likely more sensitive at lower doses and
confirming that effects on IQ can occur at very low BLLs. Data from Lanphear et al. (2005) have
been used by the European Food Safety Authority (EFSA) and by the Joint FAO/WHO Expert
Committee on Food Additives (JECFA) to establish benchmark doses (BMDs) associated with a
1% change in response (BMDL01s) of 1.2 and 0.8 µg/dL, respectively (JECFA, 2011; EFSA,
2013). A statistical re-evaluation of the data was undertaken by Crump et al. (2012). Although
the authors noted potential issues with some of the key assumptions and small errors, the
reanalysis confirmed the validity of the conclusions put forth by Lanphear et al. (2005).
There is also evidence of an association between in utero exposure to lead, as measured
by maternal BLL or cord BLL, and effects on neurodevelopment in children, although these
associations are not as strong as the evidence measured for postnatal BLLs. Maternal BLLs and

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cord BLLs below 5 µg/dL have both been associated with adverse effects on intelligence,
memory and cognition in infants aged 7–36 months (Emory et al., 2003; Jedrychowski et al.,
2009; Parajuli et al., 2013). However, negative associations have been reported in many of the
studies that have examined maternal BLLs below 10 µg/dL (Baghurst et al., 1992; Bellinger et
al., 1992; Dietrich et al., 1993b; Parajuli et al., 2014). One study reported that a mean maternal
BLL of 7.8 µg/dL at 28–36 weeks of pregnancy was associated with reduced performance on IQ
tests in children 6–10 years of age (Schnaas et al., 2006). However, the strength of the
association is limited by mean postnatal BLLs that exceeded 10 µg/dL in the children. Although
some data suggest that the developing fetus may not be affected at the very low doses at which
effects were observed in children, there is no basis to determine that the fetus is less sensitive
than the developing child to the effects of lead. An association between lead exposure in utero
and the risk of schizophrenia has also been reported by Opler et al. (2004, 2008) in 2 different
cohorts. Maternal BLLs ≥15 μg/dL (estimated via delta-aminolevulinic acid, a biologic marker
of lead exposure) was found to be associated with a doubling of the risk of schizophrenia in the
offspring when compared to offspring from mothers with BLLs <15 μg/dL.
Thus, BLLs as low as 0.8 µg/dL have been associated with adverse neurodevelopmental
effects in children. The effects are particularly related to decreases in intelligence and may also
include alterations in attention and behaviour. Although the available data to assess the
reversibility of these effects are insufficient, there are studies to suggest permanent alterations in
the brain of adults exposed to lead as infants and children (Yuan et al., 2006; Cecil et al., 2008,
2011; Brubaker et al., 2009). Most studies that have examined the effects of BLLs below 5
µg/dL on the IQ of children cannot identify a threshold below which lead no longer exerts an
adverse effect. It should be noted that one study that investigated effects on IQ in the largest
number of children with BLLs below 5 µg/dL did not report a significant inverse relationship
between BLLs and IQ at levels below 5 µg/dL and indicated a significant effect on IQ only at 5–
10 µg/dL using children with BLLs of 1–2 µg/dL as a referent group (Surkan et al., 2007).
However, taking into consideration all of the available studies, the weight of evidence suggests
that the BLL considered to cause no harm is unknown.
Relatively small changes in IQ can potentially lead to substantive population-level health
impacts. It is estimated that a 1% decrement in population IQ (corresponding to 1 IQ point
decrement) is associated with an added risk of mild mental retardation of 1 in 250 individuals
(Healey et al., 2010). As such, even subtle changes in population IQ should be considered to be
an important lead-related adverse health effect.
9.2 Effects on experimental animals

9.2.1 Acute toxicity
There is very little information on the acute toxicity of lead in animals. The lowest oral
doses of lead capable of causing death were reported as 191–1366 mg/kg bw in dogs, 313–
20 500 mg/kg bw in guinea pigs and 160 mg/kg bw in pigeons (Sax and Lewis, 1989; ATSDR,
1999). The lowest intraperitoneal injection dose reported to cause death in rats was 1000 mg/kg
bw (Sax and Lewis, 1989).
9.2.2 Short-term exposure

9.2.2.1 Neurological effects
The neurological effects of exposure to lead have been investigated in a few studies in
monkeys and rats. Adult monkeys were shown to exhibit neurological impairments relating to
spatial learning and short-term memory deficits when exposed from birth onwards to lead acetate
at doses of 50 and 100 μg/kg bw per day (Rice and Karpinski, 1988). This resulted in steady-

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state BLLs of 11 and 13 μg/dL at 50 and 100 μg/kg bw per day, respectively (unexposed animals
had BLLs of 3 μg/dL). A series of additional tests were conducted on monkeys exposed orally to
vehicle or lead acetate at 2.1 mg/kg bw per day, 5 days/week, according to three different
exposure scenarios: dosed with lead from birth onwards, dosed with lead from birth to 400 days
of age and vehicle thereafter and dosed with vehicle from birth to 300 days of age and lead
thereafter (Rice, 1990, 1992b, 1992c; Rice and Gilbert, 1990a, 1990b). The animals exhibited
BLLs ranging from 19 to 26 μg/dL during dosing and up to 32–36 μg/dL when treatment
occurred in addition to nutrition through infant formula (BLLs of controls ranged from 3 to
6 μg/dL). Various neurobehavioural tests pertaining to spatial and non-spatial discrimination as
well as fixed-interval testing in which reward for a response was delayed for a specific amount of
time were conducted from ages 6 to 9 years. For the most part, the tests were significant for all
exposure scenarios (Rice, 1990, 1992b; Rice and Gilbert, 1990a), with one exception for one
nonspatial discrimination test in which no effects were observed when exposure occurred in
infancy only (Rice and Gilbert, 1990b). These results suggest that exposures that are exclusive to
adulthood or infancy are sufficient in producing persistent adverse neurobehavioural effects in
non-human primates. Markers of Alzheimer’s disease, including altered expression of disease-
related genes (amyloid precursor protein [APP], β-site APP cleaving enzyme and transcription
factor specificity protein 1 [Sp1]) and increased β-amyloid proteins and plaques in the frontal
association cortex, were observed in the same animals exposed from birth to 400 days of age and
tested at 23 years of age (BLL = 19–26 μg/dL) (Wu et al., 2008). These data suggest that
exposure early in life can result in latent neurological effects in adulthood.
Adverse neurobehavioural effects of lead exposure have also been observed in rats. Rats
that were 21 days, 8 months or 16 months of age, to represent young, adult and old animals,
respectively, were exposed to 0, 2 or 10 mg lead acetate per day through drinking water (Cory-
Slechta and Pokora, 1991; Cory-Slechta et al., 1991). BLLs were fairly consistent at 3, 6 and 9
months and were similar in all animals for the 2 mg/day (BLL range of 10.8–18.3 μg/dL) and the
10 mg/day (BLL range of 22.6–45.2 μg/dL) lead acetate doses. Young and old animals exhibited
increased response rates, whereas adult rats demonstrated decreased response rates in fixed-
interval behavioural testing (Cory-Slechta and Pokora, 1991). However, delayed spatial
alternation performance was actually shown to improve in the lead-exposed young and old rats,
with no significant effects observed in the adults (Cory-Slechta et al., 1991). In another study,
levels of β-APP gene expression, a marker of Alzheimer’s disease development, were monitored
over the lifetime of rats exposed to lead acetate only during infancy (mean BLL of 46.43 μg/dL
during exposure and reduced to background levels thereafter). Expression was shown to be
increased 20 months after exposure ceased, suggesting that effects observed later in adulthood
may be related to previous exposure (Basha et al., 2005).
Thus, there is sufficient evidence in experimental animals that implicate lead exposure in
adverse neurological effects. Adverse effects in adulthood were observed in exposed mature
animals as well as in older animals exposed during infancy following a substantive latency
period. None of the studies addressed neurotoxicity of lead at BLLs below 10 μg/dL, and thus it
is unknown whether these effects persist at lower exposures.
9.2.2.2 Cardiovascular effects

There is strong and consistent evidence in experimental animals that chronic and
subchronic exposure to lead causes sustained increases in blood pressure, even at
environmentally relevant doses. These effects have been observed in multiple species, including
rats, dogs and pigeons (Staessen et al., 1994b). Older data published in this field have been
criticized for methodological issues, including stress in the animals capable of increasing blood

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pressure as well as the use of genetically susceptible animal models. However, these issues have
been addressed in more recent subchronic studies of rats in which statistically significant
increases in blood pressure were observed at BLLs below 20 μg/dL (Khalil-Manesh et al., 1994;
Gonick et al., 1997; Vaziri et al., 1997, 1999a, 1999b; Ding et al., 1998, 2001; Attri et al., 2003;
Fiorim et al., 2011; Silveira et al., 2014).
Studies have reported increases in blood pressure in rats with very low BLLs (< 5 μg/dL).
Attri et al. (2003) studied rats that were fed lead acetate at 100 mg/L in water (orally using a
syringe) over 3 months. Mean BLLs of 2.4 μg/dL and 4.1 μg/dL that were measured after 2 and 3
months of exposure, respectively, were associated with significant increases in systolic blood
pressure, and the rats demonstrated signs of obvious oxidative stress. In another study of rats that
were exposed to 0.01%, 0.05%, 0.1%, 0.5%, 1% and 2% lead acetate through drinking water
alongside controls over 60 days, effects on systolic and diastolic blood pressure were seen at the
lowest exposure level (corresponding to a BLL of 2.15 μg/dL) and increased with dose (Tsao et
al., 2000). Ding et al. (1998) showed that exposure of rats to drinking water containing 0.01%
lead acetate over 12 weeks resulted in significant increases in blood pressure as of week 8 and
continued to rise until the end of the exposure period, at week 12. Discontinuation of the
exposure for an additional 2 weeks resulted in sustained increases in blood pressure. Mean BLL
was measured at the 14-week time point and was 3.2 μg/dL in the treated animals.
Lead-induced increases in blood pressure are thus strongly supported in animal
experimental models at BLLs below 5 μg/dL.
9.2.2.3 Renal effects

Studies in laboratory animals with BLLs exceeding 45 μg/dL have reported decreases in
glomerular filtration rate, increases in serum creatinine and kidney weight as well as alterations
in renal histopathology (Khalil-Manesh, 1992a, 1992b). Few studies, however, have examined
the effects of environmentally relevant lead exposures on renal function.
Rats that were administered lead acetate in drinking water at 150 mg/L over 16 weeks
(BLL at 16 weeks was 26.4 μg/dL, and kidney remnant surgery was done at the 4-week time
point) developed microvascular and tubular injury and exhibited reduced creatinine clearance
(Roncal, 2007). In another study of rats, administration of lead acetate at 100 mg/L in drinking
water over 12 months resulted in mild tubular atrophy and interstitial fibrosis (Khalil-Manesh et
al., 1993). The highest mean BLL observed in the study was 29.4 μg/dL and was observed at the
3-month post-exposure time point (mean BLL was slightly above 20 μg/dL after 12 months).
9.2.3 Long-term exposure and carcinogenicity

Studies in experimental animals using various species and exposure routes have
consistently demonstrated that exposure to inorganic lead is associated with the formation of
tumours and cancer, although there is an inadequate amount of information to assess the
carcinogenicity of organic lead (IARC, 2006). For inorganic lead forms (e.g., lead acetate, lead
subacetate, lead chromate, lead phosphate), there is some evidence of cancers of the lung,
adrenal gland, testes, prostate and brain (IARC, 2006). However, the most sensitive site and the
one for which the association between lead exposure and carcinogenesis is the strongest and
most consistent is undoubtedly the kidney.
Numerous mouse and rat studies have shown that lead is associated with increased
incidences of renal proliferative lesions, adenomas or carcinomas following oral exposure. This
includes studies of lead acetate (Boyland et al., 1962; Zawirska, 1968, 1981; Azar et al., 1972;
Zawirska and Medras, 1972; Waszynski, 1977; Fears et al., 1989; Waalkes et al., 1995, 2004)
and lead subacetate (van Esch et al., 1962; Mao and Molnar, 1967; van Esch and Kroes, 1969;

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Oyasu et al., 1970; Ito et al., 1971; Ito, 1973; Kasprzak et al., 1985) at levels as low as 0.05% in
diet for lead acetate and 0.1% in water for lead subacetate. Injection (intramuscular,
subcutaneous and intraperitoneal) of lead chromate and lead phosphate in rats also induced renal
tumours when administered at total doses exceeding 70 mg for lead chromate and 120 mg for
lead phosphate (Zollinger, 1953; Tonz, 1957; Baló et al., 1965; Roe et al., 1965; Furst et al.,
1976).
The few studies that have examined multiple exposure levels have reported dose–
response trends with regards to renal proliferative lesions. Waalkes et al. (2004) examined
kidney histopathology in male mice exposed to lead acetate at 0, 1000, 2000 or 4000 mg/L in
drinking water (corresponding to approximately 0, 200, 400 and 800 mg/kg bw per day).
Exposures occurred as of 8 weeks of age and persisted up to 112 weeks of age. Incidences of
renal proliferative lesions in adult male mice, including atypical tubular hyperplasia and tumours,
were reported as 0%, 4%, 12% and 21% for the control, 1000, 2000 and 4000 mg/L treatment
groups, respectively. Significance was reached only in the 4000 mg/L dose group. Male
metallothionein I/II double knockout mice were also tested using the same exposure regimen.
Renal proliferative lesions were more common and more severe in these mice (0%, 40%, 52%
and 60% for the control, 1000, 2000 and 4000 mg/L dose groups, respectively). An additional
mouse study demonstrated that maternal exposure of mice to lead acetate at 0, 500, 750 or 1000
mg/L in drinking water (corresponding to approximately 0, 100, 150 and 200 mg/kg bw per day)
as of gestational day 12 and up to 4 weeks postpartum during lactation resulted in increased
incidences of renal proliferative lesions in offspring at 112 weeks of age. Increases in males were
4%, 16%, 24% and 48% for the control, 500, 750 and 1000 mg/L treatment groups, respectively
(in females, increases were 0%, 0%, 4% and 16% for the same groups). The renal tumours
observed occurred in the absence of significant lead-induced chronic nephropathy, suggesting
that chronic renal damage may not be the cause of tumour development (Waalkes et al., 1995).
Thus, there are data in experimental animal models that support inorganic lead–induced
renal tumorigenesis and carcinogenesis. Data in mice also suggest that exposure in utero and
early in life can lead to renal cancers in adulthood. Additional data suggest that lead-induced
cancer can occur at other sites, although the most sensitive and most consistent cancer endpoint
by far was renal cancer. Although none of the studies met the stringent guidelines recommended
for the chronic rodent cancer bioassay (two species, both sexes, three dose groups plus control
and minimum of 50 animals per treatment group) (U.S. Department of Health and Human
Services, 2006), the Waalkes et al. (1995, 2004) studies provide adequate evidence that renal
tumorigenesis occurs in mice following lead exposure and that incidences increase with dose.
9.2.4 Genotoxicity
There is sufficient evidence that implicates inorganic lead in deoxyribonucleic acid
(DNA) damage, although it is unclear if this damage is related to direct or indirect genotoxicity
or potentially to alterations in DNA repair processes. The genotoxicity and mutagenicity of lead
have been reviewed extensively in IARC (2006) and are briefly described below.
9.2.4.1 In vitro findings

The genotoxicity and mutagenicity of several lead compounds have been assessed in
various in vitro test systems.
In bacterial assays, mutagenicity was observed only following treatment with lead
chromate and lead bromide, and it is unclear if the lead component of the substance was even
involved in the induction of mutations (Nestmann et al., 1979; Maslat and Haas, 1989).
However, most tests done in mammalian cell lines revealed that various lead compounds (lead

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Lead (March 2019)
acetate, lead bromide, lead chloride, lead nitrate and lead sulphide) did induce genetic mutations,
although the concentrations at which mutagenicity occurred varied significantly with the
different cell types and experimental approaches used (Zelikoff et al., 1988; Roy and Rossman,
1992; Yang et al., 1996; Ariza et al., 1998; Ariza and Williams, 1999).
Lead acetate, lead chromate and lead nitrate were tested for their ability to induce DNA
strand breaks. These tests in various treated cells derived from humans and experimental animals
were consistently positive (Robison et al., 1984; Hartwig et al., 1990; Roy and Rossman, 1992;
Xu et al., 1992; Robbiano et al., 1999; Wozniak and Blasiak, 2003). Micronucleus formation also
occurred following treatment of mammalian cells derived from Chinese hamsters (ovary cells
and fibroblasts) with lead acetate, lead chloride and lead nitrate, generally at lower
concentrations compared with DNA strand breaks (Lin et al., 1994; Thier et al., 2003). The
results for sister chromatid exchanges and chromosomal aberrations, however, were much more
varied (IARC, 2006).
9.2.4.2 In vivo findings

There are in vivo genotoxicity data from both experimental animal and human studies.
Genotoxicity studies in animals have reported mixed findings that varied considerably depending
on the lead compound studied, the route of exposure, the dose and the test endpoint. In a
multigenerational study in which mice drank water containing lead acetate at 1 µg/mL,
significant DNA damage in lymphocytes was reported in the second and third generations,
suggesting a cumulative effect of exposure from one generation to the next (Yuan and Tang,
2001). DNA damage and micronucleus induction were observed in the kidneys of rats exposed to
three successive oral doses of lead acetate at 78 mg/kg bw (Robbiano et al., 1999). Micronucleus
induction has also been reported in bone marrow and leukocytes following the administration of
high oral and intraperitoneal injection doses of lead acetate (Muro and Goyer, 1969; Deknudt
and Gerber, 1979; Tachi et al., 1985). Studies of lead nitrate exposure through intravenous or
intraperitoneal injection in mice have reported sister chromatid exchanges in bone marrow as
well as chromosomal aberrations and aneuploidy in maternal bone marrow and foetal liver cells
at doses as low as 10 mg/kg bw (Nayak et al., 1989; Dhir et al., 1993). None of the studies took
into account the BLLs of these animals.
The results of in vivo genotoxicity studies pertaining to human exposures were largely
positive. However, it is difficult to draw firm conclusions with regard to the human studies
because of considerable co-exposure to other chemicals. All five studies examining DNA strand
breaks using the comet assay in leukocytes of lead-exposed workers were positive; the BLLs of
these workers ranged from 13 to 98.5 µg/dL (Ye et al., 1999; De Restrepo et al., 2000; Fracasso
et al., 2002; Danadevi et al., 2003; Palus et al., 2003). Similarly, induction of micronuclei in
blood lymphocytes of exposed workers was significant at BLLs ranging from 40 to 61 µg/dL
(Vaglenov et al., 1998, 2001; Hamurcu et al., 2001; Palus et al., 2003). The data for sister
chromatid exchanges and chromosomal aberrations are also mostly positive, although some
studies have reported negative findings (IARC, 2006). The lack of association does not appear to
be related to dose. Studies that have examined non-occupationally exposed populations did not
report significant genotoxicity (IARC, 2006).
9.2.5 Reproductive and developmental toxicity

9.2.5.1 Reproductive effects
The strongest evidence of adverse reproductive effects in experimental animals is related
to delayed sexual maturation. There are also data to suggest that exposure to lead during

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gestation can induce malformations in offspring and that exposure of males can affect the
reproductive system.
There is consistent evidence that exposure to lead can delay sexual maturation in
experimental animals. One study examined dietary exposure to lead acetate in female mice at
several doses ranging from 0.02 to 40 mg/kg (corresponding BLLs ranged from 0.7 to
13.2 μg/dL). Lead exposure significantly delayed puberty in the female mice in a dose–response
trend, as shown by delays in age at vaginal opening, estrus, vaginal plug formation and first
parturition. In comparison with the 0.2 mg/kg level of exposure (BLL = 1.9 μg/dL), the dose
considered to represent the typical background BLL, only the highest exposure levels,
corresponding to BLLs of 8.4 and 13.2 μg/dL, were statistically significant (Iavicoli et al., 2004).
Very similar findings were made in the second and third generations of the same mice exposed to
the same levels throughout gestation and lactation, with subsequent exposure of female offspring
at the same levels through feed. BLLs in the two highest dose groups (8.1/12.7 μg/dL and
8.1/12.9 μg/dL in the second and third generations, respectively) were statistically significant for
the 0.2 mg/kg exposure level (BLL = 0.7 μg/dL for both second and third generations). It appears
that additional exposure in utero and early in life does not increase the propensity towards
delayed puberty in exposed mice (Iavicoli et al., 2006). Conversely, delayed onset of puberty as
well as decreases in puberty-related hormones (insulin-like growth factor 1, luteinizing hormone
and estradiol) were observed in female rats exposed to lead acetate in utero exclusively, as well
as those exposed during gestation/lactation and lactation only (Dearth et al., 2002).
Several effects were also observed in males. Barratt et al. (1989) examined sperm
concentration and abnormalities in rats administered lead acetate at 0.3–300 mg/kg bw per day
over 9 weeks, with BLLs ranging from 2 to 80 μg/dL. A significant effect on sperm abnormality
was observed at the very highest dose, corresponding to a BLL of 80 μg/dL (Barratt et al., 1989).
Sperm count and sperm motility were not affected in rats treated with 5 mg/kg bw via
intraperitoneal injection (BLL = 7 μg/dL), although structural changes in spermatids and Sertoli
cells were evident (Murthy et al., 1995). Gestational exposure also resulted in effects on the male
reproductive system, as shown through structural damage to seminiferous tubules and reduced
prospermatogonia in male rats, although elevated BLLs (17.8–31.6 μg/dL) in the rat pups may
have been directly responsible for these effects (Corpas et al., 1995).
There is limited evidence to indicate that lead is teratogenic in experimental animals.
Maternal BLLs as low as 10 μg/dL in pregnant rats have resulted in increased external
malformations, with increased fetal resorptions occurring at maternal BLLs of 14 μg/dL and
above (Flora and Tandon, 1987).
Studies in experimental animals indicate that lead can induce reproductive effects,
particularly with respect to sexual maturity in female animals. These effects may potentially
occur at BLLs below 2 μg/dL.
9.2.5.2 Neurodevelopmental effects

Although no test is available to assess IQ in experimental animals, several
neurodevelopmental endpoints, including the ability to learn specific tasks, motor coordination
skills and changes in behaviour, have been examined in several species. The majority of the
evidence indicates that exposure to lead via the oral route is associated with adverse
neurodevelopmental effects and that the severity of these effects increases with the administered
dose. Moreover, cessation of exposure was in most cases not associated with a reversal to a
normal healthy state even long after exposure, suggesting that the neurodevelopmental effects of
lead are permanent and persist into adulthood. There is, however, a possibility that lead

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remobilization from bone can occur at a later time following cessation of exposure and that this
may be associated with the observed effects.
The most compelling evidence of adverse neurodevelopmental effects is from studies of
non-human primates. At least 17 studies have investigated adverse neurobehavioural effects of
lead exposure in non-human primates, with only one of these studies reporting primarily negative
results (Laughlin et al., 1999). The studies that reported adverse effects at the lowest doses were
done in cynomolgus monkeys orally exposed 5 days a week to lead acetate at 0, 50 or 100 µg/kg
bw per day, from birth onwards. This resulted in peak BLLs of 3.5, 15.4 and 25.3 µg/dL, with
subsequent steady-state BLLs of 2.9, 10.9 and 13.1 µg/dL for the 0, 50 and 100 µg/kg bw per
day doses, respectively. The treated monkeys exhibited delays in learning specific tasks at the
lowest exposure dose (BLLs 10.9–15.9 µg/dL) in a series of tests conducted between the ages of
3 and 10 years (Rice, 1984, 1985; Gilbert and Rice, 1987; Rice and Karpinski, 1988). When
monkeys were exposed continuously or during infancy exclusively to lead acetate at 1.5 mg/kg
bw per day, significant impairments on some of the neurobehavioural tests were found in both
groups relative to controls at up to 9 years of age, with increased severity in the continuously
exposed group. This provides some evidence that early-life exposure to lead can cause
neurobehavioural effects that persist into adulthood, even after cessation of lead exposure (Rice,
1990, 1992b). Performance on a series of neurobehavioural tests was also affected in monkeys
that were continuously exposed to high doses of lead (2000 µg/kg bw per day, resulting in a peak
BLL of 115 µg/dL and steady-state BLL of 33 µg/dL), then assessed as infants, juveniles and
adults (Rice, 1992a). The effects of BLLs below 10 µg/dL were not examined in non-human
primates.
There is a large body of evidence for adverse neurodevelopmental effects in various rat
strains. Prenatal and postnatal oral exposures to lead resulting in BLLs as low as 10 µg/dL have
resulted in impaired ability to learn, as shown by poor performance on specific learning tasks,
decreased memory, as shown by evasion of repeated stresses, such as shocks to the foot, and
altered conduct, including changes in rearing behaviour (Cory-Slechta and Thompson, 1979;
Cory-Slechta et al., 1981, 1983, 1985, 2013; Cory-Slechta, 1986; Chen et al., 1997, 2001; Gong
and Evans, 1997; Morgan et al., 2000; Stangle et al., 2007). There is additional evidence of
altered neurobehavioural effects in many other species. These include impaired learning and
motor coordination in herring gull chicks (Burger and Gochfeld, 1997, 2005), impaired learning
in prenatally exposed lambs (Carson et al., 1974), altered spatial exploration in offspring of
paternally exposed rabbits (Nelson et al., 1997) and aggressive behaviour in offspring of
maternally exposed mice (Donald et al., 1987).
Overall, there is sufficient evidence to conclude that prenatal and postnatal exposures to
lead to adverse neurobehavioural effects in experimental animals of various species, including
non-human primates. Data from many of the studies indicate significant interindividual
variations, suggesting that individual animals can be especially vulnerable to the effects of lead,
whereas others may be more tolerant. There is a lack of data to assess the effects of BLLs below
10 µg/dL in experimental animals. The lowest level of exposure associated with
neurobehavioural effects in experimental animals cannot be clearly established.
9.3 Mode of action

Lead is known to disrupt numerous biological processes, which can induce several
adverse effects. These include calcium mimicry, cell death, oxidative stress and interference with
vital biochemical processes. As there is no unifying mechanism of lead toxicity, it is likely that
several of these mechanisms operate in unison to induce the adverse effects observed upon

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Lead (March 2019)
chronic exposure. However, it should be noted that modes of action for the various adverse
effects of lead are generally poorly understood.
Most of the known adverse health effects of lead, other than renal tumours, have been
clearly established in human populations. As human relevance has already been strongly
established for most endpoints, the mode of action information presented below is provided only
to add to the weight of evidence for lead-induced toxicities. Modes of action have been examined
for endpoints considered critical in this assessment (i.e., developmental neurotoxicity and cancer)
as well as for increases in blood pressure, as a larger amount of information was available for
this endpoint. Additional information pertaining to the relevance of renal tumours in humans is
discussed briefly.
9.3.1 Neurodevelopmental effects

At this time, there is insufficient information to clearly establish the mode of action
involved in reductions in IQ and other neurodevelopmental effects. However, there is evidence
that developmental neurotoxicity may involve alterations in cellular functioning and signalling as
well as direct damage to the brain and central nervous system, as reviewed in Lidsky and
Schneider (2003).
Lead has been shown to interact with all cell types in the central nervous system and is
known to induce cellular oxidative stress and cause apoptosis. Depletion of antioxidant enzymes
was observed in mice following in utero exposure to lead (Wang et al., 2006). Moreover,
neuronal apoptosis was observed in the developing mouse brain following two intraperitoneal
injections of 350 mg/kg bw (Dribben et al., 2011). It is thus plausible that lead can cause direct
tissue damage that may affect neurodevelopment and cognitive function.
However, lead can also induce an array of biochemical changes that can alter
development or functioning of the central nervous system. Lead has long been known to alter
cellular functioning by mimicry of calcium and zinc. Lead’s ability to mimic calcium can cause
disruption of Ca2+ homeostasis and lead to the stimulation of kinases, cyclic adenosine
monophosphate and phosphodiesterase, affecting the functioning of voltage-dependent calcium
channels (Gu et al., 2005). Lead’s ability to mimic calcium also enables it to cross the blood–
brain barrier, thus reaching critical tissues associated with developmental neurotoxicity (Kerper
and Hinkle, 1997a, 1997b). Alterations in calcium homeostasis are hypothesized to interfere with
neurotransmitter synthesis, release, turnover and uptake (Lidsky and Schneider, 2003). Lead has
been shown to alter the release of dopamine, γ-aminobutyric acid and other neurotransmitters
(Lasley et al., 1999; Devoto et al., 2001) and causes alterations in synaptosomes (Regunathan
and Sundaresan, 1985; Jablonska et al., 1994) and neurotransmitter receptors (McCoy et al.,
1997; Lasley et al., 2001) capable of interfering with normal neurotransmission processes.
However, these responses can be dose dependent, as low doses of lead have been shown to
stimulate exocytosis of neurotransmitters (Bressler and Goldstein, 1991). Mimicry of zinc has
also been shown to interfere with DNA binding of transcription factors, including Sp1,
transcription factor IIIA and early growth response protein 1, with associated changes in gene
expression (Zawia et al., 1998; Hanas et al., 1999; Reddy and Zawia, 2000; Zawia, 2003). It is
unclear exactly how mimicry of calcium and zinc translates to adverse effects. However, critical
processes involved in neurodevelopment, including cellular growth, differentiation and
chromosome structure, are likely to be affected.
Other biochemical changes may also be involved in IQ decrements and other
neurodevelopmental effects. Lead has been shown to affect long-term potentiation (LTP) by
altering glutamate release, postsynaptic N-methyl-D-aspartate activation and neurogenesis.
Prenatal and postnatal exposures of rats to lead were shown to increase the threshold for LTP

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Lead (March 2019)
induction, decrease the magnitude of LTP and accelerate LTP decay in specific hippocampal
regions (Gilbert and Rice, 1987; Gutowski et al., 1997, 1998; Gilbert and Mack, 1998; Gilbert et
al., 1999a, 1999b). In addition, lead may delay differentiation of glial progenitors and cause
hypomyelination and demyelination in glial cells, adversely affecting their ability to support and
protect neurons (Sauer et al., 1970; Coria et al., 1984; Deng et al., 2001). The hypothalamic–
pituitary–adrenal axis, which can alter cognitive function through regulation of glucocorticoids,
can also be significantly affected by lead. Prenatal and lactational exposures in rats have been
shown to significantly alter blood corticosterone concentrations in adulthood (Cory-Slechta et
al., 2004). Finally, there is evidence that lead may operate via an epigenetic mechanism. Early-
life exposure to lead in monkeys and rats has been shown to increase brain gene expression of β-
APP and production of associated proteins later in life (Basha et al., 2005; Wu et al., 2008). The
effect occurred with a decrease in methyltransferase activity, suggesting that epigenetic
demethylation of the APP promoter region may be responsible.
There is evidence that the neurodevelopmental effects of lead in children are persistent,
as shown through lifetime studies in non-human primates and deficits in academic achievement
and intelligence that extend at least until 17 years of age in humans. It is important to note that
no threshold for this effect can be identified.
9.3.2 Cancer
The exact mechanisms linking lead to cancer are not well understood. In general, lead is
not expected to induce direct DNA damage at levels that represent relevant environmental
exposures. However, there is evidence to suggest that lead can cause indirect genotoxicity via
oxidative stress and that lead may increase susceptibility to cancer via non-genotoxic
mechanisms. Potential mechanisms have been described in Silbergeld et al. (2000) and
Silbergeld (2003).
There is sufficient evidence to determine that lead causes genotoxicity and clastogenicity,
as shown by induction of DNA strand breaks, micronuclei, chromosomal aberrations and sister
chromatid exchanges in exposed cultured cells and experimental animals, as well as in
leukocytes of occupationally exposed humans (see Section 9.2.4). Such genotoxic events are
considered essential in the development of lead-induced cancers. At very high concentrations,
lead can induce direct DNA damage via DNA cross-linking (Silbergeld, 2003). However, these
doses were generally cytotoxic and much higher than those necessary to induce cancer
(Silbergeld, 2003). Moreover, lead has been shown to induce renal tumours in the absence of any
significant tissue damage (Waalkes et al., 1995). As such, direct genotoxicity is not likely to be
associated with tumour formation observed in experimental animals. There is more substantive
evidence, however, that indirect genotoxicity via oxidative stress may be responsible for damage
to DNA at more relevant doses. Lead exposure at non-cytotoxic doses has been shown to result
in glutathione depletion in rat liver (Daggett et al., 1998) and upregulation of glutathione S-
transferase in rat kidney and liver (Columbano et al., 1988; Suzuki et al., 1996; Daggett et al.,
1998), thus rendering cells more sensitive to oxidative stress. These responses are often
accompanied by lipid peroxidation, as measured by increases in malondialdehyde (Daggett et al.,
1998). In vitro, lead increases levels of hydrogen peroxide (Ariza et al., 1998). Like many other
metals, there is evidence that lead can augment oxidative stress conditions by participating in
Fenton reactions, in which hydrogen peroxide is converted to the more reactive superoxide
radical. Cells treated with hydrogen peroxide and lead acetate alone did not exhibit substantive
DNA damage. However, co-treatment of lead with hydrogen peroxide resulted in DNA nicks and
strand breaks as well as oxidative stress–related DNA adducts, including 8-hydroxyguanine (Roy

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Lead (March 2019)
and Rossman, 1992; Yang et al., 1999). Therefore, lead-mediated Fenton reactions are likely to
be responsible for lead-induced oxidative DNA damage.
There is some evidence to suggest that non-genotoxic modes of action may mediate lead-
induced cancers. However, only limited information was available. In vitro, co-exposures to lead
and ultraviolet radiation, hydrogen peroxide, X-rays and most chemical genotoxins have been
shown to increase the DNA-damaging impact of these agents (Silbergeld, 2003). In animals,
dietary co-exposure to lead and 2-acetylaminofluorene, N-ethyl-N-hydroxyethylnitrosamine or
N-(4′-fluoro-4-biphenyl)acetamide resulted in an increased incidence of renal tumours in rats,
and a study in humans suggests that exposure to lead increases lung cancer risk among smokers
(Lustberg and Silbergeld, 2002; Healey, 2014). These data collectively suggest that lead may
inhibit DNA repair mechanisms, making genetic material more vulnerable to damage from other
sources. This may be due to lead’s ability to substitute for zinc in zinc binding proteins,
including DNA binding proteins, histones, protamines and transcription regulators. Lead binding
to zinc binding proteins can also alter their conformational structure and function. The impact of
lead on proteins can alter cellular signalling pathways, which may result in DNA repair
inhibition, repair errors and other responses involved in the progression of cancer. Indeed, lead
has been suggested to alter the expression of oncogenes and tumour suppressor genes
(Silbergeld, 2003). There is also evidence that alterations in cellular signalling pathways may be
affected by epigenetic changes to DNA (alterations in DNA methylation status) (Senut et al.,
2014). Additional research will be needed to further elucidate the potential roles of these non-
genotoxic modes of action in lead-induced carcinogenesis. There is some speculation that
exposure to lead may lead to cancer by increasing cellular proliferation in specific tissues.
However, this is thought to occur only at higher levels of exposure, and thus increased cellular
proliferation leading to higher mutation frequencies is not likely to be involved in lead-induced
cancers.
Compared with cancers at other sites (e.g., lung and brain), the development of renal
tumours was most consistently observed in lead-exposed experimental animals and occurred at
lower exposure doses. There are, however, questions surrounding the relevance of renal tumours
in humans, considering that only a few studies have established a positive association between
lead exposure and renal cancers and that these studies are limited by methodological issues, such
as a lack of appropriate exposure monitoring and failure to consider confounding effects
(Steenland et al., 1992; Pesch et al., 2000). It has been argued that only elevated cytotoxic doses
may be responsible for the induction of renal tumours. However, renal proliferative lesions,
including tubular cell carcinomas, have been shown to occur in male offspring of mice exposed
to lead acetate in the absence of extensive chronic nephropathy and lead inclusion bodies
(Waalkes et al., 1995). Moreover, the induction of α2u-globulin, leading to hyaline droplet
nephropathy, a process commonly observed in chemical-exposed male rats, has been proposed as
the main driver of renal tumours. However, as renal tumours also occur in male and female mice,
which do not produce α2u-globulin, this mechanism leading to renal tumours is not relevant
(Waalkes et al., 1995, 2004).
In conclusion, there are several plausible modes of action for lead-induced cancers.
However, there is insufficient information available to clearly identify a single mode of action
responsible for tumour induction. With the limited information available at this time, the default
assumption is that the mechanisms leading to renal tumours in animals are plausible in humans.
9.3.3 Increases in blood pressure

Multiple biological mechanisms have been linked to the lead-induced increases in blood
pressure observed in humans and experimental animals. These include oxidative stress,

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Lead (March 2019)
alterations in the levels of nitric oxide or nitric oxide signalling, as well as effects on the
adrenergic and paracrine systems. These mechanisms are described thoroughly in Vaziri (2008)
and are presented briefly below.
Deactivation, depletion or sequestration of nitric oxide, a vasodilator that plays a
significant role in regulating blood pressure, is the most plausible mechanism leading to
increases in blood pressure and hypertension. Lead-induced hypertension in rats exposed to 100
mg/L lead in drinking water has been shown to be accompanied by a reduction of available nitric
oxide in plasma and increased urinary excretion of nitric oxide metabolites (Vaziri et al., 1997,
1999b; Dursun et al., 2005). This is likely due to a lead-related induction of oxidative stress.
Induction of hypertension in rats exposed to 100 mg/L lead in drinking water is associated with
increased plasma and tissue concentrations of malondialdehyde, a marker of lipid peroxidation,
and increased concentrations of nitrotyrosine, a marker of nitric oxide oxidation (Gonick et al.,
1997; Vaziri et al., 1999a; Attri et al., 2003). Moreover, lead-treated hypertensive rats
demonstrate a compensatory upregulation of endothelial and inducible nitric oxide synthase
(Gonick et al., 1997; Vaziri et al., 1997, 1999a, 2001), and treatment with antioxidants (e.g.,
vitamin E, vitamin C) has been reported to reduce blood pressure and increase nitric oxide
availability (Vaziri et al., 1997, 1999b; Attri et al., 2003). Lead exposure is also attributed to
changes in nitric oxide signalling. Exposure to lead through diet has been shown to lower cyclic
guanosine monophosphate, an important molecule in nitric oxide–mediated vasodilation, in
plasma and urine of rats (Khalil-Manesh et al., 1993). Furthermore, oxidative stress can initiate
inflammatory responses that are known to contribute to the pathogenesis of hypertension.
There is also evidence that lead may affect the adrenergic system, either directly or
through the oxidative stress–mediated effects on nitric oxide. Stimulation of the sympathetic
nervous system can result in a “fight or flight” response, which is known to affect blood
pressure. Occupationally exposed humans and exposed rats have been shown to exhibit increased
plasma norepinephrine, which is associated with an increase in vascular tone (Chang et al., 1996;
Tsao et al., 2000). Additional adrenergic effects related to blood pressure observed in rats
include an increase in plasma catecholamines and reduced density of β-adrenergic receptors in
vascular and cardiac tissues (Chang et al., 1997; Carmignani et al., 2000; Tsao et al., 2000).
There is evidence that the adrenergic responses leading to vascular smooth muscle contraction
may be mediated through protein kinase C (Watts et al., 1995).
Additional mechanisms associated with lead-induced increases in hypertension include
altered levels of prostaglandins and endothelins, endothelial damage as well as inhibition of
sodium–potassium adenosine triphosphate in erythrocyte membranes (Vaziri, 2008).
Physiological stress has also been shown to act as an effect modifier in the relationship between
BLLs and blood pressure effects in humans (see Section 9.1.2.2). It is likely that multiple
mechanisms working simultaneously lead to the increases in blood pressure observed in exposed
humans and experimental animals.
10.0 Classification and assessment

There is extensive evidence of an association between low BLLs and both adverse
neurodevelopmental effects in children and increased blood pressure in adults, with data in
experimental animals to support these outcomes of exposure. Furthermore, lead has been shown
to induce tumours in experimental animals. Thus, both cancer and non-cancer risk assessments
were conducted.

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10.1 Cancer risk assessment
Inorganic lead compounds have been classified as probably carcinogenic to humans
(Group 2A) by IARC (2006) and by the U.S. EPA (2004). This is based on conclusive evidence
in experimental animals and suggestive evidence in humans (see Sections 9.1.2.4 and 9.2.3). As
lead in drinking water is primarily found in the inorganic form, a cancer risk assessment was
considered appropriate.
No human studies were suitable for deriving a health-based value (HBV). The two best
animal studies available have been conducted in adult male mice chronically exposed to lead
acetate (Waalkes et al., 2004) and in male and female offspring of female mice exposed to lead
acetate during gestation and lactation (Waalkes et al., 1995) (see Section 9.2.3). BMD modelling
using total renal adenomas and carcinomas as the endpoint of concern was employed to estimate
the benchmark dose associated with a default 10% change in response (BMD10) and its 95%
lower confidence limit (BMDL10) for each study. Of the two studies, the more conservative
BMD10 and BMDL10 of 159.6 mg/kg bw per day and 103.8 mg/kg bw per day, respectively, were
derived from renal tumours in male offspring in the Waalkes et al. (1995) study, using the best fit
model (second-degree multi-stage cancer). The BMDL10 was used as our point of departure.
There are currently no PBPK models available to adequately estimate BLLs in mice
following oral exposure to lead and corresponding internal and external doses in humans. As
such, the point of departure was adjusted using allometric scaling, in order to more properly
represent human exposures:
Equivalent human dose = 103.8 mg/kg bw per day × (0.03 kg/70 kg)¼
= 14.9 mg/kg bw per day
where:
• 103.8 mg/kg bw per day is the BMDL10 associated with renal adenoma and carcinoma in
lead acetate–exposed male mice (Waalkes et al., 1995);
• 0.03 kg is the default average body weight of a mouse (Health Canada, 1994);
• 70 kg is the default average body weight of a human adult (Health Canada, 1994); and
• ¼ is the allometric scaling factor to account for toxicokinetic differences between mice
and humans.
The mode of action of lead-induced carcinogenesis is poorly understood (see Section

9.3.2), and thus the default non-threshold approach for cancer endpoints was used. Using a
benchmark response of 10%, the adjusted oral dose of 14.9 mg/kg bw per day would correspond
to the dose associated with a 10−1 lifetime risk of cancer. Using a low-dose linear extrapolation, a
slope factor of 0.0067 (mg/kg bw per day)−1 was calculated and used to determine the oral doses
of 1.5 × 10−2, 1.5 × 10−3 and 1.5 × 10−4 mg/kg bw per day, associated with respective risk levels
of 10−4, 10−5 and 10−6. These oral doses can then be used to calculate corresponding
concentrations in drinking water using the following equation:
dose × body weight

Concentrations in drinking water =
daily water intake
where:

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Lead (March 2019)
• the doses are 1.5 × 10−2, 1.5 × 10−3 and 1.5 × 10−4 mg/kg bw per day, which are
associated with a 10−4, 10−5 and 10−6 lifetime risk of developing cancer, respectively;
• 70 kg is the average body weight for an adult (Health Canada, 1994); and
• 1.5 L is the daily water intake for an adult (Health Canada, 1994).
The concentrations corresponding to lifetime human cancer risks of 10−4, 10−5 and 10−6
can be estimated as 700, 70 and 7 µg/L, respectively. An excess lifetime cancer risk of 10−6 or
below is used when intake from other sources is significant (Krishnan and Carrier, 2013). As
there are other significant sources of exposure to lead (i.e., ambient air, indoor air, household
dust, soil, food), the excess lifetime cancer risk of 10−6 was used to derive a concentration of
7 µg/L. However, it is not deemed appropriate to establish an HBV through this assessment, due
to the following limitations:
• Although there is adequate information in experimental animals, epidemiological
evidence is limited.
• The type of tumour observed in exposed animals has been reported in only a few
occupational studies with known methodological limitations. The relevance of renal
tumours to humans exposed to lead remains to be elucidated.
• A perinatal study (Waalkes et al., 1995) was used instead of a longer-term study in older
animals because this provided a more conservative number. The exact implications of
this are unknown.
• In addition, the effect in the Waalkes et al. (1995) study was subtle and required the
pooling of adenomas and carcinomas together for the analysis. Consequently, there are
some questions around whether or not a true effect was observed in the study.
Nevertheless, this assessment provides an indication of the levels at which cancer effects
would become a consideration in the assessment of exposure to lead in drinking water.
10.2 Non-cancer risk assessment

BLLs below the current intervention level of 10 μg/dL have been associated with several
adverse health effects in humans, including: reduced cognition in adults, especially seniors (see
Section 9.1.2.1); increased systolic blood pressure in adults, especially in African Americans and
postmenopausal women (see Section 9.1.2.2); decreased renal function, especially in diabetic
and hypertensive individuals (see Section 9.1.2.3); reproductive effects, including delayed
puberty and early menopause in women (see Section 9.1.3.1); and developmental neurotoxicity,
including decreased intelligence and attention in infants and children (see Section 9.1.3.2). There
is extensive evidence in experimental animals to support the observations made in humans (see
Section 9.2). Of the endpoints considered, developmental neurotoxicity has been the most widely
studied effect of lead exposure. The relationship between IQ and BLLs in school-aged children
specifically was the most sensitive endpoint and can be characterized with greatest certainty due
to the large database of relevant information. Effects on IQ represent an important social
determinant of health, as lowered IQ in children has been conclusively linked to poorer academic
achievement and earning potential later in life (Herrnstein and Murray, 1994; Schwartz, 1994b;
Nevin et al., 2000; Gross et al., 2002; Health Canada, 2013a). Given the strong weight of
evidence for lead-induced decreases in IQ and the lack of a known threshold of toxicity for this
endpoint, IQ loss in children was selected as the critical health effect on which to base the non-
cancer risk assessment.
The loss of IQ points is not expected to be distributed equally across the population, due
to inter-individual variability in intellectual functioning. Variances in IQ within the population

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Lead (March 2019)
follow a normal distribution, in which an IQ of 100 represents average intelligence and
approximately 2% of the population exhibits an intellectual disability (see Figure 10.1). A mild
intellectual disability (MID) is defined as having an IQ of 70 ± 5 points, among other diagnostic
criteria, and is characterized by delayed learning as well as cognitive and behavioral problems
that can greatly affect an individual’s quality of life (American Psychiatric Association, 2013).
By decreasing the average population IQ even slightly, the number of children expected to be
diagnosed with a MID will increase and children with an existing disability may exhibit more
significant intellectual impairments. This assessment focuses on increased cases of children with
a MID due to small population shifts in IQ associated with exposure to lead through drinking
water. Population decreases of 1 IQ point or 1% shift in population IQ levels are associated with
significant impacts on society and was determined to be the most appropriate benchmark
response by international authorities including the European Food Safety Authority (EFSA,
2013) and the Joint FAO/WHO Expert Committee on Food Additives (JECFA, 2011).
Figure 1. Normal distribution of IQ presented as frequency within the population vs. IQ score
(modified from Weiss, 1988). The hashed line section under the curve represents the 2.27% of
the population with an intellectual disability.
The critical study selected for this assessment consists of an analysis of pooled data from
seven longitudinal prospective studies initiated prior to 1995, which followed children from birth
or infancy until 5–10 years of age (Lanphear et al., 2005). The study involved 1333 children
from Boston, Massachusetts, Cincinnati and Cleveland, Ohio, Rochester, New York, Mexico
City, Mexico, Port Pirie, Australia, and Kosovo, Yugoslavia. Of the existing studies on IQ
decrements in children (see Section 9.1.3.2), the meta-analysis performed by Lanphear et al.
(2005) has the highest number of individuals and diversity of subjects. Full-scale IQ was
assessed using age- and language-appropriate versions of the Wechsler Intelligence Scales for
Children. Ten covariates were examined overall and were available for most subjects, including
maternal IQ, education, marital status, prenatal alcohol use, prenatal tobacco use, HOME
inventory score, sex, birth order, birth weight and ethnicity. Four blood lead indices were used in
the analysis: (1) concurrent BLL (closest to testing), (2) maximum BLL, (3) lifetime average
BLL and (4) early-childhood BLL (mean BLL from 6 months to 2 years of age). Concurrent
BLL was selected by Lanphear et al. (2005) as the primary lead exposure index because it
exhibited the strongest relationship with IQ; in a comparative analysis of the coefficients of
determination (R2) of the linear regression models for each of the blood lead indices, concurrent

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Lead (March 2019)
blood lead was observed to explain the greatest variance in IQ. Health Canada agrees with the
choice of concurrent BLL as the dose metric for further analysis.
Individual data from concurrent BLLs of the Lanphear et al. (2005) study have been
acquired by EFSA (2013) and by JECFA (2011) to establish BMDs associated with a 1% change
on human intellectual function. Overall, EFSA provided extensive detail pertaining to its BMD
analyses with thorough justification for the choice of the piece-wise linear model as the best fit
model associated with the least uncertainty (EFSA, 2013; Budtz-Jorgensen et al., 2010). Thus,
the BMDL01 of 1.2 μg/dL associated with a benchmark response of 1 IQ point was used to
estimate the corresponding oral dose.
In order to determine corresponding external oral doses associated with exposure from
drinking water, PBPK modelling was done using all three of the available models (i.e., IEUBK,
Leggett, and O’Flaherty) (see Section 8.5). Equivalent oral administered doses for a five year old
child were determined to be 0.4, 0.2 and 0.8 μg/kg bw per day for the IEUBK, Leggett and
O’Flaherty models, respectively. Because the Leggett model has been shown to overestimate
BLLs at lower exposures (Pounds and Leggett, 1998), it was not considered any further in our
analysis. The IEUBK model, however, was considered to be an excellent model, as it is specific
to children and has been more extensively validated than other models; the external oral dose of
0.4 μg/kg bw per day (or 0.0004 mg/kg bw per day) was thus used as a point of departure in this
assessment and corresponds to the external oral dose associated with the average loss of 1 IQ
point.
At the population level, the average loss of 1 IQ point, or an approximate change of 1%
in human intellectual functioning, is associated with significant public health implications. These
include substantive increases in cases of children with a MID, increased severity of existing
intellectual disabilities and decreases in “gifted” children, as well as impacts on socioeconomic
status and productivity in general (EFSA, 2013; Health Canada, 2013a). As discussed in section
9.1.3.2, lead exposure significantly affects IQ even at very low BLLs and the lowest BLL
associated with adverse neurodevelopmental effects in children has not been identified (section
9.1.3.2). Moreover, data suggest that the damage caused by lead at very low doses is completely,
or at the very least mostly, irreversible (WHO, 2010). For these reasons, it was determined
appropriate to calculate a slope factor. A slope factor of 2500 (mg/kg bw/day)-1 was derived by
dividing the benchmark response by the external oral dose of 0.0004 mg/kg bw/day.
The average loss of intelligence associated with various drinking water concentrations of
lead can be calculated using the following equation:
drinking water concentration × daily water intake × slope factor

Average IQ loss =
body weight
Where:
• 0.9 L is the daily water intake for children 5-11 years of age (Health Canada, 1994)
• 18.2 kg is the average body weight for a 5-year-old child, as determined using data from
the IEUBK PBPK model (U.S. EPA, 1994a, 1994b; White et al., 1998); and
• 2500 (mg/kg bw per day)-1 is the slope factor
The standardized normal distribution of IQ presented in Figure 10.1 is used as a reference

for variances in intelligence across the Canadian population. The anticipated average IQ loss
associated with various drinking water concentrations of lead is used to estimate the
corresponding proportion of individuals with IQ scores expected to drop below 70 IQ points and

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Lead (March 2019)
hence to estimate the resulting additional cases of children with an intellectual disability above
background (Health Canada, 2017), as provided in Table 2.

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Lead (March 2019)
Table 2. Estimated additional cases of children with an intellectual disability associated with
various lead concentrations in drinking water
DW concentration % children expected to Estimated increase in number of
a
(µg/L) develop an MID children expected to develop an MIDa
0.1 0.004 5 in 100,000
1.0 0.045 5 in 10,000
3.0 0.137 1 in 1,000
5.0 0.232 2 in 1,000
10.0 0.483 5 in 1,000
a
Over background of 2.27% or 2 cases per 100 children with an intellectual disability (see figure
1)
The consensus in the scientific literature is that a safe level of exposure to lead in children
has not been identified. The estimates presented above provide an indication of cases of
intellectual disabilities in children above background associated with the respective levels of lead
in drinking water in order to inform risk assessment and/or risk management decisions. Although
this assessment focuses on intellectual disabilities in a sensitive sub-set of the population (i.e.,
children with a borderline MID), it should be noted that there are significant health and
socioeconomic implications of even small generalized losses in IQ regardless of intellectual
functioning (Health Canada, 2013a). Moreover, this assessment focuses on children as the most
sensitive population but it should be noted that reduced intellectual functioning, among other
health effects, is expected to occur in all age groups at low levels of exposure.
10.3 Comparison of cancer and non-cancer risk assessments

Although both the cancer and non-cancer risk assessments are not deemed appropriate to
allow the calculation of an HBV for lead in drinking water, they provide an indication of the
levels at which these effects would become a consideration in the assessment of exposure to lead
in drinking water.
Neurodevelopmental effects were found to be associated with much lower concentrations
in drinking water than cancer effects.
10.4 International considerations

This section presents the various drinking water guidelines and standards from
international organizations. Variations in these limits can be attributed to the age of the
assessments or to differing policies and approaches, including the choice of key study and the
use of different consumption rates, body weights and allocation factors.
The U.S. EPA regulates levels of lead through the Lead and Copper Rule (U.S. EPA,
1991, 2000), a treatment based rule, which established an action level of 0.015 mg/L (15 µg/L)
for lead in drinking water. The U.S. EPA has not established a maximum contaminant level for
lead in drinking water, but has a maximum contaminant level goal of zero (U.S. EPA, 2014b).
Large water systems (with more than 50 000 connections), unless determined to be non-
corrosive, are required to install “optimal corrosion control treatment” and meet specified water
quality operating limits requirements. If the 90th percentile of lead concentrations in samples
taken at customer taps at sites distributed with a specified prioritization (first-draw samples that
have stagnated for at least 6 hours) exceeds the action level of 0.015 mg/L, the system must
undertake a number of additional actions to control corrosion and provide public education. The
number of sites, frequency of monitoring and scope of required actions vary with system size.

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Currently, a major revision of the Lead and Copper Rule is under way, but is not expected to be
finalized until after 2019.
WHO reviewed the drinking water guideline value for lead in 2011and updated it in
2016, maintaining it at 10 µg/L. The guideline value is considered provisional on the basis of
treatment performance and analytical achievability (WHO, 2011, 2017). In the past, HBVs for
lead for organizations such as WHO were based on the provisional tolerable weekly intake
(PTWI) of 0.025 mg/kg bw developed by JECFA. However, in 2011, JECFA reviewed the lead
data and withdrew the PTWI, as JECFA concluded that it was not possible to establish a PTWI
that would be considered health protective (JECFA, 2011).
In 2018, the European Union (EU) adopted the proposed revisions to the EU Drinking
Water Directive for lead, reducing the parametric value for lead to 5 µg/L (sampled at the tap).
This reduction was based on the WHO recommendation that concentrations should be as low as
reasonably practical. The new value will be implemented over a period of 10 years
beginning after the Directive is finalized. However, the current value of 10 µg/L will be
maintained during the transitional period (European Union 2015, 2018).
In Australia, the National Health and Medical Research Council established a drinking
water guideline of 0.01 mg/L (10 µg/L) for lead (NHMRC, 2011).
The California Environmental Protection Agency (OEHHA, 2009) established a public
health goal of 0.2 ppb (µg/L) for lead in drinking water on the basis of new studies relating
neurobehavioural deficits to lower lead concentrations in the blood than previously reported. The
public health goal was calculated using a lower level of concern of 2.86 μg/day, primarily based
on the review and slope factor work done by Carlisle and Dowling (2006) and their analysis of
Lanphear et al. (2005) (OEHHA, 2007), using a relative source contribution of 0.2, an
uncertainty factor of 3 and a drinking water consumption rate for a child of 1 L/day. The
California Department of Public Health (OEHHA, 2009) established an action level of 15 ppb
for lead in drinking water in 1995 based on the U.S. EPA (1991) action level.
11.0 Rationale
Lead is ubiquitous in our environment. With significant reductions of lead in consumer
products such as paints and gasoline over the past several years, food and water are now more
important sources of exposure to lead. Its presence in drinking water varies greatly and is more
likely in older homes and neighbourhoods, built when lead-containing materials were routinely
used in distribution and plumbing systems.
The toxicity of lead has been extensively documented in humans using blood lead indices
as a measure of exposure. Epidemiological studies suggest a wide array of toxicity endpoints,
including reduced cognition, increased blood pressure and renal dysfunction in adults, as well as
adverse neurodevelopmental and behavioural effects in children. The strongest association
observed to date is between increased BLLs in children and reductions in IQ scores. The
threshold below which lead is no longer associated with adverse neurodevelopmental effects
cannot be identified.
Data in experimental animals corroborate findings in humans and also suggest a risk of
cancer from exposure to inorganic lead. Based on findings in animals, the International Agency
for Research on Cancer (IARC) has classified inorganic lead compounds as probably
carcinogenic to humans (Group 2A). However, a guideline based on decreased IQ would be
more conservative and considered protective for all cancer- and non-cancer-related effects of

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Lead (March 2019)
exposure to lead. Lead in drinking water is not a concern by inhalation or dermal absorption, so a
multi-route exposure assessment was not performed.
A MAC of 0.005 mg/L (5 µg/L) is established for lead in drinking water, based on the
following considerations:
• The MAC must be measurable. The U.S. EPA has established a PQL of 0.005 mg/L,
based on the ability of laboratories to measure lead within reasonable limits of precision
and accuracy using approved methods. There is no similar process in place to establish a
PQL specific to Canada. However, in Canada, analytical methods are available to reliably
measure total lead in drinking water below the MAC.
• The MAC must be achievable at reasonable cost. Municipal-scale treatment technologies
can remove lead from drinking water; however, lead is mostly present in drinking water
from leaching in the distribution and plumbing systems. Consequently, strategies for
minimizing lead at the tap should focus on controlling corrosion and removing lead-
containing components. The use of materials certified to the appropriate NSF/ANSI
standards, such as Standard 61 (Drinking Water System Components—Health Effects)
and Standard 372 (Drinking Water System Components—Lead Content), will help
reduce the concentration of lead at the tap.
• The MAC will have a significant impact on the BLLs of children, the most vulnerable
population. It is estimated that reducing the MAC from 0.01 to 0.005 mg/L would lower
the geometric mean percentage of children with BLLs exceeding 5 µg/dL by 7.2
percentage points (from 9.4% to 2.2%).
• As the primary source of lead in drinking water is the leaching from plumbing and
distribution system components, a private residential drinking water treatment device,
certified to the appropriate NSF/ANSI standard, is the best option for reducing lead
concentrations in drinking water at the tap. However, the use of such devices should not
be considered a permanent solution.
In considering both treatment and analytical achievability and the health risks associated
with exposure to lead from drinking water, the Federal-Provincial-Territorial Committee on
Drinking Water has established a MAC of 0.005 mg/L (5 µg/L) for total lead in drinking water,
based on a sample of water taken at the consumer’s tap, using the appropriate protocol for the
type of building being sampled. As this value exceeds the drinking water concentration
associated with neurodevelopmental effects in children, every effort should be made to maintain
lead levels in drinking water as low as reasonably achievable (or ALARA).
As part of its ongoing guideline review process, Health Canada will continue to monitor
new research in this area and recommend any change to the guideline that is deemed necessary.
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Appendix A: List of acronyms
30MS 30 minutes stagnation time
ACSL Advanced Continuous Simulation Language
ADHD attention deficit hyperactivity disorder
ALAD γ-aminolevulinic acid dehydratase
ALARA as low as reasonably achievable
ANSI American National Standards Institute
APP amyloid precursor protein
ASCII American Standard Code for Information Interchange
ASME American Society of Mechanical Engineers
ASV anodic stripping voltammetry
BLL blood lead level
BMD benchmark dose
BMD01 benchmark dose associated with a 1% change in response
BMD10 benchmark dose associated with a 10% change in response
BMDL01 95% lower confidence limit on the BMD01
BMDL10 95% lower confidence limit on the BMD10
bw body weight
CCME Canadian Council of Ministers of the Environment
CCPSA Canada Consumer Product Safety Act
CI confidence interval
CPSC Consumer Product Safety Commission (U.S.)
CSA Canadian Standards Association
CSMR chloride to sulphate mass ratio
DNA deoxyribonucleic acid
DOS Disk Operating System
EFSA European Food Safety Authority
EPA Environmental Protection Agency (U.S.)
FAO Food and Agriculture Organization of the United Nations
FF fully flushed
FORTRAN Formula Translating System (now known as Fortran)
GC-MS gas chromatography/mass spectrometry
GFAAS graphite furnace atomic absorption spectroscopy
HBV health-based value
HOME Home Observation for Measurement of the Environment
IARC International Agency for Research on Cancer
IEUBK Integrated Exposure Uptake Biokinetic Model for Lead in Children
ICP inductively coupled plasma
IQ intelligence quotient
JECFA Joint FAO/WHO Expert Committee on Food Additives
LTP long-term potentiation
MAC maximum acceptable concentration
MDL method detection limit
MMSE mini-mental status exam
MS mass spectrometry
NCRMP National Chemical Residue Monitoring Program
NHANES National Health and Nutrition Examination Survey (U.S.)

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NPC National Plumbing Code of Canada
NPRI National Pollutant Release Inventory
NSF NSF International
NTU nephelometric turbidity unit
OMOE Ontario Ministry of the Environment
OR odds ratio
Pb lead
PBPK physiologically based pharmacokinetic
PM2.5 particulate matter having an aerodynamic diameter of less than 2.5 μm
POE point of entry
POU point of use
PQL practical quantitation limit
PTWI provisional tolerable weekly intake
RDT random daytime
RO reverse osmosis
RR relative risk
SCC Standards Council of Canada
SM Standard Method
Sp1 specificity protein 1
WHO World Health Organization

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Guidelines for

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Recommandations pour la qualité de l’eau potable au Canada : Document technique –Le

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Published: March 2019

Guideline Technical Document

The document was prepared in collaboration with the Federal-Provincial-Territorial Committee

Any questions or comments on this document may be directed to:

Water and Air Quality Bureau

Part I. Overview and Application ................................................................................................... 1

1.0 Guideline ............................................................................................................................. 1

2.0 Executive summary............................................................................................................. 1

3.0 Application of the guideline................................................................................................ 2

Part II. Science and Technical Considerations ............................................................................... 6

4.0 Identity, use and sources in the environment ...................................................................... 6

5.0 Exposure ............................................................................................................................. 9

6.0 Analytical methods ........................................................................................................... 22

7.0 Treatment technology and distribution system considerations ......................................... 24

7.1.2.6 Mitigation strategy for impacts resulting from treatment .......... 30

8.0 Kinetics and metabolism ................................................................................................... 33

9.0 Health effects .................................................................................................................... 40

10.0 Classification and assessment ........................................................................................... 62

Guidelines for Canadian Drinking Water Quality: Guideline Technical Document

11.0 Rationale ........................................................................................................................... 69

12.0 References ......................................................................................................................... 70

Appendix A: List of acronyms .................................................................................................... 105

Guidelines for Canadian Drinking Water Quality: Guideline Technical Document

Lead in Drinking Water

2.0 Executive summary

2.1 Health effects

2.3 Analysis and treatment

2.4 International considerations

3.0 Application of the guideline

Guidelines for Canadian Drinking Water Quality: Guideline Technical Document

Guidelines for Canadian Drinking Water Quality: Guideline Technical Document

3.1.1 Monitoring in residential dwellings

3.1.2 Monitoring for schools, multi-dwelling residences and large buildings

Guidelines for Canadian Drinking Water Quality: Guideline Technical Document

Guidelines for Canadian Drinking Water Quality: Guideline Technical Document

Guidelines for Canadian Drinking Water Quality: Guideline Technical Document

4.1 Environmental fate

Guidelines for Canadian Drinking Water Quality: Guideline Technical Document

4.2 Sources of lead in drinking water

Guidelines for Canadian Drinking Water Quality: Guideline Technical Document

Guidelines for Canadian Drinking Water Quality: Guideline Technical Document

Guidelines for Canadian Drinking Water Quality: Guideline Technical Document

Objective Sampling type Protocol

Corrosion 2–5 min. flush

5.1.1 Canadian exposure to lead from drinking water

Guidelines for Canadian Drinking Water Quality: Guideline Technical Document

Guidelines for Canadian Drinking Water Quality: Guideline Technical Document

Guidelines for Canadian Drinking Water Quality: Guideline Technical Document

5.1.2 Sampling to assess exposure to lead from drinking water

Guidelines for Canadian Drinking Water Quality: Guideline Technical Document

Guidelines for Canadian Drinking Water Quality: Guideline Technical Document

Guidelines for Canadian Drinking Water Quality: Guideline Technical Document

Guidelines for Canadian Drinking Water Quality: Guideline Technical Document

Guidelines for Canadian Drinking Water Quality: Guideline Technical Document

5.3.2 Indoor air and dust