Chapter 2: Toxicology

Considers worker exposures

1
 Definitions
Toxicology: - entry of toxicants into organism
- elimination from organism Quantitative
- effects on organism
Industrial hygiene: prevention or reduction of entry
- chemical agents
- physical agents: particulates < 5 µm,
noise, radiation
Toxicity: The quality, state, or degree to which a substance is
poisonous and/or may chemically produce an injurious or deadly
effect upon introduction into a living organism.
Problem: organisms respond via a distribution of effects

Toxic hazard: A measure of the danger posed to living organisms

by a toxic agent, determined not only by the toxicity of the agent
itself, but also by the means by which it may be introduced into
the subject organisms under prevailing conditions.
2
 Toxicity

“All substances are poisons; there is

none which is not a poison. The right
dose differentiates a poison and a
remedy.”

There are no harmless substances, only

harmless ways of using substances.

3
Entry Routes for Toxicants

ROUTE ENTRY CONTROL

Ingestion Mouth, stomach Enforcement of rules on
eating, drinking, smoking
Inhalation* Mouth, nose Ventilation, respirators,
hoods, personal protective
equipment

Injection Cuts in skin Protective clothing

Dermal Absorption* Skin Protective clothing

* industrially most significant

4
Entry Routes for Toxicants

Skin absorption for males:

Foot: 1
Palm/Ankle: 5x
Back/Forearm: 10x
Forehead/Scalp: 34x

http://www.cdc.gov/niosh/topics/skin/

5
 Various Responses to Toxicants

Effects that are irreversible:

Carcinogen—causes cancer
Mutagen—causes chromosome damage
Reproductive hazard—causes damage to reproductive
system
Teratogen—causes birth defects

Effects that may or may not be reversible:

Dermatotoxic—affects skin
Hemotoxic—affects blood
Hepatotoxic—affects liver
Nephrotoxic—affects kidneys
Neurotoxic—affects nervous system
Pulmonotoxic—affects lungs 6
 Routes and elimination

DIGESTIVE TRACK BLOOD TARGET ORGAN

LIVER KIDNEYS / LUNGS

EXCRETION: Kidneys (urine), liver (bile), lungs

(breath), skin (perspiration), …
DETOXIFICATION: Liver
STORAGE: Fat tissue, bones, hair, brain, …

7
Figure 2-1 Toxic blood levels
WIDE VARIATIONS EXPECTED

Injection
BLOOD LEVEL

Inhalation

Ingestion
Dermal

TIME
8
Toxicology Experiment with Rabbits!

Start with 50 rabbits.

Expose each to a fixed concentration.
Wait for a period of time.
Get a variety of responses. 9
 Determine Response Curve

Response Number Fraction

Least 1 2 0.04
2 14 0.28
3 18 0.36
4 15 0.30
Worst 5 1 0.02
50 1.00

Average = (1x2+2x14+3x18+4x15+5x1)/50 =
= 149/50 = 2.98
10
 Plot Bar Chart

Average = 2.98

20

15
Number

10

0
1 2 3 4 5
Response

11
Repeat experiment at different doses.

Dose Average Response

D1 R = 2.98
1

D2 R
2

D R
3 3

D4 R
4

12
 Plot Response vs. Dose

Average X
Response X
X

R X
1

D1
Dose
This form not very useful, particularly at low doses.
13
 Take the log of the dose.

X
Average X

Response
X

Log ( Dose )
Get S-shaped curve - better at low dose
values 14
• If the response of interest is death or lethality, curve is called a lethal dose (LD)
curve.
• If the response to the chemical or agent is minor and reversible (such as minor eye
irritation), curve is called the effective dose (ED) curve.
• If the response to the agent is toxic (an undesirable response that is not lethal but is
irreversible, such as liver or lung damage), curve is called the toxic dose (TD).
15
 Transform into Probit
Change S-shape into straight line using a
mathematical transformation called a probit.

X
Probit
X
X

Log ( Dose)
16
 Transform into Probit

The probit transformation converts the sigmoidal response versus log dose
curve into a straight line when plotted on a linear probit scale.

17
Probit Transform

18
 Probit Transform
% 0 1 2 3 4 5 6 7 8 9
0 — 2.67 2.95 3.12 3.25 3.36 3.45 3.52 3.59 3.66
10 3.72 3.77 3.82 3.87 3.92 3.96 4.01 4.05 4.08 4.12
20 4.16 4.19 4.23 4.26 4.29 4.33 4.36 4.39 4.42 4.45
30 4.48 4.50 4.53 4.56 4.59 4.61 4.64 4.67 4.69 4.72
40 4.75 4.77 4.80 4.82 4.85 4.87 4.90 4.92 4.95 4.97
50 5.00 5.03 5.05 5.08 5.10 5.13 5.15 5.18 5.20 5.23
60 5.25 5.28 5.31 5.33 5.36 5.39 5.41 5.44 5.47 5.50
70 5.52 5.55 5.58 5.61 5.64 5.67 5.71 5.74 5.77 5.81
80 5.84 5.88 5.92 5.95 5.99 6.04 6.08 6.13 6.18 6.23
90 6.28 6.34 6.41 6.48 6.55 6.64 6.75 6.88 7.05 7.33
% 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9
99 7.33 7.37 7.41 7.46 7.51 7.58 7.65 7.75 7.88 8.09

19
 Probit Equations
Using probits, most response vs. dose
curves can be represented in the form:
Y = k1 + k2 ln(V)
where Y = Probit variable
k1, k2 are constants
V = causitive variable
See Table 2-5 for a list of probit equations
for toxic exposures, fires and explosions.
20
 Type of injury or damage Causative Probit parameters
variable
k1 k2
Firea
Burn deaths from flash fire teIe4/3/104 -14.9 2.56 te effective time duration (s)
Burn deaths from pool burning tI4/3/104 -14.9 2.56
Explosiona
Ie effective radiation intensity
(W/m2)
Deaths from lung hemorrhage po -77.1 6.91
t time duration of pool burning
Eardrum ruptures po -15.6 1.93 (s)
Deaths from impact J -46.1 4.82
I radiation intensity from pool
Injuries from impact J -39.1 4.45 burning (W/m2)
Injuries from flying fragments J -27.1 4.26
po peak overpressure (N/m2)
Structural damage po -23.8 2.92
Glass breakage po -18.1 2.79 J impulse (N s/m2)
Toxic releaseb
Ammonia deaths ∑ C2.0T -35.9 1.85 C concentration (ppm)
Carbon monoxide deaths ∑ C1.0T -37.98 3.7 T time interval (min)
Chlorine deaths ∑ C2.0T -8.29 0.92
Ethylene oxide deathsc ∑ C1.0T -6.19 1.0
Hydrogen chloride deaths ∑ C1.0T -16.85 2.0
Nitrogen dioxide deaths ∑ C2.0T -13.79 1.4
Phosgene deaths ∑ C1.0T -19.27 3.69
Propylene oxide deaths ∑ C2.0T -7.42 0.51
Sulfur dioxide deaths ∑ C1.0T -15.67 1.0
Toluene deaths ∑ C2.5T -6.79 0.41
21
 Conversion from Probit to %

 Y 5  Y  5 
P  50 1  erf   (2-6)
 Y  5  2  
P = Percentage
Y = Probit
erf = error function (available on spreadsheet)

This is very useful for spreadsheet calculations!

22
 Example

Determine the percentage of people who will die as a result

of burns from pool burning if the probit variable Y is 4.39.

From Probit table P = 27 %

23
 Example

Eisenberg reported the following data on the effect of

explosion peak overpressures on eardrum rupture in
humans:

Percentage affected Peak overpressure (N/m2)

1 16,500
10 19,300
50 43,500
90 84,300

Confirm the probit correlation for this type of exposure, as

shown in the table.
25
Solution
The percentage is converted to a probit variable. The
results are:

Percentage Probit
1 2.67
10 3.72
50 5.00
90 6.28

26
27
 Relative Toxicity
Table 2-6. Hodge-Sterner Table for Degree of Toxicity

28
 Relative Toxicity

If the response-dose curve for chemical A is to the right

of the response-dose curve for chemical B, then
chemical A is more toxic. 29
 TLV and PEL
The Threshold Limit Value (TLV) is the maximum
exposure limit to humans for 8 hours a day, 40 hours
per week, that does not cause any noticeable effect.

The TWA is the time weighted average.

The TLVs are promulgated by the American

Conference of Governmental Industrial Hygienists
(ACGIH), a professional society, and does not have
legal authority.

The Permissible Exposure (PEL) Limit is the same

thing, but is promulgated by OSHA, a government
organization, and the PEL’s do have legal authority.
30
 Threshold Limit Values
THRESHOLD DOSE: NO DETECTABLE EFFECT
Threshold Limit Value TLV: worker’s lifetime
This is for 8 hours per day, 40 hours per week.

NOT FOR CONTINUOUS EXPOSURES!

TLV - TWA * Time weighed average

TLV - STEL Short term exposure limit

TLV - C Ceiling limit

More values are available for TWAs than for

STEL or C.

31
TLV type Definition
TLV-TWA Threshold limit value—time-weighted average
The concentration for a conventional 8-hour workday and a 40-
hour workweek, to which it is believed that nearly all workers
may be repeatedly exposed, day after day, for a working lifetime
without adverse effect.
TLV-STEL Threshold limit value—short-term exposure limit
The maximum concentration to which workers can be exposed
for a period of up to 15 minutes continuous without suffering (1)
irritation, (2) chronic or irreversible tissue damage, (3) dose-
rate-dependent toxic effects, or (4) narcosis of sufficient degree
to increase the likelihood of accidental injury, impaired self-
rescue, or materially reduced work efficiency. Exposures above
the TLV-TWA up to the TLV-STEL should be less than 15
minutes, should occur no more than four times per day, and
there should be at least 60 minutes between successive
exposures in this range.
TLV-C Threshold limit value - ceiling
The concentration that should not be exceeded during any part
of the working exposure.
TLV – Example Values
Acetone 500 ppm
Ammonia 25 ppm
ppm = parts per
CO 25 ppm million by volume
Chlorine 0.5 ppm
Gasoline 300 ppm
Hexane 50 ppm
Phosgene 0.1 ppm

33
Conversion from mg/m3 to ppm
For liquid mixtures ppm = mg/m3, but this is not true
for vapors!

TLVs are reported using ppm (parts per million by volume),

mg/m3 (milligrams of vapor per cubic meter of air), or, for
dusts, mg/m3 or mppcf (millions of particles per cubic foot of
air). For vapors, mg/m3 is converted to ppm using the equation

 RgT   T 
C ppm 
PM
 
 mg/m  0.08205 
3

 PM 

mg/m 3
 
 
T is the temperature in degrees Kelvin,
P is the absolute pressure in atm, and
M is the molecular weight in gm/gm-mole. 34