Environmental Toxicology

Lecture-1 Introduction to Environmental Toxicology (EnTox) EnTox is a young (1965) and interdisciplinary science that uses both basic and applied scientific knowledge to understand natural and anthropogenic pollutants, life cycle and their i pacts upon structure and functions of biological and ecological syste s! "esearch in EnTox includes both laboratory experi ents and field studies! EnTox wants to answer two ain #uestions (1) $ow the release of a pollutant causes har ful effects% (&) 'hat can we do to pre(ent or ecological syste % ini ise risk to biological and

EnTox ob)ecti(e can be broken down into a 5*steps understanding process useful for research+regulation! , "elease of pollutant into the en(iron ent , Transport and fate into biota (with+out che ical transfor ation) , Exposure to biological and ecological syste , -nderstanding responses and+or effects ( olecular to ecological syste s) , .esign experi ents, re ediation, ini isation, conser(ation, and risk assess ent plans

To understand, eli inate, pre(ent or predict en(iron ental and hu an health pollutions situations! The EnTox confusion /eople isunderstand EnTox as a scientific discipline that only focus on che icals into the en(iron ent! 0ot true! That represents en(iron ental che istry and che odyna ics! The rich fabric of ideas, core concepts, literature body, technology and ideologies that erge together to de(elop EnTox is rather a dissi ilar process through ost educational institutions! This ay be the point in case that EnTox is a young interdisciplinary science and contro(ersy regarding what to include in a curriculu is an on going atter of discussion! How to identify the blur lines interconnecting basic conce ts "eading the ob)ecti(es for each discipline that decrease the confusion1 erge into EnTox should

2lassical toxicology protects hu an (subcellular to indi(idual) fro toxic substances at concentration that are har ful! Ecotoxicology (ecology 3 toxicology) wants to protect any indi(iduals, populations, co unities and ecosyste s fro exposure to toxic substance at concentration that are har ful! En(iron ental science is an interdisciplinary science that studies the earth, air, water, li(ing en(iron ents and social co ponents!

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 En(iron ental che istry and che odyna ics is the study of che ical sources, reactions, transports, effects and fate in the en(iron ent! EnTox e braces ecotoxicology! 4urther, it includes other sciences to ake a ore logical approach to understanding and sol(ing real and co plex pollution proble s that society faces today or will encounter in the future! The interdisciplinary core of EnTox borrows hea(ily fro a range of disciplines such as1 en(iron ental science, en(iron ental che istry and che odyna ics, analytical che istry, organic che istry, bioche istry, olecular genetics, cell biology, geno ics, phar acology, phar aco* and toxico*kinetics, physiology, athe atics and statistics, co puter odeling, risk assess ent, soil science, geology, ecology, eteorology, arine biology and oceanography, li nology, and wildlife biology! both disciplines1 classical toxicology and

 The science of toxicology is based on the principle that there is a relationship between a toxic reaction (the response) and the a ount of poison recei(ed (the dose)!

!ose "es onse "elationshi o 6s 6n i portant assu ption in this relationship is that there is al ost always a dose below which no response occurs or can be easured! 6 second assu ption is that once a axi u response is reached any further increases in the dose will not result in any increased effect! 7ne particular instance in which this dose*response relationship does not hold true is in regard to true allergic reactions!
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 6llergic reactions are special kinds of changes in the i une syste 9 they are not really toxic responses! The difference between allergies and toxic reactions is that a toxic effect is directly the result of the toxic che ical acting on cells! 6llergic responses are the result of a che ical sti ulating the body to release natural che icals which are in turn directly responsible for the effects seen! Thus, in an allergic reaction, the che ical acts erely as a trigger, not as the bullet! 4or all other types of toxicity, knowing the dose*response relationship is a necessary part of understanding the cause and effect relationship between che ical exposure and illness! 6s /aracelsus once wrote, :The right dose differentiates a poison fro a re edy!: ;eep in ind that the toxicity of a che ical is an inherent #uality of the che ical and cannot be changed without changing the che ical to another for ! The toxic effects on an organis are related to the a ount of exposure! #easures of Ex osure Exposure to poisons can be intentional or unintentional! The effects of exposure to poisons (ary with the a ount of exposure, which is another way of saying :the dose!: -sually when we think of dose, we think in ter s of taking one (ita in capsule a day or two aspirin e(ery four hours, or so ething like that! 2onta ination of food or water with che icals can also pro(ide doses of che icals each ti e we eat or drink! <o e co only used easures for expressing le(els of conta inants are listed in Table 1! These easures tell us how uch of the che ical is in food, water or air! The a ount we eat, drink, or breathe deter ines the actual dose we recei(e! 2oncentrations of che icals in the en(iron ent are ost co only expressed as pp and ppb!
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 =o(ern ent tolerance li its for (arious poisons usually use these abbre(iations! "e e ber that these are extre ely s all #uantities! 4or exa ple, if you put one teaspoon of salt in two gallons of water the resulting salt concentration would be approxi ately 1,>>> pp and it would not e(en taste salty? Table 1$ @easure ents for Expressing Ae(els of 2onta inants in 4ood and 'ater! !ose %bbrev$ #etric e&uivalent %bbrev$ % rox$ amt$ in water parts per illigra s per pp g+kg 1 teaspoon per 1,>>> gallons illion kilogra parts per icrogra s per 1 teaspoon per 1,>>>,>>> ppb ug+kg billion kilogra gallons

!ose Effect "elationshi s

The dose of a poison is going to deter ine the degree of effect it produces! The following exa ple illustrates this principle! <uppose ten goldfish are in a ten*gallon tank and we add one ounce of 1>>*proof whiskey to the water e(ery fi(e inutes until all the fish get drunk and swi upside down! /robably none would swi upside down after the first two or three shots! 6fter four or fi(e, a (ery sensiti(e fish ight! 6fter six or eight shots another one or two ight! 'ith a dose of ten shots, fi(e of the ten fish ight be swi ing upside down! 6fter fifteen shots, there ight be only one fish swi ing properly and it too would turn o(er after se(enteen or eighteen shots! The effect easured in this exa ple is swi ing upside down! Bndi(idual sensiti(ity to alcohol (aries, as does indi(idual sensiti(ity to other poisons!

 There is a dose le(el at which none of the fish swi upside down (no obser(ed effect)! There is also a dose le(el at which all of the fish swi upside down! The dose le(el at which 5> percent of the fish ha(e turned o(er is known as the E.5>, which eans effecti(e dose for 5> percent of the fish tested! The E.5> of any poison (aries depending on the effect easured! Bn general, the less se(ere the effect easured, the lower the E.5> for that particular effect! 7b(iously poisons are not tested in hu ans in such a fashion! Bnstead, ani als are used to predict the toxicity that ay occur in hu ans! 7ne of the ore co only used easures of toxicity is the A.5>! The A.5> (the lethal dose for 5> percent of the ani als tested) of a poison is usually expressed in illigra s of che ical per kilogra of body weight ( g+kg)! 6 che ical with a s all A.5> (like 5 g+kg) is (ery highly toxic! 6 che ical with a large A.5> (1,>>> to 5,>>> g+kg) is practically non* toxic! The A.5> says nothing about non*lethal toxic effects though! 6 che ical ay ha(e a large A.5>, but ay produce illness at (ery s all exposure le(els! Bt is incorrect to say that che icals with s all A.5>s are ore dangerous than che icals with large A.5>s, they are si ply ore toxic! The danger, or risk of ad(erse effect of che icals, is ostly deter ined by how they are used, not by the inherent toxicity of the che ical itself! The A.5>s of different poisons ay be easily co pared9 howe(er, it is always necessary to know which species was used for the tests and how the poison was ad inistered (the route of exposure), since the A.5> of a poison ay (ary considerably based on the species of ani al and the way exposure occurs!

 <o e poisons ay be extre ely toxic if swallowed (oral exposure) and not (ery toxic at all if splashed on the skin (der al exposure)! Bf the oral A.5> of a poison were 1> g+kg, 5> percent of the ani als who swallowed 1> g+kg would be expected to die and 5> percent to li(e! The A.5> is deter ined athe atically, and in actual tests using the A.5>, it would be unusual to get an exact 5>D response! 7ne test ight produce 5>D ortality and another ight produce C>D ortality! 6(eraged out o(er any tests, the nu bers would approach 5>D, if the original A.5> deter ination was (alid! The potency of a poison is a easure of its strength co pared to other poisons! The ore potent the poison, the less it takes to kill9 the less potent the poison, the ore it takes to kill! The potencies of poisons are often co pared using signal words or categories as shown in the exa ple in Table &! The designation toxic dose (T.) is used to indicate the dose (exposure) that will produce signs of toxicity in a certain percentage of ani als! The T.5> is the toxic dose for 5> percent of the ani als tested! The larger the T. the ore poison it takes to produce signs of toxicity! The toxic dose does not gi(e any infor ation about the lethal dose because toxic effects (for exa ple, nausea and (o iting) ay not be directly related to the way that the che ical causes death! The toxicity of a che ical is an inherent property of the che ical itself! Bt is also true that che icals can cause different types of toxic effects, at different dose le(els, depending on the ani al species tested! 4or this reason, when using the toxic dose designation it is useful to precisely define the type of toxicity easured, the ani al species tested, and the dose and route of ad inistration! Table '$ Toxicity "ating (cale and Labeling "e&uirements for )esticides$ (ignal word L!+, oral L!+, dermal )robable oral *ategory re&uired on mg-.g( m) mg-.g( m) lethal dose label

.60=E"* B /7B<70 highly toxic (skull and crossbones) BB oderately '6"0B0= toxic BBB 26-TB70 slightly toxic BF practically none re#uired non*toxic

less than 5>

less than &>>

a few drops to a teaspoon o(er 1 teaspoon to 1 ounce o(er 1 ounce

51 to 5>> o(er 5>>

&>> to &,>>> o(er &,>>>

Toxicity assess ent is #uite co plex, any factors can affect the results of toxicity tests! <o e of these factors include (ariables like te perature, food, light, and stressful en(iron ental conditions! 7ther factors related to the ani al itself include age, sex, health, and hor onal status! The 07EA (no obser(able effect le(el) is the highest dose or exposure le(el of a poison that produces no noticeable toxic effect on ani als! 4ro our pre(ious fish exa ple, we know that there is a dose below which no effect is seen! Bn toxicology, residue tolerance le(els of poisons that are per itted in food or in drinking water, for instance, are usually set fro 1>> to 1,>>> ti es less than the 07EA to pro(ide a wide argin of safety for hu ans! The TAF (threshold li it (alue) for a che ical is the airborne concentration of the che ical (expressed in pp ) that produces no ad(erse effects in workers exposed for eight hours per day fi(e days per week! The TAF is usually set to pre(ent inor toxic effects like skin or eye irritation!
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 Fery often people co pare poisons based on their A.5>Gs and base decisions about the safety of a che ical based on this nu ber! This is an o(er*si plified approach to co paring che icals because the A.5> is si ply one point on the dose*response cur(e that reflects the potential of the co pound to cause death! 'hat is ore i portant in assessing che ical safety is the threshold dose, and the slope of the dose*response cur(e, which shows how fast the response increases as the dose increases! 'hile the A.5> can pro(ide so e useful infor ation, it is of li ited (alue in risk assess ent because the A.5> only reflects infor ation about the lethal effects of the che ical! Bt is #uite possible that a che ical will produce a (ery undesirable toxic effect (such as reproducti(e toxicity or birth defects) at doses which cause no deaths at all! 6 true assess ent of che ical toxicity in(ol(es co parisons of nu erous dose*response cur(es co(ering any different types of toxic effects! The deter ination of which pesticides will be "estricted -se /esticides in(ol(es this approach! <o e "estricted -se /esticides ha(e (ery large A.5>s (low acute oral toxicity), howe(er, they ay be (ery strong skin or eye irritants and thus re#uire special handling!

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 The knowledge gained fro dose*response studies in ani als is used to set standards for hu an exposure and the a ount of che ical residue that is allowed in the en(iron ent!

6s entioned pre(iously, nu erous dose*response relationships ust be deter ined, in any different species! 'ithout this infor ation, it is i possible to accurately predict the health risks associated with che ical exposure! 'ith ade#uate infor ation, we can ake infor ed decisions about che ical exposure and work to ini ise the risk to hu an health and the en(iron ent!

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