Factors that influence toxicity

Response of a toxicant is influenced by different factors

1. FACTORS THAT
INFLUENCE TOXICITY
Aquatic Toxicology (ZOL-656)
MSc Zoology 4
th
semester
Model Science College EllahAbad
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2. FACTORS PERTAINING TO THE CHEMICALS
1.Thefactorspertainingtothechemicalsare:
i.Physicochemicalpropertiesincludingthefunctionalgroups,
ii.Solubilityinwaterandorganicsolvents,
iii.Dose/concentration,
iv.Ioniccharacteristics
v.Translocationandbiotransformation,
vi.Theirmodeofaction,and
vii.Interactionwithotherchemicals.
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3. FACTORS RELATED TO THE EXPOSURES
2. The factors related to the exposures are:
i.Routes of exposure,
ii.Exposure systems,
iii.Exposure duration
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4. THE EFFECTS OF PHYSICOCHEMICAL CHARACTERISTICS
OF WATER ON THE TOXICITY OF CHEMICALS
3. These factors are:
i.water temperature,
ii.dissolved oxygen,
iii.pH,
iv.salinity,
v.water hardness, and
vi.suspended and dissolved substances.
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5. FACTORS PERTAINING TO THE ORGANISMS
4. The factors pertaining to the organismsare:
i.Type of species,
ii.Sex,
iii.Age,
iv.Stage of the life cycle,
v.Weight and size of individual,
vi.Health and nutritional status,
vii.Seasonal physiological state, and
viii.Acclimation of individuals.
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6. ABIOTIC AND BIOTIC MODIFYING FACTORS
•Thetoxicitymodifyingfactorsrelatedtothechemical,theexposure
andthesurroundingmediummaybeconsideredtogetherandtermed
asabioticmodifyingfactors.
•Thefactorsrelatedtotheorganismsmayalsobetermedasbiotic
modifyingfactors.
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7. FACTORS THAT INFLUENCE TOXICITY
•Forthesakeofconvenience,thistopic“FACTORSTHAT
INFLUENCETOXICITY”willbedividedintofollowingfour
sections:
i.Factorspertainingtochemical,
ii.Factorspertainingtoexposure,
iii.Factorspertainingtosurroundingmedium,and
iv.Factorspertainingtoorganisms.
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8. 1. FACTORS
PERTAINING TO
CHEMICAL
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9. (I) CHEMICAL COMPOSITION :
•Thephysico-chemicalcharacteristicsofacompound,suchas
solubility,vapourpressure,ionization,functionalgroups,etc.are
largelygovernedbythechemicalconstitutionofthecompound.All
thesecharacteristicsgreatlyaffectthetoxicologicalpropertiesofthe
substance.
•Thepolar(hydrophilic)chemicalsarenoteasilysolubleinlipids.
Therefore,theycannoteasilycrossthemembranousbarriersandthus
cannoteasilyreachthetargetsitesforappropriateaction.However,
non-polarorlipophilicsubstancesarehighlysolubleinlipidsand
otherorganicsolvents.Theycanreadilypenetratethelipoprotein
layersofmembranes,hencetheyreadilyproducetheirpotentialeffects
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10. (II) DOSE OR CONCENTRATION OF CHEMICAL :
•Achemicalinducestoxiceffectsonaccountofitsinteractionwith
appropriatereceptors.Theeffectisdirectlyrelatedtoconcentrationof
thechemicalatthetargetsiteandconcentrationatthetargetsiteis
oftendirectlyproportionaltodose/concentrationofthechemical
exposed.
•Thelowerdosesofchemicalcauselesseffectswhereashigherdoses
maycausepronouncedeffects.Thus,toxicityofchemicalisdirectly
proportionaltoitsdose/concentration.
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11. (III) TRANSLOCATION OF TOXICANT :
•Therearetwotypesoftoxicants:
(a)thoseproducinglocaleffects,and(b)thoseproducingsystemiceffects.
•Incaseofthelattergroup,effectivetranslocationisakeyfactor.Unlessthe
toxicantsarereadilytranslocatedtothespecificsites,theycannotproduce
adverseeffects.Duringthecourseoftranslocation,someofthetoxicants
interactwithcertainmacromoleculespresentinthebodyoforganismsand
arethenstoredincertainrelativelyinactivetissues,i.e.storagedepots.
•Theinefficienttranslocationandstorageoftoxicantsininactiveforms
reducestheirtoxicity,whiletheireffectivetranslocationtothetargetin
activeformsenhancestheirtoxicity.
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12. (IV) BIOTRANSFORMATION OF TOXICANTS
•Certainchemicalsarenormallyinactive.Duringtranslocationsuch
chemicalsarebiocatalyticallyconvertedintoactiveforminthebody
oforganismswiththehelpofcertainenzymes.Consequently,the
toxicityofthatparticularchemicalisincreased.
•However,incertainothercasesactivexenobioticsareconvertedto
theirinactiveformsduringtranslocationandtheseformsareoften
storedinthenontargetorrelativelyinactivetissues.
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13. (V) CHEMICAL INTERACTIONS
•Innatureoftenvariouschemicalsmaybepresentandtheorganisms
arenotexposedtoonlyonechemical,buttoavarietyofchemicals.
Thesechemicalsinteractwitheachotherandsuchchemical
interactionsmayhavegreattoxicologicalsignificance.
•However,inthelaboratories,theorganismsmaybesimultaneouslyor
consecutivelyexposedtotwochemicals.Thesechemicalsinteractand
affectthetoxicityofeachother.Theseinteractionsmaycausethree
typesoftoxiceffects.
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14. (V) CHEMICAL INTERACTIONS
•(i)Thecombinedeffectoftwochemicalsmaybeequaltothesumof
theeffectofeachchemicalwhengivenalone.Thistypeofinteraction
isconsideredasadditive.
•(ii)Thecombinedeffectsoftwochemicalstotheorganismsexposed
maybegreaterthanthesumandthistypeofinteractionisdesignated
assynergistic;forexample,effectsofcarbontetrachlorideandethanol
onliver;andasbestosexposureandcigarettesmokingonthelungs.
•(iii)Thecombinedeffectoftwochemicalstotheorganismsexposed
maybelessthanthesumandthistypeofinteractionistermedas
antagonistic;forexample,chelationofheavymetalsbydimercaprol.
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15. (V) CHEMICAL INTERACTIONS
•Itmaythusbeinferredthatinteractionofonechemicalwithanother
may:(i)havenoeffectontheirtoxicity,or(ii)increasetheirtoxicity,
or(i)decreasetheirtoxicity
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16. 2. FACTORS
PERTAINING TO
EXPOSURE
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17. (I) EXPOSURE ROUTES
•Thetoxicantgainaccesstothebodyoforganismsbydermal,oraland
inhalationexposuresorbyintraperitoneal,intramuscular,
subcutaneousandintravenousinjections.Theroutesofexposure
largelyaffectthetoxicityofchemicals.
•Achemicalproducesmorerapidandgreatesteffectwhengivenby
intravenousroute,becausethroughthisroutethechemicaldirectly
reachesinactiveformtothespecificsiteandthusproducesgreatest
effects.
•Theotherexposureroutesindescendingorderoftoxicityare:
inhalation>intraperitoneal>subcutaneous>intramuscular>oral>topical.
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18. (II) EXPOSURE DURATION
•LC50orLD50valuesoftoxicantsdecreasewithincreaseinduration
ofexposure.Thevaluesevaluatedforlong-termexposuresaremuch
lessthanthosedeterminedforshort-termexposures.
•Theexposureforshortdurationhaslesseffectincomparisontolong-
termexposures.Thissimplyindicatesthatthetoxicityofsubstances
increaseswithincreaseinexposureperiod.
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19. (III) EXPOSURE SYSTEMS
•Avarietyofexposuresystemsmaybeusedfortheexposureoftoxicants.
Forinstance,inaquaticmedium,variousexposuresystemsareusedforthe
exposureoftoxicantstoorganisms,suchas:
i.Staticsystem:Wheretoxicantismixedinthewaterandtheorganisms
areexposedtoitinstillwater.
ii.Recirculatorysystem:Wherethetoxicantsolutionisrecirculated
throughcertainpumps.
iii.Renewalsystem:Wherethetoxicantsolutionisrenewedaftercertain
interval.
iv.Flowthroughsystem:Wherethetoxicantsolutionflowsintoandoutof
testchamberintermittentlyorcontinuously.
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20. 3. FACTORS
PERTAINING TO
THE SURROUNDING
MEDIUM
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21. (I) WATER TEMPERATURE
•Thewatertemperatureisexpectedtogreatlyaffectthetoxicityof
xenobiotics.Theincreasedwatertemperatureincreasesthesolubility
ofmanysubstances,affectsthechemicalformofsomeandgoverns
theamountsofdissolvedoxygeninwater.
•Temperaturechangeinaparticulardirectionmayincreaseordecrease
orcausenoeffectonthetoxicityofchemicals,dependingonthe
chemical,thespecies,theresponseandtheparticularprocedure.
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22. (II) DISSOLVED OXYGEN
•Freshwatercandissolve14.6mg/1levelofoxygenat0ºC,which
graduallydecreasesto9.1mg/1withincreaseintemperatureupto
20ºCandreachestothelevel7.5mg/1at30ºC.Itis,therefore,obvious
thatincreaseintemperaturedecreasesthedissolvedoxygencontentof
thewater.Oxygenisessentiallyrequiredforrespirationbythe
organisms.
•Thus,itmightbeexpectedthatreductionindissolvedoxygencontent
ofwaterimposesstressontheaquaticorganisms,whichmaygreatly
increasethetoxicityofachemicalinwater.
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23. (iii) pH
•pHmayhavegreatereffectsonthetoxicityofthosechemicalsthat
ionizeundertheinfluenceofpH.Usuallyundissociatedformsof
chemicalsaremoretoxictoorganisms,becausetheyeasilypenetrate
thecellmembranes.
•ThetoxicityofammoniaisknowntobegreatlyaffectedbypHofthe
water.Unionizedformofammonia(NH3)ishighlytoxictofishand
thetoxicrangeisquitelow(0.2-0.7mg/1)forsalmonids.Incontrast,
ionizedformofammonia(NH4+)hasverylittleornotoxicity.
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24. (IV) SALINITY
•Thegreatestdifferencesinchemicalcharacteristicsoffreshwaterand
seawatermaybeexpectedtoenormouslyaffectthetoxicityof
chemicals.
•Generally,Euryhalineorganismsaremoreresistantinaboutonethird
seawater(i.e.watercontaining30-40%salinity),insalinitycloseto
theirisosmoticlevel.
•However,appreciabledecreaseinsalinityofwateroftenrendersthe
marineanimalslesstolerant.Therefore,itmaybeconcludedthatthe
toxicityofxenobioticsmayincreasewithappreciabledecreaseinthe
salinityofthesurroundingmedium.
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25. (V) WATER HARDNESS
•Thetotalhardnessofwaterhaslittleeffectonthetoxicityofmostof
thechemicalsexceptformetals.Thetoxicityofammonia,phenols,
surfactantsandpesticideshasbeenreportedtobeaffectedtheleastby
thehardnessofwater.LAS,asurfactant,hasbeenreportedtobe1.5
timesastoxictobluegillsinhardwaterasinsoftwater.
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26. (VI) SUSPENDED AND DISSOLVED MATTER
•Naturalwateroftencontainssuspendedanddissolvedmatterincluding
organicligandsandchelators.Theymaypartlydetoxifysomeofthe
xenobioticchemicalsasaresultofsorptionorbinding.Themetalsare
chiefexamplesthatmaybedetoxifiedbythismechanism.
•Thetoxicityofmetalsisoftengreatlydecreasedbythesuspendedand
dissolvedmatterspresentinwaterbecauseofsorptionandbinding
whileotherxenobioticsaremuchlessaffected.
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27. 4. FACTORS
PERTAINING TO
ORGANISMS
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28. (I) TEST SPECIES
•Thetoxicityofxenobioticsgreatlyvarieswithvariationintest
organisms,asthetolerancetochemicalsdiffersindifferentgroupsof
organisms.Amongtheorganismsofsamegroup,thetoxicityof
chemicalvarieswithvariationinspeciesoftheorganisms.Evenin
differentindividualsofsamespecies,thetoxicityofchemicalsvaries
becauseofvariationinsusceptibilityowingtocertaingeneticfactors.
Thus,certainindividualsofaspeciesmaybesusceptibletoachemical
whereastheothermayberesistanttothesamechemical.
•Thetoxicityofachemicalmayvaryamongvariousfishspecies.Spear
andPierce(1979)reportedthatsalmonidsandminnowsareabout15
timesmoresusceptibletocopperthanthatofsunfish.
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29. (II) SEX
•Thetoxicityofchemicalsdifferswithrespecttosexes,becausethe
malesandfemalesdifferintheirresponsesduetohormonaland
metabolicdifferences.Malesinsomespeciesbiotransformcompounds
morerapidlythanfemales,althoughthisisnottrueforallspecies.
•Forinstance,aldrin(anorganochlorinepesticide)ismuchmoretoxic
tomaleratsthantofemalerats.
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30. (III) AGE
•Generally,theyounganimalsaremoresusceptibletoxenobiotics.For
amajorityofchemicals,theyoungare1.5to10timesmore
susceptiblethantheadults.Themainreasonsforthesusceptibilityof
youngonesmaybelessresistanceandlackofbiotransformation
enzymesystems.
•Ithasalreadybeenreportedthatthenewlybornindividualsdonot
possestheenzymesystemscatalyzingthebiotransformationreactions.
Theseenzymesystemsdevelopgradually,reachatpeakatacertain
stage,thereaftertendtodecline.
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31. (IV) LIFE-STAGE
•Thetoxicityofchemicalsvarieswithdifferentstagesofthelife-cycle.
Generally,theearlylife-stagesorimmaturestagesaremore
susceptibletotoxicantexposuresthanthelatestagesormature
individuals.Thefriesandfingerlingsoffishesaremostsensitive
stages.Omkar(1980-81,unpublisheddata)hasalsofoundjuvenilesof
freshwaterprawnstobemoresusceptibletopesticideexposuresthan
thoseofadultindividuals.
•Incertainorganismsoragroupoforganisms,aparticularstageofthe
life-cyclemaybeparticularlysusceptibletotoxicantsandexposureof
toxicantsatthisstageappreciablyaffectstheresults.Forinstance,the
timeofmoltingisparticularlysusceptibleincaseofaquatic
arthropods.
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32. (V) SIZE
•Thetoxicityofchemicalsisalsoaffectedbythesizeoftheorganisms.
Oftenlargersizedindividualsaremoreresistanttotoxicantsandthis
hasbeenfoundtrueincaseofcertainfishes.
•HearthandSprague(1978)reportedthatcoppertolerancetorainbow
troutgraduallyincreaseswithincreaseinsizeofthefish.
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33. (VI) HEALTH AND NUTRITION
•Thetoxicityofchemicalstoorganismsisaffectedbythehealthand
nutritionalstatusoforganisms.Generally,thehealthyindividualsare
moretoleranttotoxicantsthandiseasedones.Thediseasedand
parasitizedindividualshavebeenreportedtobemoresensitiveto
varioustoxicantsthanthenormalones.
•Forexample,unhealthyfisheshavebeenreportedtobemore
susceptibletosodiumchlorideandanorganophosphatepesticide,
guthion.Thetoxicityofchemicalsisalsoaffectedbythenutritional
statusoftheorganisms.
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34. (V) ACCLIMATION
•Theanimalsacclimatedtosublethallevelsofatoxicantmaybecome
moretolerantormoreweakened,dependinguponthemodeofaction
oftoxicantandthetypesofdetoxifyingmechanismoftheanimals.
•Forinstance,acclimationoftrouttosublethal(0.22mg/1)levelof
arsenicforthreeweeks,increasedthethresholdofLC50byafactorof
1.5.Whileacclimationtoone-thirdofthelethallevelofcyanideto
fishrenderedthemtobecomemoresensitivebyafactorofone-third
inthefirstweek.Thetoleranceimprovedtotheoriginallevelbythe
endofthreeweeks.
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