Exposure of toxicants

EXPOSURE OF TOXICANTS

1. EXPOSURE OF TOXICANTS
Exposureisdefinedasacontactbetweenachemicalanda
biologicalsystem.
Itisaconditionwheretheorganismsaresubjectedtocertainlevels
ofxenobiotics.
Achemicalcannotmanifestadverseeffectsinabiologicalsystem
unlessasuitableconcentrationofachemicaloritsbiotransformation
product(s)reachtheappropriatesiteinthebodyforsufficientlength
oftime.
Twomajorfactorsthatinfluencetoxicityasitrelatestothe
exposuresituationforaspecificchemicalare:
•Therouteofexposureand
•Thedurationandfrequencyofexposure.

2. Route and Site of Exposure
Themeanofexposureisdeterminedbythenatureofsubstance,the
subjectandpurposeoftheexposure.
The major routes for entry of toxic chemicals into the body are:
•The gastrointestinal tract (ingestion),
•The lungs(inhalation), and
•The skin (topical, percutaneous, or dermal).
•Injection method
Chemicalsgenerallyproducethegreatesteffectandthemostrapid
responsewhengivendirectlyintothebloodstream(theintravenous
route).
Anapproximatedescendingorderofeffectivenessfortheotherroutes
wouldbeinhalation,intraperitoneal,subcutaneous,intramuscular,
intradermal,oral,anddermal.

3. Typically,differentroutesoftoxicantentryintothebodyhavebeenassociatedwith
certaintypesofexposures.
Occupationalexposuretochemicalsmostfrequentlyresultsfrombreathing
contaminatedair(inhalation)and/ordirectandprolongedcontactoftheskinwiththe
substance(dermalexposure),whereasaccidentalandsuicidalpoisoningsoccurmost
frequentlybyoralingestion.
Acomparisonoftoxicdoses(TDs)ofachemicalbydifferentroutesofexposure
oftenprovidesusefulinformationabouttheextentofabsorptionintothebody.
WhentheTDafteroralordermaladministrationissimilartotheTDafter
intravenousadministration,theassumptionisthatthechemicalisabsorbedreadily
andrapidly.Conversely,incaseswheretheTDbythedermalrouteisseveralorders
ofmagnitudehigherthantheoralTD,itislikelythattheskinprovidesaneffective
barriertoabsorptionofthechemical

4. Duration and Frequency of Exposure
Thedurationandfrequencyforexposureofexperimental
animalstochemicalsisclassifiedaccordingtofour
categories:
•Acute:Referstoexposuretoachemicalforlessthan24
hours.
•Subacute:Referstorepeatedexposuretoachemicalfor1
monthorless.
•Sub-chronic:For1to3months
•Chronic:Formorethan3months,althoughusuallythis
referstostudieswithatleast1yearofrepeateddosing.
Thesethreecategoriesofrepeatedexposurecanbebyany
route,butmostoftentheyoccurbytheoralroute.

5. (Line A): A chemical with very slow elimination (e.g., half-life of 1 year).
(Line B): A chemical with a half-life approximately equal tofrequency of dosing
(e.g., 1 day).
(Line C): Rate of elimination faster than the dosing frequency (e.g., 5 hours).
Blue-shaded area is representative of the concentration of chemical at the target site
necessary to elicit a toxic response.