Episodic exposures to chemicals: what relevance to chemical intolerance?
Episodic exposures refer to intermittent acute exposures to chemicals that ordinarily have a rapid onset and short duration of effect. There has been a long tradition in preclinical behavioral pharmacology of using episodic-exposure paradigms in order to establish dose-response functions in individual organisms. In these experiments, stable baselines of behavior are first established and then followed by administering varying doses of a drug intermittently, for example, once or twice a week. The power of this approach is well established; the within-subjects design reduces error variance, allows exploration of the entire range of effective doses, and can be used to identify individual differences in drug sensitivity. Of course, the approach is only applicable to reversibly acting compounds, and checks need to be included to insure effects of one dose are not influenced by prior exposure to another dose. We have used baseline approaches to evaluate the effects of pesticides and solvents on the behavior of adult male rats and mice. Moreover, a novel probabilistic dose-tolerance analysis applied to the data suggests substantial individual differences in chemical sensitivity, often spanning orders of magnitude. These results suggest that individual differences in chemical sensitivity may be much greater than previously acknowledged.
MacPhail
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Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, United States Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D012721:Carbaryl / Q000008:administration & dosage / Q000633:toxicity; D002648:Child; D002675:Child, Preschool; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004334:Drug Administration Schedule; D004351:Drug Resistance; D004785:Environmental Pollutants / Q000009:adverse effects / Q000493:pharmacokinetics; D005260:Female; D005659:Fungicides, Industrial / Q000008:administration & dosage / Q000633:toxicity; D014644:Genetic Variation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007306:Insecticides / Q000633:toxicity; D008297:Male; D051379:Mice; D008875:Middle Aged; D009043:Motor Activity / Q000187:drug effects; D018777:Multiple Chemical Sensitivity / Q000209:etiology*; D051381:Rats; D012015:Reference Standards; D012107:Research Design; D018570:Risk Assessment; D012997:Solvents / Q000008:administration & dosage / Q000633:toxicity; D014116:Toxicology / Q000379:methods / Q000592:standards; D014230:Triazoles / Q000008:administration & dosage / Q000633:toxicity; D015262:Xenobiotics / Q000009:adverse effects* / Q000493:pharmacokinetics
D004785:Environmental Pollutants; D005659:Fungicides, Industrial; D007306:Insecticides; D012997:Solvents; D014230:Triazoles; D015262:Xenobiotics; C032910:triadimefon; D012721:Carbaryl