Animal models of human response to dioxins.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent member of a class of chlorinated hydrocarbons that interact with the aryl hydrocarbon receptor (AhR). TCDD and dioxinlike compounds are environmentally and biologically stable and as a result, human exposure is chronic and widespread. Studies of highly exposed human populations show that dioxins produce developmental effects, chloracne, and an increase in all cancers and suggest that they may also alter immune and endocrine function. In contrast, the health effects of low-level environmental exposure have not been established. Experimental animal models can enhance the understanding of the effects of low-level dioxin exposure, particularly when there is evidence that humans respond similarly to the animal models. Although there are species differences in pharmacokinetics, experimental animal models demonstrate AhR-dependent health effects that are similar to those found in exposed human populations. Comparisons of biochemical changes show that humans and animal models have similar degrees of sensitivity to dioxin-induced effects. The information gained from animal models is important for developing mechanistic models of dioxin toxicity and critical for assessing the risks to human populations under different circumstances of exposure.
Grassman
J A
JA
Laboratory of Computational Biology and Risk Analysis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. grassman@niehs.nih.gov
Masten
S A
SA
Walker
N J
NJ
Lucier
G W
GW
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects; D004147:Dioxins / Q000009:adverse effects* / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D006801:Humans; D009369:Neoplasms / Q000209:etiology*; D000072317:Polychlorinated Dibenzodioxins / Q000009:adverse effects* / Q000493:pharmacokinetics; D018570:Risk Assessment
D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D003577:Cytochrome P-450 Enzyme System