Extrapolation of laboratory findings to risks from environmental exposures: male reproductive effects of ethylene oxide.
The extrapolation of human risk from laboratory findings is based on physiologic and biochemical similarities between humans and test animals. While these extrapolations can be based on correlations and empiric relationships, such relationships must be derived for each agent and new set of exposure conditions. The complexity and diversity of environmental exposures severely limit the number of situations in which this may be done. An alternative approach is to use linked pharmacokinetic and pharmacodynamic models to estimate the tissue concentrations and subsequent effects associated with a given type of exposure. This approach has the advantage of allowing a determination of the tissue levels of the agent and of its effects for different time profiles of exposure and routes of entry. It permits comparisons of animal studies that use different experimental protocols. The utility of this approach was illustrated by quantitatively extrapolating from laboratory studies of male mice to mutational risk of male sterilizer operators exposed to ethylene oxide. This approach puts severe data demands on the researcher building models: extensive physiologic, biochemical and metabolic data must be available or estimable for body compartments; time-course and dose-response data must be available on the effects; and environmental exposure profiles must be available. However, it permits a degree of coordination of laboratory and epidemiologic studies that has rarely been possible. It also identifies potential new human risks, and a way of formulating testable hypotheses about human effects that are directly derived from laboratory data. Thus, this approach offers an exciting opportunity for better characterization of human effects and potential risks.
Smith
T J
TJ
Family & Community Medicine, University of Massachusetts Medical Center, Worcester 01655.
D000818:Animals; D004195:Disease Models, Animal; D005027:Ethylene Oxide / Q000009:adverse effects* / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D051379:Mice; D013093:Spermatogonia / Q000187:drug effects* / Q000378:metabolism; D013094:Spermatozoa / Q000187:drug effects*; D013737:Testis / Q000187:drug effects* / Q000378:metabolism
D005027:Ethylene Oxide