US EPA

In assessing adverse health risks from exposure to potential carcinogens, the usual practice is to use cumulative amount or total exposure received over a lifetime as the measure of dose unless there is evidence to the contrary. ifferent exposure regimens resulting in the same total dose are considered to be equivalent, and the assumption is made that a high dose of a carcinogen received over a short period of time is equivalent to a corresponding low dose spread over a lifetime. inyl chloride provides an example where both toxicologic and pharmacokinetic evidence exists to counter this default assumption. everal toxicologic studies indicate that the carcinogenic effects of vinyl chloride are greater from early-life exposure. harmacokinetic evidence together with toxicologic data indicates that the carcinogenic effects of vinyl chloride are dependent on metabolism, and that metabolism follows Michaelis-Menten kinetics. hen exposure situations are reevaluated using the specific toxicologic and pharmacokinetic information available for vinyl chloride, the estimated risks are different. hese analyses suggest exposure information that would be useful in assessing health risks when substantial toxicologic and pharmacokinetic information is available.

Cogliano, V. AND J. Parker. SOME IMPLICATIONS OF TOXICOLOGY AND PHARMACOKINETICS FOR EXPOSURE ASSESSMENT. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-93/509 (NTIS PB94135142), 1992.

Journal of Exposure Analysis & Epidemiology 1:189-207, 1992