Applicability of cancer risk assessment techniques to other toxic effects.
The purpose of this paper is to investigate the applicability of cancer risk assessment techniques to other endpoints. The discussion is limited to the problem of high to low dose extrapolation. Although developed to describe cancer data, the multistage model has a general sigmoidal shape which makes it amenable to describe the dose-response of many non-cancer endpoints. At low doses the multistage model is essentially a general polynomial model. Low-dose linear extrapolation provides an upper limit on convex (curving upward) dose-response curves. Low-dose linearity is expected if exposure to a toxic substance augments a disease process which is already operating in unexposed animals. Incorporation of pharmacokinetic information may prove useful in simplifying dose-response relationships and may result in lower estimates of risk. A descriptive model can be used to estimate a lower confidence limit on a dose expected to produce a disease incidence, for example, of 1% of the animals (LED01). Then, the LED01/100 provides an estimate of the dose for which the risk is estimated to be less than 10(-4). It appears that some of the techniques used for cancer risk assessment can be used or modified for quantal non-cancer endpoints.
Gaylor
D W
DW
National Center for Toxicological Research, Jefferson, AR 72079.
D000818:Animals; D001554:Benzene / Q000633:toxicity; D002273:Carcinogens / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008962:Models, Theoretical; D009369:Neoplasms / Q000139:chemically induced*; D051381:Rats; D011919:Rats, Inbred Strains; D012307:Risk Factors; D014116:Toxicology / Q000379:methods*
D002273:Carcinogens; D001554:Benzene