Toxicological Sciences 58, 32-42 (2000)
Copyright © 2000 by the Society of Toxicology
Carcinogenicity |
Reevaluating Cancer Risk Estimates for Short-Term Exposure Scenarios
,1
* TERRA Inc., Denver, Colorado;
Center for Environmental and Human Toxicology, University of Florida, Gainesville, Florida; and
National Institute for Environmental Health Sciences, Research Triangle Park, North Carolina
Estimates of cancer risk from short-term exposure to carcinogens generally rely on cancer potency values derived from chronic, lifetime-exposure studies and assume that exposures of limited duration are associated with a proportional reduction in cancer risk. The validity of this approach was tested empirically using data from both chronic lifetime and stop-exposure studies of carcinogens conducted by the National Toxicology Program. Eleven compounds were identified as having data sufficient for comparison of relative cancer potencies from short-term versus lifetime exposure. The data were modeled using the chronic data alone, and also using the chronic and the stop-exposure data combined, where stop-exposure doses were adjusted to average lifetime exposure. Maximum likelihood estimates of the dose corresponding to a 1% added cancer risk (ED01) were calculated along with their associated 95% upper and lower confidence bounds. Statistical methods were used to evaluate the degree to which adjusted stop-exposures produced risks equal to those estimated from the chronic exposures. For most chemical/cancer endpoint combinations, inclusion of stop-exposure data reduced the ED01, indicating that the chemical had greater apparent potency under stop-exposure conditions. For most chemicals and endpoints, consistency in potency between continuous and stop-exposure studies was achieved when the stop-exposure doses were averaged over periods of less than a lifetime—in some cases as short as the exposure duration itself. While the typical linear adjustments for less-than-lifetime exposure in cancer risk assessment can theoretically result in under- or overestimation of risks, empirical observations in this analysis suggest that an underestimation of cancer risk from short-term exposures is more likely.
Key Words: risk assessment; carcinogenicity; cancer bioassays; estimating cancer risks; stop-exposure studies.
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