Reevaluating cancer risk estimates for short-term exposure scenarios

Estimates of cancer risk from short-term exposure to carcinogens generally rely on cancer potency values derived from chronic, lifetime-exposure studi es and assume that exposures of limited duration are associated with a prop ortional reduction in cancer risk. The validity of this approach was tested empirically using data from both chronic lifetime and stop-exposure studie s of carcinogens conducted by the National Toxicology Program. Eleven compo unds were identified as having data sufficient for comparison of relative c ancer potencies from short-term versus lifetime exposure, The data were mod eled 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 t o a 1% added cancer risk (ED01) were calculated along with their associated 95% upper and lower confidence bounds. Statistical methods were used to ev aluate the degree to which adjusted stop-exposures produced risks equal to those estimated from the chronic exposures. For most chemical/cancer endpoi nt combinations, inclusion of stop-exposure data reduced the ED,,, indicati ng that the chemical had greater apparent potency under stop-exposure condi tions, For most chemicals and endpoints, consistency in potency between con tinuous 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 l ess-than-lifetime exposure in cancer risk assessment can theoretically resu lt in under- or overestimation of risks, empirical observations in this ana lysis suggest that an underestimation of cancer risk from short-term exposu res is more likely.