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 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 (ED(01)) 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 ED(01), 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.
Halmes
N C
NC
TERRA Inc., Denver, Colorado. Center for Environmental and Human Toxicology, University of Florida, Gainesville, Florida 32611, USA.
Roberts
S M
SM
Tolson
J K
JK
Portier
C J
CJ
D000818:Animals; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity*; D004334:Drug Administration Schedule; D005260:Female; D008297:Male; D051379:Mice; D008954:Models, Biological; D009374:Neoplasms, Experimental / Q000139:chemically induced; D051381:Rats; D018570:Risk Assessment; D013997:Time Factors
D002273:Carcinogens