ISSN:
1539-6924
Keywords:
Cancer dose–response modeling
;
multistage model
;
two-stage model
;
hazard functions
;
carcinogenesis
;
Benzene
;
Dieldrin
;
Ethylene Thiourea
;
Trichloroethylene
;
Vinyl Chloride
Source:
Springer Online Journal Archives 1860-2000
Topics:
Energy, Environment Protection, Nuclear Power Engineering
Notes:
Abstract We compare the regulatory implications of applying the traditional (linearized) and exact two-stage dose–response models to animal carcinogenic data. We analyze dose–response data from six studies, representing five different substances, and we determine the “goodness-of-fit” of each model as well as the 95% confidence lower limit of the dose corresponding to a target excess risk of 10−5 (the target risk dose TRD). For the two concave datasets, we find that the exact model gives a substantially better fit to the data than the traditional model, and that the exact model gives a TRD that is an order of magnitude lower than that given by the traditional model. In the other cases, the exact model gives a fit equivalent to or better than the traditional model. We also show that although the exact two-stage model may exhibit dose–response concavity at moderate dose levels, it is always linear or sublinear, and never supralinear, in the low-dose limit. Because regulatory concern is almost always confined to the low-dose region extrapolation, supralinear behavior seems not to be of regulatory concern in the exact two-stage model. Finally, we find that when performing this low-dose extrapolation in cases of dose–response concavity, extrapolating the model fit leads to a more conservative TRD than taking a linear extrapolation from 10% excess risk. We conclude with a set of recommendations.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1006946008515
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