Reconciling animal and human data in a cancer risk assessment of acrylonitrile

Objectives Bioassays of rats exposed to acrylonitrile have consistently det ected an elevated incidence of central nervous system (CNS) cancer. In cont rast, epidemiologic studies have not found a statistically stable increase in CNS cancer mortality. The purpose of this paper is to examine whether or not CNS cancers predicted from the most appropriate inhalation bioassay in rats are consistent with CNS cancers observed in 3 recent, large epidemiol ogic studies. Methods A linearized multistage model was fit to dose-response data from a rat inhalation bioassay to estimate carcinogenic potency. This potency was applied to epidemiologic studies of acrylonitrile-exposed workers. After ad justment for less than complete lifetime follow-up in the epidemiologic stu dies, consistency was examined between CNS cancers predicted by the model f it to the animal data for the exposure levels and sample sizes of the epide miologicy studies and the CNS cancers observed in the epidemiologic studies . Results The model predicted totals of 17.7, 3.6, and 7.6 CNS cancer deaths for the studies. These predictions were not far from the observed CNS cance r deaths (12, 6, and 6) and were well within their 95% confidence intervals of 6.9-22.3, 2.2--13.1, and 2.2-13.1, respectively. Conclusions The CNS cancer potency estimated from the best available inhala tion bioassay was consistent with the observed deaths in the epidemiologic studies as long as continuous lifetime exposure was chosen as the exposure metric. The lack of observed excess in CNS cancer among the studied workers may have been due to low exposures, insufficient follow-up times, or both.