Search

Carbon tetrachloride (CCl{sub 4}) has been used extensively within the Department of Energy (DOE) nuclear weapons facilities. High levels of CCl{sub 4} at these facilities represent a potential health hazard for workers conducting cleanup operations and for surrounding communities. The overall purpose of these studies is to improve the scientific basis for assessing the health risk associated with human exposure to CCl{sub 4}. Specifically, the authors will determine the toxicokinetics of inhaled and ingested CCl{sub 4} in F344/Crl rats. B6C3F{sub 1} mice, and Syrian hamsters. They will also evaluate species differences in the metabolism of CCl{sub 4} by rats, mice, hamsters, and man. Dose-response relationships will be determined in all these studies. This information will be used to improve the physiologically based pharmacokinetic (PBPK) model for CCl{sub 4} originally developed by Paustenbach et al. (1988) and more recently revised by Thrall and Kenny (1996). The authors will also provide scientific evidence that CCl{sub 4}, like chloroform, is a hepatocarcinogen only when exposure results in cell damage, cell killing, and regenerative cell proliferation.

Nuclear workers may be exposed to radiation in various forms, such as low-LET {gamma}-irradiation or {alpha}-irradiation from inhaled {sup 239}PuO{sub 2} particles. These workers may then have increased risk for lung cancer compared to the general population. Of additional concern is the possibility that interactions between radiation and other carcinogens may increase the risk of cancer induction, compared to the risks from either type of agent alone. An important and common lung carcinogen is cigarette smoke. The purpose of this project is to better determine the combined effects of chronically inhaled cigarette smoke and either inhaled {sup 239}PuO{sub 2} or external, thoracic X-irradiation on the induction of lung cancer in rats. Histologic and dosimetric evaluations of rats in the CS + {sup 239}PuO{sub 2} study continue, and the study of CS + X rays is beginning.