Improved risk estimated from carbon tetrachloride. Annual progress report, October 1, 1996--September 30, 1997

'Carbon tetrachloride (CCl{sub 4}) has been used extensively within the Department of Energy (DOE) nuclear weapons facilities. Rocky Flats was formerly the largest volume user of CCl{sub 4} in the US, with 5,000 gallons used there in 1977 alone. At the Hanford site, several hundred thousand gallons of CCl{sub 4} were discharged between 1955 and 1973 into underground cribs for storage. Levels of CCl{sub 4} in groundwater at highly contaminated sites at the Hanford. facility have exceeded the drinking water standard of 5 ppb by several orders of magnitude. High levels of CCl{sub 4} at these facilities represent a potential health hazard for workers conducting cleanup operations and for surrounding communities. The level of CCl{sub 4} cleanup required at these sites and associated costs are driven by current human health risk estimates which assume that CCl{sub 4} is a genotoxic carcinogen. 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, B6C3F1 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 CCl4 originally developed by Paustenbach et al. (1988) and more recently revised by Thrall and Kenny (1996). They 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. In combination, the studies outlined in this proposal will provide the exact types of information needed to enable refined cancer risk estimates for CCl{sub 4} under the new guidelines for risk assessment proposed by the EPA in April 1996 (US EPA, 1996).