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Improved Risk Estimates for Carbon Tetrachloride.

DE2004827270

Publication Date	2004
Page Count	104
Abstract	Carbon tetrachloride has been used extensively within the DOE nuclear weapons facilities. Rocky Flats was formerly the largest volume consumer of CCl4 in the United States using 5000 gallons in 1977 alone (Ripple, 1992). At the Hanford site, several hundred thousand gallons of CCl4 were discharged between 1955 and 1973 into underground cribs for storage. Levels of CCl4 in groundwater at highly contaminated sites at the Hanford facility have exceeded 8 the drinking water standard of 5 ppb by several orders of magnitude (Illman, 1993). High levels of CCl4 at these facilities represent a potential health hazard for workers conducting cleanup operations and for surrounding communities. The level of CCl4 cleanup required at these sites and associated costs are driven by current human health risk estimates, which assume that CCl4 is a genotoxic carcinogen. The overall purpose of these studies was to improve the scientific basis for assessing the health risk associated with human exposure to CCl4. Specific research objectives of this project were to: (1) compare the rates of CCl4 metabolism by rats, mice and hamsters in vivo and extrapolate those rates to man based on parallel studies on the metabolism of CCl4 by rat, mouse, hamster and human hepatic microsomes in vitro; (2) using hepatic microsome preparations, determine the role of specific cytochrome P450 isoforms in CCl4-mediated toxicity and the effects of repeated inhalation and ingestion of CCl4 on these isoforms; and (3) evaluate the toxicokinetics of inhaled CCl4 in rats, mice and hamsters. This information has been 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). Another major objective of the project was to provide scientific evidence that CCl4, like chloroform, is a hepatocarcinogen only when exposure results in cell damage, cell killing and regenerative proliferation. In combination, the studies were intended to provide the exact types of information needed to enable refined cancer risk estimates for CCl4 under the new EPA guidelines for risk assessment.
Keywords	Carbon tetrachloride Hazardous materials Inhalation Drinking water Contamination Cleanup Costs Health risks Genetoxic hazards Department of Energy (DOE)
Source Agency	Technical Information Center Oak Ridge Tennessee
Corporate Authors	Lovelace Biomedical and Environmental Research Inst., Albuquerque, NM.; Department of Energy, Washington, DC.; Pacific Northwest National Lab., Richland, WA.
Supplemental Notes	Prepared in cooperation with Pacific Northwest National Lab., Richland, WA. Sponsored by Department of Energy, Washington, DC.
Document Type	Technical Report
NTIS Issue Number	200510

Improved Risk Estimates for Carbon Tetrachloride.

Improved Risk Estimates for Carbon Tetrachloride.
DE2004827270

Publication Date	2004
Page Count	104
Abstract	Carbon tetrachloride has been used extensively within the DOE nuclear weapons facilities. Rocky Flats was formerly the largest volume consumer of CCl4 in the United States using 5000 gallons in 1977 alone (Ripple, 1992). At the Hanford site, several hundred thousand gallons of CCl4 were discharged between 1955 and 1973 into underground cribs for storage. Levels of CCl4 in groundwater at highly contaminated sites at the Hanford facility have exceeded 8 the drinking water standard of 5 ppb by several orders of magnitude (Illman, 1993). High levels of CCl4 at these facilities represent a potential health hazard for workers conducting cleanup operations and for surrounding communities. The level of CCl4 cleanup required at these sites and associated costs are driven by current human health risk estimates, which assume that CCl4 is a genotoxic carcinogen. The overall purpose of these studies was to improve the scientific basis for assessing the health risk associated with human exposure to CCl4. Specific research objectives of this project were to: (1) compare the rates of CCl4 metabolism by rats, mice and hamsters in vivo and extrapolate those rates to man based on parallel studies on the metabolism of CCl4 by rat, mouse, hamster and human hepatic microsomes in vitro; (2) using hepatic microsome preparations, determine the role of specific cytochrome P450 isoforms in CCl4-mediated toxicity and the effects of repeated inhalation and ingestion of CCl4 on these isoforms; and (3) evaluate the toxicokinetics of inhaled CCl4 in rats, mice and hamsters. This information has been 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). Another major objective of the project was to provide scientific evidence that CCl4, like chloroform, is a hepatocarcinogen only when exposure results in cell damage, cell killing and regenerative proliferation. In combination, the studies were intended to provide the exact types of information needed to enable refined cancer risk estimates for CCl4 under the new EPA guidelines for risk assessment.
Keywords	Carbon tetrachloride Hazardous materials Inhalation Drinking water Contamination Cleanup Costs Health risks Genetoxic hazards Department of Energy (DOE)
Source Agency	Technical Information Center Oak Ridge Tennessee
Corporate Authors	Lovelace Biomedical and Environmental Research Inst., Albuquerque, NM.; Department of Energy, Washington, DC.; Pacific Northwest National Lab., Richland, WA.
Supplemental Notes	Prepared in cooperation with Pacific Northwest National Lab., Richland, WA. Sponsored by Department of Energy, Washington, DC.
Document Type	Technical Report
NTIS Issue Number	200510