in the LI as an internal dosimeter. The United States Environmental Protection Agency currently uses the linearized multistage High doses of chloroform induced liver cancer in male and model applied to the mouse liver tumor data from the chloroform female B6C3F 1 mice when administered by gavage, kidney cancer gavage study to estimate a virtually safe dose (VSD) as a one in in male Osborne-Mendel rats when given by gavage or in the a million increased lifetime risk of cancer. The resulting value is drinking water, and kidney cancer in male BDF 1 mice when ad-an airborne exposure concentration of 0.000008 ppm. Assuming ministered by inhalation. The weight of evidence indicates that that chloroform-induced female mouse liver cancer is secondary to chloroform is acting through a nongenotoxic-cytotoxic mode of events associated with necrosis and regenerative cell proliferation, action. The present study was designed to investigate the dose-then no increases in liver cancer in female mice would be predicted response relationships for chloroform-induced lesions and regen-at the NOAEL of 10 ppm or below based on the results reported erative cell proliferation in B6C3F 1 mice as the basis for formula-here. Applying an uncertainty factor of 1000 yields an estimate of tion of a biologically based risk assessment for inhaled chloroform. a VSD at 0.01 ppm. This estimate relies on inhalation data and Different groups of female and male B6C3F 1 mice were exposed is more consistent with the mode of action of chloroform. ᭧ 1996 to atmospheric concentrations of 0, 0.3, 2, 10, 30, and 90 ppm Society of Toxicology chloroform 6 hr/day, 7 days/week for exposure periods of 4 days or 3, 6, or 13 consecutive weeks. Some additional exposure groups were exposed for 5 days/week for 13 weeks or were exposed for 6The most prevalent water disinfection process in the weeks and then examined at 13 weeks. Bromodeoxyuridine was administered via osmotic pumps implanted 3.5 days prior to nec-United States is chlorination with sodium hypochlorite or ropsy, and the labeling index (LI, percentage of nuclei in S-phase) chlorine dioxide. One of the most common chlorinated bywas evaluated immunohistochemically from histological sections. products produced in trace amounts by this process is chloroComplete necropsy and microscopic evaluation revealed treat-form (Bunn et al., 1975; Symons et al., 1975). Industrial ment-induced dose-and time-dependent lesions only in the livers processes such as the bleaching of paper can also discharge and nasal passages of the female and male mice and in the kidneys chloroform and other chlorinated organic compounds into of the male mice. Large, sustained increases in the liver LI were the environment (Butler and Dal Pont, 1992). Chloroform Jo et al., 1990). and regenerative cell proliferation were seen in the male mice at Chloroform induced liver cancer in male and female 30 and 90 ppm with 7 days/week exposures and also at 10 ppm B6C3F 1 mice when administered by gavage (National Cancer Institute, 1976), kidney cancer ...

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AESTRACIThe mesothelium is a target of the toxic and carcinogenic effects of certain natural mineral and man-made fibers. Long-term inhalation of a ceramic fiber (RCF-1) results in a high incidence of pleural mesotheliomas in Syrian golden hamsters but not in identically exposed Fischer-344 rats. The present study compared the histopathology of the early pleural response in rats and hamsters instilled with artificial fibers. Groups of Syrian golden hamsters and Fischer-344 rats were instilled with ceramic (RCF-1) or glass (MMVF-10) fibers directly into the pleural space. Each species received approximately equal numbers of long, thin fibers per g body weight. Fiber-induced lesions were compared 7 and 28 days postinstillation. Both hamsters and rats developed qualitatively similar dose-dependent inflammatory lesions that were not fiber-type specific. Both species developed fibrosis in conjunction with inflammation in the visceral pleura, but a striking interspecies difference was noted in the pattern of mesothelial cell response. Hamsters developed greater surface mesothelial cell proliferation and had focal aggregates of mesothelial cells embedded deep within regions of visceral pleural fibrosis. It is hypothesized from the present study that the marked fiber-induced proliferative mesothelial cell response of the hamster visceral pleura may explain the high number of pleural mesotheliomas found in long-term fiber studies in this species.