Knowledge of patterns of lesion distribution can provide insight into the relative roles played by regional tissue dose and local tissue susceptibility in toxic responses to xenobiotics in the nose and assist assessment of potential human risk. A consistent approach is needed for recording lesion distribution patterns in the complex nasal airways of rats and mice. The present work provides a series of diagrams of the nasal passages of the Fischer-344 rat and B6C3F1 mouse, designed for mapping nasal lesions. The diagrams present each of the major cross-sectional airway profiles, provide adequate space for nasal mucosal lesion recording, and are suitable for duplication in a commercial photocopier. Sagittal diagrams are also provided to permit transfer of lesion location data observed in transverse sections onto the long axis of the nose. The distribution of lesions induced by a selected range of xenobiotics is presented. Approaches to application of the diagrams and interpretation of results obtained are discussed in relation to factors responsible for lesion distribution in the nose and their relevance to interspecies extrapolation. A modified approach to anatomical classification of the ethmoturbinates of the rodent is also presented.

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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