The weight of evidence indicates that chloroform then held until analysis 10, 30, 90, and 180 days induces cancer in the female B6C3F 1 mouse liver postexposure. Livers from DMN-treated mice exhibvia a nongenotoxic-cytotoxic mode of action. How-ited a dose-related 2-to 5-fold increase over control ever, it is probable that DNA damage occurs sec-mutant frequencies and remained at those levels for ondary to events associated with cytolethality and 10 through 180 days postexposure. Thus, following regenerative cell proliferation. The purpose of the the initial induction by DMN no selective mutation present study was to evaluate the potential muta-amplification or loss was seen for this extended pegenic activity of chloroform in the B6C3F 1 lacI riod of time. Female B6C3F 1 lacI mice were extransgenic mouse liver mutagenesis assay including posed daily for 6 hr/day 7 days/week to 0, 10, mutagenic events that might occur secondary to cy-30, or 90 ppm chloroform by inhalation, representtolethality. The positive control, dimethylnitrosamine ing nonhepatotoxic, borderline, or overtly hepato-(DMN) is a DNA-reactive mutagen and carcinogen. toxic chloroform exposures. Timepoints for determi-DMN-induced mutations were anticipated to re-nation of lacI mutant frequency were 10, 30, 90, quire only a brief exposure and without further treat-and 180 days of exposure. No increase in lacI ment were predicted to remain unchanged over time mutant frequency in the liver was observed at any at those frequencies. Chloroform-induced mutations dose or timepoint with chloroform, indicating a lack secondary to toxicity were anticipated to require of DNA reactivity. DNA alterations secondary longer exposure periods and to occur only under to toxicity either did not occur or were of a type conditions that produced sustained cytolethality and not detectable by lacI mutant frequency analysis, regenerative cell proliferation. Female B6C3F 1 lacI such as large deletions. Environ. Mol. Mutagen. transgenic mice were treated with daily doses of 2, 31:248 -256, 1998 แญง 1998 Wiley-Liss, Inc. 4, or 8 mg/kg of DMN by gavage for 4 days and