The Ames II Salmonella mutagenicity assay procedure was used to test 71 chemicals, and the results were compared with those from the traditional Ames Salmonella test using the NTP database as the reference. All Ames II tests were performed using a fluctuation procedure in microplate format, using TAMix for the detection of base pair substitutions and TA98 to detect frameshift mutations. There was 84% agreement between the two procedures in identifying mutagens and non-mutagens, which is equivalent to the intra- and interlaboratory reproducibility of 87% for the traditional test. The two tests also performed similarly in their predictions of rodent carcinogenicity.

To elucidate possible mechanism(s) of carcinogenic action of tetrahydrofuran (THF) that had been demonstrated in previous inhalation studies, groups of male F344 rats and female B6C3F(1) mice were exposed to dynamic atmospheric concentrations of 0, 600, 1800, or 5400 mg/m(3) for 6 h per day, either for 5 consecutive days or for a period of 4 weeks (5 days per week). The reversibility of treatment-related changes was investigated in rats and mice exposed for 5 days and sacrificed 21 days after the last exposure. Female B6C3F(1) mice exposed to 5400 mg/m(3) showed significantly increased cytochrome P450 content, increased ethoxyresorufin-O-deethylase and pentoxyresorufin-O-depentylase activities, increased cell proliferation (5-bromo-2'-deoxyuridine-method) and an increased mitotic index in liver zones 2 (midzonal region) and 3 (central vein region). The changes were found to be reversible after a 3-week treatment-free period (cell proliferation examined, only). Male F344 rats showed dose-related alpha2u-globulin (alpha2u) accumulation in the renal cortex after 5 or 20 exposures, and there were no signs of reversal after a 3-week treatment-free period. After 20 exposures at 5400 mg/m(3), the alpha2u accumulation was found to be associated with increased cell proliferation in "hot spots" of the renal cortex and increased apoptosis. Increased cell proliferation was also detected after 20 exposures at 1800 mg/m(3). There were no effects at 600 mg/m(3). It is concluded that THF enhances tumor formation in male rat kidney and female mouse liver via induction of cell proliferation. These features present essential elements that should be taken into account for the carcinogenic risk assessment of THF.

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