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The National Toxicology Program (NTP) developed the chronic 2-year bioassay as a mechanism for predicting the carcinogenic potential of chemicals in humans. The cost and duration of these studies has limited their use to small numbers of selected chemicals. Many different short-term methods aimed at increasing predictive accuracy and the number of chemicals evaluated have been developed in attempts to successfully correlate their results with evidence of carcinogenicity (or lack of carcinogenicity) are assessed. Using NTP studies, the effectiveness of correlating prechronic liver lesions with liver cancer encompassing multiple studies using mice (83 compounds) and rats (87 compounds). These lesions include hepatocellular necrosis, hepatocellular hypertrophy, hepatocellular cytomegaly, bile duct hyperplasia, and hepatocellular degeneration, along with increased liver weight. Our results indicate that pooling 3 of these prechronic data points (hepatocellular necrosis, hepatocellular hypertrophy, and hepatocellular cytomegaly) can be very predictive of carcinogenicity in the 2-year study ( p < 0.05). The inclusion of increased liver weight as an endpoint in the pool of data points increases the number of rodent liver carcinogens that are successfully predicted ( p < 0.05), but also results in the prediction of increased numbers of noncarcinogenic chemicals as carcinogens. The use of multiple prechronic study endpoints provides supplementary information that enhances the predictivity of identifying chemicals with carcinogenic potential. [ABSTRACT FROM AUTHOR]

Vanadium pentoxide (V2O5) is a slightly soluble compound found in airborne particle emissions from metallurgical works and oil and coal burning. Because the carcinogenic potential of V2O5 was not known, F344/N rats and B6C3F1 mice (N = 50/sex/species) were exposed to V205at concentrations of 0, 0.5 (rats only), 1, 2, or 4 (mice only) mg/m3, by whole-body inhalation for 2 years. The survival and body weights of rats were minimally affected by exposure to V2O5. The survival and body weights of male mice exposed to 4 mg/m3and body weights of all exposed groups of female mice were lower than the controls. Alveolar/bronchiolar (A/B) neoplasms occurred in male rats exposed to 0.5 and 2 mg/m3 at incidences exceeding the National Toxicology Program (NTP) historical control ranges. A marginal increase in A/B neoplasms was also observed in female rats exposed to 0.5 mg/m3. Increases in chronic inflammation, interstitial fibrosis, and alveolar and bronchiolar hyperplasia/metaplasia and squamous metaplasia were observed in exposed male and female rats. A/B neoplasms were significantly increased in all groups of exposed mice. As with rats, increases in chronic inflammation, interstitial fibrosis, and alveolar and bronchiolar epithelial hyperplasia were observed in mice exposed to V205. Thus, V205 exposure was a pulmonary carcinogen in male rats and male and female mice. The marginal tumor response in the lungs of female rats could not be attributed conclusively to exposure to V205. These responses were noted at and slightly above the OSHA permissible occupational exposure limit of 0.5 mg/m3 (dust) (National Institute for Occupational Safety and Health,NIOSH Pocket Guide to Chemical Hazards, U.S. Department of Health and Human Services, Washington, DC, 1997, p. 328). [ABSTRACT FROM AUTHOR]

Five categories of evidence of carcinogenicity in rats and mice were used to group interpretative results on 86 chemicals studied in recent carcinogenicity tests carried out by the National Toxicology Program (NTP). Of these studies, 50% (43/86) were regarded as showing carcinogenic effects, 42% (36/86) gave no evidence of carcinogenicity, 6% (5/86) showed equivocal evidence of carcinogenicity, and 2% (2/86) were regarded as inadequate experiments. The liver was the most frequent site of cancer in male and female Fischer‐344 rats and in male and female B6C3F1 mice. Male rats appeared more sensitive than female rats to the induction of neoplasia, while for mice the females seemed more responsive. The routes of administration yielding the highest percentage (80–83%) of positive studies were gavage and inhalation; approximately one‐third of the feed, drinking water, and dermal studies showed carcinogenic effects. In feeding studies, overall survival in dosed and control groups were similar, while the majority of gavage studies showed significantly reduced survival in one or more dosed groups relative to the corresponding controls. The overall percentage of studies showing carcinogenic effects (50%) agrees closely with the rate reported by other investigators for nearly 200 earlier carcinogenicity experiments conducted by the National Cancer Institute. [ABSTRACT FROM PUBLISHER]