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AlTLO:fOTIVE GASOLINE 65-20 higher_ At one high-Volume station. zhe mean concentration to which an _ individual filling his own tank of gas was exposed (for ten minutes) -was 4.2 ppm (2283) . e-q. 65.3 HUMAN' HEALTH CONSIDERATIONS 65.3.1 Animal Studies Y, 65.3.1.1 Carcinogenicity -- Host of the evidence regarding carcinogenicity of gasoline has , been provided by a study conducted for the American Petroleum Institute (AFI) (2298) . Reports of this study appear in several forms throughout the literature. A chronic inhalation study of gasoline vapor was - conducted in mice and rats; the gasoline employed was unleaded. with the benzene content adjusted to 2%. Groups of both sexes of B6C3F1 -' mice and Fischer 344 rats were exposed to vapor at concentrations of _ 67, 292 or 2056 ppm for 6 hours per day, 5 days per week for periods ranging from 103 to 1.13 weeks. After as little as three months of exposure to 2056 ppm, macroscopic lesions were evident in the kidney of male rats. Microscopic observations -included an increased incidence of renal disease with tubular degeneration. regeneration or cystic ; dilatation among males exposed to 292 or 2056 ppm. At 24 months, an -� Increase in the occurrence of primary renal neoplasm was seen in the 4 male rats at all doses. with some evidence of a dose-response relation- ship. In addition, a compound related increase in liver nodules and masses was seen in female mice exposed to the intermediate and high levels. Histopathologic examination revealed primary hepatocellular tsmsors (adenomas and carcinomas) in these animals. { These unexpected findings of species and sex-specific carcinogenic effects were not evident until lace in the study. To better understand the significance to human health, the American Petroleum Institute con- tracted with Universities Associated for Research and Education in Pathology, Inc. (UAREP) for assistance in interpretation of the find- ings. The UAREP reviewed the chronic inhalation study, "old rat nephropathy" syndrome. and the basic morphological and functional similarities and differences in the kidneys of the rat. mouse, and man (2299) . This review concluded that the significance of the I hepatocellular carcinoma in female mice was questionable. The UAREP felt that other studies on different hydrocarbons demonstrated acute toxic effects on the female liver including fatty metamorphosis whereas • these effects were nor reported in the API chronic inhalation study. The finding of renal carcinoma in male rats was clearly significant. The lesions were seen as early as 90 days and were dose-related. The lesions could be clearly distinguished from the old rat nephropathy, which is composed of chronic lesions involving all components of the kidney. However, administration of unleaded gasoline appeared to accentuate all the lesions characteristic of old rat . .- nephropathy. It was not possible to evaluate the potential role of the 6/87 . - P