A chronic inhalation study of unleaded gasoline vapor was conducted in mice and rats. The gasoline employed was typical of gasoline used in the US and contained 2% benzene. Groups of both sexes of B6C3F1 mice and Fischer 344 rats were exposed to three concentrations of vapor, 67, 292, and 2056 ppm. Exposures were for 6 hours per day, 5 days per week, for periods ranging from 103 to 113 weeks. Interim sacrifices were conducted at 3, 6, 12, and 18 months. Laboratory studies, including hematological and biochemical determinations, were performed on rats at the interim sacrifices and at termination. Histopathological studies were conducted on both species at every interval. No consistent compound-related changes were seen in pharmacotoxic signs, mortality, hematological, or biochemical indices in either species. Significant depression of body weight gain was seen in both sexes of rats and male mice exposed to the highest level of gasoline vapor. On gross necropsy, a compound-related increase in liver nodules and masses was seen in female mice exposed to the high level. The most interesting observations were made on histopathological examination of the rats' tissues, and, of these, pathological changes in the kidneys were the most striking. Renal carcinomas or sarcomas, in the cortex or near the renal poles, were seen in the male rats at all dose levels, with some evidence of a dose-response relationship. One female rat in the intermediate dose group exhibited a renal sarcoma. Two mice had renal tumors, considered to be spontaneous neoplasms. Mention is made of new studies that have been prompted by the present findings.

Antler abnormalities of deer and other cervids often result from testicular lesions and decreased levels of testosterone, inhibiting normal cycles of antler growth. Affected males have antlers with retained velvet, numerous short, misshapen points ("cactus bucks"), and failure to shed these abnormal antlers annually. In Colorado, US, we observed a high occurrence of "cactus bucks" in mule deer (Odocoileus hemionus) populations after management efforts to increase the number of mature male deer in the state. Affected males consistently had antibody to epizootic hemorrhagic disease virus serotype 2 (EHDV-2), and examination of the testes of these animals demonstrated nonspecific end-stage lesions of chronic inflammation, fibrosis, and mineralization. To examine more acute stages of testicular lesions, and to screen for EHDV specifically within the testes, we sampled 16 male mule deer from affected herds, but with essentially normal antlers (n = 14) or retained velvet only (n = 2). Testicular and epididymal lesions identified from these samples included necrotizing vasculitis (n = 2), hemorrhage (n = 6), edema (n = 2), seminiferous tubular necrosis (n = 5), orchitis (n = 5), epididymitis (n = 10), hypospermia (n = 6), and end-stage lesions of seminiferous tubular loss (n = 2), fibrosis (n = 2), and mineralization (n = 2). Each of the 16 cases was blindly scored on the basis of number of histologic lesions, with a median score of two. Five of seven (71%) testes that were PCR positive for EHDV had lesion scores above the median, whereas none of the nine (0%) EHDV PCR-negative testes had lesion scores above the median, suggesting an association between testicular lesions and detection of EHDV RNA in the testes (P = 0.003). Although the role of EHDV infection remains unconfirmed, the association between testicular and epididymal lesions and presence of EHDV RNA in the affected tissues suggests that cactus buck antlers may be a sequela of EHDV infection.

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