Two hundred twenty-six specific pathogenfree male and female F344 rats were exposed to nickel sulfide inhalations for 78 weeks (5 days/wk, 6 hr/day) and observed for an adiditional 30-week period. For the same amount of time, 214 rats were exposed to filtered room air and served as controls. Rats exposed to nickel sulfide showed a significantly higher incidence of pulmonary hyperplastic and neoplastic lesions originating from the bronchial and bronchiloo-alveloar segments. The overall incidence of lung tumors in the animals treated with nickel sulfide was 14 percent compared with 1 percent in the controls. Pulmonary inflammatory reactions were also greatly increased. Injection of an agent (hexachlorotetra-fluorobutane) that induced lung infarction did not increase the proportion of animals having lesions, nor did it alter the type of lesions found in animals exposed to nickel sulfide.

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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.

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