A Chronic Inhalation Study with Unleaded Gasoline Vapor

Abstract

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.

Chronic Carcinogenicity Study of Gasoline Vapor Condensate (GVC) and GVC Containing Methyl Tertiary-Butyl Ether in F344 Rats

“…However, overall combination of incidence and severity of the lesion, assessed using the Kolmogorov–Smirnoff test, was significantly greater in the mid- and high-level exposure groups. This finding in males is consistent with male-rat-specific light hydrocarbon-induced alpha-2μ globulin overload nephropathy that was reported previously in studies with wholly vaporized unleaded gasoline ( MacFarland et al, 1984 ). In F344 male rats, after approximately 1 yr of age, alpha-2μ globulin overload nephropathy is essentially masked by age-related chronic progressive nephropathy, since both forms of nephropathy share similar if not identical diagnostic hallmarks.…”

“…The control incidence in the parallel GVC study was 4/40 (8%). Additionally, increases in this neoplasm have not been observed in previous studies with neat MTBE or wholly vaporized gasoline ( Cruzan et al, 2007 ; MacFarland et al, 1984 ). Therefore, it is judged unlikely that the increased incidence in female mammary-gland fibroadenoma was treatment-related.…”

“…Previous studies evaluated the toxicity of chronically inhaled wholly vaporized gasoline ( MacFarland et al, 1984 ). In this published study, F344 rats and B6C3F1 mice were exposed 6 h/d, 5 d/wk for 24 to 27 mo to 67, 292 or 2056 ppm (approximately 0.2–6.3 g/m 3 ) wholly vaporized unleaded gasoline.…”

Epidemiology and Risk Factors of Kidney Cancer

“…But recent reviews of cohort studies found little or no evidence of an excess risk of kidney cancer 46,47 . Gasoline came under suspicion as a risk factor for renal cell cancer when male rats exposed long-term to vapors of unleaded gasoline developed a signifi cant excess of renal cancers 48 . A number of epidemiological studies have examined the eff ect of gasoline exposure with inconsistent results 42,[49][50][51] .…”

Epidemiologic evidence for an association between gasoline and kidney cancer.

“…A chronic inhalation study has shown that unleaded gasoline vapor caused kidney carcinomas and sarcomas in male rats with some evidence of a dose-response relationship (1). Also observed was an increase in liver masses and modules in female mice.…”