1,4-Dichlorobenzene-Induced Nephrotoxicity: Similarity with Unleaded Gasoline (UG)-Induced Renal Effects

Abstract

1,4-Dichlorobenzene (1,4-DCB) administered (150 or 300 mg/kg/day, po) 5 days per week for 104 weeks caused a dose-related increase in the incidence of renal adenomas and/or carcinomas in male rats, but not female F-344 rats or either sex of B6c3f1 mice (NTP, 1987). 1,2-Dichlorobenzene (1,2-DCB), an isomer of 1,4-DCB, caused no increase in the incidence of male rat renal tumours (NTP, 1985); the doses used were, however, 2.5 times lower than those employed for the 1,4-DCB study. Exposure to vapours of unleaded gasoline (UG) for 114 weeks also produced a doserelated increase in the incidence of renal adenomas and carcinomas in male, but not female F-344 rats or either sex of mice (Kitchen, 1984). The incidence of male rat renal tumours was dose-dependent but relatively low for both compounds. Assessment of the genotoxic properties of 1,4-DCB and UG by a battery of tests has shown that the chemicals are nongenotoxic. Our hypothesis to explain renal tumour formation is based on a multi-stage carcinogenesis model: Cells, in which spontaneous DNA alterations naturally occur, replicate following chemically-induced cell proliferation causing a mutated cell. Mutated cells undergo clonal expansion due to increased cell proliferation. This greatly increases the likelihood of additional spontaneous mutations occurring, leading to an increased incidence of renal cancer.