Subchronic inhalation toxicity of benzene in rats and mice

Abstract

A subchronic inhalation toxicity study of benzene was conducted in CD-1 mice and Sprague-Dawley rats. Four groups of animals consisting of 150 mice and 50 rats/sex each were exposed to concentrations of 1, 10, 30, and 300 ppm benzene vapor, 6 hours/day, 5 days/week, for 13 weeks. Additional groups of mice and rats, of equal size, were exposed under similar conditions to filtered air and served as control groups. Thirty mice and 10 rats/sex in each group were sacrificed after 7, 14, 28, 56, and 91 days of treatment. Criteria used to evaluate exposure-related effects included behavior, body weights, organ weights, clinical pathology, gross pathology, and histopathology. Fifty animals per sex of each species were exposed concurrently for cytogenetic studies. In addition, blood serum was obtained for immunological assays. The results of these two studies will be reported separately. No consistent exposure-related trends were seen in the clinical observations and body weight data. Exposure-related clinical pathology changes were seen in the high-level (300 ppm) animals of both species. In the mice, these changes included decreases in hematocrit, total hemoglobin, erythrocyte count, leukocyte count, platelet count, myeloid/erythroid ratios, and percentage of lymphocytes. Mean cell volume, mean cell hemoglobin, glycerol lysis time, and the incidence and severity of red cell morphologic changes were increased in the mice. In the rats, decreased lymphocyte counts and a relative increase in neutrophil percentages were the only exposure-related clinical pathology alterations. Histopathologic changes were present in the thymus, bone marrow, lymph nodes, spleen, ovaries, and testes of mice exposed to 300 ppm and in most cases the incidence and severity of the lesions were greater in the males. These changes in the testes and ovaries at 300 ppm were also seen at lower concentrations, but they were of doubtful biological significance. In rats, the only exposure-related lesion consisted of slightly decreased femoral marrow cellularity in the animals exposed to 300 ppm.

Occupational health survey on workers exposed to 2-bromopropane at low concentrations

“…This trace of benzene would be too little to cause anemia, since no hematological effects were observed at less than 10 ppm in either epidemiological studies [Hancock et al, 1984;Collins et al, 1991] or animal experiments [Deichmann et al, 1963;Green et al, 1981;Ward et al, 1985;Li et al, 1986].…”

Multiple-site carcinogenicity of benzene in Fischer 344 rats and B6C3F1 mice.

“…Fetal (118) reported that CD-1 mice exposed to 300 ppm benzene for 13 weeks exhibited ovarian cysts, testicular degeneration, atrophy, and decreased spermatozoa; animals exposed to 1, 10, or 30 ppm benzene vapor showed no adverse effects.…”

Influence of acetylsalicylic acid on hematotoxicity of benzene

“…Changes in the number of neutrophilic granulocytes have been accompanied by structural disturbances, involving cell nuclei, presence of toxic granules as well as traits of cytoplasmic degeneration. Granulocytosis was observed in the rats exposed to benzene (300 ppm) for 13 weeks and in the mice exposed to benzene (100 and 300 ppm for the entire lifetime), and they related it to the intensified proliferation of promyelocytes and myelocytes [28,29]. In contrast, Hazel et al [30] suggested that hydroquinone created in benzene biotransformation inhibited differentiation of bone marrow granulocytes at the stage of myelocytes.…”

“…In our studies, we have detected lymphopenia which has been intensified by prolongation of exposure to benzene. Studies with benzene demonstrated lowered numbers of peripheral blood lymphocytes and B and T cells in spleen, thymus and bone marrow as well as dose-dependent decreases in CD4 + -T cells, CD4 + /CD8 + ratio and B cells [9,20,28,31]. The observed alterations may have been linked with a hydroquinone-and catechol-induced decrease in the number of precursor cells, and damaged structure of DNA as well as ribonucleotide reductase activity [32].…”