Subchronic inhalation toxicity of benzene in rats and mice.

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.

Effect of lysine and diethanolamine-rutin on blood levels, withdrawal reaction, and acute toxicity of ethanol in mice.

The effects of L-Lysine and diethanolamine-rutin on blood ethanol levels and withdrawal convulsions following a 4-day exposure to ethanol vapors were evaluated in 30-40-g male Swiss-Webster mice. The animals were exposed in groups, along with simultaneous controls, in a 34-liter dynamic Plexiglas exposure chamber. Blood was collected by retro-orbital puncture and analyzed enzymatically for ethanol. At the end of the inhalation period, convulsions on handling were scored over 24 hr. In addition, the effects of L-Lysine and diethanolamine-rutin on blood ethanol levels and on acute ethanol toxicity following oral and intraperitoneal administration were evaluated. L-Lysine lowered blood ethanol levels following inhalation or oral administration of ethanol. Diethanolamine-rutin had no effect on blood ethanol levels. Both L-Lysine and diethanolamine-rutin decreased the withdrawal reaction in dependent mice. L-Lysine increased the oral LD50 of ethanol, while diethanolamine-rutin decreased the intraperitoneal LD50 of ethanol.