Influences of gender, development, pregnancy and ethanol consumption on the hematotoxicity of inhaled 10 ppm benzene.

The hematotoxic effects of benzene in both humans and animals are well documented. Current estimates concerning the risks associated with benzene exposure are usually based on adult, male cohort studies; however, there are indications that females may respond differently than males to benzene and that fetuses may respond differently than adults. Another factor to be considered in risk estimates is the impact of personal habits. In experimental animals, ethanol consumption is known to increase the hematotoxicity of benzene; therefore, alcohol consumption may also alter the potential risk of individuals exposed to benzene. To address some of the factors that may confound risk estimates for benzene exposure, a series of experiments were performed. Age-matched male as well as pregnant and virgin female Swiss Webster mice were exposed to 10 ppm benzene for 6 h a day over 10 consecutive days (days 6 through 15 of gestation for the pregnant females). Half of the animals also received 5% ethanol in the drinking water during this period. On day 11, bone marrow cells from the adults and liver cells from the fetuses were assayed for the numbers of erythroid colony-forming units (CFU-e). CFU-e assays were also performed on bone marrow cells isolated from 6-week postpartum dams exposed during gestation and from in utero-exposed 6-week old males and females. Gender differences were clearly observed in the responses to the various exposure protocols. Depressions in CFU-e numbers were only seen in male mice while elevations in CFU-e numbers were only seen in female mice. Male mice exposed as adults for 10 days to benzene (B), ethanol (E) or benzene+ethanol (B+E) exhibited depressed CFU-e levels as did male fetal mice exposed to B in utero. In addition, adult male mice which had been exposed in utero to either B or to E individually displayed depressed CFU-e levels. In contrast, none of the groups of female mice exhibited any depressions in CFU-e numbers after any of the exposures. Elevations in CFU-e numbers were observed among pregnant females exposed to E and among adult females exposed to B+E in utero. In summary, a majority (6/9) of the exposure protocols produced depressions in the CFU-e numbers of male mice, whereas a majority (7/9) of the exposure protocols produced no changes in the CFU-e numbers of female mice. Those changes that were observed in females consisted of elevations of CFU-e numbers. These results suggest that the male erythron is more susceptible than the female erythron to the hematotoxicants benzene and ethanol, regardless of whether exposures occur in utero or during adulthood.