Ethanol consumption potentiates benzene hematotoxicity and reduces urinary trans, trans muconic acid levels in mice

Ingestion of ethanol has been shown to increase the hematotoxicity of benzene (300 ppm) in C57B1/6J mice (Baarson et al., 1982). In this study, the effect of ethanol on hematopoietic parameters was examined in mice exposed to low levels of benzene vapors. Urinary trans,trans-muconic acid (t,tMA) was also measured as an indicator of benzene exposure. Male CD-1 mice treated with ethanol (5% alcohol in a liquid diet) for 3 weeks and pair-fed controls were exposed to 10 ppm benzene vapors, 6 h per day, 5 days per week for 2 weeks, starting from the 2nd week of ethanol administration. Urinary t,tMA was measured by HPLC in samples collected during the last 6 h-exposure session, at the end of each week. Hematotoxicity was assessed on hematopoietic progenitors of the bone marrow erythroid lineage (CFU/E, colony-forming unit-erythroid, and BFU/E, burst-forming unit-erythroid) and myeloid lineage (CFU/GM, colony-forming unit-granulocyte/macrophage). Both benzene and ethanol decreased the CFU/E, BFU/E and CFU/GM cells. Cellularity was reduced by 40–50 and 20–30% in benzene- and ethanol-treated mice, respectively. The cell reduction was more severe in animals exposed to benzene in combination with ethanol. The average urinary t,tMA levels were 280±109 µg/ml (mean±SD) in benzene-treated mice and 0.135±0.05 µg/ml in animals given ethanol alone. Mice given both benzene and ethanol showed urinary t,tMA levels significantly lower (63±25 µg/ml) than those measured after administration of benzene alone. Ethanol administration potentiates benzene hematotoxicity and, in addition, may reduce the predictivity of t,tMA measured in mice as a marker of benzene exposure.