Ethylene glycol ethers as hemopoietic toxins--in vitro studies of acute exposure

Ethylene glycol ethers and their acetate derivatives were analyzed for their toxicity in vitro on several hemopoietic cell lines, either growth-factor-dependent or leukemic, in mouse, rat, and human species. Considering the concentrations that reduced the cell viability in culture by 50%, most of the ethylene glycol ethers and in particular ethylene glycol monoethyl ether (EGEE) or ethylene glycol monobutyl ether (EGBE) should be considered as hemopoietic toxins. EGBE was found to be the most potent toxin on the human promyelocytic cell line, NB4 (median inhibitory concentration (IC50) 5 mM at 6 h; IC50 0.1 mM at 96 h) but also on the factor-dependent cell line DA1 (IC50 80 microM at 48 h). Factor-dependent cell lines were not significantly more sensitive than leukemic cell lines. The toxicity of these compounds falls in the same range of concentration as benzene or phenol, but hydroquinone was significantly more toxic in the same assay (IC50 3-15 microM at 48 h). Toxic effects increased linearly with time. The toxicity of ethylene glycol ethers was confirmed by both assays for colony-forming units in culture medium (CFU-C) (human blood cord cells) and murine bone marrow long-term culture (IC50 5-10 mM). Stromal cells in the adherent layer were more resistant than hemopoietic cells. An all or none toxicity was found within a narrow range of concentration (2-5 mM for EGBE), and chronic exposure over two months did not show cumulative effects on the culture cellularity. The possibility that fibroblastic or macrophage cells worked at the detoxification of the culture is suggested. Results are discussed with regard to epidemiological and in vivo experimental data presently available.