Cell transformation and genotoxicity induced by bis(2,3-dichloro-1-propyl) ether

Bis(dichloropropyl) ether isomers have been identified in a petrochemical plant effluent through a toxicity identification evaluation study in the United States. They have also been observed in the microgram per liter range along one of the largest rivers in Europe, the Elbe River. In the present investigation the genotoxic and transforming activity of a bis(dichloropropyl) ether isomer, bis(2,3-dichioro-1 -propyl) ether, was assayed in vitro. The results demonstrate that bis(2,3-dichioro-1-propyl) ether is a potent mutagen in Salmonella typhimurium strains TA 100, TA 1535, and to a lesser extent in strain TA 98, but only when tested in the presence of a metabolic activation system (S9 mix). We have also investigated the induction of micronuclei by bis(2,3-dichioro-1-propyl) ether in the metabolically competent cell line, MCL-5. A linear, dose-dependent increase in micronuclei was observed following exposure to bis(2,3-dichloro-1-propyl) ether. The DNA stand-breaking capacity of this chemical was assessed in the alkaline single-cell gel electrophoresis (" comet ") assay with MCL-5 cells. Bis(2,3-dichloro-1-1propyl) ether clearly induced DNA stand breaks in the 4.5-45.5 mu g/ml dose range. The ether also induced malignant tranformation in C3H/M2 mouse fibroblasts after metabolic activation (S9 mix). Thus, it must be suspected that bis(2,3-dichloro-1-propyl) ether may possess a carcinogenic potential. Since the compound along with its isomers is present in considerable concentrations in surface water, their elimination is a matter of significant public concern. (C) 2000 Wiley-Liss Inc.