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

Bis(dichloropropyl) ether isomers have been identified in a petrochemical p lant effluent through a toxicity identification evaluation study in the Uni ted States. They have also been observed in the microgram per liter range a long one of the largest rivers in Europe, the Elbe River. In the present in vestigation the genotoxic and transforming activity of a bis(dichloropropyl ) ether isomer, bis(2,3-dichioro-1 -propyl) ether, was assayed in vitro. Th e results demonstrate that bis(2,3-dichioro-1-propyl) ether is a potent mut agen in Salmonella typhimurium strains TA 100, TA 1535, and to a lesser ext ent in strain TA 98, but only when tested in the presence of a metabolic ac tivation system (S9 mix). We have also investigated the induction of micron uclei by bis(2,3-dichioro-1-propyl) ether in the metabolically competent ce ll line, MCL-5. A linear, dose-dependent increase in micronuclei was observ ed following exposure to bis(2,3-dichloro-1-propyl) ether. The DNA stand-br eaking capacity of this chemical was assessed in the alkaline single-cell g el electrophoresis (" comet ") assay with MCL-5 cells. Bis(2,3-dichloro-1-1 propyl) 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 fibr oblasts after metabolic activation (S9 mix). Thus, it must be suspected tha t bis(2,3-dichloro-1-propyl) ether may possess a carcinogenic potential. Si nce the compound along with its isomers is present in considerable concentr ations in surface water, their elimination is a matter of significant publi c concern. (C) 2000 Wiley-Liss Inc.