Investigations on metabolism, genotoxic effects and carcinogenicity of 2,2'-dichlorodiethylether

Abstract

Either 40 mumole or 160 mumole 2,2'-DDE was injected into male Wistar rats and the metabolites, TdGA and HEMA, were determined in the 24-h urine specimens. Comparative investigations were carried out giving equimolar amounts of chloroethanol and 2-chloroacetaldehyde diethyl acetal. In a further step, inhalation experiments were performed to determine urinary excretion of the two metabolites after an 8-h exposure of male Wistar rats to 10, 50, 100, and 500 ppm 2,2'-DDE and to 50, 200, und 1,000 ppm vinyl chloride. A long-term study was conducted to investigate the possible carcinogenicity of 2,2'-DDE in male and female Sprague-Dawley rats following s.c. injections of 4.36 mumole and 13.1 mumole 2,2'-DDE in DMSO per week. The evaluation of tumor development in treated groups and controls were based on macroscopic inspection and histological examinations of the suspect organs and tissues. Analysis of the metabolites showed that HEMA excretion was much lower than the excretion of TdGA following the uptake of 2,2'-DDE, 2-chloroethanol and 2-chloroacetaldehyde diethyl acetal. Contrary to these, vinyl chloride uptake resulted in a higher urinary excretion of HEMA than TdGA. There was no appreciable increase in the number of tumors detected in 2,2'-DDE-treated animals when compared with untreated or DMSO-treated groups. Since irradiation of 2,2'-DDE with UV did not elevate mutagenic activity of the compound against Salmonella typhimurium TA100, the high mutagenicity of the compound found in a desiccator cannot be due to the liberation of mutagenic compounds produced under the influence of UV light.