The effect of subchronic feeding of 1,1-dichloro-2,2-bis(4'-chlorophenyl)ethene (DDE) on its metabolism in mice

Abstract

1,1-Dichloro-2,2-bis(4'-chlorophenyl)ethene (DDE), a major lipophilic metabolite of 1,1,1-trichloro-2,2-bis(4'-chlorophenyl)ethane (DDT), is a hepatic carcinogen in both the mouse and hamster upon chronic exposure. DDT is tumorigenic only in the former species. The metabolism in the mouse of [14C-UL-phenyl]DDE with and without 5-month DDE pretreatment, is reported. The urine, feces and liver were analyzed and in all cases most of the radioactivity observed was identified as unchanged DDE. The only metabolite identified was the phenolic derivative 1,1-dichloro-2-(4'-chlorophenyl)-2-(3"-hydroxy-4"-chlorophenyl)ethene, which was found in significant amounts only in the feces. No other potential metabolites derived from the oxidation of DDE were observed. The effect that pretreatment with DDE had on its own metabolism was to decrease the urinary excretion of DDE and to increase the hepatic levels. It appears from these results that any oxidative metabolism of DDE constitutes a very insignificant pathway in the mouse. It is also concluded that there is no significant change in the metabolism of DDE after prolonged exposure to the pesticide, and there is no indication for the metabolism of DDE to a reactive electrophilic species.