Metabolism of a DDT metabolite via a chloroepoxide

Abstract

The 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethene (DDT) metabolic intermediate 1-chloro-2,2-bis(p-chlorophenyl)ethene (DDMU) is partially metabolized in vivo by mice to 2-hydroxy-2,2-bis(p-chlorophenyl)acetic acid (alpha OH-DDA) and other metabolites which are excreted in urine. The subsequent DDT metabolic intermediates 1-chloro-2,2-bis(p-chlorophenyl)ethane (DDMS) and 1,1-bis(p-chlorophenyl)ethene (DDNU) are metabolized to alpha OH-DDA to a much lesser extent. These results imply that DDMU may be metabolized via an alpha-chloroepoxide. The authentic DDMU-epoxide, which after oral administration is excreted as alpha OH-DDA, is mutagenic in the Ames assay, and thermally rearranges rapidly to the corresponding alpha-chloroaldehyde, 2,2-bis(p-chlorophenyl)-2-chloroacetaldehyde (alpha Cl-DDCHO). As expected alpha Cl-DDCHO yielded the same urinary metabolites as DDMU-epoxide. This suggested metabolic pathway for DDMU via a chloroepoxide intermediate may account for the tumorigenicity of DDT in mice.