A mechanistic study of the metabolism of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethane (DDD) to 2,2-bis(p-chlorophenyl)acetic acid (DDA).
The metabolism of [1-2H]-1,1-dichloro-2,2-bis(p-chlorophenyl)ethane (DDD-d) and [1-2H]-1-chloro-2,2-bis(p-chlorophenyl)ethene (DDMU-d) and their corresponding non-deuterated isomers DDD and DDMU was studied in female Swiss mice over a 96-hr period. The only detected urinary metabolite of DDD-d and DDD was 2,2-bis(p-chlorophenyl)acetic acid (DDA). Animals administered DDD excreted approximately 2.4-fold more DDA than those treated with DDD-d over the total collection period. The initial (0-36 hr) linear excretion rates of DDA for DDD and DDD-d were 17.1 and 5.5 micrograms/hr respectively. DDMU- and DDMU-d-treated mice excreted significant quantities of DDA, 2,2-bis(p-chlorophenyl)ethanol (DDOH) and 2,2-bis(p-chlorophenyl)ethanol (DDCHO). The only quantitative difference between DDMU and DDMU-d was that the non-deuterated isomer afforded approximately 1.8 times more DDA over the 96-hr collection. The initial (0-36 hr) linear excretion rates of DDMU and DDMU-d were 10.7 and 6.2 micrograms/hr respectively. The qualitative and quantitative results are consistent with DDD being metabolized to DDA via enzyme-mediated hydroxylation on the C-1 side chain carbon.
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D003634:DDT / Q000031:analogs & derivatives* / Q000378:metabolism; D003633:Dichlorodiphenyl Dichloroethylene / Q000031:analogs & derivatives / Q000378:metabolism; D003632:Dichlorodiphenyldichloroethane / Q000378:metabolism*; D004790:Enzyme Induction; D005260:Female; D006900:Hydroxylation; D051379:Mice
D003633:Dichlorodiphenyl Dichloroethylene; C000849:bis(p-chlorophenyl)acetic acid; D003577:Cytochrome P-450 Enzyme System; D003634:DDT; D003632:Dichlorodiphenyldichloroethane