Disposition of the flame retardant, tris (1,3-dichloro-2-propyl) phosphate, in the rat
Lynn, R.K.; Wong, K.; Garvie-Gould, C.; Kennish, J.M.
Drug Metabolism and Disposition the Biological Fate of Chemicals 9(5): 434-441
1981
ISSN/ISBN: 0090-9556 PMID: 6117442 Document Number: 5176
The metabolism, distribution, and excretion of the flame retardant, tris(1,3-dichloro-2-propyl) phosphate (TDCP), were studied in the rat. Five days after iv administration of 14C-TDCP, 92% of the administered radiolabel had been excreted in the urine (54%), feces (16%), and expired air (22% as 14CO2); 4% was recovered in the body. The major urinary, fecal, and biliary metabolite was identified as bis(1,3-dichloro-2-propyl) phosphate (BDCP). In disposition studies performed 5 days after iv administration of TDCP, 63% of the administered phosphate was recovered as BDCP. Other metabolites included the mono ester, 1,3-dichloro-2-propyl phosphate, and the bacterial mutagen, 1,3-dichloro-2-propanol. Less than 0.1% of the administered radiolabel was recovered as TDCP in the excreta. Kinetic and distribution studies demonstrated that TDCP was eliminated primarily by rapid metabolism whereas the slowly metabolized BDCP was eliminated by excretion. A major portion of the radiolabel excreted in bile underwent enterohepatic recirculation. In the presence of phenobarbital-induced liver homogenates, TDCP was mutagenic to Salmonella typhimurium (TA100), whereas its major metabolite, BDCP, and a minor metabolite, 1,3-dichloro-2-propyl phosphate, were nonmutagenic. Another metabolite, 1,3-dichloro-2-propanol, was mutagenic in the same system without liver homogenate activation.
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