Studies of chemical metabolism and disposition are designed to provide both applied knowledge of the fate of chemicals in intact animals in support of toxicity tests conducted by the National Toxicology Program and basic knowledge of mechanisms of chemical toxicity. These studies are designed to determine the mechanisms of chemical toxicity. These studies are designed to determine the absorption, tissue distribution, metabolism and clearance of chemicals and the effect of such factors as dose and route of exposure on each of these parameters. Tris(2-chloroethyl)phosphate (TRCP), a flame retardant plasticizer used widely in industrial and consumer products, has been demonstrated to cause an unusual lesion in the hippocampus of rats administered this compound orally. The hippocampal lesion was more pronounced in female than male rats and was not observed in mice. Studies to characterize the fate of TRCP in male and female rats and mice have established that this compound is readily absorbed and distributed systemically, that metabolism is rapid and that the major metabolite is somewhat unique. The major metabolite has been identified as bis(2-chloroethyl) carboxymethyl phosphate and the second major metabolite has been identified as bis(2-chloroethyl) hydrogen phosphate. Neither of these metabolites is thought to account for the neurotoxicity of TRCP, rather it appears that the greater sensitivity of female rats may be due to the fact they clear this compound more slowly in the first few minutes following dosing. In a study of the fate of oxymetholone (OXM), a synthetic androgen, it was determined that this compound is absorbed from the gastrointestinal tract at a moderate rate to result in peak blood levels 2 to 4 hr. post oral dosing. It was also determined that OXM is metabolized and eliminated in bile, 35% in 7 hr. and that 80% of the dose eliminated in feces in 72 hr.
