Brain distribution and fate of tris(2-chloroethyl) phosphate in Fischer 344 rats

Tris(2-chloroethyl) phosphate (TRCP) is a flame retardant that has a wide variety of industrial applications. In subchronic studies, oral administration of TRCP to rats and mice has been reported to produce dose-, sex-, and species-dependent lesions in the hippocampal brain region. The present investigation has examined the metabolism, elimination, and regional brain distribution of [14C]TRCP in male and female rats. [14C]TRCP was administered by gavage (0, 175, 350, or 700 mg/kg) and urine, feces, exhaled volatiles, CO2, and selected tissues were collected. Regional brain distribution of 14C was determined 2 hr following single doses of TRCP to male and female rats, and 24 hr after a single dose and the last of 14 daily doses of TRCP to female rats. Results of these studies indicate that TRCP is readily absorbed from the gastrointestinal tract, distributed to all brain regions, and that metabolism and excretion are nearly complete in 72 hr. Most of the TRCP-derived radioactivity was excreted in urine (up to 85%), with feces, volatiles, and CO2 combined accounting for less than 10% of the dose. Predominant signs of toxicity associated with TRCP administration (350 and 700 mg/kg) were seizures within 2 hr of treatment, when most of the TRCP-derived radioactivity present in brain tissue was in the form of the parent compound. Traces of inextractable 14C were detected at later times, but this material was not concentrated in brain relative to other tissues.(ABSTRACT TRUNCATED AT 250 WORDS)