Toxicokinetics of [14C]-saligenin cyclic-o-tolyl phosphate in anesthetized male F-344 rats.
Saligenin cyclic o-tolyl phosphate (SCOTP) has been proposed as the active metabolite of tri-o-cresyl phosphate (TOCP), a neurotoxic organophosphate. TOCP is also toxic to the testis and SCOTP mimics some of this toxicity. The stability of SCOTP in vivo and its uptake by selected tissues has been measured. Total radioactivity and SCOTP-associated radioactivity were determined in male F-344 rats treated i.v. with 1 mg of [14C]-SCOTP/kg. The half-life of SCOTP in blood was 8.0 +/- 1.1 min. Testes, brain, and muscle had lower concentrations of [14C]-SCOTP-derived radioactivity than blood. Liver and kidney had higher concentrations of radioactivity than blood. HPLC analysis of liver, kidney, testes, and blood extracts showed that 2.8, 48, 11, and 18%, respectively, of the radioactivity present at 5 min was SCOTP. The amount of SCOTP declined rapidly, and at 30 min SCOTP could be detected only in kidney. It appears that SCOTP, although reactive, has sufficient stability to be transported from organ to organ. There is no evidence, however, of active uptake of SCOTP from blood by the testes. Evidence was obtained that SCOTP may act as an alkylating agent.
Burka
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National Toxicology Program, National Institute of Environmental Health Sciences Research, Triangle Park, North Carolina 27709.
Chapin
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D000111:Acetylcysteine / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D008297:Male; D009943:Organophosphorus Compounds / Q000493:pharmacokinetics / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D013056:Spectrophotometry, Ultraviolet; D013737:Testis / Q000378:metabolism; D014018:Tissue Distribution; D014317:Tritolyl Phosphates / Q000493:pharmacokinetics / Q000633:toxicity*
D009943:Organophosphorus Compounds; D014317:Tritolyl Phosphates; C000516:2-(2-cresyl)-4H-1-3-2-benzodioxaphosphorin-2-oxide; D000111:Acetylcysteine; C025541:tri-o-cresyl phosphate