Comparative genotoxicity and nephrotoxicity studies of the two halogenated flame retardants tris(1,3-dichloro-2-propyl)phosphate and tris(2,3-dibromopropyl)phosphate.
Tris(1,3-dichloro-2-propyl)phosphate (Tris-CP) was metabolized to products which were mutagenic for Salmonella typhimurium TA100 in the presence of liver microsomes from phenobarbital (PB)-pretreated rats and NADPH. Effects of various inhibitors and inducers of cytochrome P-450 on Tris-CP mutagenicity were in accordance with PB-inducible forms of this enzyme system being responsible for the formation of mutagenic product(s). A comparison was made between the toxic potential of the two halogenated flame retardants Tris-CP and tris(2,3-dibromopropyl)phosphate (Tris-BP) in 5 in vitro tests. Tris-CP was much less potent than Tris-BP with respect to bacterial (Salmonella/microsome or Salmonella/hepatocyte assay) and mammalian (V79 cells) mutagenicity, as well as DNA repair synthesis in hepatocytes. On the other hand, Tris-CP and Tris-BP were both equally effective in transforming Syrian hamster embryo cells in vitro. Tris-CP was not nephrotoxic to rats after a single dose of 500 mg/kg intraperitoneally, whereas Tris-BP caused extensive tubular necrosis accompanied by elevated levels of plasma urea and creatinine.
D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004260:DNA Repair / Q000187:drug effects; D005411:Flame Retardants / Q000633:toxicity*; D066298:In Vitro Techniques; D007674:Kidney Diseases / Q000139:chemically induced*; D008647:Mesocricetus; D009152:Mutagenicity Tests; D009153:Mutagens; D010755:Organophosphates / Q000633:toxicity*; D009943:Organophosphorus Compounds / Q000633:toxicity*; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000235:genetics; D013347:Subcellular Fractions / Q000378:metabolism
D005411:Flame Retardants; D009153:Mutagens; D010755:Organophosphates; D009943:Organophosphorus Compounds; C012085:tris(2,3-dibromopropyl)phosphate; C016805:tris(1,3-dichloro-2-propyl)phosphate