Comparative genotoxicity and nephrotoxicity studies of the two halogenated flame retardants tris(1,3-dichloro-2-propyl)phosphate and tris(2,3-dibromopropyl)phosphate.

Abstract

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.