Nephrotoxicity of the flame retardant,tris(2,3-dibromopropyl) phosphate,and its metabolites

A single ip injection of the carcinogenic flame retardant, tris(2,3-dibromopropyl) phosphate (TRIS-BP), when administered to male Sprague-Dawley rats, caused polyuric acute renal failure with tubular necrosis involving the late proximal tubule. Glomerular filtration rate and in vitro transport of the organic acid, para-aminohippurate and the organic base, N-[¹⁴C]methylnicotinamide, were depressed. An approximately equimolar dose of the TRIS-BP metabolite, bis(2,3-dibromopropyl) phosphate (BIS-BP), caused significantly more severe renal failure. In contrast, the metabolite 2,3-dibromopropanol (BP) was nonnephrotoxic. These data suggest that TRIS-BP nephrotoxicity is mediated via its metabolite BIS-BP.