Disposition and nephrotoxicity of hexachloro-1,3-butadiene

Hexachloro-1,3-butadiene (HCBD) administration to rats results in impaired kidney function. The time course of nephrotoxicity and disposition of HCBD were examined. Within 4 h after HCBD (300 mg/kg, i.p.) compromised kidney function was found as decreased urine osmolality, glomerular filtration rate (GFR) and drug excretion. At 24 h elevated blood urea nitrogen (BUN) was found. However, no definitive signs of hepatotoxicity were observed up to 48 h after HCBD. Control ralts excreted 40% of tracer dose (0.1 mg/kg, i.p.) of [14C]HCBD in feces and 30% in urine in 48 h. Rats with HCBD-induced nephrotoxicity excreted much less, 7% in feces and 6% in urine. Aliquots of these samples were extracted with hexane. All of 14C in bile and 87% of that in urine was water soluble, indicating that HCBD was biotransformed into polar metabolites.