Unexpected nephrotoxicity induced by tetrabromobisphenol A in newborn rats

The repeated dose toxicity of tetrabromobisphenol A (TBBPA), a flame retardant, was examined in male and female newborn rats given TBBPA orally at 0, 40, 200, or 600 mg/kg per day for 18 days from 4 days of age until weaning at 21 days of age. Half the rats in each dose group were sacrificed for a full gross necropsy and a histopathology on the organs and the tissues at 22 days of age and the remaining rats were reared without any treatment from post-weaning until 84 days of age to examine the recovery and the delayed occurrence of toxic effects. Treatment with 200 or 600 mg/kg TBBPA-induced nephrotoxicity characterized by the formation of polycystic lesions, and some deaths occurred in the 600 mg/kg group. There was no gender difference of nephrotoxicity and there were no other critical toxicities. At 85 days of age, nephrotoxic lesions were still present in the 200 and 600 mg/kg groups, but no abnormalities indicating delayed occurrence of toxic effects were found in the treated groups. In order to investigate the specificity of the nephrotoxicity induced by TBBPA in newborn rats, TBBPA was given to male and female young rats (5 weeks old) by oral administration at 0, 2000, or 6000 mg/kg per day for 18 days. The kidneys showed no histopathological changes even at the high dose. These results clearly indicate that the nephrotoxicity of TBBPA is specific for newborn rats although the toxic dose level was relatively high. To gain insight into the possible effects on human infants, the mechanism of this unexpected nephrotoxicity of TBBPA in newborn rats should be examined. (C) 2004 Elsevier Ireland Ltd. All rights reserved.