Developmental neurotoxicity and immunotoxicity of 2,4,6-tribromophenol in Wistar rats

Pregnant Wistar rats were exposed to 2,4,6-Tribromophenol (TBP) by whole body inhalation (0, 0.03, 0.1, 0.3, 1.0 mg/m3, 24 hr/day, 7 days/weeks, from day 1 to 21 of gestation). Significant decreases in orientation reactions were noted at concentrations of 1.0 mg/m3 (p < 0.05) in the open field test. Nonsignificant trends (p > 0.05) toward decreased horizontal movement and emotionality in the open field and increased electrical impulse skin pain threshold (SPT) were observed. No significant exposure-related differences in the nonspecific immunological status (phagocytosis and blood anti-microbe activity) of pregnant rats were seen after the exposure. Preimplantation and postimplantation embryo losses were significantly increased in a dose-dependent manner and were seen in all treated groups except the lowest concentration (0.03 mg/m3) group. Signs of retarded fetal skeletal development and increased frequencies of visceral abnormalities were found at concentrations of 0.1 and 1.0 mg/m3. Significant effects were found for lower incisor eruption and ear unfolding at a concentration of 0.3 mg/m3. The grooming behavior of 30-day old male progeny was significantly less than control in all experimental groups. Grooming behavior in female subjects exposed to a concentration of 0.3 mg/m3 and emotionality in subjects exposed to a concentration of 1 mg/m3 were decreased significantly. At 60 days of age emotional reactions were significantly decreased in female subjects from the 0.03, 0.3 and 1.0 mg/m3 groups. SPT was significantly increased in the 1 mg/m3 group for both male and female pups. Thus, evidence of CNS depression influence of TBP both in maternal and offspring groups was found. The NOEL (No Observed Effect Level) for developmental neurotoxicity is thus < 0.03 mg/m3, and the NOEL for maternal neurotoxicity is 0.3 mg/m3. These results suggest that exposure to TBP for 24 hr/day throughout gestation may cause developmental neurotoxicity, embryotoxicity and fetotoxicity, but not immunotoxicity.