Effect of polybrominated biphenyls on bromobenzene lethality in mice

Abstract

Polybrominated biphenyls (PBBs) are inducers of hepatic microsomal cytochrome P450 and P₁ 450 in rats and mice. The purpose of this study was to determine, in mice, the effect of PBBs on the lethality of the hepatotoxin bromobenzene. Female NMRI mice were administered a single ip injection of 150 mg/kg PBBs and other mice received phenobarbital (PB), 100 mg/kg daily for 3 days, or 3‐methylcholanthrene (MC), 20 mg/kg daily for 3 days. At 24 hr after PB or MC and 24, 48, and 96 hr after PBBs animals received 3,150 mg/kg bromobenzene ip (LD₈₅) and the time to death was recorded. Both PB and MC enhanced bromobenzene lethality and decreased the median time to death (LT₅₀) from 23 hr in controls to 4.6 and 10 hr, respectively. The bromobenzene LT₅₀ was decreased to 12, 3.7, and 6.4 hr at 24, 48, and 96 hr after pretreatment with PBBs. When bromobenzene was administered 24 or 48 hr after PBBs, or to PB‐treated animals, no change in the slope of the time‐lethality curve was observed, but the slope of the bromobenzene time‐lethality curve was significantly different from that for other treatment groups when determined 96 hr after PBBs or MC. Pretreatment of mice with PB or with PBBs 24 and 48 hr prior to a small dose of bromobenzene (150 mg/kg) enhanced the bromobenzene‐induced depletion of hepatic glutathione relative to the depletion noted with bromobenzene alone or after pretreatment with MC. The results suggest that the effects of PBBs on bromobenzene lethality change from PB‐like at early times after exposure to MC‐like at later times after exposure.