The irradiation of 2,4,5,2',4',5'-hexabromobiphenyl (2,4,5-HBB) by ultraviolet light created a mixture of lower brominated polybrominated biphenyl (PBB) congeners. Three photoproducts, 2,4,5,3',4'-pentabromobiphenyl (-PBB), 2,4,5,2',5'-PBB, and 3,4,3',4'-tetrabromobiphenyl (3,4-TBB), as well as 2,4,5-HBB and the photolyzed 2,4,5-HBB mixture, were administered to rats as a single ip injection (90 mg/kg, except 3,4-TBB, which was given at 2 mg/kg) 2 weeks before sacrifice. All treatments except 3,4-TBB induced NADPH-cytochrome P-450 reductase and aminopyrine-N-demethylase activities while all treatments except 2,4,5-HBB induced ethoxyresorufin-O-deethylase and UDP-glucuronosyltransferase activities. Thymus to body weight and spleen to body weight ratios were unchanged compared to controls for all treatments whereas an increase in the liver weights was observed for all treatment groups. Histologic examination revealed that the photolyzed 2,4,5-HBB mixture caused moderate to severe hepatocyte enlargement. Results of tissue analysis for the pure PBB congeners indicated that 2,4,5,2',5'-PBB and 3,4-TBB were metabolized in vivo and this was confirmed by in vitro metabolism studies. The results revealed that the photolyzed 2,4,5-HBB mixture caused a mixed-type induction of hepatic drug-metabolizing enzymes. This is most likely due to the effect of 2,4,5-HBB and toxic congeners formed during the irradiation of 2,4,5-HBB. 2,4,5,3',4'-PBB, which is toxic and apparently not metabolized, is believed to be the major congener contributing to the increased toxicity of the photolyzed 2,4,5-HBB mixture since 3,4-TBB was metabolized and appeared not to be as potent as inducer of aryl hydrocarbon hydroxylase activity.

The in vitro metabolism of polybrominated biphenyl (PBB) congeners by cytochrome P-450-dependent monooxygenases was investigated using hepatic microsomes isolated from immature male rats pretreated with 3-methylcholanthrene (MC) or phenobarbital (PB). MC pretreatment increased the NADPH-dependent microsomal metabolism of pure PBB congeners which possessed adjacent nonhalogenated ortho and meta carbons on at least one ring. 4,4'-Dibromobiphenyl (-DBB) was metabolized at the fastest rate, followed by 3,4,4'-tribromobiphenyl, 3,4,3',4'-tetrabromobiphenyl (-TBB), 2,3,3',4'-TBB, 2,5,3',4'-TBB, and 2,4,2',5'-TBB in decreasing order. It appeared that further bromination prevented metabolism since 2,4,5,3',4'-pentabromobiphenyl (-PBB), 2,3,4,2',4',5'-hexabromobiphenyl (-HBB), and 2,3,4,5,3'.4'-HBB were not metabolized although they possess adjacent nonhalogenated ortho and meta carbons. PB pretreatment increased in vitro rat hepatic microsomal metabolism of PBB congeners which possessed adjacent nonhalogenated meta and para carbons on at least one ring. 2,2'-DBB was metabolized at the fastest rate, followed by 2,4,2',5'-TBB, 2,5,2',5'-TBB, 2,3,3',4'-TBB, 2,5,3',4'-TBB, and 2,4,5,2',5'-PBB in decreasing order. The results suggest that the rates of metabolism of PBB congeners are dependent upon the positions of bromine and the form of cytochrome P-450 induced. In vitro rates of metabolism of 3,4,3',4'-TBB using hepatic microsomes isolated from rats pretreated with either 3,4,5,3',4',5'-HBB or 3,4,3',4'-TBB were also investigated. There was good correlation between the rates of 3,4,3',4'-TBB metabolism, induction of microsomal ethoxyresorufin-O-deethylase activity, and specific content of MC-inducible cytochrome P-450 (P-450 beta NF-B). The results suggest that the isozyme P-450 beta NF-B is responsible for the metabolism of 3,4,3',4'-TBB.

2,4,5,2′,4′,5′-Hexabromobiphenyl (2,4,5-HBB) was irradiated with ultraviolet light in hexane with stirring, and photolysis was monitored by gas chromatography (GC). 2,4,5-HBB decomposed at an average rate of 0.66 ± 0.02 μmol/min and the reaction appeared zero order from 0.159 to 1.59 mm 2,4,5-HBB. Several polybrominated biphenyl (PBB) congeners were identified as photoproducts of 2,4,5-HBB. 2,4,5,2′,5′-Pentabromobiphenyl (-PBB), formed by para debromination, accumulated at a higher rate than did 2,4,5,3′,4′-PBB, formed by ortho debromination. 2,4,5,2′,4′-PBB was formed by meta debromination. 3,4,3′,4′-Tetrabromobiphenyl (-TBB) was found as a secondary photoproduct, formed by ortho debromination of 2,4,5,3′,4′-PBB. 2,5,2′,5′-TBB and 2,4,2′,5′-TBB were formed by debromination of 2,4,5,2′,5′-PBB para and meta, respectively. 2,5,3′,4′-TBB could be formed by either ortho debromination of 2,4,5,2′,5′-PBB or para debromination of 2,4,5,3′,4′-PBB. Rates of degradation and accumulation of the penta- and tetrabrominated biphenyls were also studied. The ultraviolet spectra of the 2,4,5-HBB photolysis mixture, as well as the purified components, were studied and are also reported.

Immature male rats were given a single equimolar dose (21.3 mumol/kg body wt) of 3,4,5,3',4',5'-hexabromobiphenyl (HBB) or 3,4,3',4'-tetrabromobiphenyl (TBB) and terminated at various times up to 14 days after treatment. Hepatic microsomal aryl hydrocarbon hydroxylase (AHH) activity for the TBB treatment group was maximal at Day 2 and then steadily decreased, whereas this activity was induced in 1 day and remained high for the HBB treatment group. Tissue concentrations of HBB appeared to be unchanged over time whereas tissue concentrations of TBB decreased in a biphasic manner. Rates of in vitro metabolism of TBB with hepatic microsomes from TBB-treated animals showed a similar time-course relationship to AHH induction. HBB caused moderate to severe hepatic changes while TBB-treated rats had only mild hepatic changes. The relative binding of TBB by the hepatic receptor for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was about 10 times that of HBB. The results suggest that even though the receptor-binding affinities imply that TBB should be more toxic than HBB, it is less toxic than HBB because it is metabolized. Studies with the chlorinated analogs of TBB and HBB suggested that PCB behave similarly. These results also suggest that receptor binding and AHH induction do not accurately reflect toxicity for polyhalogenated aromatic hydrocarbons which are metabolized, presumably because continued occupation of the receptor and persistent induction of some enzyme activity are required for toxicity.