Toxicokinetics of 2,2′,4,4′,5,5′‐hexabromobiphenyl in the rat

Abstract

Abstract The polybrominated biphenyl (PBB) constituents of Firemaster FF‐1 were determined using gas chromatography—electron capture (GC‐EC), The distribution and clearance of the major component of the mixture, 2,2’,4,4'5,5'‐hexabromobiphenyl (HxBBb), in rat whole blood and various tissues were determined at times up to 16 wk after a single dose of 10 mg/kg of Firemaster FF‐1 given orally. A three‐comparment linear mammiliary model obtained from blood data was compared to a first‐order linear n‐compartment mammiliary model derived through direct curve‐fitting to tissue and blood concentrations. It was found that most tissues analyzed naturally correspond to compartments derived through analysis of blood data alone. Comportment 1 (C1) consisted of whole blood, spleen, kidney, and heart; compartment 2 (C2) consisted of cerebral grey and white matter, cerebellum, lung, liver, and testes; and compartment 3 (C3) consisted of subcutaneous fat. Jejunum, a tissue that does not satisfy the assumptions of a mammiliary model, could not be classified. Simulations of the kinetics for varying body‐fat proportions were obtained for obese (250% average fat), average adult, and emaciated (25% average fat) rats. It was found that the half‐life predicted in emaciated rats, 60.5 d, was markedly decreased from the measured 145 d in average rats. Obese rats were predicted to have a HxBBb half‐life of 311 d. Simulations of daily dosing based on the predicted single‐dose kinetics for these rat body types showed that at the end of three wk, C1 levels in emaciated rats were 8 times higher than the predicted C1 levels in obese rats, while C2 levels were 5 times higher and C3 levels were 4 times higher. Levels in the first two compartments returned to similar levels in all three animal types within a wk following cessation of dosing. Within 49 d, C1 levels in the lean rats fell below those of the average rat. Although levels in C3 remained elevated in the lean rats for many wk, within 4.5 mo C3 levels fell below those of the average rat. These results suggest that studies of PBB toxicity in man based upon blood and fat levels should take into account not only the amount of PBB ingested but also the pattern of ingestion, the individual body types, and the time when PBB levels were measured.