EFFECTS OF EXPOSURE TO POLYBROMINATED BIPHENYLS ON URINARY STEROID METABOLIC PROFILES IN MAN AND RATS AS DETERMINED BY CAPILLARY GC AND GC/MS/DS

Polyhalogenated organic compounds have been shown to be potent inducers of mixed-function oxidases (MFOs) responsible for the metabolism of a wide range of compounds including steroid hormones. Since induction of MFO enzyme systems increases the metabolism of steroids and since alterations in steroid hormone secretion and metabolism may be reflected by changes in the urinary steroid metabolic profile, the effects of exposure to PBBs (potent MFO inducers) on steroid hormone excretion were investigated by examining urinary steroid metabolic profiles in exposed humans and in an experimental model (rats).;Advantages and disadvantages of using capillary column GC/FID and packed and capillary columns GC/MS/MSSMET (an off-line reverse library search analysis) were investigated. Capillary GC/FID was adequate for quantitative analysis of most steroids isolated from human urine. The major drawback to using capillary GC/FID was the time involved in analysis of the GC traces. Generation of human urinary steroid metabolic profiles by GC/MS/MSSMET was faster, but a major drawback was the relative insensitivity of this method compared to capillary column GC/FID.;Exposure of male and female rats to PBBs etc was observed to alter the urinary steroid metabolic profile in the corticosteroid region of the profile.;Urinary 6(beta)-hydroxycortisol, a well-characterized indicator hepatic cytochrome P-450 mixed function oxidase activity, was increased in the PBBs-exposed humans (non-smoking healthy adult male subjects with greater than 50 ppb PBBs in their serum). This effect was less than that seen following chronic exposure to high therapeutic doses of phenobarbital, but was similar in magnitude to increases in urinary 6(beta)-hydroxycortisol excretion reported for workers exposed to DDT. Certain other steroids, all but one of adrenal origin, appeared to be elevated in the PBBs exposed population.