INTERINDIVIDUAL VARIATION IN THE LEVELS OF CERTAIN URINARY POLYCYCLICAROMATIC HYDROCARBON METABOLITES FOLLOWING MEDICINAL EXPOSURE TO COAL-TAR OINTMENT

Determination of human exposure to polycyclic aromatic hydrocarbons (P AHs) is challenging because they are so broadly distributed in the env ironment and often difficult to quantitate using questionnaire methods . To enhance the ability to non-invasively evaluate markers of both in ternal dose and biologically effective dose we have developed methods for the identification and quantitation of l-hydroxypyrene-glucuronide and ,t-9,c-10-tetrahydroxy-7,8,9,1O-tetrahydrobenzo[a] (BP-7,10/8,9-t etrol) in human urine. In the current study we applied these assays to urine samples collected from 43 hospitalized psoriasis patients treat ed with coal tar medication and 39 non-treated volunteer controls, BP- 7,10/8,9-tetrol was detected in 20 of 43 (47%) patients, ranging from less than or equal to 1 (not detected) to 124 fmol mu mol(-1) creatini ne. In contrast, BP-7,10/8,9-tetrol was detected in only 4 of 39 (10%) controls, range less than or equal to 1 to 20.6 fmol mu mol(-1) creat inine (p = 0.0006, Wilcoxon rank sum test). A second, more polar PAH m etabolite, identified as 1-hydroxypyrene-glucuronide, was present in a ll urine samples, Mean 1-hydroxypyrene-glucuronide levels were 40.96+/ -72.62 pmol mu mol(-1) creatinine in patients and 0.38+/-0.32 pmol mu mol(-1) creatinine in control subjects (p less than or equal to 0.0001 ). The ratio of urinary levels of BP-7,10/8,9-tetrol to l-hydroxypyren e-glucuronide was examined in the coal tar-treated patients, This rati o was found to vary by approximately 6000-fold, This parameter cannot be explained by measurement error because the coefficients of variatio n for these assays are only 12 and 10% respectively, nor can it be exp lained by use of different coal tar products. These results provide fu rther evidence that substantial interindividual variation in activatio n of benzo[a]pyrene and other PAHs exists, which may have implications for disease risk.