Interindividual variation in the levels of certain urinary polycyclic aromatic hydrocarbon metabolites following medicinal exposure to coal tar ointment

Determination of human exposure to polycyclic aromatic hydrocarbons PAHs is challenging because they are so broadly distributed in the environment and often difficult to quantitate using questionnaire methods. To enhance the ability to non invasively evaluate markers of both internal dose and biologically effective dose we have developed methods for the identification and quantitation of 1 hydroxypyrene-glucuronide and r 7, t 8, t 9, c 10 tetrahydroxy 7,8,9,10 tetrahydrobenzo a pyrene BP 7,10 8,9 tetrol in human urine. In the current study we applied these assays to urine samples collected from 43 hospitalized psoriasis patients treated 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 1 not detected to 124 fmol mumol-1 creatinine. In contrast, BP 7,10 8,9 tetrol was detected in only 4 of 39 10 controls, range 1 to 20.6 fmol mumol-1 creatinine p = 0.0006, Wilcoxon rank sum test. A second, more polar PAH metabolite, identified as 1 hydroxypyrene-glucuronide, was present in all urine samples. Mean 1 hydroxypyreneglucuronide levels were 40.96 72.62 pmol mumol-1 creatinine in patients and 0.38 0.32 pmol mumol-1 creatinine in control subjects p 0.0001 . The ratio of urinary levels of BP 7,10 8,9 tetrol to 1 hydroxypyrene-glucuronide was examined in the coal tar treated patients. This ratio was found to vary by approximately 6000 fold. This parameter cannot be explained by measurement error because the coefficients of variation for these assays are only 12 and 10 respectively, nor can it be explained by use of different coal tar products. These results provide further evidence that substantial interindividual variation in activation of benzo a pyrene and other PAHs exists, which may have implications for disease risk.