Metabolites of polycyclic aromatic hydrocarbons in urine of exposed workers

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Abstract
During the last decade, the work at our department has been focused on the development of exposure tests for mutagens and carcinogens. The thioether assay and the urinary mutagenicity assay are well‐known examples. However, the normal range of occupational exposure to polycyclic aromatic hydrocarbons (PAH) is too low for these tests. Therefore, an HPLC method was developed to determine hydroxylated‐PAH in urine at the nmol/1 level. Urine specimens of a reference population and of people exposed to PAH were assayed to test the applicability in practice. A trace amount of 1‐hydroxypyrene occurred in referents’ urine. The level in urine of smoking referents was not significantly increased compared to the level of non‐smoking referents. After therapeutical treatment of dermatological patients with a coal tar ointment, the level of 1‐hydroxypyrene in urine was 100–1000 times the background level and 3‐hydroxybenzo(a)pyrene was detectable. Three workers of a creosote impregnating plant showed a highly increased level of 1‐hydroxypyrene in urine. The time course in the urinary excretion of the pyrene metabolite over a period of 10 days indicated an accumulation during the working week. The urinary level of 1‐hydroxypyrene of workers of a coal tar distillation plant highly exceeded the upper 95‐percentile of the smoking reference population. The representativeness of 1‐hydroxypyrene for the biological potency of PAH‐mixtures in coal tar was studied in vivo and in vitro. In the urine of rats, treated with coal tar solutions on the dorsal skin, a significant correlation was found between urinary 1‐hydroxypyrene and urinary mutagenicity. The mutagenicity of coal tar using metabolic activation systems of human origin in vitro correlated highly with the simultaneously determined formation of 1‐hydroxypyrene. The data suggest that the urinary 1‐hydroxypyrene is a sensitive and specific marker for the assessment of exposure to PAH from tarry products.

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