title: Benchmark guideline for urinary 1-hydroxypyrene as biomarker of occupational exposure to polycyclic aromatic hydrocarbons.
abstract: Many individual polycyclic aromatic hydrocarbons (PAH) are genotoxic carcinogens. One of the parent PAH, pyrene, undergoes simple metabolism to 1-hydroxypyrene. 1-Hydroxypyrene and its glucuronide are excreted in urine. Biological monitoring of exposure to PAH has rapidly been expanded since urinary 1-hydroxypyrene was suggested as a biological index of dose of pyrene. Since pyrene is always present in PAH mixtures, the biological indicator is not only an indicator of uptake of pyrene, but also an indirect indicator of all PAH. At present, several hundreds of papers reporting on urinary concentrations of 1-hydroxypyrene in workers' urine are available. It appeared that urinary 1-hydroxypyrene is a sound biomarker and that the analytical method is robust and non-laborious. Since epidemiological studies of cancer mortality related to long-term average urinary 1-hydroxypyrene concentration are lacking, a sound health-based limit value of 1-hydroxypyrene in urine cannot be set as yet. Since PAH exposure is widespread and the dermal uptake is substantial among exposed workers, an attempt was made to propose a three-level benchmark guideline for urinary 1-hydroxypyrene. The reference value as a 95th percentile in non-occupational exposed controls is 0.24 micromol mol(-1) creatinine and 0.76 micromol mol(-1) creatinine for non-smokers and smokers, respectively. This is the first level of the benchmark guideline. A no-biological-effect-level of 1-hydroxypyrene in urine of exposed workers was found at 1.4 micromol mol(-1) creatinine. It is the lowest reported level at which no genotoxic effects were found and therefore the estimate for the second level of the benchmark guideline. In two types of industry, coke ovens and primary aluminium production, the regression of airborne PAH concentrations and urinary 1-hydroxypyrene concentrations in exposed workers has been studied. The correlation of airborne concentrations and urinary 1-hydroxypyrene in urine of workers from coke ovens and in the primary aluminium industry was used to estimate the level of urinary 1-hydroxypyrene equal to the present occupational exposure limit (OEL) of PAH. The concentration of 1-hydroxypyrene in urine equal to the OEL is 2.3 micromol mol(-1) creatinine and 4.9 micromol mol(-1) creatinine, respectively, in these two industries. These latter values present the third level of the benchmark guideline.
authors.affiliation: IndusTox Consult, PO Box 31070, NL-6503 CB, Nijmegen, The Netherlands. frans.jongeneelen@industox.nl
authors.forename: F J
authors.initials: FJ
authors.lastname: Jongeneelen
mesh_terms: D019985:Benchmarking / Q000592:standards*; D015415:Biomarkers / Q000652:urine; D004784:Environmental Monitoring / Q000379:methods*; D006801:Humans; D009153:Mutagens / Q000378:metabolism*; D016273:Occupational Exposure / Q000592:standards*; D011084:Polycyclic Aromatic Hydrocarbons / Q000652:urine*; D017410:Practice Guidelines as Topic; D011721:Pyrenes / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D009153:Mutagens; D011084:Polycyclic Aromatic Hydrocarbons; D011721:Pyrenes; C033146:1-hydroxypyrene