Occupational exposure to polycyclic aromatic hydrocarbons in German industries: association between exogenous exposure and urinary metabolites and its modulation by enzyme polymorphisms.
ABSTRACT A cross-sectional study was conducted in 170 German workers exposed to polycyclic aromatic hydrocarbons (PAH) to investigate the role of 11 polymorphisms of CYP1A1, CYP1A2, CYP1B1, CYP3A4, EPHX1, GSTM1, GSTT1, and GSTP1 in the association between occupational exposure to PAH and urinary PAH metabolites. Polymorphisms were genotyped with real-time PCR. Exposure to 16 PAH was measured by personal air sampling. Urinary concentrations of 1-hydroxypyrene (1-OHP) and the sum of 1-, 2+9-, 3-, and 4-hydroxyphenanthrenes (OHPhe) were determined post-shift. Urinary 1-OHP and OHPhe correlated significantly with exogenous pyrene (Spearman r=0.52, p<0.0001) and phenanthrene (Spearman r=0.72, p<0.0001), respectively. ANCOVA was applied to investigate potential predictors of the metabolite levels. Current smoking and type of industry turned out to be predictors of 1-OHP but not of OHPhe. CYP1A1 3801TC carriers showed 1.6-fold higher OHPhe levels than 3801TT carriers (p=0.03). EPHX1 113HH was associated with higher and 139RR with lower metabolite levels when compared with the corresponding reference genotypes (113YY; 139HH). In comparison to GSTP1 114AA, carriers of the V allele had 1.5-fold higher 1-OHP (p=0.03) and 2-fold higher OHPhe concentrations (p=0.001). OHPhe turned out to be also a suitable biomarker of occupational PAH exposure. The association with ambient PAH exposure and the influence of polymorphisms was more pronounced for OHPhe.
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ABSTRACT: Occupational exposure limits for carcinogens are increasingly based on excess lifetime risks of cancer. Acceptable limits in some countries in Europe are set at 4/1,000 (= highest tolerable risk level) and 4/100,000 (= acceptable risk level) based on 40 year working exposure for the occupational population. When an exposure metric is used that is fairly new, epidemiology does not offer dose-response data that is needed for the derivation of a science based limit value. The urinary concentration of 1-hydroxypyrene is a fairly new bioindicator of exposure to Polycyclic Aromatic Hydrocarbons (PAH). Nowadays, measurements of 1-hydroxypyrene in urine are routinely applied to control industrial exposure to PAH as present in coke ovens and primary aluminium production and to control exposure of professionals when handling coal tar derived products. Due to lacking dose-response data from epidemiological studies, a cancer risk based limit of 1-hydroxypyrene in urine cannot be derived. An alternative derivation procedure is proposed for the limit value that can be used as guidance for the intermediate period. For the period in-between, it is suggested to take the ‘no observed genotoxic effect level’ (= NOGEL) in PAH-exposed workers as the point-of-departure for setting the limit value. The genotoxic endpoints are genotoxic effects in white blood cells of PAH-exposed workers (chromosomal aberrations, sister chromatid exchanges, micronuclei, comet assay, DNA adducts). In order to assess the point-of-departure for limit setting, cross-sectional studies were searched for that report on the response of early genotoxic effects in white blood cells of workers that could be related to the degree of PAH-exposure (expressed as 1-hydroxypyrene in urine). Nine cross-sectional studies were traced that met these requirements. From each study, the concentration of 1-hydroxypyrene in end-of-shift urine samples was determined, at which no genotoxic effects was found. From 4 out of 9 studies a no-observed genotoxic effect level could be derived, the lowest level was 1.0 μmol/mol creatinine. This limit level is recommended as a state-of-the-art guidance, valid when the PAH-profile in the work environment is similar to that of coke oven with a typical pyrene/BaP ratio of 2.5. For work environments with a deviating PAH-profile an adjustment procedure with the pyrene/BaP ratio is suggested.Toxicology Letters 12/2014; · 3.36 Impact Factor
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ABSTRACT: In this study we investigated the clinico-chemical parameters and the level of exposure of brick kiln workers to polycyclic aromatic hydrocarbons (PAHs) in Punjab (Pakistan). The brick kiln workers and a non-occupationally exposed group were recruited for comparative analysis of urinary biomarkers of PAH exposure (i.e. 1-hydroxypyrene (1-OHPyr), α-naphthol and β-naphthol) and blood level of superoxide dismutase (SOD), as a biomarker of oxidative stress and other hematologic parameters. Questionnaires were used to document information on socio-demographic characteristics of all the subjects. The analysis of urinary biomarkers showed higher median concentrations of 1-OHPyr, and α- and β-naphthols in brick kiln workers (1.53, 3.65 and 1.53μmol/mol-Cr, respectively) than non-occupationally exposed group (0.62, 0.64 and 0.66μmol/mol-Cr, respectively). The 1-OHPyr in brick kiln workers was above the occupational exposure level. Among the clinical parameters of brick kiln workers, hemoglobin (Hb) and red blood cells (RBCs) were very low and closely associate with 1-OHPyr and β-naphthol. Additionally, the white blood cells (WBCs) and superoxide dismutase (SOD) were also elevated in brick kiln workers, which suggested inflammatory symptoms and high oxidative stress. The results show that regardless of possibly being affected by the poor nutrition, the anemic state and hematological changes observed in brick kiln workers may be associated with their exposure to smoke present in the environment of brick kilns.Science of The Total Environment 05/2014; 490:521–527. · 3.16 Impact Factor
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ABSTRACT: Genetic polymorphisms of xenobiotic metabolizing enzymes have been associated with cancer risk. We evaluated the influences of genetic polymorphisms of polycyclic aromatic hydrocarbon (PAH) metabolizing enzymes on urinary 1-hydroxypyrene (1-OHP) excretion in Turkish coke oven workers. Urinary 1-OHP was analyzed by HPLC after enzymatic hydrolysis. Lymphocyte DNA was used for PCR-based genotyping of cytochrome P450 (CYP) polymorphisms (CYP1A1 and CYP1B1) and glutathione S-transferases (GST) polymorphisms (GSTM1, GSTT1 and GSTP1). The mean urinary 1-OHP levels of coke oven workers were significantly higher than that of controls. No significant difference was detected in the mean urinary 1-OHP levels of smokers and non-smokers either for coke oven workers or controls. Genetic polymorphisms of the CYPs and GSTs studied had no significant influence on 1-OHP excretion in coke oven workers, but in the control group the urinary 1-OHP levels of individuals carrying the GSTT1- genotype were significantly higher than those of individuals carrying GSTT1+ genotype. The duration of occupational exposure and metabolic genotype for GSTT1 were the significant predictors of urinary 1-OHP levels. The control individuals carrying combined GSTM1-/GSTT1- genotypes also had significantly higher levels of urinary 1-OHP than those of individuals carrying GSTM1+/GSTTI+, GSTM1-/GSTT1+, and GSTM1+/GSTT1- genotypes. These results indicate that urinary 1-OHP is a sensitive indicator of recent human exposure to PAHs and that genetic polymorphism of GSTT1 may also to some extent reflect the interindividual variation in susceptibility to PAHs only at low PAH exposure.Genetics and Molecular Biology 12/2006; 30(3):511-519. · 0.88 Impact Factor