Urinary Excretion Of 1-hydroxypyrene Research Articles

Association between a urinary biomarker for exposure to PAH and blood level of the acute phase protein serum amyloid A in coke oven workers

BackgroundCoke oven workers are exposed to both free and particle bound PAH. Through this exposure, the workers may be at increased risk of cardiovascular diseases. Systemic levels of acute phase response proteins have been linked to cardiovascular disease in epidemiological studies, suggesting it as a marker of these conditions. The aim of this study was to assess whether there was association between PAH exposure and the blood level of the acute phase inflammatory response marker serum amyloid A (SAA) in coke oven workers.MethodsA total of 87 male Polish coke oven workers from two different plants comprised the study population. Exposure was assessed by means of the individual post-shift urinary excretion of 1-hydroxypyrene, as internal dose of short-term PAH exposure, and by anti-benzo[a]pyrene diolepoxide (anti-B[a]PDE)-DNA), as a biomarker of long-term PAH exposure. Blood levels of acute phase proteins SAA and CRP were measured by immunoassay. C-reactive protein (CRP) levels were included to adjust for baseline levels of SAA.ResultsMultiple linear regression showed that the major determinants of increased SAA levels were urinary 1-hydroxypyrene (beta = 0.56, p = 0.030) and serum CRP levels (beta = 7.08; p < 0.0001) whereas anti-B[a]PDE-DNA, the GSTM1 detoxifying genotype, diet, and smoking were not associated with SAA levels.ConclusionsUrinary 1-hydroxypyrene as biomarker of short-term PAH exposure and serum levels of CRP were predictive of serum levels of SAA in coke oven workers. Our data suggest that exposure of coke oven workers to PAH can lead to increased systemic acute response and therefore potentially increased risk of cardiovascular disease.

Biological monitoring of exposure to polycyclic aromatic hydrocarbons and to metallic elements in Italian Navy workers operating near the industrial area in Taranto (South Italy).

Objectives:To assess, by means of biological monitoring, exposure to polycyclic aromatic hydrocarbons (PAHs) and to metallic elements in Italian Navy workers operating near the industrial area in Taranto, and thereby estimate the health risk.Methods:A total of 450 workers in the Italian Navy were examined; they had office type jobs, and 150 of them worked near the industrial area in Taranto (exposed group), 150 in Taranto but far from this area (internal control group) and 150 in Brindisi (external control group). The recruited workers were administered a questionnaire inquiring about current and previous working activities, personal medical history, lifestyle and dietary habits, and their residence location. Then they collected a urine sample for the determination of 1-hydroxypyrene, 2-naphthol, cotinine and the metallic elements As, Cd, Co, Cr, Mn, Ni, Pb, Cu, Zn and Hg. The latter were measured in 110 workers in each group. In addition, in some of the work sites of the three groups, environmental samplings were carried out to determine PAHs and the 10 metallic elements, also taking into account the wind direction.Results:Airborne benzo(a)pyrene concentrations at the different sampling sites ranged from 0.02 to 0.06 ng/m3 and naphthalene between <25 and 65.3 ng/m3, regardless of the wind direction. Among the metallic elements, As, Cd, Co, Cr, Hg, Pb, Cu and Zn were present at concentrations below or just above the limit of detection (LOD). Mn and Ni were slightly higher in the work sites of the exposed group. The urinary concentrations of 1-hydroxypyrene, 2-naphthol and the single metallic elements were not higher in the exposed workers group than in the other 2 groups. Smokers had significantly higher urinary 1-hydroxypyrene and 2-naphthol concentrations, whereas cigarette smoking did not condition a higher urinary elimination of metallic elements in the three groups with the exception of Cd and Pb. Moreover, residence location conditioned Mn, Hg and As urinary excretion, consumption of shellfish and/or crustaceans in the 72 hours before urine collection conditioned As elimination, and consumption of legumes in the 72 hours before urine collection conditioned Ni elimination.Conclusions:This research did not find a higher urinary excretion of 1-hydroxypyrene, 2-naphthol and As, Cd, Co, Cr, Mn, Ni, Pb, Cu, Zn and Hg in the exposed workers group as compared to the internal control group working far from the industrial area of Taranto, nor in the group working in another city far away from Taranto, Brindisi. Therefore, it indicated that workers in the Italian Navy operating near the industrial area in Taranto were not exposed to a greater risk attributable to exposure to PAHs and metallic elements than the two control groups.

Association between polycyclic aromatic hydrocarbon exposure and peripheral blood mononuclear cell DNA damage in human volunteers during fire extinction exercises.

This study investigated a number of biomarkers, associated with systemic inflammation as well as genotoxicity, in 53 young and healthy subjects participating in a course to become firefighters, while wearing personal protective equipment (PPE). The exposure period consisted of a 3-day training course where the subjects participated in various live-fire training exercises. The subjects were instructed to extinguish fires of either wood or wood with electrical cords and mattresses. The personal exposure was measured as dermal polycyclic aromatic hydrocarbon (PAH) concentrations and urinary excretion of 1-hydroxypyrene (1-OHP). The subjects were primarily exposed to particulate matter (PM) in by-stander positions, since the self-contained breathing apparatus effectively prevented pulmonary exposure. There was increased dermal exposure to pyrene (68.1%, 95% CI: 52.5%, 83.8%) and sum of 16 polycyclic aromatic hydrocarbons (ƩPAH; 79.5%, 95% CI: 52.5%, 106.6%), and increased urinary excretion of 1-OHP (70.4%, 95% CI: 52.5%; 106.6%) after the firefighting exercise compared with the mean of two control measurements performed 2 weeks before and 2 weeks after the firefighting course, respectively. The level of Fpg-sensitive sites in peripheral blood mononuclear cells (PBMCs) was increased by 8.0% (95% CI: 0.02%, 15.9%) compared with control measurements. The level of DNA strand breaks was positively associated with dermal exposure to pyrene and ƩPAHs, and urinary excretion of 1-OHP. Fpg-sensitive sites were only associated positively with PAHs. Biomarkers of inflammation and lung function showed no consistent response. In summary, the study demonstrated that PAH exposure during firefighting activity was associated with genotoxicity in PBMCs.

Cardiovascular health effects following exposure of human volunteers during fire extinction exercises

BackgroundFirefighters have increased risk of cardiovascular disease and of sudden death from coronary heart disease on duty while suppressing fires. This study investigated the effect of firefighting activities, using appropriate personal protective equipment (PPE), on biomarkers of cardiovascular effects in young conscripts training to become firefighters.MethodsHealthy conscripts (n = 43) who participated in a rescue educational course for firefighting were enrolled in the study. The exposure period consisted of a three-day training course where the conscripts participated in various firefighting exercises in a constructed firehouse and flashover container. The subjects were instructed to extinguish fires of either wood or wood with electrical cords and mattresses. The exposure to particulate matter (PM) was assessed at various locations and personal exposure was assessed by portable PM samplers and urinary excretion of 1-hydroxypyrene. Cardiovascular measurements included microvascular function and heart rate variability (HRV).ResultsThe subjects were primarily exposed to PM in bystander positions, whereas self-contained breathing apparatus effectively abolished pulmonary exposure. Firefighting training was associated with elevated urinary excretion of 1-hydroxypyrene (105%, 95% CI: 52; 157%), increased body temperature, decreased microvascular function (−18%, 95% CI: -26; −9%) and altered HRV. There was no difference in cardiovascular measurements for the two types of fires.ConclusionObservations from this fire extinction training show that PM exposure mainly occurs in situations where firefighters removed the self-contained breathing apparatus. Altered cardiovascular disease endpoints after the firefighting exercise period were most likely due to complex effects from PM exposure, physical exhaustion and increased core body temperature.

Using urinary 1-hydroxypyrene concentrations to evaluate polycyclic aromatic hydrocarbon exposure in women using biomass combustion as main energy source

Context: The use of solid fuels for cooking and heating is likely to be the largest source of indoor air pollution on a global scale. Objective: The aim of this study was to investigate the urinary excretion of 1-hydroxypyrene (1-OHP) in women living in a rural community, where biomass combustion is used as main energy source during a working day. Materials and methods: The study was performed on urine samples collected in 2012, of 30 healthy women who were residents of a rural community in San Luis Potosi, Mexico. Urine was collected from each woman at three time points (morning, post-lunch and evening) during a working day. The analysis of urinary 1-OHP was performed using high-performance liquid chromatography (HPLC). Also, a health-risk assessment was conducted. Results: The highest levels of 1-OHP in this study were found in the samples taken in the evening (geometric mean ± SD; 0.36 ± 0.13 µg/g creatinine). However, no significant differences among 1-OHP concentrations in the evening and post-lunch samples (0.27 ± 0.10 µg/g creatinine; 0.58 ± 0.67 µg/L) were observed. But, the 1-OHP levels (0.17 ± 0.13 µg/g creatinine; 0.19 ± 0.21 µg/L) found in samples collected in the morning were significantly lower than the 1-OHP levels found in samples collected during post-lunch and evening time. Discussion and conclusion: The data shown in this study demonstrated an increment in the exposure levels to PAHs in women across the shift. However, no health risk was found in this study.

Simulation of urinary excretion of 1-hydroxypyrene in various scenarios of exposure to polycyclic aromatic hydrocarbons with a generic, cross-chemical predictive PBTK-model

A physiologically based toxicokinetic (PBTK) model can predict blood and urine concentrations, given a certain exposure scenario of inhalation, dermal and/or oral exposure. The recently developed PBTK-model IndusChemFate is a unified model that mimics the uptake, distribution, metabolism and elimination of a chemical in a reference human of 70 kg. Prediction of the uptake by inhalation is governed by pulmonary exchange to blood. Oral uptake is simulated as a bolus dose that is taken up at a first-order rate. Dermal uptake is estimated by the use of a novel dermal physiologically based module that considers dermal deposition rate and duration of deposition. Moreover, evaporation during skin contact is fully accounted for and related to the volatility of the substance. Partitioning of the chemical and metabolite(s) over blood and tissues is estimated by a Quantitative Structure-Property Relationship (QSPR) algorithm. The aim of this study was to test the generic PBTK-model by comparing measured urinary levels of 1-hydroxypyrene in various inhalation and dermal exposure scenarios with the result of model simulations. In the last three decades, numerous biomonitoring studies of PAH-exposed humans were published that used the bioindicator 1-hydroxypyrene (1-OH-pyrene) in urine. Longitudinal studies that encompass both dosimetry and biomonitoring with repeated sampling in time were selected to test the accuracy of the PBTK-model by comparing the reported concentrations of 1-OHP in urine with the model-predicted values. Two controlled human volunteer studies and three field studies of workers exposed to polycyclic aromatic hydrocarbons (PAH) were included. The urinary pyrene-metabolite levels of a controlled human inhalation study, a transdermal uptake study of bitumen fume, efficacy of respirator use in electrode paste workers, cokery workers in shale oil industry and a longitudinal study of five coke liquefaction workers were compared to the PBTK-predicted values. The simulations showed that the model-predicted concentrations of urinary pyrene and metabolites over time, as well as peak-concentrations and total excreted amount in different exposure scenarios of inhalation and transdermal exposure were in all comparisons within an order of magnitude. The model predicts that only a very small fraction is excreted in urine as parent pyrene and as free 1-OH-pyrene. The predominant urinary metabolite is 1-OH-pyrene-glucuronide. Enterohepatic circulation of 1-OH-pyrene-glucuronide seems the reason of the delayed release from the body. It appeared that urinary excretion of pyrene and pyrene-metabolites in humans is predictable with the PBTK-model. The model outcomes have a satisfying accuracy for early testing, in so-called 1st tier simulations and in range finding. This newly developed generic PBTK-model IndusChemFate is a tool that can be used to do early explorations of the significance of uptake of pyrene in the human body following industrial or environmental exposure scenarios. And it can be used to optimize the sampling time and urine sampling frequency of a biomonitoring program.

Efecto antioxidante e hipolipemiante del pimentón ahumado en individuos sanosAntioxidant and hypolipidaemic effect of smoked paprika in healthy subjects

The healthy properties and antioxidant activity of smoked paprika in healthy male non-smoking students (age 20.6 ± 1.7 years), from Universidad de Extremadura (Spain), who consumed (2 g/day, 20 times, over 30 days) smoked (La Vera, Extremadura, Spain) or non-smoked (Novelda, Alicante, Spain) paprika were investigated. Anthropometric and cardiovascular measurements and blood and urine samples were taken from overnight fasted subjects for biochemical, hematological, and immunological measurements. The ingestion of smoked paprika increased the urinary excretion of 1-hydroxypyrene (from 38.6 ± 24.9 to 109.2 ± 85.6 nmol/mol; p < 0.05). Plasma triglyceride and total cholesterol levels were significantly (p < 0.05) reduced after the consumption of either smoked or non-smoked paprika. Plasma lipoperoxidation levels measured both as thiobarbituric acid (3.1 ± 0.5 versus 2.7 ± 0.5 μmol/L; p < 0.05) and as malonaldehyde (0.9 ± 0.4 versus 0.6 ± 0.3 μmol/L; p < 0.01) were reduced after consuming smoked paprika. Plasma levels of carotenoids, lycopenes, vitamin C, vitamin E, and selenium were similar after the ingestion of smoked or non-smoked paprika. The smoked paprika from La Vera seems to produce an antioxidant effect by enhancing the activity of the endogenous antioxidant defenses.

Oxidative damage in foundry workers occupationally co-exposed to PAHs and metals

Occupational exposure to polycyclic aromatic hydrocarbons (PAHs) has been reported in foundries. A higher risk for DNA damage or oxidative damage lesions was also found in occupationally PAH-exposed groups. The aim of this study was to assess PAH exposure by urinary excretion of 1-hydroxypyrene (1-OHP), a biological exposure marker. Furthermore, we aimed to evaluate the oxidative damage of foundry workers with different job tasks and the association between 1-OHP, metal exposure and oxidative damage in foundry workers exposed to pervasive carcinogens. A higher concentration of 1-OHP was found in the exposed group (0.322+/-0.289 microg/g creatinine) relative to the control group (0.178+/-0.289 microg/g creatinine) (p<0.05). Moreover, higher levels of 1-OHP were found in workers involved in manufacturing processes (0.346 microg/g creatinine) compared to administrative workers (0.018 microg/g creatinine). A positive correlation was identified between levels of 1-OHP and 8-hydroxydeoxyguanosine (8-OH-dG), DNA strand breakage and malondialdehyde (MDA) in all study subjects. However, when foundry workers were considered based on their specific job categories, a similar trend for 1-OHP and three oxidative damage markers was only found for DNA strand breakage, but not for 8-OH-dG or MDA. Other factors such as furnace equipment, PAH types, and job categories may contribute to different PAH emissions. The study also suggested that co-exposure to metal and PAHs, and smoking status in foundry industries may also cause the oxidative damage in foundry workers.

The occupational exposure of dermatology nurses to polycyclic aromatic hydrocarbons – evaluating the effectiveness of better skin protection

We studied the uptake of polycyclic aromatic hydrocarbons (PAH) in nurses who apply ointments containing coal tar to patients and investigated the effectiveness of skin protection methods. We determined gas-phase PAH on XAD-2 and particle-associated PAH on filters. We also used pads to determine PAH on the skin. Pyrene and benzo(a)pyrene were analyzed by gas chromatography/mass spectrometry and gas chromatography/tandem mass spectrometry; their respective urinary metabolites 1-hydroxypyrene and 3-hydroxybenzo(a)pyrene were analyzed using high performance liquid chromatography with fluorescence detection. We ruled out the inhalation of airborne pyrene and benzo(a)pyrene as the sources of PAH exposure. However, substantial amounts of pyrene and benzo(a)pyrene were observed on the hands of the nurses (median 33.0 and 16.4 ng/cm (2), respectively). Excretion of urinary 1-hydroxypyrene indicated an increased uptake of pyrene in 8 out of 12 nurses. We asked 35 nurses to perform a treatment with gloves followed by a second treatment without gloves. The use of gloves changed the excretion of 1-hydroxypyrene by -0.58 mumol (range -5.1-1.0 mumol), corresponding to a median reduction of 51.5% (P<0.001). Based on this finding, a new protocol was adopted, involving the permanent use of vinyl gloves and Tyvek sleeves. The effectiveness of this protocol was tested against pre-existing work practices and showed a 97% reduction in skin contamination with pyrene and benzo(a)pyrene, and a lowering in urinary excretion of 1-hydroxypyrene of 57%. Protecting the skin more stringently reduced pyrene and benzo(a)pyrene contamination of the hands, and lowered urinary excretion of 1-hydroxypyrene.

Urinary levels of oxidative DNA and RNA damage among workers exposed to polycyclic aromatic hydrocarbons in silicon production: Comparison with 1‐hydroxypyrene

Polycyclic aromatic hydrocarbons (PAH) are ubiquitous occupational and environmental pollutants and the urinary excretion of 1-hydroxypyrene (1-OHP) is classically measured for the determination of PAH exposure internal dose. Some of PAH are tumorigenic due to their metabolites ability to generate DNA adducts and oxidative DNA damage through the production of reactive oxygen species during metabolism. 8-hydroxy-7,8-dihydro-2'-deoxyguanosine (8-OHdGuo) is one of the major oxidative DNA lesions and its use as a potential biomarker of genotoxic PAH occupational exposure should be evaluated. Indeed conflicting results are frequently reported in occupational studies in terms of correlation between 8-OHdGuo urinary levels and PAH exposure. The aim of our study was therefore to determine the potential for PAH occupational exposure to increase urinary oxidative DNA damage. The population consisted of 68 male workers employed in silicon production. The urinary concentrations of 8-OHdGuo and its homologue in RNA, 8-hydroxy-7,8-dihydroguanosine (8-OHGuo) were determined using high performance liquid chromatography (HPLC) coupled to tandem mass spectrometry, whereas those of 1-OHP were measured using HPLC with fluorescence detection. Individual variation rates were calculated on a working day and a working week. The results indicated that, while 1-OHP levels strongly increased on a working day and even more on a working week, 8-OHdGuo and 8-OHGuo urinary levels did not show similar significant increases. Moreover, no correlation between 1-OHP and oxidative DNA and RNA lesions was found. Consequently, urinary 8-OHdGuo and 8-OHGuo did not seem to be relevant biomarkers of genotoxic PAH exposure in the case of the silicon plant studied.

Assessment of Exposure to Polycyclic Aromatic Hydrocarbons (PAH) in Italian Asphalt Workers

The purpose of the work was the assessment of exposure to Polycyclic Aromatic Hydrocarbons (PAH), a family of ubiquitous pollutants of which some are carcinogens, in 100 Italian asphalt workers (exposed to bitumen fumes and diesel exhausts) and in a reference group of 47 ground construction operators (exposed only to diesel exhausts, reference group). The protocol included interview via questionnaires, environmental air-monitoring (active personal sampling during the work shift), dermal contamination measures (six pads placed on worker's wrist, neck, arm, chest, thigh, and ankle), and biological monitoring (determination of 1-hydroxypyrene in urine spot samples collected three at different moments: baseline after two days of vacation, before shift, and at end shift on a day in the second half of the week). Analysis of the most relevant PAH, according to the American Environmental Protection Agency, EPA, was performed by High Performance Liquid Chromatography (HPLC) by fluorimetric detector. Median airborne levels of PAH ranged from 426 to below 0.03 ng/m3. Vapor-phase PAH, apart from naphthalene, were significantly higher in asphalt workers than in the reference group. Particle-phase PAH were similar and very low (< 1 ng/m3) in both exposure groups. Exposure levels did not vary in different work-tasks. Excretion of urinary 1-hydroxypyrene (expressed by ng/g creatinine) showed a significant increase at different sampling moments in asphalt workers, smokers, and non-smokers: baseline was lower than at the beginning of the workshift, and values were even higher in the end workshift sample. Comparing the two groups, a significant difference in the levels of metabolite does not appear, whereas this trend can be viewed observing the non-smokers. All body regions monitored by pads showed equivalent values levels of Dermal Deposition Density in both exposure groups. The measured amount of dermal contamination was significantly higher in asphalt workers than in ground construction operators. In asphalt workers, skin contamination was significantly higher during asphalt paving than during asphalt mixing. Dermal Exposure Rate was calculated about threefold higher than Airborne Exposure Rate; whereas considering toxicokinetical information (Kp, lag time, experimental dermal absorption data) and hygienistic data (particle size of bitumen fume), the relevance of dermal absorption is lower than respiratory. The results of this study demonstrate that asphalt workers experience slight occupational exposure to PAH, both by inhalatory and dermal routes, resulting in a significant increase of urinary 1-hydroxypyrene during the workweek.

Effects of Lifestyle on Urinary 1‐hydroxypyrene Concentration

This study aimed to clarify the variation of urinary excretion of 1-hydroxypyrene, which is a major metabolite of pyrene, in relation to lifestyle, including factors such as diet and smoking. The study subjects were 251 workers (male: 196, female: 55, mean age: 44.3) who were not occupationally exposed to PAHs. Urine specimens were collected from 8:00 a.m. to 11:00 a.m. and their 1-hydroxypyrene concentrations were determined by HPLC. A questionnaire was distributed in order to learn gross aspects of the subjects' lifestyles, i.e., smoking, alcohol consumption, coffee/black tea intake, and dietary habits. Multiple linear regression analysis revealed that cigarette consumption most strongly affected the 1-hydroxypyrene level in urine, followed by dietary balance. The urinary 1-hydroxypyrene concentrations of smokers were about 2 times higher than those of non-smokers. Subjects who ate more meat and/or fish excreted 1.5-2 times more 1-hydroxypyrene in urine than those who ate more vegetables.

Effect of Urban Traffic, Individual Habits, and Genetic Polymorphisms on Background Urinary 1-Hydroxypyrene Excretion

Potential sources of exposure to polycyclic aromatic hydrocarbons (PAHs) and genetic polymorphisms were investigated in relation to their contribution to interindividual variation in baseline levels of urinary 1-hydroxypyrene (1-OHP) excretion in subjects without occupational exposure to PAHs. Urinary excretion of 1-OHP was measured in 114 subjects, including 48 women and 66 men. Questionnaire information was collected on possible environmental and individual sources of PAH exposure. A subset of 70 individuals also was evaluated for a single-nucleotide polymorphism (Ex7+295C-->T) in the cytochrome P-450 1A2 (CYP1A2) gene, and 61 of these also were evaluated for the glutathione transferase T1 (GSTT1) gene polymorphism. 1-OHP values did not show a significant seasonal variability and were unaffected by age; education; body mass index; smoking status, including passive smoking; or the C-->T base substitution in position 295 of exon 7 of the CYP1A2 gene. After reciprocal adjustment with logistic regression, living in a heavily trafficked urban area (odds ratio, 4.9; 95% confidence interval, 1.0-24.9), and frequent intake of grilled meat (odds ratio, 6.9; 95% confidence interval, 1.1-43.5) were significant predictors of background urinary 1-OHP levels of 0.50 microg/g creatinine or greater. Elevated risks also were associated with daily alcohol intake greater than 65 g and the nonnull GSTT1 genotype. Our study shows that exposure to urban traffic, dietary habits, and the nonnull GSTT1 genotype may contribute to interindividual variation in background levels of 1-OHP urinary excretion in subjects without occupational exposure to PAHs.

Dermal Exposure to Polycyclic Aromatic Hydrocarbons among Road Pavers

Dermal exposure to polycyclic aromatic hydrocarbons (PAHs) and the role of an industrial by-product, coal fly ash, on workers' PAH exposure were investigated during stone mastic asphalt (SMA) paving and remixing. PAH exposure was measured at eight sites during the laying of SMA containing coal fly ash or limestone (conventional SMA) as the filler. Six of the surveys were carried out during SMA paving and two during remixing of SMA (hot recycling at the paving site). Dermal PAH exposure was measured by hand washing (using sunflower oil and wiping with Kleenex tissues) before and after the work shift, and by placing exposure pads on the workers' wrists during the work shift. The analyses included 15 native PAHs from the hand-washing samples determined using high-performance liquid chromatography equipped with a two-channel fluorescence detector and 16 native PAHs and four methylated PAHs from the exposure pads using gas chromatography with mass-selective detection. The PAH results obtained using the pad and hand-washing methods (concentrations after the work shift) were equivalent and showed a strong correlation (r = 0.757, P < 0.001, N = 23 for total PAHs). There was a statistically significant difference between pre- and post-shift samples as measured by hand washing. The skin contamination by PAHs was significantly higher (P < 0.01) during remixing than during SMA paving. The variation in PAH contamination on the skin explained more of the variation in the excretion of urinary 1-hydroxypyrene and phenanthrols than the variation in the respiratory PAH concentrations. The industrial by-product investigated in asphalt, coal fly ash, had no statistically significant effect on the workers' dermal PAH exposure. The dermal exposure of paving workers to PAHs was higher during remixing than during SMA paving.

CYP1A2 phenotype and genotype in a population from the Carboniferous Region of Coahuila, Mexico

CYP1A2 regulation by polycyclic aromatic hydrocarbons (PAHs) exposure and polymorphism was investigated in 46 male volunteers from the Carboniferous Region in northern Coahuila, Mexico. PAH exposure was estimated by the urinary excretion of 1-hydroxypyrene (1-OHP), whereas the regulatory effects were assessed by the caffeine metabolic ratio (CMR). Genotype was evaluated by determining 5′-flanking region (−2964) and intron I (734) polymorphisms. A statistically significant difference in the urinary 1-OHP geometric means of Barroterán, Cloete and Juárez (2.30, 0.45 and 0.04, respectively) was observed. As for the genotype, the intron I distribution was 0% C/C, 46% C/A and 54% A/A, whereas that of the 5′-flanking region was 26% G/G, 42% G/A and 32% A/A. Both distributions were in agreement with the Hardy-Weinberg equilibrium model. A greater enzyme activity was observed in the A/A compared to C/A individuals according to the CMR ( P < 0.001), whereas the 5′-flanking region polymorphism showed no effect on CYP1A2 enzymatic activity. These results suggest that intron I polymorphism and PAH exposure are relevant factors that modulate CYP1A2 enzymatic activity.

Dietary fibers reduce the urinary excretion of 1-hydroxypyrene following intravenous administration of pyrene.

During biological monitoring of exposure to a chemical, a possible source of interindividual variability in the measurement of a urinary metabolite that undergoes enterohepatic cycling is the presence of dietary fiber in the gastrointestinal tract. This study examined the effect of diets containing either the insoluble fiber Alphacel (nonnutritive bulk cellulose) or the soluble pectin (from citrus fruit, MW 20,000-40,000). Five groups of male Sprague-Dawley rats received one of the following diets: poor (5% w/w) or rich (15% w/w) in Alphacel, poor (5% w/w) or rich (15% w/w) in pectin, or no fiber (NF). Five micromol/kg of pyrene was administered by iv injection immediately after feeding the animals with their respective diet, and urine and feces collections started for the determination of 1-hydroxypyrene (1-OHP), a metabolite of pyrene. The type of fiber had no influence on the results. The rats receiving diets both poor and rich in fiber excreted less 1-OHP (18 +/- 8 and 15 +/- 7 pmol per g of rat, respectively) in the 24-h urine samples than the NF group (28 +/- 6 pmol/g). There was a nonstatistically significant trend towards increased fecal and total (urinary + fecal) 1-OHP excretion with increasing amount of fiber in the diet. An in vitro experiment showed an inverse correlation (r(2) = 0.98) between the amount of Alphacel in suspension in a 1-OHP aqueous solution and the recovery of 1-OHP from the soluble fraction. The reduction in urinary output of the metabolite due to fiber reaching approximately 40% may contribute to its interindividual variability observed in occupational and environmental studies.

Monitoring human occupational and environmental exposures to polycyclic aromatic compounds.

Many research groups have been carrying out studies to develop biomarkers of exposure to polycyclic aromatic compounds (PACs) and apply these for human biomonitoring. The main objectives of the use of biomarkers are to determine specific occupational and environmental exposures to monitor the effectiveness of exposure controls and prediction of the risk of disease. This article presents a review of the literature in the field of biomarkers of human exposure to PACs and an evaluation of the relevant biomarkers for monitoring exposure to PACs in a range of exposure situations from coke ovens to bitumen handling and environmental exposures. For this evaluation, the relationships between external PAC exposures and the corresponding biomarker levels have been studied. The literature data indicate that urinary excretion of 1-hydroxypyrene correlates well with external PAC exposure and this compound appears to be a suitable marker for internal exposure to PACs. DNA adducts, mostly measured in white blood cells, do not show satisfactory correlations with exposure to PACs in a variety of workplace and exposure situations. It is not clear which factors are mainly responsible for this poor correlation. Micronuclei and sister chromatid exchanges measured in peripheral white blood cells are also unsatisfactory as biomarkers for PAC exposure. From the relatively limited data available, chromosome aberrations appear to show considerable promise as indicators of exposure to PACs. Because of their strong association with cancer, chromosome aberrations are considered suitable indicators of increased cancer risk arising from exposure to PACs.

Highly increased urinary 1-hydroxypyrene excretion rate in patients with atopic dermatitis treated with topical coal tar

Coal tar preparations, as used in dermatological practice, contain numerous polycyclic aromatic hydrocarbons of which many are proven animal carcinogens. Increased urinary 1-hydroxypyrene excretion in patients with atopic dermatitis treated with topical coal tar preparations has been demonstrated. Little is known about the relationship between the dermal uptake of polycyclic aromatic hydrocarbons on the one hand and the amount of tar applied to the skin, the total body area affected, the condition of the epidermal barrier and the severity of the dermatitis on the other. We compared urinary 1-hydroxypyrene excretion rate with these variables. The urinary 1-hydroxypyrene excretion rate was highly dependent on the total amount of tar applied to the skin and the total body area affected, and less on the severity of the atopic dermatitis or the condition of the epidermal barrier. Exposure to therapeutic doses of coal tar leads to much higher rates of urinary 1-hydroxypyrene excretion than occupational exposure. Because of the potential carcinogenicity of coal tar, as clearly demonstrated both in animal studies and from occupational exposure, careful consideration should be given to the use of coal tar preparations in dermatological practice. However, the risk of short-term high exposure is unknown. Restriction of the use of coal tar should be based on epidemiological studies and/or appropriate risk models taking into account its relative safety established over many years of clinical use.

Urinary 1-hydroxypyrene levels in workers exposed to coke oven emissions at various locations in a coke oven plant.

Polycyclic aromatic hydrocarbons, which are carcinogenic and mutagenic to humans, are primary compounds in coke oven emissions generated by the coking process. The authors examined the relationship between coke oven workers' urinary 1-hydroxypyrene levels and their exposure to polycyclic aromatic hydrocarbons, as determined on the basis of work category and pre- and postshift effects in a steel plant in Taiwan. Eighty-eight coke oven workers constituted the exposed group, and 61 office workers in a steel plant located 1.5 km from the coke plant constituted the control group. The benzene-soluble fraction in personal air samples, and 1-hydroxypyrene in urine samples, were measured for 3 consecutive days. The 3-day urinary 1-hydroxypyrene sampling results for topside workers (i.e., those most heavily exposed to emissions) in the coke oven group, and for the control group, as determined from postshift geometric means, were 23.8 microg/gm creatinine and 0.3 microg/gm creatinine, respectively. These values increased to 13.4 and 0.1 microg/gm creatinine, respectively, after an 8-hr work period. The major source of polycyclic aromatic hydrocarbons for the exposed group was occupational; therefore, the closer workers were to the coke oven, the greater their exposure, and, consequently, the greater their metabolite level. Urinary 1-hydroxypyrene levels of the exposed group were 80 times higher than those of the control group. Smoking had no significant effect on the excretion of urinary 1-hydroxypyrene. 1-hydroxypyrene levels in the workers' urine during an 8-day period was cumulative (half-life = 18.6 hr). The authors concluded that it would be desirable to switch highly exposed workers to a low-exposure work area, after a period of rest. In addition, urinary 1-hydroxypyrene was a confirmed, useful biological indicator for exposure to polycyclic aromatic hydrocarbons.

Excretion of Urinary 1-Hydroxypyrene in Relation to the Penetration Routes of Polycyclic Aromatic Hydrocarbons

In order to determine the respective contribution of cutaneous and respiratory exposure to urinary PyOH excretion, some experimental follow-ups were carried out during cathode relining in the aluminum industry, leading to qualitative (excretion profiles) and quantitative assessments (excreted PyOH/inhaled pyrene). The procedure was as follows: no exposure on Monday, Wednesday, and Friday; polluting operations on Tuesday and Thursday without or with different protections. For workers with cutaneous protection only, a significant peak of PyOH concentration is observed at the postshift, which is followed by a fast decrease to the background level. For workers with respiratory protection, the maximum is in the shape of a plateau which extends for several hours after the postshift and then decreases slowly. For people with contaminated working clothes, a significant amount of PyOH is excreted on the days with no exposition. The mean ratio of urinary excreted PyOH to inhaled pyrene dose is 15.3% for workers with cutaneous protection and 24.5% for workers with no protection.