Impact of diesel exhaust exposure on urinary 1-hydroxypyrene in underground salt and potash workers.

BACKGROUND: Diesel engine exhaust (DEE) and some of the polycyclic aromatic hydrocarbons (PAH) it contains are carcinogenic to humans (for example benzo(a)pyrene) and can cause lung cancer in workers. The objective of this study was to assess exposures to DEE and its component PAH and the potential associations between these two health hazards in a salt and potash mining population. METHODS: Between 2017 and 2019, 1003 underground workers (mining n = 801, maintenance n = 202) and 243 above-ground facility workers from two German mines participated. Personal exposure to DEE was assessed in air as elemental carbon for diesel particulate matter (EC-DPM), whereas exposure to PAH was assessed in pre- and post-shift urine samples in terms of 1-hydroxypyrene (1-OHP). Associations between EC-DPM and 1-OHP were studied using linear regression models. RESULTS: The highest EC-DPM exposures were measured in mining workers (median 0.06 mg/m³) followed by workers in the maintenance (0.03 mg/m3) and facility areas (<0.02 mg/m3). Exposures above the current German occupational threshold level of 0.05 mg/m3 were observed in 56%, 17%, and 5% of mining, maintenance and facility workers, respectively. 1-OHP increased statistically significantly across a work shift in underground workers but not in facility workers. Regression analyses revealed an increase of post-shift 1-OHP by almost 80% in mining and 40% in maintenance compared with facility workers. 1-OHP increased with increasing EC-DPM among underground workers. However, internal exposure of 1-OHP mainly remained at levels similar to those of the German general population in more than 90% of the urine samples. CONCLUSIONS: While exposures to DEE above the current German OEL for EC-DPM are quite common in the studied population of underground salt and potash miners (39.5% overall), urinary concentrations of 1-OHP did not reflect these findings.

Children's exposure to polycyclic aromatic hydrocarbon (PAHs): a review on urinary 1-hydroxypyrene and associated health effects.

This article reviewed the published studies on the environmental exposure to polycyclic aromatic hydrocarbons (PAHs) among children and assessed the urinary 1-hydroxypyrene (1-OHP) level as a biomarker of exposure to PAHs. The current knowledge of the potential health effects of increased 1-OHP in children was reviewed. Additionally, the influence of genetic polymorphism on the urinary 1-OHP level was discussed in this review. The assembled data showed that children who are attending schools or living close to industrial and polluted urban areas might have greater exposure to higher concentrations of PAHs with a higher level of urinary 1-OHP when compared to those children living in rural areas. Urinary 1-OHP may be a reliable biomarker for determining the genotoxic effects, oxidative stress and inflammation caused by exposure to PAHs. Strong research evidence indicated that the total body burden of PAHs should be evaluated by biomonitoring of 1-OHP in line with other urinary PAHs metabolites (with 2-3 rings) to evaluate recent total exposure to PAHs. Overall, the study suggests implementing a mitigation plan to combat air pollution to provide a cleaner environment for children.

Exposure to Nicotine and Toxicants Among Dual Users of Tobacco Cigarettes and E-Cigarettes: Population Assessment of Tobacco and Health (PATH) Study, 2013-2014.

INTRODUCTION: Concurrent use of tobacco cigarettes and e-cigarettes ("dual use") is common among tobacco users. Little is known about differences in demographics and toxicant exposure among subsets of dual users. AIMS AND METHODS: We analyzed data from adult dual users (current every/some day users of tobacco cigarettes and e-cigarettes, n = 792) included in the PATH Study Wave 1 (2013-2014) and provided urine samples. Samples were analyzed for biomarkers of exposure to nicotine and selected toxicants (tobacco-specific nitrosamine NNK [NNAL], lead, cadmium, naphthalene [2-naphthol], pyrene [1-hydroxypyrene], acrylonitrile [CYMA], acrolein [CEMA], and acrylamide [AAMA]). Subsets of dual users were compared on demographic, behavioral, and biomarker measures to exclusive cigarette smokers (n = 2411) and exclusive e-cigarette users (n = 247). RESULTS: Most dual users were predominant cigarette smokers (70%), followed by daily dual users (13%), non-daily concurrent dual users (10%), and predominant vapers (7%). Dual users who smoked daily showed significantly higher biomarker concentrations compared with those who did not smoke daily. Patterns of e-cigarette use had little effect on toxicant exposure. Dual users with high toxicant exposure were generally older, female, and smoked more cigarettes per day. Dual users who had low levels of biomarkers of exposure were generally younger, male, and smoked non-daily. CONCLUSIONS: In 2013-2014, most dual users smoked cigarettes daily and used e-cigarettes occasionally. Cigarette smoking appears to be the primary driver of toxicant exposure among dual users, with little-to-no effect of e-cigarette use on biomarker levels. Results reinforce the need for dual users to stop smoking tobacco cigarettes to reduce toxicant exposure. IMPLICATIONS: With considerable dual use of tobacco cigarettes and e-cigarettes in the United States, it is important to understand differences in toxicant exposure among subsets of dual users, and how these differences align with user demographics. Findings suggest most dual users smoke daily and use e-cigarettes intermittently. Low exposure to toxicants was most common among younger users, males, and intermittent smokers; high exposure to toxicants was most common among older users, females, and heavier cigarette smokers. Results underscore the heterogeneity occurring within dual users, and the need to quit smoking cigarettes completely in order to reduce toxicant exposure.

Filaggrin Polymorphisms and the Uptake of Chemicals through the Skin-A Human Experimental Study.

BACKGROUND: The filaggrin protein is important for skin barrier structure and function. Loss-of-function (null) mutations in the filaggrin gene FLG may increase dermal absorption of chemicals. OBJECTIVE: The objective of the study was to clarify if dermal absorption of chemicals differs depending on FLG genotype. METHOD: We performed a quantitative real-time polymerase chain reaction (qPCR)-based genetic screen for loss-of-function mutations (FLG null) in 432 volunteers from the general population in southern Sweden and identified 28 FLG null carriers. In a dermal exposure experiment, we exposed 23 FLG null and 31 wild-type (wt) carriers to three organic compounds common in the environment: the polycyclic aromatic hydrocarbon pyrene, the pesticide pyrimethanil, and the ultraviolet-light absorber oxybenzone. We then used liquid-chromatography mass-spectrometry to measure the concentrations of these chemicals or their metabolites in the subjects' urine over 48 h following exposure. Furthermore, we used long-range PCR to measure FLG repeat copy number variants (CNV), and we performed population toxicokinetic analysis. RESULTS: Lag times for the uptake and dermal absorption rate of the chemicals differed significantly between FLG null and wt carriers with low (20-22 repeats) and high FLG CNV (23-24 repeats). We found a dose-dependent effect on chemical absorption with increasing lag times by increasing CNV for both pyrimethanil and pyrene, and decreasing area under the urinary excretion rate curve (AUC(0-40h)) with increasing CNV for pyrimethanil. FLG null carriers excreted 18% and 110% more metabolite (estimated by AUC(0-40h)) for pyrimethanil than wt carriers with low and high CNV, respectively. CONCLUSION: We conclude that FLG genotype influences the dermal absorption of some common chemicals. Overall, FLG null carriers were the most susceptible, with the shortest lag time and highest rate constants for skin absorption, and higher fractions of the applied dose excreted. Furthermore, our results indicate that low FLG CNV resulted in increased dermal absorption of chemicals. https://doi.org/10.1289/EHP7310.

OGG1 DNA Repair Gene Polymorphism As a Biomarker of Oxidative and Genotoxic DNA Damage.

Background: Single nucleotide polymorphisms in 8-oxoguanine DNA glycosylase-1 (OGG1) gene modulates DNA repair capacity and functions as one of the first lines of protective mechanisms against 8-hydroxy-2'-deoxyguanosine (8-OHdG) mutagenicity. OGG1-Cys326 gene polymorphism may decrease DNA repair function, causing oxidative stress due to higher oxidative DNA damage. The main purpose of this study was to examine the link of oxidative and genotoxic DNA damage with DNA repair OGG1 gene polymorphism, in charcoal workers exposed to polyaromatic hydrocarbons. Methods: Urinary 8-OHdG excretion (a biomarker of oxidative DNA damage) was determined in both exposed and control populations. Genotyping of OGG1 DNA repair gene in the blood samples of subjects was carried out by PCR-RFLP method. Results: The 8-OHdG urinary concentration was significantly higher (p < 0.05) in the exposed (geometric mean 12.33 ± 3.78) than in the unexposed (geometric mean 7.36 ± 2.29) population. DNA damage, as measured by 8-OHdG and tail moment content, was found to be significantly higher in OGG1 homozygous mutants (mt/mt; 18.81 ± 3.34; 6.04 ± 0.52) as compared to wild-type genotypes (wt/wt; 10.34 ± 2.25; 5.19 ± 2.50) and heterozygous (wt/mt) mutants (12.82 ± 2.81; 6.04 ± 0.93) in the exposed group. Conclusion: We found a significant association of OGG1 heterozygous (wt/mt) and homozygous (mt/mt) variants with oxidative and genotoxic damage, suggesting that these polymorphisms may modulate the effects of polycyclic aromatic hydrocarbons exposure in occupational workers.

Estimated 24-hour urinary sodium excretion as a risk factor for oxidative stress in Zambian adults: A cross-sectional study.

INTRODUCTION: Persistent oxidative stress predisposes to various non-communicable diseases (NCDs), whose occurrence is increasing in sub-Saharan Africa. The aim of this study was to evaluate the link between markers of oxidative stress and some risk factors for NCDs in a Zambian cohort. METHODS: We assessed oxidative stress by measuring 8-isoprostane (lipid oxidative stress) and 8-hydroxydeoxyguanosine (DNA oxidative stress). In addition, we measured mycotoxins (aflatoxin M1 and ochratoxin A), salt intake estimated from 24-hour sodium excretion calculated using the Tanaka and Kawaski formulae, and 1-hydroxypyrene (a metabolite of polycyclic aromatic hydrocarbons). Data on lifestyle risk factors were collected using questionnaires. RESULTS: Included were 244 participants; 128 (52%) were female and the median age was 48 years (IQR 39-58). The median level of 8-isoprostane was 0.13 ng/mg creatinine (IQR 0.08-0.23) while that of 8-hydroxydeoxyguanosine (8-OHdG) was 4 ng/mg creatinine (IQR 2-10). The median 24-hour sodium excretion was 21 g (IQR 16-25 g), with none being less than the 5 g recommended by WHO. Unadjusted urinary levels of 8-isoprostane were moderately correlated with 1-hydroxypyrene (Spearman r = 0.30, p<0.001) and estimated 24-hour urine sodium (Spearman r = 0.38, p<0.001). Urinary levels of 8-OHdG were not correlated with 1-hydroxypyrene, estimated 24-hour urine sodium, aflatoxin M1 or ochratoxin A (all p-values >0.05). Using logistic regression, adjusted and unadjusted 8-isoprostanes levels were associated with 1-hydroxypyrene (p = 0.02 and p = 0.001 respectively) and estimated 24-hour urine sodium method (p = 0.003 and p<0.001 respectively). However, only unadjusted 8-OHdG was associated with 1-hydroxypyrene (p = 0.03) and age (p = 0.007). CONCLUSIONS: Estimated 24-hour urinary sodium is high among Zambians and it is associated with lipid but not DNA oxidative stress. High exposure to polycyclic aromatic hydrocarbons is also associated with oxidative stress.

Association between urinary polycyclic aromatic hydrocarbons and hypertension in the Korean population: data from the Second Korean National Environmental Health Survey (2012-2014).

Polycyclic aromatic hydrocarbons (PAHs) are environmental and occupational pollutants derived from incomplete combustion of organic materials, including wood and fossil fuels. Epidemiological studies have evaluated the association between PAH exposure and hypertension or cardiovascular disease in the general population, but the evidence is limited. In this study, we evaluated the association between urinary PAH metabolites and hypertension in the Korean adult population. A total of 6478 adults who participated in the Second Korean National Environmental Health Survey (2012-2014) were included. The differences in urinary concentrations of four PAH metabolites, including 1-hydroxypyrene, 2-hydroxyfluorene, 1-hydroxyphenanthrene, and 2-naphthol, were compared according to hypertension status using a general linear model. Adjusted odds ratios (aORs) for hypertension were calculated according to the quartile groups of urinary PAH metabolites after adjusting for age, sex, body mass index (BMI), smoking, and alcohol consumption in multiple logistic regression analyses. The estimated mean concentrations of urinary 1-hydroxyphenanthrene were significantly higher in the hypertension group than in the non-hypertension group. In 1-hydroxyphenanthrene, the OR for hypertension was significantly higher in the third and fourth quartile groups than in the first quartile group (third: OR 1.707, 95% CI 1.203-2.423, fourth: OR 1.604, 95% CI 1.158-2.223). No significant associations were detected for the other metabolites. Our results suggest an association between exposure to PAHs and hypertension in a Korean adult population. Further studies are required to evaluate the effects of low-dose long-term exposure to PAHs on hypertension and cardiovascular disease.

Rapid Screening of Urinary 1-Hydroxypyrene Glucuronide by Multisegment Injection-Capillary Electrophoresis-Tandem Mass Spectrometry: A High-Throughput Method for Biomonitoring of Recent Smoke Exposures.

Urinary 1-hydroxypyrene (HP) is a widely used biomarker of polycyclic aromatic hydrocarbon exposure relevant for biomonitoring the deleterious health impacts from tobacco smoke and ambient air pollution, as well as the hazards of certain occupations. Conventional methods for urinary HP analysis based on liquid chromatography with native fluorescence detection or tandem mass spectrometry (MS/MS) and gas chromatography-mass spectrometry (GC-MS) are limited by low sample throughput and complicated sample workup protocols that are prone to bias. Herein, we introduce a high throughput method to directly analyze the intact glucuronide conjugate of HP (HP-G) in human urine after a simple acidified ether extraction procedure when using multisegment injection-capillary electrophoresis-tandem mass spectrometry (MSI-CE-MS/MS). Multiplexed analyses of 13 independent urine extracts are achieved in a single run (<3 min/sample) with stringent quality control while avoiding enzyme deconjugation and precolumn chemical derivatization. Method validation demonstrates good technical precision (CV = 7.7%, n = 45) and accuracy with a mean recovery of (93 ± 3%) for urinary HP-G at three concentration levels with adequate detection limits (7 ng/L, S/N = 3). An interlaboratory method comparison of urine samples collected from firefighters deployed in the 2016 Fort McMurray wildfire also confirms good mutual agreement with an acceptable negative bias (mean bias = 15%, n = 55) when measuring urinary HP-G by MSI-CE-MS/MS as compared to total hydrolyzed urinary HP by GC-MS due to the low residual levels of free HP and its sulfate conjugate. This multiplexed separation platform is optimal for large-scale biomonitoring studies of air pollution relevant to global health as well as occupational smoke exposures in firefighters susceptible to dermal PAH absorption when using personal protective equipment.

The association between prenatal exposure to polycyclic aromatic hydrocarbons and birth weight: A meta-analysis.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are a kind of endocrine disruptors, which can enter human body by the inhalation of PAH-containing matter and the ingestion of PAH-containing foodstuffs. Studies showed that PAHs can cross the placental barrier and might cause adverse effects on the fetus. OBJECTIVES: This meta-analysis aimed to estimate the associations between prenatal exposure to PAHs and birth weight. METHODS: Articles published in English until May 8, 2020 and reported the effects of prenatal exposure to PAHs on birth weight were searched in multiple electronic databases including PubMed, the Web of Science, EMBASE and the Cochrane Library. The included studies were divided into three groups in accordance with the measurement of PAHs exposure. Then coefficient was extracted, conversed and synthesized by random-effects meta-analysis. And risk of bias was assessed for each study. RESULTS: A total of 3488 citations were searched and only 11 studies were included finally after double assessment. We found that there were no association between PAH-DNA adducts in cord blood (low/high) (OR: 1.0, 95%CI: 0.97, 1.03), 1-hydroxy pyrene (1-HP) concentration in maternal urine (OR: 1.0, 95%CI: 0.97, 1.03) and prenatal maternal airborne PAHs exposure (OR: 0.97, 95%CI: 0.93, 1.01) and birth weight. However, we observed ethnicity may change the effects of PAHs exposure on birth weight. CONCLUSIONS: There is no significant relationship between prenatal exposure to PAHs and birth weight in our meta-analysis. Further studies are still needed for determining the effects of prenatal PAHs exposure on birth weight.

Influence of polycyclic aromatic hydrocarbon exposure on IVF: now is the time to focus on women.

RESEARCH QUESTION: Is polycyclic aromatic hydrocarbon (PAH) exposure associated with the reproductive outcomes of IVF treatment? DESIGN: A prospective, small-scale monocentric cohort study of couples who underwent IVF treatment between January 2018 and June 2019. Both members of each couple answered a questionnaire on PAH exposure and provided urine samples to measure urinary 1-hydroxypyrene (1-OHP) the day before oocyte retrieval and semen collection for fertilization. To assess the specific PAH exposure of gamete cells, immunostaining was conducted on both spermatozoa and granulosa cells obtained during IVF with an anti-benzo(a)pyrene diol epoxide (BPDE) monoclonal antibody that recognizes BDPE-DNA adducts. To assess DNA damage, a comet assay on spermatozoa was conducted. The PAH exposure was compared between couples who had positive HCG and couples who had negative HCG on day 14 after embryo transfer. RESULTS: Eighteen couples were included. The mean 1-OHP level in women whose HCG tests were positive (n = 6) was significantly lower than that in women with negative HCG tests (0.098 [0.042-0.170] versus 0.177 [0.067-0.812] µg/g creatinine; P = 0.048). The presence of BPDE-DNA adducts in granulosa cells of women with a negative (29.7 [16.2-57.5] arbitrary units) or positive HCG test (20.3 [9.3-23.3] arbitrary units) were not significantly different (P = 0.092). The urinary 1-OHP levels of men and BPDE-DNA adducts in spermatozoa showed no differences between groups. CONCLUSIONS: This exploratory research should encourage further studies to determine the effect of women's exposure to PAHs on reproductive outcomes of IVF treatment.

Ultrasound-assisted dispersive micro-solid-phase extraction based on N-doped mesoporous carbon and high-performance liquid chromatographic determination of 1-hydroxypyrene in urine samples.

In this research, a new ultrasound-assisted dispersive micro-solid-phase extraction method based on N-doped mesoporous carbon sorbent followed by high-performance liquid chromatography equipped with diode array detector for trace measurement of 1-hydroxypyrene as a metabolite of exposure to polycyclic aromatic hydrocarbons was optimized. Herein, the hard template method was used for the preparation of N-doped mesoporous carbon sorbent. The prepared sorbent was characterized using the Brunauer-Emmett-Teller method, transmission electron microscopy, and elemental analysis. Parameters affecting the extraction of the target metabolite were investigated using the Box-Behnken design method. Considering optimum parameters, the plotted calibration curve for 1-hydroxypyrene was linearly correlated with the concentration span of 0.1-50 µg/L for urine media. The accuracy of the optimized procedure was examined through the relative recovery tests on the fortified urine specimens. The relative recoveries fell between 95 and 101%. The method detection limit of the proposed procedure was also calculated to be 0.03 µg/L.

Aggregation-induced photoluminescence enhancement of protamine-templated gold nanoclusters for 1-hydroxypyrene detection using 9-hydroxyphenanthrene as a sensitizer.

In this study, we confirmed that protamine-templated gold nanoclusters (PRT-AuNCs) exhibit aggregation-induced emission properties (AIE-PRT-AuNCs). 1-Hydroxypyrene (1-OHPy) further induced the aggregation of AIE-PRT-AuNCs via hydrogen bonding and electrostatic and hydrophobic interactions, resulting in the aggregation-induced photoluminescence enhancement of AIE-PRT-AuNCs. 9-Hydroxyphenanthrene was able to decrease the background signal, thus increasing the sensitivity of the method. Based on these findings, a cost-effective, highly sensitive and selective strategy was proposed for the quantitative detection of 1-OHPy. This method displayed a wide linear range of 0.924 - 74.1 nmol/L with a low detection limit of 0.277 nmol/L, showing great potential for the monitoring of 1-OHPy in human urine. This strategy may provide a theoretical basis for future studies of the AIE properties of metal nanoclusters and their applications in the field of chemical and biological sensing.

Association between polycyclic aromatic hydrocarbons exposure and bone turnover in adults.

BACKGROUND: Cigarette smoking is a risk factor of osteoporosis and bone fracture. Tobacco smoke contains several polycyclic aromatic hydrocarbons. Thus, we hypothesized that environmental polycyclic aromatic hydrocarbon exposure is associated with bone loss and fracture risk. The present study examined the association between polycyclic aromatic hydrocarbon exposure and bone turnover in the general adult population. METHODS: A total of 1408 eligible participants from the National Health and Nutrition Examination Survey (NHANES 2001-2006) were included in this cross-sectional analysis. The levels of urinary N-telopeptide and serum bone-specific alkaline phosphatase, which are biomarkers of bone resorption and formation, respectively, were assessed. Meanwhile, polycyclic aromatic hydrocarbon exposure was evaluated using the concentrations of urinary polycyclic aromatic hydrocarbon metabolites. The association between polycyclic aromatic hydrocarbon exposures and N-telopeptide, and bone-specific alkaline phosphatase levels was assessed using a multivariate linear regression model. RESULTS: All polycyclic aromatic hydrocarbon metabolites except 3-phenanthrene were significantly associated with increased N-telopeptide levels (P < 0.05) after adjustment of relevant covariables. However, no significant relationship was observed between polycyclic aromatic hydrocarbon metabolites and bone-specific alkaline phosphatase levels. This relationship remained significant after the participants were assessed according to sex (P < 0.05). Additionally, all polycyclic aromatic hydrocarbon metabolites showed a positive association with N-telopeptide levels in participants aged <60 years (P < 0.05). CONCLUSION: Polycyclic aromatic hydrocarbon exposure is associated with increased bone resorption among the general adult population in the United States. Further studies must assess the potential mechanisms associated with the adverse effects of polycyclic aromatic hydrocarbon exposure on bone loss.

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

BACKGROUND: Coke 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. METHODS: A 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. RESULTS: Multiple 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. CONCLUSIONS: Urinary 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.

Urinary and Genetic Biomonitoring of Polycyclic Aromatic Hydrocarbons in Egyptian Coke Oven Workers: Associations between Exposure, Effect, and Carcinogenic Risk Assessment.

BACKGROUND: Coke oven workers are exposed to polycyclic aromatic hydrocarbons (PAHs) with possible genotoxicity and carcinogenicity. Metabolizing enzymes genes and DNA repair genes are suspected to be correlated with the level of DNA damage. They may contribute to variable individual sensitivity to DNA damage induced by PAHs exposure at workplace. OBJECTIVE: To investigate the relationship between biomarkers of PAHs: 1-hydroxypyrene (1-OHP), DNA adducts, and 8-hydroxy-2-deoxyguanosine (8-OHdG) in coke oven workers, and to assess the role of cytochrome P2E1 (CYP2E1) gene expression and DNA repairing gene (XRCC1) polymorphism in detecting workers at risk. METHODS: 85 exposed workers and 85 unexposed controls were enrolled into this study. Urinary 1-OHP, 8-OHdG, and BPDE-DNA adduct were measured. CYP2E1 gene expression and genotyping of XRCC1 399 Arg/Gln were evaluated by real-time PCR. RESULTS: The median urinary 1-OHP levels (6.3 µmol/mol creatinine), urinary 8-OHdG (7.9 ng/mg creatinine), DNA adducts (6.7 ng/µg DNA) in the exposed group were significantly higher than those in the unexposed group. Carriers of the variant allele (Gln) of XRCC1 had the highest levels of 1-OHP, DNA adducts and 8-OHdG, and the lowest level of CYP2E1 gene expression. In exposed workers, significant positive correlations were found between 1-OHP level and each of the work duration, 8-OHdG, and DNA adducts levels. There was a significant negative correlation between 1-OHP level and CYP2E1 gene expression. Work duration and CYP2E1 gene expression were predictors of DNA adducts level; 1-OHP level and work duration were predictors of urinary 8-OHdG level. CONCLUSION: Workers with higher exposure to PAH were more prone to oxidative DNA damage and cancer development. DNA adducts level reflects the balance between their production by CYP2E1 and elimination by XRCC1 gene.

Measurement of urinary 1-aminopyrene and 1-hydroxypyrene as biomarkers of exposure to diesel particulate matter in gold miners.

Metabolites of polycyclic aromatic hydrocarbons measured in human samples are often used as biomarkers of exposure to diesel engine exhaust (DEE). The aim of this study was to assess the changes in urinary levels of 1-aminopyrene (1-AP) and 1-hydroxypyrene (1-OHP) and their relationship with Elemental Carbon (EC), as a component of diesel engine exhaust exposure, among a hard-rock gold-mining population. Urine samples were collected at the beginning and end of a 12-hour work shift from 100 underground and above ground gold miners. Miners were fitted with personal exposure monitoring equipment to quantify exposure to DEE, measured as Elemental Carbon (EC), across their 12-hour work shift. General linear regression assessed associations of the post-shift urinary 1-AP and 1-OHP concentrations with EC, controlling for age, gender, the pre-shift biomarker level, Body Mass Index (BMI), days on current shift, time in mining, smoking status and second-hand smoke exposure. The concentrations of 1-AP and 1-OHP increased significantly across a 12-hour mining work shift. Moreover, consistent with the sensitivity analysis, the concentration of 1-AP was significantly associated with EC after adjustments. Urinary 1-OHP, but not 1-AP was significantly associated with current smoking. Urinary 1-AP may be a more robust and specific biomarker of DEE than 1-OHP.

Coupling of micro-solid-phase extraction and internal extractive electrospray ionization mass spectrometry for ultra-sensitive detection of 1-hydroxypyrene and papaverine in human urine samples.

Quantification of ultra-trace analytes in complex biological samples using micro-solid-phase extraction followed by direct detection with internal extractive electrospray ionization mass spectrometry (µSPE-iEESI-MS) was demonstrated. 1-Hydroxypyrene (1-OHP) and papaverine at attomole levels in human raw urine samples were analyzed under negative and positive ion detection mode, respectively. The µSPE was simply prepared by packing a disposable syringe filter with octadecyl carbon chain (C18)-bonded micro silica particles, which were then treated as the "bulk sample" after the analytes were efficiently enriched by the C18 particles. Under the optimized experimental conditions, the analytes were readily eluted by isopropanol/water (80/20, V/V) at a high voltage of ± 4.0 kV, producing analyte ions under ambient conditions. The limit of detection (LOD) was 0.02 pg/L (9.2 amol) for 1-hydroxypyrene and 0.02 pg/L (5.9 amol) for papaverine. The acceptable linearity (R2 > 0.99), signal stability (RSD ≤ 10.7%), spike recoveries (91-95%), and comparable results for real urine samples were also achieved, opening up possibilities for quantitative analysis of trace compounds (at attomole levels) in complex bio-samples. Graphical abstract.

Urinary mutagenicity and other biomarkers of occupational smoke exposure of wildland firefighters and oxidative stress.

Background: Wildland firefighters conducting prescribed burns are exposed to a complex mixture of pollutants, requiring an integrated measure of exposure. Objective: We used urinary mutagenicity to assess if systemic exposure to mutagens is higher in firefighters after working at prescribed burns versus after non-burn work days. Other biomarkers of exposure and oxidative stress markers were also measured. Methods: Using a repeated measures study design, we collected urine before, immediately after, and the morning after a work shift on prescribed burn and non-burn work days from 12 healthy subjects, and analyzed for malondialdehyde (MDA), 8-isoprostane, 1-hydroxypyrene (OH-pyrene), and mutagenicity in Salmonella YG1041 +S9. Particulate matter (PM2.5) and carbon monoxide (CO) were measured by personal monitoring. Light-absorbing carbon (LAC) of PM2.5 was measured as a surrogate for black carbon exposure. Linear mixed-effect models were used to assess cross-work shift changes in urinary biomarkers. Results: No significant differences occurred in creatinine-adjusted urinary mutagenicity across the work shift between burn days and non-burn days. Firefighters lighting fires had a non-significant, 1.6-fold increase in urinary mutagenicity for burn versus non-burn day exposures. Positive associations were found between cross-work shift changes in creatinine-adjusted urinary mutagenicity and MDA (p = 0.0010), OH-pyrene (p = 0.0001), and mass absorption efficiency which is the LAC/PM2.5 ratio (p = 0.2245), respectively. No significant effect of day type or work task on cross-work shift changes in MDA or 8-isoprostane was observed. Conclusion: Urinary mutagenicity may serve as a suitable measure of occupational smoke exposures among wildland firefighters, especially among those lighting fires for prescribed burns.

Simultaneous HPLC-MS determination of 8-hydroxy-2'-deoxyguanosine, 3-hydroxyphenanthrene and 1-hydroxypyrene after online in-tube solid phase microextraction using a graphene oxide/poly(3,4-ethylenedioxythiophene)/polypyrrole composite.

The exploration of monohydroxy polycyclic aromatic hydrocarbons and 8-hydroxy-2'-deoxyguanosine (8-OHdG) produced by oxidative stress and DNA damage is a powerful and non-invasive tool to study the health risk of exposure to polycyclic aromatic hydrocarbons (PAHs). A nanocomposite prepared from graphene oxide, poly(3,4-ethylenedioxythiophene) and polypyrrole was electrodeposited on the internal surface of a stainless-steel tube for online in-tube solid phase microextraction (IT-SPME) of 8-OHdG, 3-hydroxyphenanthrene and 1-hydroxypyrene from urine. The coating possesses excellent chemical and mechanical stability, high extraction efficiency, good resistance to matrix interference, and a long lifespan. An online IT-SPME-high performance liquid chromatography-mass spectrometry method was developed for the determination of these three metabolite biomarkers in human urine. Figures of merit include (a) enrichment factors of 30-48; (b) low limits of detection (4-41 pg·mL-1 at S/N = 3); (c) wide linear ranges (0.05-50 ng·mL-1); (d) good recoveries from spiked samples (71.6-109.5%); and (e) acceptable repeatability (2.3-14.6%). The method offers the advantages of low cost, simplicity, sensitivity, rapidity and automation. Graphical abstract Schematic illustration of online in-tube solid phase microextraction using graphene oxide/poly(3,4-ethylenedioxythiophene)/polypyrrole composites as adsorbent in a stainless-steel (SS) tube for the enrichment and simultaneous determination of 8-hydroxy-2'-deoxyguanosine, 3-hydroxyphenanthrene and 1-hydroxypyrene prior to HPLC-MS analysis.

Urinary 1-hydroxypyrene and Skin Contamination in Firefighters Deployed to the Fort McMurray Fire.

BACKGROUND: In May 2016, firefighters from the province of Alberta, Canada deployed to a fire that engulfed the urban area of Fort McMurray. During the first days of the fire, firefighters experienced heavy smoke exposures during greatly extended work shifts. Urinary samples were collected post-deployment from three fire services for estimation of 1-hydroxypyrene (1-HP) concentration, reflecting exposure to polycyclic aromatic hydrocarbons (PAHs), to determine the effects of respiratory protective equipment (RPE) and skin hygiene in reducing internal dose. METHODS: Urine samples from one fire service (n = 62) were analyzed for 1-HP by two laboratories, using different assays (LC-MS/MS: GC-MS): remaining samples were analyzed just by LC-MS/MS. A Skin Exposure Mitigation Index (SEMI) was computed from questions on opportunities for changing clothing, showering, and washing during breaks. Regression analyses, using 1-HP ng/g creatinine as the dependent variable, assessed the effect of RPE and skin factors on PAH absorption, allowing for environmental exposure and potential confounders. Stratification identified key groups with equal delay in sample collection. RESULTS: 1-HP was detected in 71.0% of 62 samples by LC-MS/MS and 98.4% by GC-MS, with good mutual agreement between the methods. In 171 post-fire samples, 1-HP corrected for creatinine was related to current cigarette smoking and recent barbeque. Among those with samples collected within 48 h, urinary 1-HP was correlated with estimated exposure(r = 0.53, P < 0.001). In those with only one rotation before urine sample collection, no effect was seen of RPE use but I-HP was significantly lower (P = 0.003) in those with those with a high score on the SEMI scale, indicating better access to factors mitigating skin absorption. CONCLUSION: Skin exposure to PAHs is an important route of absorption in firefighters, which can be mitigated by good skin hygiene.