1-hydroxypyrene Concentrations Research Articles

Effect of combined exposure to phthalates and polycyclic aromatic hydrocarbons during early pregnancy on gestational age and neonatal size: A prospective cohort study

Many studies have indicated that individual exposure to phthalates (PAEs) or polycyclic aromatic hydrocarbons (PAHs) affects pregnancy outcomes. However, combined exposure to PAEs and PAHs presents a more realistic situation, and research on the combined effects of PAEs and PAHs on gestational age and newborn size is still limited. This study aimed to assess the effects of combined exposure to PAEs and PAHs on neonatal gestational age and birth size. Levels of 9 PAE and 10 PAH metabolites were measured from the urine samples of 1030 women during early pregnancy from the Zunyi Birth Cohort in China. Various statistical models, including linear regression, restricted cubic spline, Bayesian kernel machine regression, and quantile g-computation, were used to study the individual effects, dose–response relationships, and combined effects, respectively. The results of this prospective study revealed that each ten-fold increase in the concentration of monoethyl phthalate (MEP), 2-hydroxynaphthalene (2-OHNap), 2-hydroxyphenanthrene (2-OHPhe), and 1-hydroxypyrene (1-OHPyr) decreased gestational age by 1.033 days (95 % CI: −1.748, −0.319), 0.647 days (95 % CI: −1.076, −0.219), 0.845 days (95 % CI: −1.430, −0.260), and 0.888 days (95 % CI: −1.398, −0.378), respectively. Moreover, when the concentrations of MEP, 2-OHNap, 2-OHPhe, and 1-OHPyr exceeded 0.528, 0.039, 0.012, and 0.002 µg/g Cr, respectively, gestational age decreased in a dose–response manner. Upon analyzing the selected PAE and PAH metabolites as a mixture, we found that they were significantly negatively associated with gestational age, birth weight, and the ponderal index, with 1-OHPyr being the most important contributor. These findings highlight the adverse effects of single and combined exposure to PAEs and PAHs on gestational age. Therefore, future longitudinal cohort studies with larger sample sizes should be conducted across different geographic regions and ethnic groups to confirm the impact of combined exposure to PAEs and PAHs on birth outcomes.

Systemic oxidative stress levels during the course of pregnancy: Associations with exposure to air pollutants

Increased systemic oxidative stress, implicated in adverse pregnancy outcomes for both mothers and fetuses, has been associated with gestational exposure to air pollutants such as polycyclic aromatic hydrocarbons (PAHs), fine particulate matter (PM2.5), and nitrogen dioxide (NO2). However, it is unclear whether exposure to pollutants at levels below the current air quality standards can increase oxidative stress in pregnant women. In a cohort of 305 pregnant persons residing in western New York, we examined the association between exposure to PM2.5, NO2, and PAHs (measured as urinary 1-hydroxypyrene) and urinary biomarkers of oxidative stress (malondialdehyde [MDA] and 8-hydroxy-2′-deoxyguanosine [8-OHdG]) measured in each trimester. After controlling for gestational stage, maternal age, lifestyles, and socioeconomic factors, each interquartile range (IQR) increase in 1-hydroxypyrene concentration (65.8 pg/ml) was associated with a 7.73% (95%CI: 3.18%,12.3%) higher in MDA levels throughout the pregnancy and in the first and second trimester. An IQR increase in PM2.5 concentration (3.20 μg/m3) was associated with increased MDA levels in the first trimester (8.19%, 95%CI: 0.28%,16.1%), but not the 2nd (−7.99%, 95% CI: 13.8%, −2.23%) or 3rd trimester (−2.81%, 95% CI: 10.0%, 4.38%). The average cumulative PM2.5 exposures in the 3–7 days before urine collection were associated with increased 8-OHdG levels during the second trimester, with the largest difference (22.6%; 95% CI: 3.46%, 41.7%) observed in relation to a one IQR increase in PM2.5 concentration in the previous 7 days. In contrast, neither oxidative stress biomarker was associated with NO2 exposure. Observed in pregnant women exposed to low-level air pollution, these findings expanded previously reported associations between systemic oxidative stress and high-level PM2.5 and PAH concentrations. Further, the first and second trimesters may be a susceptible window during pregnancy for oxidative stress responses to air pollution exposure.

Effects of polycyclic aromatic hydrocarbon exposure on mitochondrial DNA copy number.

Airborne polycyclic aromatic hydrocarbon (PAH) exposure can adversely affect human health by generating reactive oxygen species (ROS) and increasing oxidative stress, which causes changes in mitochondrial DNA copy number (mtDNAcn), a key indicator of mitochondrial damage and dysfunction. This study aimed to determine the effects of atmospheric benzo[a]pyrene (BaP) and 1-nitropyrene (1-NP) exposure on mtDNAcn in humans. One hundred and eight adults living in Cheongju, South Korea, were included in this study. Atmospheric BaP and 1-NP concentrations and urinary 6-hydroxy-1-nitropyrene (6-OHNP), N-acetyl-1-aminopyrene (1-NAAP), and 1-hydroxypyrene concentrations were measured. Blood samples were also collected to assess mtDNAcn. The mean mtDNAcn was 9.74 (SD 4.46). mtDNAcn decreased significantly with age but was not significantly associated with sex, sampling season, or smoking habit. While there was a borderline significant increase in mtDNAcn with increasing ambient total PAH levels, ambient PAH or urinary 1-hydroxypyrene concentrations showed no significant association with mtDNAcn. However, urinary 6-OHNP or 1-NAAP concentrations, 1-NP metabolites, were significantly associated with mtDNAcn. These results suggest that the metabolism of absorbed NPs generates excess ROS, which damages mitochondrial DNA, resulting in increased mtDNAcn.

Exposure to Benzo[a]pyrene and 1-Nitropyrene in Particulate Matter Increases Oxidative Stress in the Human Body.

Polycyclic aromatic hydrocarbons (PAHs) have been reported to cause oxidative stress in metabolic processes. This study aimed to evaluate the relationship between exposure to PAHs, including benzo[a]pyrene (BaP) and 1-nitropyrene (1-NP), in the atmosphere and oxidative stress levels in the human body. This study included 44 Korean adults who lived in Cheongju, Republic of Korea. Atmospheric BaP and 1-NP concentrations and urinary 6-hydroxy-1-nitropyrene (6-OHNP), N-acetyl-1-aminopyrene (1-NAAP), and 1-hydroxypyrene (1-OHP) concentrations were measured. The oxidative stress level was assessed by measuring urinary thiobarbituric acid-reactive substances (TBARS) and 8-hydroxydeoxyguanosine (8-OHdG) concentrations. Urinary TBARS and 6-OHNP concentrations significantly differed between winter and summer. BaP exposure was significantly associated with urinary 8-OHdG concentrations in summer. However, atmospheric 1-NP did not show a significant correlation with oxidative stress marker concentrations. Urinary 1-NAAP concentration was a significant determinant for urinary 8-OHdG concentration in summer. Oxidative stress in the body increases in proportion to inhalation exposure to BaP, and more 8-OHdG is produced in the body as the amount of 1-NP, which is metabolized to 1-AP or 1-NAAP, increases.

Human biomonitoring and reference values of urinary 1-hydroxypyrene among Iranian adults population.

Polycyclic aromatic hydrocarbons (PAHs) are one of the most important environmental pollutants. Urinary concentrations of 1-hydropyren metabolites of PAHs have been used as biomarkers of these chemicals' exposure in humans. This cross-sectional study was conducted on 468 healthy Iranian adults over 25 years old and non-smokers in six provinces who were selected based on the clustering method. Fasting urine sampling and body composition and demographic measurements were performed. Urine samples were analyzed by GC-MS. The analysis included descriptive statistics and analytical statistics using multiple linear regression by Python software. 1-Hydroxypyrene was found in 100% of samples, and the mean (Reference Value 95%) concentration of 1-hydroxypyrene was 6.12 (RV 95%: 20) μg/L and 5.95 (21) μg/gcrt. There was a direct relationship between the amount of body composition (body fat, visceral fat), BMI, and age with the urinary concentrations of 1-hydropyren metabolites, and this relationship was significant for BMI with urinary concentrations of 1-hydropyren metabolites (P = 0.045). The amount of 1-hydroxypyrene in healthy Iranian adults has been higher than in similar studies in other countries. These results provide helpful information regarding the exposure of Iranian adults to 1-hydroxypyrene, and these data can be used to supplement the national reference values of human biomonitoring for the interpretation of biomonitoring results.

Urinary concentrations of polycyclic aromatic hydrocarbon metabolites and childhood obesity

ObjectivesExisting literature provides limited information on the association between childhood obesity and polycyclic aromatic hydrocarbons (PAHs), which are potentially obesogenic. We examined the association between urinary concentrations of PAH metabolites and obesity in the Korean pediatric population. MethodsWe analyzed the data of 2286 children/adolescents aged 3–17 years who participated in the Korean National Environmental Health Survey between 2015 and 2017. Urinary concentrations of 2-naphthol, 2-hydroxyfluorene, 1-hydroxyphenanthrene, and 1-hydroxypyrene were assayed using gas chromatography–mass spectrometry. Overweight/obesity was defined as a body mass index (BMI) for age ≥85th percentile. Multiple linear and logistic regression models were used to analyze the relationship of BMI z-score and overweight with urinary concentrations of PAH metabolites after adjusting for age, sex, household income, parental education level, physical activity, fast-food consumption, and environmental tobacco smoke exposure. ResultsBMI z-score was positively associated with 2-naphthol concentrations in children aged 6–11 and 12–17 years and with 1-hydroxypyrene concentrations in children aged 6–11 years. In the overall population, a significant rise in odds ratios for overweight/obesity across 2-naphthol quartiles was noted. Specifically, the 3rd and 4th quartiles displayed odds ratios of 1.39 [1.03, 1.88] and 1.46 [1.08, 1.99] respectively, compared to the 1st quartile (P-for-trend = 0.006). Similar associations between 2-naphthol and overweight/obesity status were observed in the 6–11- and 12–17-year age groups. There was little evidence of an association between overweight/obesity and other PAH hydroxy derivatives. ConclusionsPAH exposure may be associated with increased childhood adiposity, a potential risk factor for adult obesity and adverse metabolic outcomes.

Biomarkers for polycyclic aromatic hydrocarbons in human excreta: recent advances in analytical techniques-a review.

Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental pollutants that are generated by the incomplete combustion of organic materials. The main anthropogenic sources of PAHs are the combustion of solid fuels for heating purposes, illegal waste incineration, road transport and industries based on fossil fuels. PAHs can easily enter the body because they are present in all elements of the environment, including water, soil, air, and food. Due to their ubiquitous presence, PAHs, may exert a harmful effect on human health. Assessing PAH exposure through biomonitoring mostly involve techniques to measure the concentration of 1-hydroxypyrene in human urine. Nevertheless, through recent progress in analytical techniques, other common metabolites of PAHs in human biospecimens can be detected. A scientific literature search was conducted to determine which hydroxy derivatives of PAHs are markers of PAHs exposure and to reveal the leading sources of these compounds. Techniques for analyzing biological samples to identify OH-PAHs are also discussed. The most frequently determined OH-PAH in human urine is 1-hydroxypyrene, the concentration of which reaches up to a dozen ng/L in urine. Apart from this compound, the most frequently determined biomarkers were naphthalene and fluorene metabolites. The highest concentrations of 1- and 2-hydroxynaphthalene, as well as 2-hydroxyfluorene, are associated with occupational exposure and reach approximately 30ng/L in urine. High molecular weight PAH metabolites have been identified in only a few studies. To date, PAH metabolites in feces have been analyzed only in animal models for PAH exposure. The most frequently used analytical method is HPLC-FLD. However, compared to liquid chromatography, the LOD for gas chromatography methods is at least one order of magnitude lower. The hydroxy derivatives naphthalene and fluorene may also serve as indicators of PAH exposure.

Polycyclic aromatic hydrocarbons and changes in brain cortical thickness and an Alzheimer's disease-specific marker for cortical atrophy in adults: A longitudinal neuroimaging study of the EPINEF cohort

Although several epidemiological studies have suggested that exposure to polycyclic aromatic hydrocarbons (PAHs) may induce brain atrophy, no longitudinal study has investigated the effect of PAH exposure on brain structural changes. This study examined the longitudinal associations between urinary PAH metabolites and brain cortical thickness. We obtained urinary concentrations of PAH metabolites and brain magnetic resonance images from 327 adults (≥50 years of age) without dementia at baseline and 3-year follow-up. We obtained whole-brain and regional cortical thicknesses, as well as an Alzheimer's disease (AD)-specific marker for cortical atrophy (a higher score indicated a greater similarity to patients with AD) at baseline and follow-up. We built a linear mixed-effect model including each of urinary PAH metabolites as the time-varying exposure variable of interest. We found that increases in urinary concentrations of 1-hydroxypyrene (β = −0.004; 95% CI, −0.008 to −0.001) and 2-hydroxyfluorene (β = −0.011; 95% CI, −0.015 to −0.006) were significantly associated with a reduced whole-brain cortical thickness. A urinary concentration of 2-hydroxyfluorene was significantly associated with an increased AD-specific cortical atrophy score (β = 2.031; 95% CI, 0.512 to 3.550). The specific brain regions showing the association of urinary concentrations of 1-hydroxypyrene, 2-naphthol, 1-hydroxyphenanthrene, or 2-hydroxyfluorene with cortical thinning were the frontal, parietal, temporal, and cingulate lobes. These findings suggested that exposure to PAHs may reduce brain cortical thickness and increase the similarity to AD-specific cortical atrophy patterns in adults.

Urinary 1-hydroxypyrene in pregnant women in a Northeastern U.S. city: socioeconomic disparity and contributions from air pollution sources.

Maternal exposure to polycyclic aromatic hydrocarbons (PAHs), ubiquitous constituents of air pollution, has been associated with adverse birth outcomes. Yet it remains unclear whether and how socioeconomic status (SES) affects gestational PAH exposure. To examine whether there are socioeconomic disparities in PAHs exposure among pregnant women from Rochester, NY, and if so, to what extent disproportionate proximity to air pollution sources, measured by residential distance to transportation-related sources, contributed to the exposure disparity. We measured 1-hydroxypyrene concentrations in 726 urine samples collected from 305 pregnant women up to three samples throughout pregnancy. Residential distances to transportation-related sources were calculated based on participants' home addresses. We used linear mixed-effects models with random intercepts of participants to examine associations between 1-hydroxypyrene, SES indicators, and distance to transportation-related sources. We used structural equation modelling to assess to what extent distance to transportation-related sources contributes to the socioeconomic disparity in 1-hydroxypyrene concentrations. Reduced household income and maternal education level were both significant SES predictors of 1-hydroxypyrene concentrations, after the adjustment for other maternal demographic characteristics. Eachinterquartile range (IQR) increases in residential proximity to the airport (from 14.3 to 6.0 km), the railroad yard (from 22.3 to 6.0 km), and annual average daily traffic within 300 m (from 3796 to 99,933 vehicles/year) were associated with 15.0% (95%CI: 7.0-22.2%), 15.4% (95%CI: 6.5-23.5%), and 13.6% (95%CI: 4.7-23.3%) increases in 1-hydroxypyrene concentrations, respectively. Proximity to these sources jointly explained 10% (95%CI: 1.6-18.4%) of the 1-hydroxypyrene concentration change associated with decreases in SES as a latent variable defined by both household income and education level. Our findings suggest that efforts to address disproportionate residential proximity to transportation-related sources may reduce the socioeconomic disparity in PAH exposure.

ODP277 Urinary Concentrations of Polycyclic Aromatic Hydrocarbons and Childhood Obesity

Abstract Background Polycyclic aromatic hydrocarbons (PAHs), primarily produced by incomplete combustion of organic materials, have been suggested as obesogens, but information on PAHs and obesity, especially in children, is limited. We examined the cross-sectional association between urinary concentrations of PAHs and obesity in the Korean pediatric population. Methods We analyzed the data of 2286 children and adolescents aged 3–17 years who participated in the Korean National Environmental Health Survey (KoNEHS) 2015–2017. Urinary concentrations of 2-naphthol, 2-hydroxyfluorene, 1-hydroxyphenanthrene, and 1-hydroxypyrene were assayed using gas chromatography-mass spectrometry. Covariate-adjusted standardization method was used for the urinary dilution adjustment. Overweight and obesity were defined as BMI-for-age ≥85th percentile and ≥95th percentile, respectively. Multiple linear and logistic regression models were performed to analyze the relationship of BMI z-score and overweight with urinary concentrations of PAHs after adjusting for age, sex, household income, parental education level, physical activity, fast-food consumption, and ETS exposure. Results Obese children showed significantly higher urinary 2-naphthol concentrations than normal-weighted children in the overall population [3.62 µg/L (95% confidence intervals (95% CI): 3.20, 4. 09) vs. 2.88 µg/L (95% CI: 2.62, 3.16)]. Similar findings were observed in the age groups 6-11 and 12-17 years. Significant increases in BMI z-scores for 10 times increase in urinary 2-naphthol concentrations were observed in the age groups 6-11 [0.31 z-score units, (95% CI: 0.13, 0.49), P = 0. 001] and 12-17 years [0.33 z-score units, (95% CI: 0. 05, 0.60), P=0. 02]. A significant but smaller association was observed between change in BMI z-score and 1-hydroxypyrene concentrations in the 6-11 year group [0.14 z-score units, (95% CI: 0. 02, 0.27), P=0. 03]. The multiple logistic regression models for overweight showed significant positive associations with the quartiles of 2-NAP in the overall population [OR (95% CI); 1.14 (0.83-1.55), 1.39 (1. 03, 1.88), 1.46 (1. 08, 1.99) in the 2nd, 3rd, and 4th quartile, respectively, compared with the 1st quartile; P-for-trend=0. 006]. Similar associations between 2-naphthol and overweight status were also observed in the 6-11 year and 12-17 year groups. Conclusion This result suggests a possible link between PAH exposure, particularly 2-naphthol, and obesity in the Korean pediatric population. Given the growing obesity rates among Asian children and adolescents, this finding warrants further studies on the impacts of long-term exposure of PAHs on childhood obesity and possible mechanisms for this association. Presentation: No date and time listed

Urinary polycyclic aromatic hydrocarbon, arsenic, and metal exposure and correlation with emphysema in smokers

PurposeEnvironmental exposure to metals and chemicals can increase the risk of acute and chronic pulmonary diseases in the human population. This study aimed to analyze seven forms of polycyclic aromatic hydrocarbons (PAHs), seven types of arsenic species, fourteen types of urinary metals including antimony, barium, cadmium, cesium, cobalt, lead, manganese, mercury, molybdenum, strontium, thallium, tin, tungsten, uranium, and the link with emphysema in the US adult cigarette smoking population. MethodsA specialized weighted complex survey design analysis using 2011–2016 National Health and Nutrition Examination Survey (NHANES) datasets was conducted. Multivariate logistic regression models were used to assess the association between urinary metals, arsenic, PAHs, and emphysema in adult smokers. R software was used to conduct the statistical analysis. ResultsAll 4th quantile concentrations of PAHs, including 1-hydroxynaphthalene, 2-hydroxynaphthalene, 3-hydroxyfluorene, 2-hydroxyfluorene, 1-hydroxypyrene, 1-hydroxyphenanthrene, and 2 & 3-hydroxyphenanthrene, were significantly associated with emphysema in smokers. The 3rd quantile of 1-hydroxypyrene were also associated with increased odds of emphysema in smokers. Among arsenic and metals, the 4th quantile of cadmium was associated with an increased odds of emphysema in smokers. The 3rd quantile of dimethylarsinic acid (DMA) and 4th quantile of mercury were found to have inverse relationships with emphysema in smokers. Several demographic factors had significant associations with emphysema in smokers. ConclusionUrinary PAHs and cadmium were associated with increased odds of emphysema in smokers. DMA and mercury had an inverse association with emphysema in smokers.

Aryl hydrocarbon receptor activation-mediated vascular toxicity of ambient fine particulate matter: contribution of polycyclic aromatic hydrocarbons and osteopontin as a biomarker

BackgroundExposure to ambient fine particulate matter (PM2.5) is associated with vascular diseases. Polycyclic aromatic hydrocarbons (PAHs) in PM2.5 are highly hazardous; however, the contribution of PM2.5-bound PAHs to PM2.5-associated vascular diseases remains unclear. The ToxCast high-throughput in vitro screening database indicates that some PM2.5-bound PAHs activate the aryl hydrocarbon receptor (AhR). The present study investigated whether the AhR pathway is involved in the mechanism of PM2.5-induced vascular toxicity, identified the PAH in PM2.5 that was the major contributor of AhR activation, and identified a biomarker for vascular toxicity of PM2.5-bound PAHs.ResultsTreatment of vascular smooth muscle cells (VMSCs) with an AhR antagonist inhibited the PM2.5-induced increase in the cell migration ability; NF-κB activity; and expression of cytochrome P450 1A1 (CYP1A1), 1B1 (CYP1B1), interleukin-6 (IL-6), and osteopontin (OPN). Most PM2.5-bound PAHs were extracted into the organic fraction, which drastically enhanced VSMC migration and increased mRNA levels of CYP1A1, CYP1B1, IL-6, and OPN. However, the inorganic fraction of PM2.5 moderately enhanced VSMC migration and only increased IL-6 mRNA levels. PM2.5 increased IL-6 secretion through NF-κB activation; however, PM2.5 and its organic extract increased OPN secretion in a CYP1B1-dependent manner. Inhibiting CYP1B1 activity and silencing OPN expression prevented the increase in VSMC migration ability caused by PM2.5 and its organic extract. The AhR activation potencies of seven PM2.5-bound PAHs, reported in the ToxCast database, were strongly correlated with their capabilities of enhancing the migration ability of VSMCs. Benzo(k)fluoranthene (BkF) contributed the most to the AhR agonistic activity of ambient PM2.5-bound PAHs. The association between PM2.5-induced vascular toxicity, AhR activity, and OPN secretion was further verified in mice; PM2.5-induced intimal hyperplasia in pulmonary small arteries and OPN secretion were alleviated in mice with low AhR affinity. Finally, urinary concentrations of 1-hydroxypyrene, a major PAH metabolite, were positively correlated with plasma OPN levels in healthy humans.ConclusionsThe present study offers in vitro, animal, and human evidences supporting the importance of AhR activation for PM2.5-induced vascular toxicities and that BkF was the major contributor of AhR activation. OPN is an AhR-dependent biomarker of PM2.5-induced vascular toxicity. The AhR activation potency may be applied in the risk assessment of vascular toxicity in PAH mixtures.

Exposure assessment of polycyclic aromatic hydrocarbons in refined coal tar sealant applications.

Refined coal tar sealant (RCTS) emulsions are used to seal the surface of asphalt pavement. Nine of the 22 polycyclic aromatic hydrocarbons (PAHs) evaluated in this study are classified as known, probable, or possible human carcinogens. Exposure assessment research for RCTS workers has not been published previously. The overall objective of this study was to develop a representative occupational exposure assessment of PAH exposure for RCTS workers based on worksite surveys. The specific aims were to: 1) quantify full-shift airborne occupational exposures to PAHs among RCTS workers; 2) quantify workers' dermal exposures to PAHs; 3) quantify biomarkers of PAH exposure in workers' urine; 4) identify specific job titles associated with RCTS exposure; and 5) apply these results to a biological exposure index to assess risk of potential genotoxicity from occupational exposures. A total of twenty-one RCTS workers were recruited from three companies. Personal and area air samples were collected using a modification of NIOSH Method 5515. Dermal exposure was assessed by hand and neck wipes before and after shifts. Twenty-two PAHs were quantified via gas chromatography-mass spectrometry selected ion monitoring. Internal dose was estimated by quantifying select PAH metabolites in pre- and post-shift urine samples using on-line solid phase extraction-high performance liquid chromatography-tandem mass spectrometry. PAH levels in the worker breathing zones were highest for naphthalene, acenaphthene, and phenanthrene, with geometric means of 52.1, 11.4, and 9.8μg/m3, respectively. Hand wipe levels of phenanthrene, fluoranthene and pyrene were the highest among the 22 PAHs with geometric means of 7.9, 7.7, and 5.5μg/cm2, respectively. Urinary PAH biomarkers for naphthalene, fluorene, phenanthrene, and pyrene were detected in all workers and were higher for post-shift samples than those collected pre-shift. Urinary concentrations of the metabolite 1-hydroxypyrene were greater than the American Conference of Governmental Industrial Hygienists (ACGIH) Biological Exposure Index (BEI) for this metabolite in 89 percent of post-shift samples collected on the final day of the work week or field survey. Statistically significances were found between concentrations of fluorene, naphthalene, and phenanthrene in the breathing zone of workers and their corresponding urinary PAH biomarkers. Workers were placed in two work place exposure groups: applicators and non-applicators. Applicators had higher total PAH concentrations in personal breathing zone (PBZ) air samples than non-applicators and were more likely to have post-shift hand wipe concentrations significantly higher than pre-shift concentrations. Concentrations of post-shift urinary biomarkers were higher, albeit not significantly, for applicators than non-applicators. The exposure results from RCTS worker samples cannot be explained by proximal factors such as nearby restaurants or construction. Air and skin concentration levels were substantially higher for RCTS workers than previously published levels among asphalt workers for all PAHs. PAH profiles on skin wipes were more consistent with RCTS sealant product than air samples. Last day post-shift urinary concentrations of 1-hydroxypyrene greatly exceeded the ACGIH BEI benchmark of 2.5μg/L in 25 of 26 samples, which suggests occupational exposure and risk of genotoxicity. When pyrene and benzo[a]pyrene were both detected, concentration ratios from personal exposure samples were used to calculate the adjusted BEI. Concentrations of 1-hydroxypyrene exceeded the adjusted BEIs for air, hand wipes, and neck wipes in most cases. These results indicate the need to increase safety controls and exposure mitigation for RCTS workers.

Environmental endocrine disruptor concentrations in urine samples from Mexican Indigenous women

The Indigenous communities in Mexico show significant degrees of vulnerability to pollution due to the lack of knowledge of health risks, traditions, low levels of support, and restricted access to healthcare. As a result, exposure to environmental endocrine disruptors increases in these populations through plastic components or indoor air pollution. Therefore, the aim of the study was to evaluate the exposure to phthalate metabolites, 1-hydroxypyrene, and bisphenol A through biomonitoring data from indigenous Mexican women. A total of 45 women from the Tocoy community in San Luis Potosí, Mexico, were included. Urine samples were analyzed for Bisphenol Aand 4 phthalate metabolites by ultra-performance liquid chromatography couples to tandem mass spectrometry; additionally, the 1-hydroxypyrene concentrations were evaluated by high-performance liquid chromatography coupled to a fluorescence detector. Among the main pollution sources were the use of plastic containers and burning garbage (98-100%). Indigenous women presented an exposure of 100% to mono-2-ethyl phthalate, mono-n-butyl phthalate, and 1-hydroxypyrene, with a median (25th-75th percentiles) of 17,478 (11,362-37,355), 113.8 (61.7-203.5), and 1.2 (0.9-1.7) µg/g creatinine, respectively. The major findings show urinary mono-2-ethyl phthalate concentrations higher than those measured from other studies. Therefore, these results show an impressive exposure to di(2-ethylhexyl) phthalate in Indigenous women. The current study reflects the absence of regulatory policies in marginalized populations. It highlights the need to design strategies that mitigate exposure and the importance of biological monitoring to evaluate and prevent health risk associated with exposure to environmental endocrine disruptors.

Effects of polycyclic aromatic hydrocarbons exposure on prognosis of high risk human papillomavirus infection: a prospective cohort study

Objective: To investigate the effects of polycyclic aromatic hydrocarbons (PAHs) exposure on the prognosis of high risk human papillomavirus (HR-HPV) infection. Methods: In this prospective study, 564 patients with low-grade cervical intraepithelial neoplasia confirmed by pathology were selected from the natural cohort population established by our research group in Shanxi province in 2014. Based on the baseline data of demographic characteristics and factors related to HPV infection, the concentrations of 1-hydroxypyrene in urine samples of the patients were determined by high performance liquid chromatography to define the exposure level of PAHs. At baseline survey and follow-up after 24 months, flow-through hybridization was used to detect HPV infection types, and to evaluate the prognosis of HR-HPV (persistent infection, negative conversion, positive conversion and persistent negative status). Results: Of the 564 subjects, 483 completed the follow-up, with a follow-up rate of 85.6% (483/564). Among them, the persistent infection rate was 52.4% (75/143), the persistent homotype infection rate was 35.7% (51/143), the negative conversion rate was 47.6% (68/143), the positive conversion rate was 19.7% (67/340), and the persistent negative rate was 80.3% (273/340). The follow-up results showed that the persistent infection rate (aRR=3.22, 95%CI: 1.85-5.62) and positive conversion rate (aRR=2.84, 95%CI: 1.64-4.94) of HR-HPV in high PAHs exposure group were higher than those in low PAHs exposure group, while the persistent negative rate (aRR=0.55, 95% CI: 0.43-0.70) of HR-HPV in high PAHs exposure group were lower than those in low PAHs exposure group. Based on restrictive cubic spline analysis, the results showed that the effects of PAHs exposure on persistent HR-HPV infection and persistent homotype infection showed an ascending linear dose-response relationship, while on HR-HPV positive conversion and persistent negative status showed an ascending and declining nonlinear dose-response relationship respectively (P<0.01). Conclusions: High PAHs exposure could promote persistent HR-HPV infection and persistent homotypic infection. Reducing PAHs exposure might conducive to HR-HPV continuous negative maintenance. Active prevention and control of PAHs exposure is of great significance to prevent HR-HPV infection and persistent infection.

Urinary Polycyclic Aromatic Hydrocarbon Metabolites Are Associated with Biomarkers of Chronic Endocrine Stress, Oxidative Stress, and Inflammation in Adolescents: FLEHS-4 (2016-2020).

Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants of public health concern. Multiple biological mechanisms have been hypothesized to contribute to PAHs-associated adverse health effects. Little is known about the impact of PAHs on endocrine stress and inflammation in adolescence. We examined 393 Flemish adolescents (14–15 years) cross-sectionally, measured urinary concentrations of hydroxylated naphthalene, fluorene, phenanthrene and pyrene metabolites, and calculated the sum of all measured metabolites. We determined hair cortisol concentration (HCC) as endocrine stress biomarker, leucocyte counts and neutrophil–lymphocyte ratio (NLR) in peripheral blood as inflammatory biomarkers, and urinary 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodG) concentration as oxidative stress biomarker. Exposure–response associations were analyzed by multiple regression, adjusted for a priori selected covariates. A doubling of 1-hydroxypyrene concentration was associated with a factor of 1.13 (95% CI: 1.03, 1.24) increase in HCC and a factor of 1.07 (95% CI: 1.02, 1.13) increase in 8-oxodG. Doublings of 2- and 3-hydroxyphenanthrene concentrations were associated with a factor of 1.08 (95% CI: 1.02, 1.14) and 1.06 (95% CI: 1.00, 1.12) increase in 8-oxodG, respectively. Doubling of 2-hydroxyphenanthrene and of the sum of 2- and 3-hydroxyfluorene was associated with, respectively, a factor of 1.08 (95% CI: 1.02, 1.14) and 1.06 (95% CI: 1.01, 1.13) increase in NLR. Our results indicate the glucocorticoid pathway as a potential target for PAH exposure in adolescents and suggest oxidative stress, endocrine stress, and inflammation in adolescence as underlying mechanisms and early markers for PAH-related adverse health effects.

Association Between PAHs and Chronic Kidney Disease in the US Adult Population

BACKGROUND AND AIM: Polycyclic aromatic hydrocarbons (PAHs) are a group of chemicals produced from the incomplete combustion of carbon-containing products. Exposure to PAHs is linked to respiratory disease, heart disease, liver disease, and cancer. Chronic kidney disease (CKD) is irreversible, progressive, and linked with higher cardiovascular risk. Very few studies have investigated the association between exposure to PAHs and CKD in humans. The rationale of this study was to assess seven types of urinary PAHs (1-hydroxynaphthalene, 2-hydroxynaphthalene, 3-hydroxyfluorene, 2-hydroxyfluorene, 1-hydroxyphenanthrene, 1-hydroxypyrene, and 2 & 3-hydroxyphenanthrene) concentrations and the correlation with CKD in adult US population. METHODS: A cross-sectional analyses using the 2015-2016 National Health and Nutrition Examination Survey (NHANES) dataset was conducted. A specialized complex survey design analysis package was used in analyzing the NHANES data. Chronic kidney disease was defined as estimated glomerular filtration rate (eGFR) 60 ml/min/1.73m2 or albumin to creatinine ratio (ACR) 30 mg/gm. Prior to analysis, the urinary PAH concentrations were normalized by the urinary creatinine concentration to account for dilution effects. Multivariate Logistic Regression Analysis of Complex Survey models were used to study the correlation between urinary PAH concentrations (seven types) and kidney disease associated with abnormal eGFR or ACR. Models were adjusted for demographic and lifestyle factors. RESULTS:The total study population analyzed included 4,117 adults aged 20 years and older, of whom 49.6% were males and 50.4% females. The analysis showed urinary 2-Hydroxynaphthalene [Odds Ratio (OR): 1.60, 95% Confidence Interval (CI): 1.41, 2.24] was significantly associated with increased odds of chronic kidney diseases. The other six types of urinary PAHs were not associated with CKD. CONCLUSIONS:The study concluded that urinary 2-Hydroxynaphthalene form of PAHs is significantly associated with CKD. KEYWORDS: polycyclic aromatic hydrocarbons, chronic kidney disease, urinary 2-Hydroxynaphthalene, NHANES, environmental pollution

Benchmark dose analysis for PAHs hydroxyl metabolites in urine based on mitochondrial damage of peripheral blood leucocytes in coke oven workers in China

ObjectivesThe aim was to explore the dose-response relationship between occupational polycyclic aromatic hydrocarbons (PAHs) exposure and mitochondrial damage in coke oven plants workers. Methods544 workers and 238 healthy people were recruited. The ultra-high performance liquid chromatography was used to determine the level of 1-hydroxypyrene, 1-hydroxynaphthalene, 2-hydroxynaphthalene and 3-hydroxyphenanthrene. The real-time fluorescence quantitative polymerase chain reaction was used to determine the mitochondrial DNA copy number (mtDNAcn). The benchmark dose software was used to analyze the benchmark dose. ResultsThe mtDNAcn in the exposure group was lower than that in the control group. The concentrations of 1-hydroxypyrene, 1-hydroxynaphthalene, 2-hydroxynaphthalene and 3-hydroxyphenanthrene in the exposure group were higher than those in the control group. There is a dose-response relationship between 1-hydroxypyrene, 3-hydroxyphenanthrene and mitochondrial DNA damage. The benchmark dose lower confidence limit (BMDL) of 1-hydroxypyrene were 0.045, 0.004, and 0.058 pg/μg creatinine in the total, male, and female population, respectively. The BMDL of 3-hydroxyphenanthrene were 5.142, 6.099, and 2.807 pg/μg creatinine in the total, male, and female population, respectively. ConclusionsThe BMDL of 1-hydroxypyrene and 3-hydroxyphenanthrene initially explored can provide a reference to establish occupational exposure biological limits.

Concentrations of selected monohydroxy polycyclic aromatic hydrocarbons across various stages of glomerular function

The objective of this study was to evaluate the variabilities in the concentrations of selected monohydroxy polycyclic aromatic hydrocarbons (OH-PAH) in urine across various stages of glomerular function. Data from National Health and Nutrition Examination Survey for US adult smokers (N = 3125) and nonsmokers (N = 6793) were selected for analysis to meet the objectives of the study. OH-PAHs selected for analysis were as follows: 1-hydroxynaphthalene, 2-hydroxynaphthalene, 2-hydroxyfluorene, 3-hydroxyfluorene, 9-hydroxyfluorene, 1-hydroxyphenanthrene, 2-hydroxyphenanthrene, 3-hydroxyphenanthrene, and 1-hydroxypyrene. Stages of glomerular function (GF) considered were as follows: hyperfiltrators (GF-1A, eGFR ≥ 110mL/min/1.73m2), normal filtrators (GF-1B, 90 < eGFR < 110mL/min/1.73m2), GF-2 (60 ≤ eGFR < 90mL/min/1.73m2), GF-3A (45 ≤ eGFR < 60mL/min/1.73m2), and GF-3B/4 (15 ≤ eGFR < 45mL/min/1.73m2). For the analysis of data for smokers, however, data for GF-3A and GF-3B/4 were merged because of small sample sizes for these GF stages for smokers. Among nonsmokers, (i) there was almost a straight-line decrease in adjusted concentrations of 2-hydroxyfluorene, 3-hydroxyfluorene, 9-hydroxyfluorene, 1-hydroxyphenanthrene, 2-hydroxyphenanthrene, 3-hydroxyphenanthrene, and 1-hydroxypyrene over GF-1A through GF-3B/4; (ii) concentrations of these OH-PAHs at GF-3B/4 varied from being 37.5% for 1-hydroxypyrene to being 87% for 9-hydroxyfluorene of what they were at GF-1A; and (iii) while concentrations of 1-hydroxynaphthalene were located on an inverted U-shaped curve, concentrations of 2-hydroxynaphthalene were located on a U-shaped curve with pints of inflections at GF-3A. Among smokers, concentrations of all nine OH-PAHs in urine were located on inverted U-shaped curves with points of inflections located at GF-2 and concentrations of these OH-PAHs at GF-3/4 varied from being 48.7% for 1-hydroxypyrene to being 116.1% for 9-hydroxyfluorene of what they were at GF-1A. The kidneys differ in how they process urinary metabolites of PAHs among smokers and nonsmokers.

Global H3K79 di-methylation mediates DNA damage response to PAH exposure in Chinese coke oven workers.

Polycyclic aromatic hydrocarbons (PAHs) are the main contaminants of coke oven emissions which can induce serious genetic damage in coke oven workers. Epigenetic alternations play essential roles in the regulation of DNA damage effect of PAHs. Previous studies indicate that H3K79 di-methylation (H3K79me2) is integral in DNA damage repair. However, the potential role of H3K79me2 in DNA damage response (DDR) following PAHs exposure is still unclear. In this study, we recruited 256 male coke oven workers and control workers, and examined H3K79me2 and DNA damage in their peripheral blood lymphocytes (PBLCs). The results showed that global H3K79me2 of coke oven workers was 29.3% less than that of the controls (P<0.001). The H3K79me2 was negatively correlated with the concentration of urinary 1-hydroxypyrene (1-OHP) (β=-0.235, P<0.001) and level of genetic damage evaluated by comet assay (βTail DNA %=-0.313, P<0.001; βOTM=-0.251, P=0.008). Consistently, we found that benzo(a)pyrene (BaP) inhibited H3K79me2 in immortalized human bronchial epithelial (HBE) cells in a time-dependent manner. In order to explore the function of H3K79me2 in PAHs DDR, we established histone 3.1/3.3 K79A mutant cells (H3K79A) to suppress H3K79me2. H3K79A cells showed more serious DNA damage and decreased cell viability than control cells after BaP treatment. In addition, we also found that the expression of DOT1L, the only methyltransferase in H3K79, was repressed by BaP dose-dependently. DOT1L knockdown resulted in decreased H3K79me2 level and aggravated DNA damage after BaP exposure. This suggests that BaP induces H3K79me2 repression via inhibiting DOT1L expression. In conclusion, these findings indicate that PAH exposure decreases the level of global H3K79me2, which is integral for DNA damage response regulation of PAHs.