Prepubertal exposure to polycyclic aromatic hydrocarbons are associated with early pubertal development onset in boys: A longitudinal study.

OBJECTIVE: To investigate the effects of polycyclic aromatic hydrocarbons(PAHs) on puberty in boys. METHODS: 695 subjects were selected from four primary schools in Chongqing, China. 675 urine samples from these boys were collected four PAH metabolites: 1-hydroxypyrene, 2-hydroxynaphthoic, 2-hydroxyfluorene, and 9-hydroxyphenanthrene. Pubertal development of 695 boys was assessed at follow-up visits starting in December 2015 and occurring every six months thereafter until now, data used in this article ending in June 2021. A total of 12 follow-up visits were performed. Cox proportional hazards regression models were used to analyze the relationship between PAH metabolite concentrations and indicators of pubertal timing. RESULTS: The mean age at puberty onset of testicular volume, facial hair, pubic hair, first ejaculation, and axillary hair in boys was 11.66, 12.43, 12.51, 12.72 and 13.70 years, respectively. Cox proportional hazards regression models showed that boys with moderate level of 1-OHPyr exposure was associated with earlier testicular development (hazard ratio [HR] = 1.276, 95% confidence interval [CI]: 1.006-1.619), with moderate level of 2-OHNap were at higher risk of early testicular development (HR = 1.273, 95% CI: 1.002-1.617) and early axillary hair development (HR = 1.355, 95% CI: 1.040-1.764), with moderate level of 2-OHFlu was associated with earlier pubic hair development (HR = 1.256, 95% CI: 1.001-1.577), with high level of 9-OHPhe were at higher risk of early fisrt ejaculation (HR = 1.333, 95% CI: 1.005-1.767) and early facial hair development (HR = 1.393, 95% CI: 1.059-1.831). CONCLUSION: Prepubertal exposure to PAHs may be associated with earlier pubertal development in boys.

Association of mixed polycyclic aromatic hydrocarbons exposure with oxidative stress in Korean adults.

Polycyclic aromatic hydrocarbons (PAHs) are widespread pollutants associated with several adverse health effects and PAH-induced oxidative stress has been proposed as a potential mechanism. This study evaluated the associations of single and multiple PAHs exposure with oxidative stress within the Korean adult population, using serum gamma glutamyltransferase (GGT) as an oxidative stress marker. Data from the Second Korean National Environmental Health Survey (2012-2014) were analyzed. For analysis, 5225 individuals were included. PAH exposure was assessed with four urinary PAH metabolites: 1-hydroxyphenanthrene, 1-hydroxypyrene, 2-hydroxyfluorene, and 2-naphthol. After adjusting for age, sex, body mass index, drinking, passive smoking, and current smoking (model 1), as well as the presence of diabetes and hepatobiliary diseases (model 2), complex samples general linear model regression analyses for each metabolite revealed a significant positive association between Ln(1-hydroxyphenanthrene) and Ln(GGT) (model 1: ß = 0.040, p < 0.01 and model 2: ß = 0.044, p < 0.05). For the complete dataset (n = 4378), a significant positive association was observed between mixture of four urinary PAH metabolites and serum GGT in both the quantile g-computation and the Bayesian kernel machine regression analysis. Our study provides evidence for the association between mixed PAH exposure and oxidative stress.

Healthy lifestyle and essential metals attenuated association of polycyclic aromatic hydrocarbons with heart rate variability in coke oven workers.

Whether adopting healthy lifestyles and maintaining moderate levels of essential metals could attenuate the reduction of heart rate variability (HRV) related to polycyclic aromatic hydrocarbons (PAHs) exposure are largely unknown. In this study, we measured urinary metals and PAHs as well as HRV, and constructed a healthy lifestyle score in 1267 coke oven workers. Linear regression models were used to explore the association of healthy lifestyle score and essential metals with HRV, and interaction analysis was performed to investigate the potential interaction between healthy lifestyle score, essential metals, and PAHs on HRV. Mean age of the participants was 41.9 years (84.5% male). Per one point higher healthy lifestyle score was associated with a 2.5% (95% CI, 1.0%-3.9%) higher standard deviation of all normal to normal intervals (SDNN), 2.1% (95% CI, 0.5%-3.6%) higher root mean square of successive differences in adjacent NN intervals (r-MSSD), 4.3% (95% CI, 0.4%-8.2%) higher low frequency, 4.4% (95% CI, 0.2%-8.5%) higher high frequency, and 4.4% (95% CI, 1.2%-7.6%) higher total power, respectively. Urinary level of chromium was positively associated with HRV indices, with the corresponding ß (95% CI) (%) was 5.17 (2.84, 7.50) for SDNN, 4.29 (1.74, 6.84) for r-MSSD, 12.26 (6.08, 18.45) for low frequency, 12.61 (5.87, 19.36) for high frequency, and 11.31 (6.19, 16.43) for total power. Additionally, a significant interaction was found between healthy lifestyle score and urinary total hydroxynaphthalene on SDNN (Pinteraction = 0.04), and higher level of urinary chromium could attenuate the adverse effect of total hydroxynaphthalene level on HRV (all Pinteraction <0.05). Findings of our study suggest adopting healthy lifestyle and maintaining a relatively high level of chromium might attenuate the reduction of HRV related to total hydroxynaphthalene exposure.

Associations between Urinary Concentrations of Polycyclic Aromatic Hydrocarbons and Overactive Bladder in US Adults: Data from the National Health and Nutrition Examination Survey 2005-2016.

INTRODUCTION: Polycyclic aromatic hydrocarbons (PAHs) are a group of chemicals that can induce oxidative stress and related cytotoxicity. Whether urinary concentrations of PAHs have effects on overactive bladder (OAB) in the general population is still unclear. This study investigated the associations between urinary PAHs and OAB. METHODS: 7,146 adults aged over 20 who participated in the US National Health and Nutrition Examination Survey 2005-2016 were studied. The impact of the six PAHs on OAB was evaluated by multivariate logistic regression, and percent changes related to different quartiles of those six PAH levels were calculated. Confounders including age, logarithmic urinary creatinine, gender, race, body mass index, educational level, marriage, poverty income ratio, diabetes, hypertension, and metabolic syndrome were controlled. RESULTS: There is a significant positive correlation between urinary concentrations of the six PAHs we include in the study and the occurrence of OAB. Furthermore, individuals with higher PAH levels also reported a more severe OAB symptom score (OABSS). CONCLUSIONS: Our findings revealed that adult men in the USA with higher urinary PAHs had a higher risk of OAB incidence. These findings suggest the importance of strong environmental regulation of PAHs to protect population health. However, the underlying mechanisms still need further exploration.

Repeated measurements and mixture effects of urinary bisphenols, parabens, polycyclic aromatic hydrocarbons, and other chemicals on biomarkers of oxidative stress in pre- and postpartum women.

The association between oxidative stress and exposure to bisphenols, parabens, phenols, polycyclic aromatic hydrocarbons (PAH), and volatile organic compounds (VOCs) has been investigated by many in vitro and in vivo studies. However, most of these findings are based on cross-sectional studies, as a result of which the combined effects of these compounds have been rarely analyzed. In this study, our objective was to assess urinary bisphenols, parabens, PAHs, and VOCs, in relation to oxidative stress during pre-and postpartum periods, analyze the association between these chemicals and oxidative stress via repeated measurements using a linear mixed model (LMM), and evaluate the combined effects exerted by these chemicals on oxidative stress using Bayesian Kernel Machine Regression (BKMR). A total 529 urine samples were collected from 242 pregnant women during the 1st and 2nd trimesters, as well as postpartum follow-ups. Three bisphenols, four parabens, benzopheone-3 (BP-3), triclosan (TCS), four PAHs, two VOCs, and 3- phenoxy-benzoic acid (3-PBA) were analyzed. We also measured 8-hydroxydeoxyguanosine (8-OHdG) and malondialdehyde (MDA), which serve as oxidative stress biomarkers in maternal urine samples. During this period, 8-OHdG decreased steadily, whereas MDA increased during pregnancy and decreased after childbirth. LMM indicated that Bisphenol A, Prophyl-paraben, BP-3, and 1-hydroxypyrene (1-OHP) showed a significant association with increased MDA levels. The BKMR models revealed that the mixture effect exerted by these 16 chemicals had changed MDA levels, which indicate oxidative stress, and that both Butyl Paraben (BP) and 1-hydroxypyrene (1-OHP) had contributed to such oxidative stress. Mixtures of each subgroup (bisphenols, parabens, and PAHs) were associated with increased MDA levels. These findings suggest that exposure to some phenols and PAHs during pre- and post-partum stages may cause oxidative stress, and that exposure to these chemicals should be minimized during this period.

Association of urinary polycyclic aromatic hydrocarbon metabolites with gestational diabetes mellitus and gestational hypertension among pregnant women in Southwest China: A cross-sectional study.

The association of polycyclic aromatic hydrocarbons (PAHs) with gestational diabetes mellitus (GDM) and gestational hypertension during pregnancy has not yet been established. To investigate the association between PAH exposure and GDM and gestational hypertension, we conducted a cross-sectional study of 4206 pregnant women from the Zunyi birth cohort in southwestern China. Gas chromatography/mass spectrometry was used to detect the urinary levels of 10 monohydroxylated PAHs (OH-PAHs). GDM and gestational hypertension were diagnosed and the relevant information was documented by specialist obstetricians and gynecologists. Logistic regression and restricted cubic spline regression were employed to investigate their single and nonlinear associations. Stratified analyses of pregnancy and body mass index data were conducted to determine their moderating effects on the abovementioned associations. Compared with the first quartile of urinary ∑OH-PAHs, the third or fourth quartile in all study participants was associated with an increased risk of GDM (quartile 3: odds ratio [OR] = 1.35, 95% confidence interval [CI]: 1.03-1.77) and gestational hypertension (quartile 3: OR = 1.88, 95% CI: 1.26-2.81; quartile 4: OR = 1.58, 95% CI: 1.04-2.39), respectively. Nonlinear associations of 1-OH-PYR with GDM (cutoff level: 0.02 µg/g creatinine [Cr]) and 1-OH-PHE with gestational hypertension (cutoff level: 0.06 µg/g Cr) were also observed. In pregnant women with overweight or obesity, 1-OH-PHE and 3-OH-PHE were more strongly associated with gestational hypertension. Our results indicate that exposure to PAH during pregnancy may significantly increase the maternal risks of GDM and gestational hypertension; however, this finding still needs to be confirmed through larger-scale prospective studies and biological evidence.

Magnetic solid phase extraction coupled to HPLC-UV for highly sensitive analysis of mono-hydroxy polycyclic aromatic hydrocarbons in urine.

BACKGROUND: As a common pollutant, the carcinogenic properties of polycyclic aromatic hydrocarbons have garnered considerable attention. Trace metabolites of polycyclic aromatic hydrocarbons can be detected in urine as a non-invasively approach to monitor the exposure level. Nonetheless, the urine samples have the disadvantages of being large in volume and containing numerous impurities. Given the growing demand to study metabolites with low abundance and potential biomarkers, there is a pressing need for a preconcentration and high-throughput technique for effectively handling complex liquid samples. RESULTS: Polystyrene-coated magnetic nanoparticles were used to establish a novel magnetic extraction method for monohydroxy polycyclic aromatic hydrocarbons in urine samples. Polystyrene magnetic nanoparticles are an ideal absorbent for solid-phase extraction. After the material was mixed with the sample and adsorbed the target analyte, the analytes on the material were eluted and quantified using high-performance liquid chromatography. Influencing factors were optimized, and the proposed method achieved desirable sensitivity in analyzing low-abundance metabolites in large volumes of complex urine samples. The recoveries of intra-day and inter-day were 78.0-118.0 % and 81.0 %-115.0 %, respectively. The intra-day and inter-day reproducibility were less than 4.5 % and 8.6 %, respectively. The limits of detection were in the range of 0.009-0.041 ng mL-1, and the limits of quantification were in the range of 0.030-0.135 ng mL-1. SIGNIFICANCE AND NOVELTY: The application of reusable polystyrene-coated magnetic solid-phase nanoparticles as adsorbents makes the extraction of monohydroxy polycyclic aromatic hydrocarbons from urine samples economical and environmentally benign. The proposed method is simple, sensitive, and efficient compared to existing techniques. The nanoparticles are easy to prepare, showing potential for rapid screening of complex bulk bio-samples in batches with high efficiency and low budget.

Maternal and newborn metabolomic changes associated with urinary polycyclic aromatic hydrocarbon metabolite concentrations at delivery: an untargeted approach.

INTRODUCTION: Prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with adverse human health outcomes. To explore the plausible associations between maternal PAH exposure and maternal/newborn metabolomic outcomes, we conducted a cross-sectional study among 75 pregnant people from Cincinnati, Ohio. METHOD: We quantified 8 monohydroxylated PAH metabolites in maternal urine samples collected at delivery. We then used an untargeted high-resolution mass spectrometry approach to examine alterations in the maternal (n = 72) and newborn (n = 63) serum metabolome associated with PAH metabolites. Associations between individual maternal urinary PAH metabolites and maternal/newborn metabolome were assessed using linear regression adjusted for maternal and newborn factors while accounting for multiple testing with the Benjamini-Hochberg method. We then conducted functional analysis to identify potential biological pathways. RESULTS: Our results from the metabolome-wide associations (MWAS) indicated that an average of 1% newborn metabolome features and 2% maternal metabolome features were associated with maternal urinary PAH metabolites. Individual PAH metabolite concentrations in maternal urine were associated with maternal/newborn metabolome related to metabolism of vitamins, amino acids, fatty acids, lipids, carbohydrates, nucleotides, energy, xenobiotics, glycan, and organic compounds. CONCLUSION: In this cross-sectional study, we identified associations between urinary PAH concentrations during late pregnancy and metabolic features associated with several metabolic pathways among pregnant women and newborns. Further studies are needed to explore the mediating role of the metabolome in the relationship between PAHs and adverse pregnancy outcomes.

Urinary Amino-PAHs in relation to diesel engine emissions and urinary mutagenicity.

Diesel exhaust has long been of health concern due to established toxicity including carcinogenicity in humans. However, the precise components of diesel engine emissions that drive carcinogenesis are still unclear. Limited work has suggested that nitrated polycyclic aromatic hydrocarbons (NPAHs) such as 1-nitropyrene and 2-nitrofluorene may be more abundant in diesel exhaust. The present study aimed to examine whether urinary amino metabolites of these NPAHs were associated with high levels of diesel engine emissions and urinary mutagenicity in a group of highly exposed workers including both smokers and nonsmokers. Spot urine samples were collected immediately following a standard work shift from each of the 54 diesel engine testers and 55 non-tester controls for the analysis of five amino metabolites of NPAHs, and cotinine (a biomarker of tobacco smoke exposure) using liquid chromatography-mass spectrometry. An overnight urine sample was collected in a subgroup of non-smoking participants for mutagenicity analysis using strain YG1041 in the Salmonella (Ames) mutagenicity assay. Personal exposure to fine particles (PM2.5) and more-diesel-specific constituents (elemental carbon and soot) was assessed for the engine testers by measuring breathing-zone concentrations repeatedly over several full work shifts. Results showed that it was 12.8 times more likely to detect 1-aminopyrene and 2.9 times more likely to detect 2-aminofluorene in the engine testers than in unexposed controls. Urinary concentrations of 1-aminopyrene were significantly higher in engine testers (p < 0.001), and strongly correlated with soot and elemental carbon exposure as well as mutagenicity tested in strain YG1041 with metabolic activation (p < 0.001). Smoking did not affect 1-aminopyrene concentrations and 1-aminopyrene relationships with diesel exposure. In contrast, both engine emissions and smoking affected 2-aminofluorene concentrations. The results confirm that urinary 1-aminopyrene may serve as an exposure biomarker for diesel engine emissions and associated mutagenicity.

Association of Polycyclic Aromatic Hydrocarbons Urine Metabolites with Type 1 Diabetes.

Purpose: Polycyclic aromatic hydrocarbons (PAHs) are believed to be a possible factor in the development of cancer, ischemic heart disease, obesity, and cardiovascular disease. The objective of this study was to explore the association between certain metabolites of urinary PAH and type 1 diabetes (T1D). Methods: In Isfahan City, a case-control study was carried out involving 147 T1D patients and an equal number of healthy individuals. The study measured the levels of urinary metabolites of PAHs, specifically 1-hydroxynaphthalene, 2-hydroxynaphthalene, and 9-hydroxyphenanthrene, in both the case and control groups. The levels of these metabolites were then compared between the two groups to assess any potential association between the biomarkers and T1D. Results: The mean (SD) age of participants in the case and control groups was 8.4 (3.7) and 8.6 (3.7) years old, respectively, (P > 0.05). In terms of gender distribution, 49.7% and 46% of participants in the case and control groups were girls, respectively (P > 0.05). Geometric mean (95% CI) concentrations were: 36.3 (31.4-42) µg/g creatinine for 1-hydroxynaphthalene, 29.4 (25.6-33.8) µg/g creatinine for 2-hydroxynaphthalene, and 72.26 (63.3-82.5) µg/g creatinine for NAP metabolites. After controlling for variables such as the child's age, gender, maternal and paternal education, duration of breastfeeding, exposure to household passive smoking, formula feeding, cow's milk consumption, body mass index (BMI), and five dietary patterns, it was observed that individuals in the highest quartile of 2-hydroxynaphthalene and NAP metabolites had a significantly greater odd ratio for diabetes compared to those in the lowest quartile (P < 0.05). Conclusion: Based on the findings of this study, it is suggested that exposure to PAH might be linked to an increased risk of T1D in children and adolescents. To clarify a potential causal relationship related to these findings, further prospective studies are needed.

Biomonitoring of polycyclic aromatic hydrocarbons in Brazilian pregnant women: Urinary levels and health risk assessment.

Over the years, humans have been continuously exposed to several compounds directly generated by industrial processes and/or present in consumed products. Polycyclic aromatic hydrocarbons (PAHs) are legacy pollutants ubiquitous in the environment and represent the main chemical pollutants in urban areas. Worldwide, studies that aim to understand the impacts of exposure to these chemicals have gained increasing prominence due to their potential toxicity profile, mainly concerning genotoxicity and carcinogenicity. Human biomonitoring (HB) is an analytical approach to monitoring population exposure to chemicals; however, these studies are still limited in Brazil. Thus, this work aimed to evaluate the exposure of Brazilian pregnant women to PAHs through HB studies. Besides, the risk characterization of this exposure was performed. For this purpose, urine samples from 358 Brazilian pregnant women were used to evaluate 11 hydroxylated metabolites of PAHs employing gas chromatography coupled to mass spectrometry. The 1OH-naphthol and 2OH-naphthol were detected in 100% of the samples and showed high levels, corresponding to 16.99 and 3.62 µg/g of creatinine, respectively. 2OH-fluorene (8.12 µg/g of creatinine) and 9OH-fluorene (1.26 µg/g of creatinine) were detected in 91% and 66% of the samples, respectively. Benzo(a)pyrene (BaP) metabolites were detected in more than 50% of the samples (0.58-1.26 µg/g of creatinine). A hazard index of 1.4 and a carcinogenic risk above 10-4 were found for BaP metabolites in the risk characterization. Therefore, our findings may indicate that exposure to PAHs poses a potential risk to pregnant women's health and a high probability of carcinogenic risk due to their exposure to BaP. Finally, this work shows the need for more in-depth studies to determine the sources of exposure and the implementation of health protection measures regarding the exposure of the Brazilian population to PAHs.

Urine 2-hydroxyphenanthrene is associated with current asthma: evidence from NHANES 2007-2012.

OBJECTIVE: The current study aims to explore the effects of nine urine monohydroxy PAH metabolites (OHPAH) including 1-hydroxynaphthalene (1-OHNAP), 2-hydroxynaphthalene (2-OHNAP), 3-hydroxyfluorene (3-OHFLU), 9-hydroxyfluorene (9-OHFLU), 1-hydroxyphenanthrene (1-OHPHE), 2-hydroxyphenanthrene (2-OHPHE), 3-hydroxyphenanthrene (3-OHPHE), and 1-hydroxypyrene (1-OHPYR) on current asthma in people in the United States using a variety of statistical techniques. METHODS: A cross-sectional examination of a subsample of 3804 adults aged ≥20 from the National Health and Nutrition Examination Survey (NHANES) was conducted between 2007 and 2012. To investigate the relationship between urine OHPAHs levels and current asthma, multivariate logistic regression, Bayesian kernel machine regression (BKMR), and quantile g-computation (qgcomp) were utilized. RESULTS: In the multivariate logistic regression model, after controlling for confounders, urine 2-OHPHE was associated with current asthma in both male (AOR = 7.17, 95% CI: 1.28-40.08) and female (AOR = 2.91, 95% CI: 1.06-8.01) smokers. In the qgcomp analysis, 2-OHPHE (39.5%), 1-OHNAP (33.1%), and 2-OHNAP (22.5%) were the major positive contributors to the risk of current asthma (OR = 2.29, 95% CI: 0.99, 5.25), and in female smokers, 9-OHFLU (25.8%), 2-OHFLU (21.5%), and 2-OHPHE (15.1%) were the major positive contributors (OR = 2.19, 95% CI: 1.06, 4.47). The results of the BKMR model basically agreed with qgcomp analysis. CONCLUSION: Our results demonstrate a strong association of urine 2-OHPHE with current asthma, and further longitudinal studies are needed to understand the precise relationship between PAH exposure and current asthma risk.

Firefighters and the liver: Exposure to PFAS and PAHs in relation to liver function and serum lipids (CELSPAC-FIREexpo study).

INTRODUCTION: Firefighting is one of the most hazardous occupations due to exposure to per- and polyfluoroalkyl substances (PFAS) and polycyclic aromatic hydrocarbons (PAHs). Such exposure is suspected to affect the cardiometabolic profile, e.g., liver function and serum lipids. However, only a few studies have investigated the impact of this specific exposure among firefighters. METHODS: Men included in the CELSPAC-FIREexpo study were professional firefighters (n = 52), newly recruited firefighters in training (n = 58), and controls (n = 54). They completed exposure questionnaires and provided 1-3 samples of urine and blood during the 11-week study period to allow assessment of their exposure to PFAS (6 compounds) and PAHs (6 compounds), and to determine biomarkers of liver function (alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin (BIL)) and levels of serum lipids (total cholesterol (CHOL), low-density lipoprotein cholesterol (LDL) and triglycerides (TG)). The associations between biomarkers were investigated both cross-sectionally using multiple linear regression (MLR) and Bayesian weighted quantile sum (BWQS) regression and prospectively using MLR. The models were adjusted for potential confounders and false discovery rate correction was applied to account for multiplicity. RESULTS: A positive association between exposure to PFAS and PAH mixture and BIL (ß = 28.6%, 95% CrI = 14.6-45.7%) was observed by the BWQS model. When the study population was stratified, in professional firefighters and controls the mixture showed a positive association with CHOL (ß = 29.5%, CrI = 10.3-53.6%) and LDL (ß = 26.7%, CrI = 8.3-48.5%). No statistically significant associations with individual compounds were detected using MLR. CONCLUSIONS: This study investigated the associations between exposure to PFAS and PAHs and biomarkers of cardiometabolic health in the Czech men, including firefighters. The results suggest that higher exposure to a mixture of these compounds is associated with an increase in BIL and the alteration of serum lipids, which can result in an unfavourable cardiometabolic profile.

Single and joint associations of exposure to polycyclic aromatic hydrocarbons with blood coagulation function during pregnancy: A cross-sectional study.

Association linking polycyclic aromatic hydrocarbons (PAHs) to blood coagulation function during pregnancy remains absent. Hence, we conducted a cross-sectional study including 679 late pregnant women (27.2 ± 5.1 years old) drawn from Zunyi birth cohort, Southwest China. During late pregnancy, ten urinary PAHs metabolites and four clinical blood coagulation parameters were measured, including activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), and fibrinogen (FIB). Multiple linear regression, Restricted cubic spline (RCS) regression, Bayesian kernel machine regression (BKMR), and quantile g-computation (Q-g) regression were used to investigate their single, nonlinear, and mixed associations. Each 2.7-fold increment in 2-hydroxyfluorene (2-OHFlu), 9-hydroxyfluorene (9-OHFlu), 1-hydroxyphenanthrene (1-OHPhe), 2-hydroxyphenanthrene (2-OHPhe), and 3-hydroxyphenanthrene (3-OHPhe) were associated with 0.287 s, 0.190 s, 0.487 s, and 0.396 s shorter APTT, respectively; each 2.7-fold increment in 2-OHPhe was associated with a 0.047 s longer PT; each 2.7-fold increment in 9-hydroxyphenanthrene (9-OHPhe) and 1-hydroxypyrene (1-OHPyr) were associated with 0.087 s and 0.031 s shorter TT, respectively; and each 2.7-fold increment in 1-hydroxynaphthalene (1-OHNap) was associated with 0.032 g/L higher FIB level. The nonlinear association of 2-OHPhe with APTT and 1-OHNap with FIB were also observed. Furthermore, the shortened APTT and TT associated with PAHs mixture were indicated by BKMR and Q-g model. BKMR also revealed a nonlinear association of 2-OHPhe with PT and an interaction effect of 2-OHPhe and 3-OHPhe on APTT. Our results indicate that urinary PAHs was associated with shortened coagulation time and increased FIB. Therefore, more attention should be paid for late pregnant women to prevent PAHs-associated risk of thrombosis. Future perspective studies to confirm our findings and explore the underlying biological mechanism are warranted.

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.

Bitumen fumes and PAHs in asphalt road paving: Emission characteristics, determinants of exposure and environmental impact.

BACKGROUND: Asphalt road paving and its subsequent complex airborne emissions have raised concerns about occupational exposures and environmental impacts. Although several studies described bitumen fumes or Polycyclic Aromatic Hydrocarbons (PAH) emissions at specific worksites, no comprehensive studies have characterised road paving emissions and identified the main determinants of exposure. METHODS: A 10-year study from 2012 to 2022 was performed to examine the pollutants resulting from bitumen fume emissions and covering the main processes used in road paving (asphalt production, mechanical rolled asphalt paving, manual paving, mastic asphalt paving, emulsion paving, and coal-tar asphalt milling). A total of 623 air samples were collected at 63 worksites (on 290 workers, in the environment and near emission sources), and bitumen fumes, PAHs, aldehydes and volatile organic compounds were analysed. Biomonitoring campaigns were performed on 130 workers to assess internal exposure to PAHs. RESULTS: Fume emissions revealed complex mixtures of C10-C30 compounds, including linear saturated hydrocarbons (C6-C12), alicyclic hydrocarbons and aliphatic ketones. PAHs were dominated by 2-3 aromatic ring compounds (naphthalene, fluorene, and phenanthrene), and C1-C13 aldehydes were identified. Binder proportion, paving temperature, outdoor temperature, workload and job category influenced airborne concentrations. A significant temporal trend was observed over the time period of the study, with decreasing BF and PAH exposures. PAH biomonitoring was consistent with air samples, and urinary metabolites of 2-3 ring PAHs dominated over 4-5 ring PAHs. Occupational exposures were generally far lower than exposure limits, except coal-tar asphalt milling activities. Very low environmental concentrations were measured, which highlights a negligible contribution of paving emissions to global environmental pollution. CONCLUSION: The present study confirmed the complex nature of bitumen fumes and characterised the main determinants of exposure. The results highlight the need to reduce the paving temperature and binder proportion. Recycled asphalt pavement use was not associated with higher emissions. The impact of paving activities on environmental airborne pollution was deemed negligible.

External Quality Assurance Schemes (EQUASs) and Inter-laboratory Comparison Investigations (ICIs) for human biomonitoring of polycyclic aromatic hydrocarbon (PAH) biomarkers in urine as part of the quality assurance programme under HBM4EU.

Polycyclic aromatic hydrocarbons (PAHs) were included as priority substances for human biomonitoring (HBM) in the European Human Biomonitoring Initiative (HBM4EU), which intended to harmonise and advance HBM across Europe. For this project, a specific Quality Assurance and Quality Control (QA/QC) programme applying Inter-laboratory Comparison Investigations (ICIs) and External Quality Assurance Schemes (EQUASs) was developed to ensure the comparability and accuracy of participating analytical laboratories. This paper presents the results of four ICI/EQUAS rounds for the determination of 13 PAH metabolites in urine, i.e. 1-naphthol, 2-naphthol, 1,2-dihydroxynaphthalene, 2-, 3- and 9-hydroxyfluorene, 1-, 2-, 3-, 4- and 9-hydroxyphenanthrene, 1-hydroxypyrene and 3-hydroxybenzo(a)pyrene. However, 4 PAH metabolites could not be evaluated as the analytical capacity of participating laboratories was too low. Across all rounds and biomarkers, 86% of the participants achieved satisfactory results, although low limits of quantification were required to quantify the urinary metabolites at exposure levels of the general population. Using high-performance liquid or gas chromatography coupled with mass spectrometry (HPLC-MS; GC-MS) and isotope dilution for calibration as well as performing an enzymatic deconjugation step proved to be favourable for the accurate determination of PAHs in urine. Finally, the HBM4EU QA/QC programme identified an international network of laboratories providing comparable results in the analysis of urinary PAH biomarkers, although covering all parameters initially selected was still too challenging.

Association of polycyclic aromatic hydrocarbons with systemic inflammation and metabolic syndrome and its components.

OBJECTIVE: This study aimed to evaluate the relationship of polycyclic aromatic hydrocarbon (PAH) exposure with metabolic syndrome (MetS) and its components and to explore the potential mechanism. METHODS: Participants from the National Health and Nutrition Examination Survey (NHANES 2001-2016) were included. RESULTS: A total of 6532 adults and 1237 adolescents were included in the present analysis. For adults, the odds ratios (ORs) and 95% CIs for each one-unit increase in the log-transformed level of 1-hydroxynaphthalene (1-OHNa), 2-hydroxynaphthalene (2-OHNa), 3-hydroxyfluorene (3-OHFlu), 2-hydroxyfluorene (2-OHFlu), 1-hydroxyphenanthrene (1-OHPh), 1-hydroxypyrene (1-OHP), 2- and 3-hydroxyphenanthrene (2&3-OHPh), and total urinary PAH metabolites (∑OH-PAHs) with MetS were 1.11 (1.03-1.20), 1.18 (1.07-1.29), 1.10 (1.01-1.12), 1.18 (1.07-1.30), 1.17 (1.03-1.33), 1.09 (1.01-1.22), 1.24 (1.09-1.40), and 1.17 (1.06-1.29), respectively. They were 1.61 (1.21-2.14) for 2-OHNa, 1.27 (1.01-1.60) for 2-OHFlu, 1.53 (1.15-2.03) for 1-OHPh, and 1.61 (1.20-2.15) for ∑OH-PAHs among adolescents. C-reactive protein was not only positively associated with urinary PAH metabolites, but also positively related to MetS, and it mediated 10.23% to 20.21% for urinary PAH metabolites and MetS among adults. CONCLUSIONS: PAH exposure is associated with a higher prevalence of MetS or MetS components among adults and adolescents. Systemic inflammation partly mediated the association among adults.

Polycyclic aromatic hydrocarbon (PAH) exposure during pregnancy and child anthropometry from birth to 10 years of age: Sex-specific evidence from a cohort study in rural Bangladesh.

Polycyclic aromatic hydrocarbons (PAHs) have endocrine disrupting properties and they cross the placental barrier, but studies on gestational exposure and child anthropometry are inconclusive. We aimed to elucidate the impact of early gestational PAH exposure on anthropometry from birth to 10 years of age in 1295 mother-child pairs from a nested sub-cohort of the MINIMat trial in Bangladesh. Several PAH metabolites [1-hydroxyphenanthrene (1-OH-Phe), Σ2-,3-hydroxyphenanthrene (Σ2-,3-OH-Phe), 4-hydroxyphenanthrene (4-OH-Phe), 1-hydroxypyrene (1-OH-Pyr), Σ2-,3-hydroxyfluorene (Σ2-,3-OH-Flu)] were quantified in spot urine collected around gestational week 8 using LC-MS/MS. Child weight and height were measured at 19 occasions from birth to 10 years. Multivariable-adjusted regression models were used to assess associations of maternal PAH metabolites (log2-transformed) with child anthropometry. The median concentration of 1-OH-Phe, Σ2-,3-OH-Phe, 4-OH-Phe, 1-OH-Pyr and Σ2-,3-OH-Flu was 1.5, 1.9, 0.14, 2.5, and 2.0 ng/mL, respectively. All maternal urinary PAH metabolites were positively associated with newborn weight and length and all associations were more pronounced in boys than in girls (p interaction for all <0.14). In boys, the strongest associations were observed with Σ2-,3-OH-Phe and Σ2-,3-OH-Flu for which each doubling increased mean birth weight by 41 g (95% CI: 13; 69 and 12; 70) and length by 0.23 cm (0.075; 0.39) and 0.21 cm (0.045; 0.37), respectively. Maternal urinary PAH metabolites were not associated with child anthropometry at 10 years. In longitudinal analysis, however, maternal urinary PAH metabolites were positively associated with boys' weight-for-age (WAZ) and height-for-age Z-scores (HAZ) from birth to 10 years, but only the association of 4-OH-Phe with HAZ was significant (B: 0.080 Z-scores; 95% CI 0.013, 0.15). No associations were observed with girls' WAZ or HAZ. In conclusion, gestational PAH exposure was positively associated with fetal and early childhood growth, especially in boys. Further studies are needed to confirm causality and to explore long-term health effects.

Exposure to volatile organic compounds and polycyclic aromatic hydrocarbons is associated with the risk of non-alcoholic fatty liver disease in Korean adolescents: Korea National Environmental Health Survey (KoNEHS) 2015-2017.

Non-alcoholic fatty liver disease (NAFLD) is one of the most frequent liver diseases among adolescents. Several animal studies have suggested that volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs) increase NAFLD risk. However, few epidemiological studies have confirmed the association between VOCs, PAHs and NAFLD in the general adolescent population. Therefore, we analyzed 798 adolescents from the Korean National Environmental Health Survey (KoNEHS), 2015-2017, to examine the associations of urinary metabolites of VOCs and PAHs with serum alanine aminotransferase (ALT) activity and NAFLD prevalence. We performed linear regression, logistic regression, and Bayesian kernel machine regression (BKMR) to evaluate the association of urinary VOCs and PAHs metabolites with ALT levels and NAFLD prevalence. After adjusting for all covariates, urinary benzylmercapturic acid and 2-hydroxyfluorene levels were found to increase ALT activity and NAFLD prevalence. Additionally, the BKMR analyses showed a significantly positive overall effect on ALT activity and NAFLD prevalence with urinary concentrations of VOCs and PAHs metabolites, with 2-hydroxyfluorene as the biggest contributor. Our study suggests that exposure to low-level VOCs and PAHs may have a detrimental effect on NAFLD risk in adolescents. Given the increasing prevalence of NAFLD in adolescents, future cohort studies are confirmed to comprehend the effect of these chemicals on NAFLD risk.