Urinary Polycyclic Aromatic Hydrocarbons Research Articles

Investigating industrial PAH air pollution in relation to population exposure in major countries: A scoring approach

Polycyclic aromatic hydrocarbons (PAHs) are common air pollutants worldwide, associated with industrial processes. In the general population, both modeling and field studies revealed a positive correlation between air PAH concentrations and urinary PAH metabolite levels. Many countries lack population urinary data that correspond to local PAH air concentrations. Thus, we proposed a scoring-based approximate approach to investigating that correlation in selected countries, hypothesizing that PAH air concentrations in selected regions could represent the national air quality influenced by industrial emission and further correlate to PAH internal exposure in the general population. This research compiled 85 peer-reviewed journal articles and 9 official monitoring datasets/reports covering 34 countries, 16 of which with both atmospheric PAH data and human biomonitoring data. For the air pollution score (AirS), Egypt had the highest AirS at 0.94 and Pakistan was at the bottom of the score ranking at −1.95, as well as the median in the UK (AirS: 0.50). For the population exposure score (ExpS), China gained the top ExpS at 0.44 and Spain was with the lowest ExpS of −1.52, with the median value in Italy (ExpS: 0.43). Through the correlation analysis, atmospheric PAHs and their corresponding urinary metabolites provided a positive relationship to a diverse extent, indicating that the related urinary metabolites could reflect the population's exposure to specific atmospheric PAHs. The findings also revealed that in the 16 selected countries, AirS indexes were positively correlated with ExpS indexes, implying that higher PAH levels in the air may lead to elevated metabolite urinary levels in general populations. Furthermore, lowering PAH air concentrations could reduce population internal PAH exposure, implying that strict PAH air regulation or emission would reduce health risks for general populations. Notably, this study was an ideal theoretical research based on proposed assumptions to some extent. Further research should focus on understanding exposure pathways, protecting vulnerable populations, and improving the PAH database to optimize PAH pollution control.

Association of the urinary polycyclic aromatic hydrocarbons with sex hormones stratified by menopausal status older than 20 years: a mixture analysis

We examined the relationships between exposure to polycyclic aromatic hydrocarbons (PAH) metabolites and sex hormones in pre- and postmenopausal women from the 2013-2016 National Health and Nutrition Examination Survey. The study comprised 648 premenopausal and 370 postmenopausal women (aged 20years or older) with comprehensive data on PAH metabolites and sex steroid hormones. To evaluate the correlations between individual or mixture of the PAH metabolites and sex hormones stratified by menopausal status, we used linear regression and Bayesian kernel machine regression (BKMR). After controlling for confounders, 1-Hydroxynaphthalene (1-NAP) was inversely associated with total testosterone (TT), and 1-NAP, 3-Hydroxyfluorene (3-FLU), and 2-Hydroxyfluorene (2-FLU) were inversely associated with estradiol (E2). 3-FLU was positively associated with sex hormone-binding globulin (SHBG) and TT/E2, whereas 1-NAP and 2-FLU were inversely associated with free androgen index (FAI). In the BKMR analyses, chemical combination concentrations at or above the 55th percentile were inversely connected to E2, TT, and FAI values but positively correlated with SHBG when compared with the matching 50th percentile. In addition, we only found that mixed exposure to PAHs was positively associated with TT and SHBG in premenopausal women. Exposure to PAH metabolites, either alone or as a mixture, was negatively associated with E2, TT, FAI, and TT/E2 but positively associated with SHBG. These associations were stronger among postmenopausal women.

Polycyclic aromatic hydrocarbons exposure and plasma lncRNA signature: A profile and functional analysis

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants that pose detrimental effects on human health, and the exploration of the associations of PAHs exposure with long non-coding RNA (lncRNA) may provide novel clues to the underlying mechanisms. In the present study, we detected 10 urinary PAHs metabolites by GC–MS and plasma lncRNAs levels by Human LncRNA Array v4 among 230 participants from two panels (160 in the Shiyan panel and 70 in the Wuhan-Zhuhai panel). We applied linear regression models to assess the associations between PAHs metabolites and lncRNAs separately in each panel and combined the results using fixed-effect meta-analysis. To explore the potential origin of PAHs-related lncRNAs in plasma, we estimated their tissue-specificity and associations between lncRNAs levels in plasma and leukocytes. Leukocytes mRNA sequencing data and RNA binding proteins were utilized to explore implicated pathways of identified lncRNAs. We found that urinary 1-hydroxyphenanthrene (1-OH-Phe) was inversely associated with 8 lncRNAs and positively associated with 1 lncRNA, as well as 9-hydroxyphenanthrene (9-OH-Phe) was inversely associated with 11 lncRNAs (FDR < 0.1). Tissue specificity analysis using Genome Tissue Expression database suggested that several identified lncRNAs might specifically express in organs targeted by PAHs exposure (lung, liver, heart, kidney, and brain). Besides, plasma levels of 1-OH-Phe related ENSG00000260616 and 9-OH-Phe related STARD4-AS1 were inversely associated with their intra-leukocytes levels (P value < 0.05). Notably, STARD4-AS1 was positively associated with the expression levels of its neighboring protein-coding gene (CAMK4 and STARD4) in leukocytes and were involved in pathways related to cellular response to DNA damage, which we further confirmed using DNA damage biomarker, 8-hydroxydeoxyguanosine. Functional analysis also revealed vital pathways related to cytokine-mediated signaling and glucose homeostasis. Our findings provided novel insights into plausible biological mechanisms underlying the adverse effects of PAHs exposure.

Association of occupational exposure to polycyclic aromatic hydrocarbons in workers with hypertension from a northeastern Chinese petrochemical industrial area

Elevated urinary polycyclic aromatic hydrocarbon metabolites have been linked to an increased risk of cardiovascular diseases (CVDs). However, for petrochemical workers with potentially high PAH exposure, it remains largely unknown whether the link will be amplified. Thus, this work aimed to investigate 14 urinary mono-hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) in 746 petrochemical workers working in a Chinese petrochemical industrial area and their association with the risk of hypertension using the binary logistic regression. Metabolites of naphthalene, fluorene, phenanthrene, and pyrene were frequently detected in the 746 urine samples analyzed (>98%), with Σ10OH-PAH concentration in the range of 0.906–358 ng/mL. 2-hydroxynaphthalene accounted for the largest proportion of ten detected OH-PAHs (60.8% of Σ10OH-PAHs). There were significant correlations between these metabolites and other factors, including gender, age, and body mass index. Diastolic blood pressure, not systolic blood pressure, was significant positively associated with the urinary Σ10OH-PAH concentrations of the petrochemical workers. Elevated urinary 2/3-OH-Flu was significantly associated with an increased risk of hypertension (adjusted odds ratio: 1.96, 95% confidence interval: 1.20–3.18, p = 0.007), suggesting that PAH exposure in petrochemical workers was a driving factor of hypertension. In the stratified analysis, the association was more pronounced in those who were overweight with older age. Although the PAH exposure risk in petrochemical workers based on the estimated daily intakes was relatively low. Given the long-term impact, we call attention to CVDs of petrochemical workers.

Association of polycyclic aromatic hydrocarbons with osteoarthritis among adults: an analysis of the NHANES 2001-2016.

Polycyclic aromatic hydrocarbons (PAHs) are environmental endocrine-disrupting compounds, which have been widely recognised as a risk factor for human health. However, the relationship between PAHs exposure and the risk of osteoarthritis has rarely been reported. This study aimed to investigate the association between individual and mixed exposure to PAHs and osteoarthritis. In this cross-sectional study, participants aged ≥20 years with data on urinary PAHs and osteoarthritis were extracted from the National Health and Nutrition Examination Survey (NHANES) between 2001 and 2016. Logistic regression analysis was utilised to assess the relationship between individual PAHs exposure and osteoarthritis. The quantile-based g computation (qgcomp) analysis and Bayesian kernel machine regression (BKMR) analysis were performed to assess the effect of mixed exposure to PAHs on osteoarthritis, respectively. A total of 10,613 participants were enrolled, 980 (9.23%) of whom had osteoarthritis. Exposure to high levels of 1-hydroxynaphthalene (1-NAP) [odds ratio (OR)=1.06, 95% confidence interval (CI): 1.01-1.10], 3-hydroxyfluorene (3-FLU) (OR=1.09, 95%CI: 1.02-1.17), and 2-hydroxyfluorene (2-FLU) (OR=1.06, 95%CI: 1.01-1.13) were all associated with greater odds of osteoarthritis after adjusting for age, sex, body mass index, drinking alcohol, and hypertension. The qgcomp analysis showed that the joint weighted value of mixed PAHs exposure (OR=1.11, 95%CI: 1.02-1.22; p=0.017) was significantly related to higher odds of osteoarthritis. The BKMR analysis demonstrated that mixed exposure to PAHs was positively correlated with the risk of osteoarthritis. Both individual and mixed exposure to PAHs were positively correlated with the risk of osteoarthritis.

Sex-specific effect of urinary metabolites of polycyclic aromatic hydrocarbons on thyroid profiles: results from NHANES 2011-2012.

The current study aims to evaluate the associations between 10 urinary polycyclic aromatic hydrocarbon (PAH) metabolites and thyroid profiles. The levels of 10 PAH metabolites and thyroid profiles were obtained from National Health and Nutrition Examination Survey (NHANES) 2011-2012. Spearman analysis was utilized to evaluate the correlation coefficients among these 10 PAH metabolites. Multivariate linear and logistic regression models assessed the relationship between urinary PAH metabolite levels, thyroid hormones, and thyroid autoantibodies after adjusting potential confounders. Stratified analysis by gender was performed to evaluate sex-specific effect of urinary metabolites of PAH on thyroid profiles. One thousand six hundred forty-five eligible adult participants with complete research data were enrolled. Of note, the concentrations of the majority of urinary PAH metabolites were remarkedly higher in females compared with males. 2-hydroxyfluorene (2-FLU) was associated with higher total triiodothyronine (T3) levels in whole population (β = 2.113, 95% CI 0.339-3.888). In males, positive associations were observed in 1-hydroxynaphthalene (1-NAP) and free thyroxine (T4) (β = 0.0002, 95% CI 0.0000-0.0004). 2-FLU was also found positively associated with total T3 (β = 2.528, 95% CI 0.115-4.940) in male subjects. While in female participants, 2-hydroxynaphthalene (2-NAP) was associated with free T3 (β = 0.002, 95% CI 0.000-0.005). 2-FLU was associated with total T3 (β = 2.683, 95% CI 0.038-5.328), free T3 (β = 0.050, 95% CI 0.012-0.087), and total T4 (β = 0.195, 95% CI 0.008-0.382). 2-Hydroxyphenanthrene (2-OHP), 1-hydroxypyrene (1-HP), and 9-hydroxyfluorene (9-FLU) were all positively related to total T3 levels, and the corresponding coefficients were 16.504, 6.587, and 3.010. 9-FLU was also associated with free T3 (β = 0.049, 95% CI 0.008-0.090). No statistical significances were found between PAH metabolite levels and increased prevalence of increased thyroglobulin antibody (TgAb)/thyroid peroxidase antibody (TPOAb) when PAH metabolites were treated as continuous variables. Meanwhile, in the quartile analyses, increased prevalence of elevated TgAb was observed in participants with quartile 2 2-NAP compared with lowest quartile (OR = 1.753, 95% CI 1.021-3.008). Male subgroup analyses indicated that increased prevalence of elevated TgAb was observed in higher quartile of 1-NAP, 2-NAP, and 3-hydroxyfluorene (3-FLU). Increased prevalence of elevated TPOAb was associated with higher 2-NAP quartile. However, in subgroup analysis of females, no statistical significances were found between PAH quartiles and increased TgAb/TPOAb. Significant correlations were found among these 10 PAH metabolites. In conclusion, the cross-sectional study indicated that exposure to PAH might disturb the concentrations of thyroid hormones and thyroid autoantibodies. It is noteworthy that significant differences existed in males and females. Further prospective research is warranted to explore the causal relationship and underlying mechanism of PAH exposure on thyroid dysfunction.

Polycyclic aromatic hydrocarbon exposure burden: Individual and mixture analyses of associations with chronic obstructive pulmonary disease risk

Accumulating data demonstrate that polycyclic aromatic hydrocarbons (PAH) exposure is linked to compromised respiratory diseases. This study aimed to analyze urinary PAH metabolites and their associations with chronic obstructive pulmonary disease (COPD) in a sample size of 3015 subjects from a total population of 50,588 from the National Health and Nutrition Examination Survey (NHANES) in 2007–2016. Results showed that the most predominant metabolite was 1-Hydroxynaphthalene (1-NAP, 84%) with a geometric mean concentration of 50,265 ng/L, followed by its homologue 2-NAP (10%), both of which arose from sources including road emission, smoking and cooking. Multiple logistic regression showed that seven of the ten major PAH metabolites were correlated with increased COPD risk: including 1-NAP (OR: 1.83, 95%CI: 1.25, 2.69), 2-Hydroxyfluorene (2-FLU, OR: 2.29, 95%CI: 1.42, 3.68) and 1-Hydroxyphenanthrene (1-PHE, OR: 2.79, 95%CI: 1.85, 4.21), when compared to the lowest tertile after adjusted for covariates. Total exposure burden per PAH congener sub-group demonstrated persistent positive correlation with COPD for ∑PHE (OR: 1.80, 95%CI: 1.34, 2.43) and ∑FLU (OR: 2.74, 95%CI: 1.77, 4.23) after adjusted for covariates. To address the contribution of PAH exposure as mixture towards COPD, weighted quantile sum (WQS) regression analyses revealed that 1-NAP, 9-Hydroxyfluorene (9-FLU), 3-Hydroxyfluorene (3-FLU) and 1-PHE were among the top contributors in the associations with COPD. Our results demonstrate the contemporary yet ongoing exposure burden of PAH exposure for over a decade, particularly towards NAPs and FLUs that contribute significantly to COPD risk, calling for more timely environmental regulation.

The combined effect of heavy metals and polycyclic aromatic hydrocarbons on arthritis, especially osteoarthritis, in the U.S. adult population

The evaluation of heavy metals (HMs) and polycyclic aromatic hydrocarbons (PAHs) impact on arthritis is usually limited to the analysis of the arthritis subtype (rheumatoid arthritis, RA), whereas studies on osteoarthritis (OA) are relatively sparse. Furthermore, the combined effect of HMs and PAHs co-exposure on arthritis also has rarely been analyzed. Herein, we aimed to comprehensively estimate the association between HMs and PAHs (three blood HMs and six urinary PAHs metabolites) co-exposure and arthritis. Using data from the National Health and Nutrition Examination Survey (NHANES), 2003–2016, we included 9735 adults, of whom 2464 had total arthritis, 1371 had OA, and 468 had RA. The logistic regression model was conducted to estimate the single effect of HMs and PAHs on arthritis. Moreover, weighted quantile sum (WQS) regression, quantile-based g computation (qgcomp), and Bayesian kernel machine regression (BKMR) were separately performed to assess the combined effect of HMs and PAHs co-exposure on arthritis. In the single-exposure analyses, cadmium (Cd) and lead (Pb) statistically grew the risk of total arthritis, OA, and RA. Among PAHs, 1-hydroxynaphthalene (1-NAP) and 3-hydroxyfluorene (3-FLU) showed a positive association with total arthritis, OA, and RA. Meanwhile, 2-NAP also was significantly associated with total arthritis. 2-NAP, 2-FLU, and 1-hydroxyphenanthrene (1-PHE) also were significantly associated with RA. Furthermore, the three complementary models consistently demonstrated that co-exposure to high levels of HMs and PAHs was positively associated with total arthritis, OA, and RA risk. The above associations were more obvious in young and medium-aged people. Interestingly, BKMR analyses indicated that 1-NAP might interact with Cd and 3-FLU in total arthritis, while Pb might interact with Cd in OA. Therefore, this study provided novel evidence that co-exposure to HMs and PAHs positively correlated with arthritis, especially OA, and these results were worthy of further prospective studies.

The association between urinary polycyclic aromatic hydrocarbon metabolites and liver function among US population: a cross-sectional study.

Most studies have focused on the pulmonary toxicity of inhaled PAHs to date; therefore, their hepatotoxic consequences are yet unknown. The main aim of this study is to examine the association between urinary polycyclic aromatic hydrocarbons (PAHs) and liver function parameters among the US population. The data included in this study were from the National Health and Nutritional Examination Survey (NHANES) 2003-2016. Finally, we included 2515 participants from seven cycles of the NHANES. Logistic regression was performed to calculate the association between each PAH and liver function parameters (elevated vs. normal) with odds ratio (OR) and 95% confidence intervals (CIs), along with adjustment for confounding variables. P < 0.05 was considered to indicate a statistically significant difference. All analyses were performed using R software 4.0.1. In the present study, all 2515 individuals were aged ≥ 18years, 1211 males, and 1304 females. The average age normal was 45.56 ± 20.20, and the elevated was 46.04 ± 19.73years, respectively. The results of logistic regression indicated that increased 9-hydroxyfluorene (OR = 2.11, 95% CI = [1.52, 2.95], P < 0.001), 2-hydroxyfluorene (OR = 1.61, 95% CI = [1.23, 2.11], P < 0.001), and 3-hydroxyfluorene (OR = 1.54, 95% CI = [1.21, 1.95], P < 0.001) were associated with elevated GGT. In conclusion, 9-hydroxyfluorene is associated with elevated GGT level, and the effect of 9-hydroxyfluorene on GGT is modified by other PAHs, which means that 9-hydroxyfluorene has a greater influence on GGT when other PAHs are increased.

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.

Exposure to Hazardous Substances and Their Health Effects Among Residents Living Near Three Industrial Waste Incinerators in Korea.

This study aimed to evaluate exposure to various hazardous substances emitted by incineration facilities and their likely effect on the health for residents of Bugi-myeon, Cheongju, Korea, which has three incineration facilities. Heavy metals, polycyclic aromatic hydrocarbons (PAHs), and dioxin concentrations in the air and soil of exposed and control areas were measured. Moreover, the exposure levels to harmful substances and its effects on health were investigated in 1,124 exposed and 232 control adults. PAHs and dioxin concentrations in the air in the exposed area were significantly higher than in the control area. Urinary cadmium and PAHs metabolite concentrations were significantly higher in the exposed group than in the control group. The exposure group also had a higher prevalence of depression and self-reported allergic symptoms than the control group. The possibility of residents in Bugi-myeon being exposed to hazardous substances at incineration facilities cannot be ruled out. To prevent them from further exposure to hazardous substances, it is necessary to prohibit the expansion of additional incineration facilities in this area and to implement continuous monitoring projects for residents.

Occupational exposure to polycyclic aromatic hydrocarbons in Korean adults: evaluation of urinary 1-hydroxypyrene, 2-naphthol, 1-hydroxyphenanthrene, and 2-hydroxyfluorene using Second Korean National Environmental Health Survey data.

Polycyclic aromatic hydrocarbons (PAHs) are occupational and environmental pollutants generated by the incomplete combustion of organic matter. Exposure to PAHs can occur in various occupations. In this study, we compared PAH exposure levels among occupations based on 4 urinary PAH metabolites in a Korean adult population. The evaluation of occupational exposure to PAHs was conducted using Second Korean National Environmental Health Survey data. The occupational groups were classified based on skill types. Four urinary PAH metabolites were used to evaluate PAH exposure: 1-hydroxypyrene (1-OHP), 2-naphthol (2-NAP), 1-hydroxyphenanthrene (1-OHPHE), and 2-hydroxyfluorene (2-OHFLU). The fraction exceeding the third quartile of urinary concentration for each PAH metabolite was assessed for each occupational group. Adjusted odds ratios (ORs) for exceeding the third quartile of urinary PAH metabolite concentration were calculated for each occupational group compared to the "business, administrative, clerical, financial, and insurance" group using multiple logistic regression analyses. The "guard and security" (OR: 2.949; 95% confidence interval [CI]: 1.300-6.691), "driving and transportation" (OR: 2.487; 95% CI: 1.418-4.364), "construction and mining" (OR: 2.683; 95% CI: 1.547-4.655), and "agriculture, forestry, and fisheries" (OR: 1.973; 95% CI: 1.220-3.191) groups had significantly higher ORs for 1-OHP compared to the reference group. No group showed significantly higher ORs than the reference group for 2-NAP. The groups with significantly higher ORs for 1-OHPHE than the reference group were "cooking and food service" (OR: 2.073; 95% CI: 1.208-3.556), "driving and transportation" (OR: 1.724; 95% CI: 1.059-2.808), and "printing, wood, and craft manufacturing" (OR: 2.255; 95% CI: 1.022-4.974). The OR for 2-OHFLU was significantly higher in the "printing, wood, and craft manufacturing" group (OR: 3.109; 95% CI: 1.335-7.241) than in the reference group. The types and levels of PAH exposure differed among occupational groups in a Korean adult population.

Supported liquid extraction and ultra-high performance liquid chromatography-tandem mass spectrometry for the determination of urinary polycyclic aromatic hydrocarbon metabolites and their application for human biomonitoring

Polycyclic aromatic hydrocarbons (PAHs) are a class of highly lipophilic and ubiquitous, persistent organic pollutants with carcinogenic and mutagenic toxicities. They are a great public health concern, and avoiding exposure to them is a high priority. Human biomonitoring is critical for the evaluation of exposure levels to PAHs by the general population. In this work, we demonstrated the biomonitoring of eleven hydroxylated PAHs (OHPAHs) in urine samples from 226 volunteers from Guangzhou, and evaluated the health risks. The urinary PAH metabolites were released by enzymatic deconjugation, separated, and enriched by supported liquid extraction, and then quantified by ultra-high performance liquid chromatography-tandem mass spectrometry. The limit of quantification of the individual OHPAHs ranged from 10 ng/L to 40 ng/L, and satisfactory recoveries were obtained, ranging from 92.6% to 97.6%. The detection frequencies of the OHPAHs were 100%, and naphthalene metabolites were found at the highest concentrations with a geometric mean of 8.61 μg/L. The mean total OHPAH level in the urine samples of males (13.2 μg/L) was significantly higher than that of females (5.84 μg/L). Pearson correlation analyses indicated significant and positive correlations among urinary OHPAHs. The total estimated daily intake of PAHs was calculated, and a low health risk was obtained by evaluating their hazard quotients and hazard indexes.

Associations between repeated measurements of urinary polycyclic aromatic hydrocarbon metabolites and thyroid hormones among reproductive-aged men

BackgroundPolycyclic aromatic hydrocarbons (PAHs) have been shown to disrupt thyroid function in toxicological studies, but epidemiological evidence is inconsistent. Furthermore, little is known on potential effects of mixtures of PAHs. ObjectiveThis study aimed to examine the associations of exposure to PAHs as individual chemicals and mixtures with thyroid hormones. MethodsWe included 378 men from a Reproductive Medicine Center in Wuhan, China. Ten monohydroxylated PAH (OH-PAH) metabolites in repeated urine specimens collected at two-time points and three thyroid hormones [thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3)] in one serum sample were measured. Multivariable linear regression models were applied to assess the associations between individual OH-PAH metabolites and thyroid hormones, and the associations with mixtures of OH-PAH metabolites were assessed by Bayesian kernel machine regression (BKMR) models. ResultsMultivariable linear regression models showed inverse associations between urinary 1-OHNa and TSH, between urinary 1-OHPh and 9-OHPh and FT3, as well as between urinary 2-OHPh, 3-OHPh, 9-OHPh and ∑OHPh and FT4, regardless of these individual OH-PAH metabolites modeled as continuous or tertile variables (e.g., −21.57 % in TSH; 95 % CI: −35.33 %, −4.88 % for the third vs first tertiles of 1-OHNa; p for trend = 0.014). BKMR models showed negative overall effects of all urinary OH-PAH metabolite mixtures on TSH, FT3, and FT4, and 1-OHNa, 9-OHPh, and 2-OHPh as the most important contributors, respectively, with linear inverse exposure–response associations when holding other OH-PAH metabolites at their median concentrations. ConclusionUrinary OH-PAH metabolites as individual chemicals and mixtures were adversely associated with thyroid hormones among reproductive-aged men.

Urinary polycyclic aromatic hydrocarbon metabolites are positively related to serum testosterone levels of males and serum estradiol levels of females among U.S. adults.

It has been reported for several years that polycyclic aromatic hydrocarbons (PAHs) could disturb human endocrine function. However, there is still a short of consistent conclusion about the relationship between PAH exposure and levels of sexual hormones. The aim of our study is to explore whether exposure to PAHs and how PAHs affect the levels of serum testosterone (T) and estradiol (E2) in adults, hoping to fulfill the knowledge gap. This study included adults aged 20 and above who participated in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2016. We included 10 PAH metabolites in this study. The levels of urinary PAH metabolites were log-transformed and divided into quartiles. The associations between PAH metabolites and both serum T levels of males and E2 levels of females were investigated using multivariate regression models. We furtherly calculated PAHs scores by sum of ranks across 10 PAHs metabolites, which represented the exposure levels of PAHs mixtures, and the association between PAHs scores and serum T and E2 levels were analyzed. A total of 4,654 subjects were included in this study, including 2,460 males and 2,194 females. After adjusting for confounders, 2-hydroxynapthalene and 3-hydroxyfluorene were positively associated with serum T levels of males (p-value for trend=0.047, and p-value for trend=0.006, respectively), while 1-hydroxyphenanthrene was positively associated with serum E2 levels of females (p-value for trend=0.013). In the adjusted models, no significant association was found between PAHs scores and either T levels of males or E2 levels of females (p-value for trend=0.615, and p-value for trend=0.241, respectively). This study showed urinary 2-hydroxynapthalene and 3-hydroxyfluorene were associated with increased T levels of males, and urinary 1-hydroxyphenanthrene was associated with increased E2 levels of females. The observed association indicated disrupting effects of PAH exposure on reproductive health.

Effectiveness of dermal cleaning interventions for reducing firefighters’ exposures to PAHs and genotoxins

Firefighters are exposed to carcinogenic and mutagenic combustion emissions, including polycyclic aromatic hydrocarbons (PAHs). Fire service and firefighter cancer advocacy groups recommend skin cleaning using wipes or washing with detergent and water after exposure to smoke, although these strategies have not been proven to reduce exposures to harmful combustion products such as PAHs. This study assessed dermal decontamination methods to reduce PAH exposures by firefighters participating in live fire training scenarios. Study participants (n = 88) were randomly assigned to an intervention group (i.e., two types of commercial skin wipes, detergent and water, or a control group who did not use any skin decontamination). PAHs were measured in personal air (during the fire) and dermal wipe samples (before and after fire suppression and after dermal decontamination). PAH metabolites and mutagenicity were measured in urine samples before and after fire suppression. Airborne PAH concentrations during the fire ranged between 200 and 3,970 μg/m3 (mean = 759 μg/m3, SD = 685 μg/m3). Firefighters had higher total PAHs and high-molecular-weight PAHs on their skin after the fire compared to before (1.3- and 2.2-fold, respectively, p < 0.01). Urinary PAH metabolites increased significantly following exposure to the training fires by 1.7 to 2.2-fold (depending on the metabolite, p < 0.001). Urinary mutagenicity did not differ significantly between pre- and post-fire for any of the decontamination methods. Detergent and water was the only intervention that removed a significant amount of total PAHs from the skin (0.72 ng/cm2 preintervention vs. 0.38 ng/cm2 postintervention, p < 0.01). However, fold changes in urinary PAH metabolites (i.e., pre- vs. post-exposure levels) did not differ among any of the dermal decontamination methods or the control group. These data suggest that despite on-site attempts to remove PAHs from firefighters’ skin, the examined interventions did not reduce the internal dose of PAHs. Future work should investigate preventing initial exposure using other interventions, such as improved personal protective equipment.

Association among urinary polycyclic aromatic hydrocarbons metabolites, SAHH activity and H19 expression in coke oven workers

Objective: To investigate the relationship of polycyclic aromatic hydrocarbons (PAHs) exposure, S-adenosylhomocysteine hydrolase (SAHH) activity and long noncoding RNA H19 gene expression in the urine of coke oven workers. Methods: In September 2019, in a coking plant in Taiyuan City, 146 male workers who had worked in coke oven operations for one year were selected through a completely random sampling method, and their basic personal information was collected by questionnaire survey, and blood and urine samples were collected. The levels of 4 PAHs metabolites 2-hydroxfluorene (2-FLU), 2- hydroxynaphthalene (2-NAP), 9-hydroxyphenanthren (9-PHE), and 1-hydroxypyrene (1-OHP) in urine were detected by high performance liquid chromatography (HPLC) -fluorescence detection method. HPLC-UV detection method was used to detect the content of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) in plasma, and the SAHH activity value was obtained by calculating the ratio. Reverse transcription PCR method was used to determine the H19 gene expression level. Urine levels of 2-FLU, 2-NAP, 9-PHE, and 1-OHP were divided into Q(1), Q(2), Q(3), and Q(4) groups according to quartiles (P(25), P(50), P(75)). Regression, trend test and restricted cubic splines were used to analyze the relationship among PAHs metabolites, SAHH activity, H19 gene expression and their dose-response. Results: The median age of coke oven workers was 39.60 years old, the median length of service was 20.38 years, and the urinary levels of 2-FLU, 2-NAP, 9- PHE, and 1-OHP were 0.29, 0.74, 0.09, and 0.06 μg/mmol Cr, respectively. The levels of 2-FLU, 2-NAP and 9-PHE in the urine of workers were significantly different between groups with different 1-OHP levels (P<0.05). After adjusting for age, length of service, smoking, drinking, and levels of 2-FLU, 2-NAP and 9-PHE, SAHH activity decreased with the increase of urinary 1-OHP level (OR=0.63, 95%CI: 0.41-0.98, P=0.038), showing a nonlinear relationship (P(nonlinear)= 0.030). H19 gene expression increased with the increase of urinary 1- OHP level (OR=1.51, 95%CI: 1.03-2.19, P=0.033), there was a linear relationship (P(trend)= 0.058). The relationship between the other three metabolites in urine and SAHH activity and H19 gene expression was not statistically significant (P>0.05) . Conclusion: Urinary 1-OHP level may be a risk factor for decreased SAHH activity and increased H19 gene expression in coke oven workers.

Prenatal polycyclic aromatic hydrocarbon (PAH) exposure in relation to placental corticotropin releasing hormone (pCRH) in the CANDLE pregnancy cohort.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous endocrine-disrupting combustion by-products that have been linked to preterm birth. One possible mechanism is through disruption of placental corticotropin releasing hormone (pCRH), a key hormone implicated in parturition. As an extension of recent research identifying pCRH as a potential target of endocrine disruption, we examined maternal PAH exposure in relation to pCRH in a large, diverse sample. Participants, drawn from the CANDLE cohort, part of the ECHO-PATHWAYS Consortium, completed study visits at 16-29 weeks (V1) and 22-39 weeks (V2) gestation (n=812). Seven urinary mono-hydroxylated PAH metabolites (OH-PAHs) were measured at V1 and serum pCRH at V1 and V2. Associations between individual log-transformed OH-PAHs (as well as two summed PAH measures) and log(pCRH) concentrations across visits were estimated using mixed effects models. Minimally-adjusted models included gestational age and urinary specific gravity, while fully-adjusted models also included sociodemographic characteristics. We additionally evaluated effect modification by pregnancy complications, fetal sex, and maternal childhood trauma history. We observed associations between 2-OH-Phenanthrene (2-OH-PHEN) and rate of pCRH change that persisted in fully adjusted models (β=0.0009, 0.00006, 0.0017), however, positive associations with other metabolites (most notably 3-OH-Phenanthrene and 1-Hydroxypyrene) were attenuated after adjustment for sociodemographic characteristics. Associations tended to be stronger at V1 compared to V2 and we observed no evidence of effect modification by pregnancy complications, fetal sex, or maternal childhood trauma history. In conclusion, we observed modest evidence of association between OH-PAHs, most notably 2-OH-PHEN, and pCRH in this sample. Additional research using serial measures of PAH exposure is warranted, as is investigation of alternative mechanisms that may link PAHs and timing of birth, such as inflammatory, epigenetic, or oxidative stress pathways.

Long-term exposure to low concentrations of polycyclic aromatic hydrocarbons and alterations in platelet indices: A longitudinal study in China.

Long-term exposure to low polycyclic aromatic hydrocarbon (PAH) concentration may ave detrimental effects, including changing platelet indices. Effects of chronic exposure to low PAH concentrations have been evaluated in cross-sectional, but not in longitudinal studies, to date. We aimed to assess the effects of long-term exposure to the low-concentration PAHs on alterations in platelet indices in the Chinese population. During 2014-2017, we enrolled 222 participants who had lived in a village in northern China, 1-2 km downwind from a coal plant, for more than 25 years, but who were not employed by the plant or related businesses. During three follow-ups, annually in June, demographic information and urine and blood samples were collected. Eight PAHs were tested: namely 2-hydroxynaphthalene, 1-hydroxynaphthalene, 2-hydroxyfluorene, 9-hydroxyfluorene (9-OHFlu), 2-hydroxyphenanthrene (2-OHPh), 1-hydroxyphenanthrene (1-OHPh), 1-hydroxypyrene (1-OHP), and 3-hydroxybenzo [a] pyrene. Five platelet indices were measured: platelet count (PLT), platelet distribution width (PDW), mean platelet volume (MPV), platelet crit, and the platelet-large cell ratio. Generalized mixed and generalized linear mixed models were used to estimate correlations between eight urinary PAH metabolites and platelet indices. Model 1 assessed whether these correlations varied over time. Models 2 and 3 adjusted for additional personal information and personal habits. We found the following significant correlations: 2-OHPh (Model1 β1 = 18.06, Model2 β2 = 18.54, Model β3 = 18.54), 1-OHPh (β1 = 16.43, β2 = 17.42, β3 = 17.42), 1-OHP(β1 = 13.93, β2 = 14.03, β3 = 14.03) with PLT, as well as 9-OHFlu with PDW and MPV (odds ratio or Model3 ORPDW[95%CI] = 1.64[1.3-2.06], ORMPV[95%CI] = 1.33[1.19-1.48]). Long-term exposure to low concentrations of PAHs, indicated by2-OHPh, 1-OHPh, 1-OHP, and 9-OHFlu, as urinary biomarkers, affects PLT, PDW, and MPV. 9-OHFlu increased both PDW and MPV after elimination of the effects of other PAH exposure modes.

PAHs exposure and its association with oxidative stress and neurotransmitter levels in coal miners

Objective: To learn the investigate of polycyclic aromatic hydrocarbons (PAHs) and to explore the association between PAHs exposure and oxidative stress' neurotransmitter levels in coal miners. Methods: A cross-sectional survey was conducted in 652 coal miners (239 in the underground first line group, 280 in the underground auxiliary group and 133 in the surface group) from April to June 2017. The levels of urinary monohydroxy PAHs metabolites (OH-PAHs) , oxidative stress and neurotransmitters in blood were determined. A linear regression model was used to evaluate the correlation between OH-PAHs and oxidative stress' neurotransmitter levels. The mediating role of oxidative stress between urinary OH-PAHs and neurotransmitters change was assessed by mediation analysis. Results: The levels of 2-hydroxynaphthalene (2-NAP) 、2-hydroxy uorene (2-FLU) 、1-hydroxypyrene (1-OHP) in urine OH-PAHs of coal miners in different workplaces were significantly different (H=33.64, 9.63, 26.82, P<0.01, =0.008, <0.01) . The levels of neurotransmitters [5-hydroxytryptamine (5-HT) , norepinephrine (NE) , epinephrine (E) , dopamine (DA) , acetylcholine (Ach) , acetylcholinesterase (AChE) ] and oxidative stress [malondialdehyde (MDA) (F=36.81, 15.58, 79.16, 179.58, 33.48, 67.63, 4.96, P<0.01) ] in the blood of three groups of coal miners were significantly different. After controlling the potential confounding factors, NE content was negatively correlated with 2-FLU level, and AChE activity was also negatively correlated with 1-OHP level (β=-134.99, 95% CI: -250.74~-19.23, P=0.02; β=-0.80, 95%CI: -1.54~-0.05, P=0.036) . Positive correlation was found between Ach content and 9-hydroxyphenanthrene (9-PHE) level, AChE activity was also positively correlated with 2-NAP level and 9-PHE level (β=0.96, 95%CI: 0.26~1.64, P=0.007; β=1.78, 95%CI: 0.75~2.82, P=0.001; β=0.77, 95%CI: 0.07~1.47, P=0.031) . In addition, superoxide dismutase activity was correlated with 1-OHP level and AChE activity (β=0.32, 95%CI: 0.02~0.62, P=0.034; β=-0.23, 95%CI: -0.43~-0.02, P=0.032) . Mediation analysis indicated that 1-OHP level may directly affect AChE activity (P<0.05) . Conclusion: The level of PAHs in underground coal miners is relatively higher, and may lead to changes of neurotransmitter levels. The mediating effect of oxidative stress has not been observed.