Urinary 1-hydroxypyrene Concentration Research Articles

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.

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.

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.

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

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.

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.

Association between exposure to polycyclic aromatic hydrocarbons and brain cortical thinning: The Environmental Pollution-Induced Neurological EFfects (EPINEF) study

BackgroundAlthough some studies have suggested that exposure to polycyclic aromatic hydrocarbons (PAHs) induces neurodevelopmental disturbances in children and neurodegeneration in animals, the neurotoxic effect of PAH exposure is unclear in adults. The aim was to examine the associations of PAH exposure with brain structure and neuropsychological function in adults without known neurological diseases. MethodsThis study included 421 men and 528 women dwelling in four cities in the Republic of Korea. Urinary concentrations of four PAH metabolites (1-hydroxypyrene, 2-naphthol, 1-hydroxyphenanthrene, and 2-hydroxyfluorene) were obtained. Participants underwent brain 3 T magnetic resonance imaging and neuropsychological tests. Cortical thickness and volume were estimated using the region-of-interest method. Separate generalized linear models were constructed for each sex, adjusting for age, years of education, cohabitation status, income, tobacco use, alcohol consumption, and vascular risk factors. ResultsThe mean (standard deviation) age was 68.3 (6.6) years in men and 66.4 (6.1) years in women. In men, those in quartile 4 (versus quartile 1, the lowest) of urinary 2-naphthol concentration had cortical thinning in the global (β = −0.03, P = .02), parietal (β = −0.04, P = .01), temporal (β = −0.06, P < .001), and insular lobes (β = −0.05, P = .02). Higher quartiles of urinary 2-naphthol concentration were associated with cortical thinning in the global (P = .01), parietal (P = .004), temporal (P < .001), and insular lobes (P = .01). In women, those in quartile 4 (versus quartile 1) of urinary 1-hydroxypyrene concentration had cortical thinning in the frontal (β = −0.03, P = .006) and parietal lobes (β = −0.03, P = .003). Higher quartiles of urinary 1-hydroxypyrene concentration were associated with cortical thinning in the frontal (P = .006) and parietal lobes (P = .001). In both sexes, verbal learning and memory scores significantly declined with an increase in quartile of urinary 1-hydroxypyrene concentration. ConclusionsPAH exposure was associated with cortical thinning and decline in verbal learning and memory function in cognitively healthy adults. This suggests PAHs as an environmental risk factor for neurodegeneration.

GSTs polymorphisms are associated with epigenetic silencing of CDKN2A gene in esophageal squamous cell carcinoma.

Esophageal cancer is the eighth most common cancer and the sixth most frequent cause of cancer mortality worldwide. Exposure to polycyclic aromatic hydrocarbons formed by incomplete combustion of organic matter is an important risk factor. Genetic polymorphisms in genes encoding PAH-metabolizing enzymes like glutathione S-transferases (GSTM1, GSTP1, GSTT1) which conjugate glutathione to PAHs for reduction of oxidative stress may affect an individual's response to PAH exposure. Genomic DNA from 50 esophageal squamous cell carcinoma patients extracted from peripheral blood. PCR-RFLP technique was employed to determine GSTM1, GSTT1, and GSTP1 polymorphisms. Aberrant promoter methylation of CDKN2A was applied by methylation-specific PCR technique. Concentration of urinary 1-hydroxypyrene was determined using a HPLC system. About 38.7% showed the null GSTM1 genotype (54% cases and 13% controls), 23.7% showed GSTT1 null genotype (30% cases and 13% controls), and 62.5% were GSTP1 A/A genotype (66% cases and 56% controls). Polymorphic variants of GSTM1 and GSTT1 were significantly associated with aberrant methylation of CDKN2A gene. The null state of GSTT1 was significantly associated with high concentrations of 1-OHP in urea (p < 0.01). There was significant association between methylated states of CDKN2A and high concentrations of 1-OHP in urine (p < 0.01). We identified significant association between polymorphism of GSTs genes and epigenetic silencing of tumor suppressor gene CDKN2A in esophageal squamous cell carcinoma.

Dose-related telomere damage associated with the genetic polymorphisms of cGAS/STING signaling pathway in the workers exposed by PAHs

Telomeres are located at the end of eukaryotic chromosomes and vulnerable to exogenous chemical compounds. Exposure to coke oven emissions (COEs) leads to a dose-related telomere damage, and such chromosomal damage might trigger the cGAS/STING signaling pathway which plays an important role in immune surveillance. However, the relationship between the genetic variations in the cGAS/STING signaling pathway and telomere damage in the COEs-exposure workers has not been investigated. Therefore, we recruited 544 coke oven workers and 238 healthy control participants, and determined the level of COEs exposure, concentration of urinary 1-hydroxypyrene (1-OHPYR), genetic polymorphisms and telomere length. The results showed that the telomere length significantly decreased from the control-to high-exposure groups as defined by the external exposure level (P < 0.05). The results also indicated that STING rs7447927 CC, cGAS rs34413328 AA, and cGAS rs610913 AA could inhibit telomere shortening in the exposure group (P < 0.05), and cGAS rs34413328, urine 1-OHPYR and cumulative exposure dose (CED) had a significant association with telomere length by generalized linear model. In conclusion, telomere shortening was a combined consequence of short-term exposure, long-term exposure, and genetic variations among the COEs-exposure workers.

Association of polycyclic aromatic hydrocarbon exposure and CYP1A1 gene and enzyme activity of peripheral blood monocyte cells in coke oven workers

Objective: To explore the association between polycyclic aromatic hydrocarbons (PAHs) exposure and cytochrome P450 CYP1A1 expression at gene and enzyme activity levels in the peripheral blood monocyte cells in coke oven workers, and to provide a certain basis for the biological monitoring of health damage in coke oven workers. Methods: We surveyed 118 coke oven workers and 63 controls (energy power workers in the same company) using self-designed questionnaire, determined their post-shift urinary 1-hydroxypyrene (1-OH-Py) concentration using high performance liquid chromatography (HPLC)-fluorescence detector method. We also isolated the peripheral blood mononuclear cell (PBMC) from fasting venous blood, and detected DNA damage using comet assay, CYP1A1 mRNA level using the real-time fluorescent quantitative PCR (FQ-PCR), and EROD activity using spectrophotometry. Statistical analyses including one-way analysis of variance and multiple linear regressions were used to analyze the association of urinary 1-OH-Py and CYP1A1 mRNA level and EROD activity. Results: Compared to the control group, the urinary 1-OH-Py concentration and PBMC DNA tail moment were significantly increased in coke oven workers (P<0.05), and CYP1A1 gene level and EROD activity in PBMC were significantly decreased (P<0.05). Multiple linear regression showed that a ten-fold increase of urinary 1-OH-Pycon centration was associated with a decrease of 0.77 (95%CI: -1.33--0.21) in CYP1A1 gene level, and a decline of 0.15 (95%CI: -0.76--0.16) in EROD activity of PBMC in coke oven workers (P<0.05). Conclusion: Occupational PAHs exposure induced DNA damage, which was associated with the decreased level in CYP1A1 gene cavel and EROD activity in PBMC of coke oven workers.

Health Implications of Occupational Exposure of Butchers to Emissions from Burning Tyres.

Background:Flames from burning scrap tyres are used in de-furring animals for human consumption in most parts of Nigeria. Emissions from tyres are known to contain a myriad of toxic mixtures especially particulate matter (PM), volatile organic compounds, hazardous air pollutants, and inspirable metals, some of which are known human carcinogens. This cross-sectional study investigated the deleterious health effects of these emissions in occupationally-exposed workers at the Dei-Dei Abattoir, Abuja, Nigeria.Methods:A total of 156 respondents were divided into two groups. Group 1 (124 butchers) and group 2 [32 administrative staff (AS)]. Data from digital spirometry were used to determine the association between chronic exposure to tyre emissions and lung function. Urinary 1-Hydroxypyrene concentration, phenolic compounds levels and heavy metal concentrations were determined. Also ambient PM and polycyclic aromatic hydrocarbons (PAHs) concentrations at 3 delineated points in the abattoir were measured.Findings:Spirometry results showed significant deterioration of lung function in the butchers. The concentration of 1-Hydroxypyrene (μg/molCret) in the post-shift urine samples of the butchers was significantly higher (P < 0.05) in butchers relative to the AS (0.52 ± 0.13 Vs 0.20 ± 0.07, respectively). Similarly the concentrations of zinc and nickel (mg/l) were significantly higher in the butchers compared to the AS (zinc: 0.91 ± 0.19 Vs 0.31 ± 0.28, respectively; nickel: 0.11 ± 0.06 Vs 0.06 ± 0.02, respectively). Anthracene, fluoranthene, pyrene, benzo-a- pyrene, and PM concentrations were significantly higher at the de-furring point when compared to the wash bay and the administrative building, especially between 8.00 and 8.30 am.Conclusion:Occupational exposure to scrap tyre emissions resulted in significant adverse health effects. The existing laws banning the use of burning tyres in meat processing should be enforced while the use of personal protective equipment should be encouraged in abattoirs.

Relationship between residence characteristics and polycyclic aromatic hydrocarbon exposure in housewives: second Korean National Environmental Health Survey (2012\u20132014)

BackgroundPolycyclic aromatic hydrocarbons (PAHs) produced by incomplete combustion have negative effects on human health due to their carcinogenicity and teratogenicity. Indoor sources of PAHs include tobacco smoke, heating sources, and cooking. This study evaluated the relationship between human PAH exposure and residence characteristics.MethodThis study was based on the second Korean National Environmental Health Survey (2012–2014). Non-smoking housewives were included in the analyses (n = 1269). The concentrations of urinary PAH metabolites (2-naphthol, 2-hydroxyfluorene, 1-hydroxyphenanthrene, and 1-hydroxypyrene) were adjusted by urine creatinine level. The geometric mean concentrations of urinary PAH metabolites by residential factors were examined. Logistic regression models were used to evaluate associations between residential variables and PAH exposures.ResultsThe adjusted geometric mean concentrations of urinary 2-hydroxyfluorene and 1-hydroxyphenanthrene were significantly higher in the group residing within 100 m of a major road (p < 0.05) than in those residing > 100 m from a major road. In logistic regression analyses, the odds ratio (OR) for exceeding the third quartile of urinary 1-hydroxypyrene concentration was significantly higher in the group using coal or wood fuel for residential heating than in the group using gas (OR = 2.745, 95% confidence interval [CI] = 1.295–5.819). The detached house group had a significantly higher OR for 1-hydroxyphenanthrene compared with the apartment group (OR = 1.515, 95% CI = 1.023–2.243).ConclusionOur study shows the evidence of associations between some urinary PAH metabolite levels (1-hydroxyphenanthrene and 1-hydroxypyrene) and residence characteristics. Additional studies are needed to clarify these associations.

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

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

Reduced serum club cell protein as a pulmonary damage marker for chronic fine particulate matter exposure in Chinese population

BackgroundExposure to fine particulate matter (PM2.5) pollution is associated with increased morbidity and mortality from respiratory diseases. However, few population-based studies have been conducted to assess the alterations in circulating pulmonary proteins due to long-term PM2.5 exposure. MethodsWe designed a two-stage study. In the first stage (training set), we assessed the associations between PM2.5 exposure and levels of pulmonary damage markers (CC16, SP-A and SP-D) and lung function in a coke oven emission (COE) cohort with 558 coke plant workers and 210 controls. In the second stage (validation set), significant initial findings were validated by an independent diesel engine exhaust (DEE) cohort with 50 DEE exposed workers and 50 controls. ResultsSerum CC16 levels decreased in a dose response manner in association with both external and internal PM2.5 exposures in the two cohorts. In the training set, serum CC16 levels decreased with increasing duration of occupational PM2.5 exposure history. An interquartile range (IQR) (122.0μg/m3) increase in PM2.5 was associated with a 5.76% decrease in serum CC16 levels, whereas an IQR (1.06μmol/mol creatinine) increase in urinary 1-hydroxypyrene (1-OHP) concentration was associated with a 5.36% decrease in serum CC16 levels in the COE cohort. In the validation set, the concentration of serum CC16 in the PM2.5 exposed group was 22.42% lower than that of the controls and an IQR (1.24μmol/mol creatinine) increase in urinary 1-OHP concentration was associated with a 12.24% decrease in serum CC16 levels in the DEE cohort. ConclusionsSerum CC16 levels may be a sensitive marker for pulmonary damage in populations with high PM2.5 exposure.

Influence on serum asymmetric dimethylarginine (ADMA) concentrations of human paraoxonase 1 polymorphism (Q192R) and exposure to polycyclic aromatic hydrocarbons (PAHs) in Mexican women, a gene-environment interaction

It has been demonstrated that Cardiovascular Diseases (CVD) are a consequence of the combination of genetic and environmental factors and/or the interaction between them. Therefore, the aim of this study was to evaluate the impact of polycyclic aromatic hydrocarbon (PAHs) exposure and PON1 Q192R polymorphism (genetic susceptibility) on serum asymmetric dimethylarginine (ADMA) levels in Mexican women (n = 206). Urinary 1-hydroxypyrene concentrations (1-OHP; exposure biomarker for PAHs) were quantified using a high-performance liquid chromatography technique, PON1 Q192R polymorphism was genotyped using TaqMan probes and serum ADMA concentrations were evaluated using a commercially available ELISA kit. Urinary 1-OHP levels detected in this study ranged from 0.07 to 9.37 μmol/mol of creatinine (0.13–18.0 μg/g of creatinine). Regarding allele frequency (PON1 Q192R polymorphism), the 192Q-allele frequency was 0.43 and for the 192R-allele it was 0.57. In relation to serum ADMA levels, the levels ranged from 0.06 to 1.46 μmol/L. Moreover, multiple linear regression analysis was performed and associations between urinary 1-OHP levels (β = 0.05, p = 0.002), PON1 Q192R polymorphism (β = 0.04, p = 0.003) and serum ADMA concentrations were found. Besides, an interaction (gene-environment interaction) of both independent variables (1-OHP and PON1 polymorphism) on serum ADMA levels was found (β = 0.04, p = 0.02) in the constructed multiple linear model. Therefore, according to the significance of this research, it is necessary to execute health programs to reduce cardiovascular risk in the assessed population.

Protective Effect of White-fleshed Peach (Prunus persica (L.) Batsch) on Chronic Nicotine-induced Toxicity.

BackgroundNicotine is a major toxic component of tobacco smoke and has been recognized as a risk factor to induce oxidative tissue damage, which is a precursor to cardiovascular diseases, lung-related diseases, and cancers. Peaches (Prunus persica) have been used for the treatment of degenerative disorders, such as hypermenorrhea, dysmenorrhea, and infertility in Asian countries. In this study, we investigated the effects of white-fleshed peach on the excretion of nicotine metabolites and 1-hydroxypyrene in smokers and chronic nicotine-induced tissue damages in mice.MethodsThe concentrations of cotinine and 1-hydroxypyrene were measured in urine of smokers before or after intake of white-fleshed peaches. In addition, ICR mice were injected with nicotine (5 mg/kg body weight) and then orally administered with white-fleshed peach extracts (WFPE) (250 or 500 mg/kg body weight) for 36 days. The oxidative stress parameters and the activities of antioxidant enzymes were measured in liver and kidney tissues. Also, histological changes and nitrotyrosine expression were assessed.ResultsIntake of white-fleshed peaches increased the urinary concentration of nicotine metabolites and 1-hydroxypyrene in 91.67% and 83.33% of smokers, respectively. WFPE decreased the malondialdehyde levels and recovered the activities of antioxidant enzymes in nicotine-injected mice. In addition, WFPE inhibited nitrotyrosine expression and inflammatory responses in the liver, kidney, and lung tissues of nicotine-treated mice.ConclusionsWhite-fleshed peaches may increase the metabolism of toxic components in tobacco smoke in smokers and protect normal tissues against nicotine toxicity in mice. Therefore, supplementation of white-fleshed peaches might be beneficial to smokers.

Tracing biomarker of PAH-exposure and susceptibility factor (GSTM-polymorphism) among cancer patients in Pakistan

We studied cancer patients for possible PAH exposure, using urinary concentration of 1-hydroxypyrene (1-OHP) as a biomarker of internal dose of polycyclic aromatic hydrocarbons (PAHs). The subjects included in this study belonged to various socio-demographic backgrounds, and were diagnosed with cancer (i.e. lung, head and neck or digestive tract cancer). In general, we observed high concentration of urinary 1-OHP among digestive tract cancer patients, compared with the controls (CN) (mean 1.06, median 1.03 and mean 0.62, median 0.63 μmol/mol-Cr in digestive tract cancer patients and controls respectively). The concentrations of urinary 1-OHP were higher than the background level of PAHs; therefore, these groups could have been exposed to PAHs. Highest urinary 1-OHP concentration was observed in digestive tract cancer patients (median 1.25 μmol/mol-Cr) with GSTM-1 genotype. The results of PCA were consistent with qualitative and quantitative data analysis. The contribution of urinary 1-OHP eigenvector revealed a relatively high PAH-exposure among cancer patients compared with CN, while diet and age were influential parameters among cancer patients, which could have a strong link in cancer etiology in the selected exposure groups.

Impact of environmental volatile organic compounds on otitis media in children: Correlation between exposure and urinary metabolites

IntroductionVolatile organic compounds (VOCs) induce inflammatory responses. Tobacco smoke contains numerous VOCs and is a risk factor for otitis media effusion (OME); however, no previous studies have investigated the association between VOCs and OME. ObjectivesWe used urinary metabolites and exposure to environmental risk factors to investigate the association between VOC and polycyclic aromatic hydrocarbon exposure and recurrent OME in children. MethodsChildren with recurrent OME who visited the Otorhinolaryngology Department of Seoul National University Hospital between November 2014 and June 2015 were prospectively enrolled in the study. Recurrent OME was defined as more than two OME episodes over a 6-month period lasting longer than 2 months. The control group consisted of children without OME in the last year. Demographic information, including age, sex, and previous medical history was obtained, and endoscopic examinations of the tympanic membrane were performed. Urinary concentrations of 1-hydroxypyrene, 2-naphthol, hippuric acid, trans, trans-muconic acid (t,t-MA), mandelic acid, phenyl glyoxylic acid, and methyl hippuric acid were analyzed using high-performance liquid chromatography/tandem mass spectroscopy. Environmental factors assessed included house type, age, renovations, the presence of furniture <6 months old, proximity to a road, and exposure to passive smoking. ResultsWe enrolled 11 children with OME and 39 controls. Age and sex did not differ between groups. Exposure to passive smoking was significantly more common in the OME group than in the controls (P < 0.001). Urinary concentrations of t.t.-MA were significantly higher in the OME group (126.33 μg/g cr) than in controls (52.661 μg/g cr; P = 0.003). Other metabolites including 1-hydroxypyrene, 2-naphthol, hippuric acid, mandelic acid, phenyl glyoxylic acid, and methyl hippuric acid did not demonstrated significant relation with the OME. ConclusionsLevels of t,t-MA, a biomarker of benzene exposure, were significantly higher in the OME group than in controls. Passive smoking was significantly more common in the OME group. Our findings suggest that high t,t-MA levels which were probably originated from passive smoking and other pollutants could be indicative OME in children.

Exposure to widespread environmental endocrine disrupting chemicals and human sperm sex ratio

In recent years, a trend toward a declining proportion of male births has been noted in several, but not all, industrialized countries. The underlying reason for the drop in the sex ratio is unclear, but one theory states that widespread environmental endocrine disrupting chemicals affecting the male reproductive system in a negative manner could be part of the explanation. The present study was designed to investigate whether the urinary phthalate, pyrethroids and polycyclic aromatic hydrocarbons metabolites concentrations were associated with sperm Y:X ratio.The study population consisted of 194 men aged under 45 years of age who attended infertility clinic in Lodz, Poland for diagnostic purposes with normal semen concentration of 20–300 mln/ml or with slight oligozoospermia (semen concentration of 15–20 mln/ml) (WHO, 1999). The Y:X ratio was assessed by fluorescent in situ hybridization. Urinary concentrations of 1-hydroxypyrene were measured by high performance liquid chromatography, phthalate metabolites were analyzed using a procedure based on the LC-MS/MS methods and metabolites of synthetic pyrethroids were assessed by gas chromatography ion-tap mass spectrometry method.After adjustment for potential confounders (past diseases, age, abstinence, smoking, alcohol consumption, sperm concentration, motility, morphology) 5OH MEHP, CDCCA to TDCCA and 1-OHP was negatively related to Y:X sperm chromosome ratio (p = 0.033, p < 0.001, p = 0.047 respectively).As this is the first study to elucidate the association between the level of metabolites of widespread environmental endocrine disrupting chemicals (phthalates, synthetic pyrethroids, polycyclic aromatic hydrocarbons) on sex chromosome ratio in sperm therefore, these findings require further replication in other populations.