Urinary polycyclic aromatic hydrocarbon excretion and regional body fat distribution: evidence from the U.S. National Health and Nutrition Examination Survey 2001-2016.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants that may contribute to the etiology of obesity. However, it is unclear whether PAHs from environmental sources are associated with regional body fat distribution, and whether the association varies across racial/ethnic groups who may have differential PAH exposure patterns. OBJECTIVES: To examine correlations between PAHs and body fat distribution, and potential racial/ethnic differences among U.S. adults. METHODS: Ten PAHs were measured in spot urine samples from 2691 non-smoking adults (age ≥ 20 years) in the NHANES 2001-2016. Dual-energy X-ray absorptiometry was used to measure fat mass percent (FM%). Partial Pearson correlation coefficients (r) with multivariable adjustment were used to assess PAH-FM% associations. RESULTS: In the total population, 1-naphthalene, 3-fluorene, and 1-pyrene were inversely correlated with total FM% or trunk FM% (adjusted r ranged: - 0.06 to - 0.08), while 2-naphthalene, 9-fluorene, and 4-phenanthrene were positively correlated with the FM% measurements (r: 0.07-0.11). PAH levels are highest among non-Hispanic Blacks, followed by Hispanics and Whites and some of the correlations were different by these races/ethnicities. Among non-Hispanic Whites, no PAH was correlated with FM%. In contrast, 9-fluorene was positively correlated with total FM% (r = 0.20) and trunk FM% (r = 0.22) among Blacks, and 4-phenanthrene was positively correlated with total FM% (r = 0.23) and trunk FM% (r = 0.24) among Hispanics (P-interaction: 0.010-0.025). DISCUSSION: In this US adult population, certain PAHs are significantly associated with higher body fat contents among non-Hispanic Blacks and Hispanics but not non-Hispanic Whites, suggesting that minority groups might be particularly susceptible to PAH's obesogenic effects or the effects of other factors that determine the PAH exposure levels. Alternatively, differences in body composition may contribute to differential PAH metabolism in minority groups. Future studies are warranted to explore the racial/ethnic disparity in PAH exposures, drivers of these exposure differences, and mechanisms through which PAHs may influence body composition by races/ethnicities.

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

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

Fluorene exposure among PAH-exposed workers is associated with epigenetic markers related to lung cancer.

OBJECTIVES: Exposure to high-molecular-weight polycyclic aromatic hydrocarbons (PAHs) may cause cancer in chimney sweeps and creosote-exposed workers, however, knowledge about exposure to low-molecular-weight PAHs in relation to cancer risk is limited. In this study, we aimed to investigate occupational exposure to the low-molecular-weight PAHs phenanthrene and fluorene in relation to different cancer biomarkers. METHODS: We recruited 151 chimney sweeps, 19 creosote-exposed workers and 152 unexposed workers (controls), all men. We measured monohydroxylated metabolites of phenanthrene and fluorene in urine using liquid chromatography coupled to tandem mass spectrometry. We measured, in peripheral blood, the cancer biomarkers telomere length and mitochondrial DNA copy number using quantitative PCR; and DNA methylation of F2RL3 and AHRR using pyrosequencing. RESULTS: Median PAH metabolite concentrations were higher among chimney sweeps (up to 3 times) and creosote-exposed workers (up to 353 times), compared with controls (p<0.001; adjusted for age and smoking). ∑OH-fluorene (sum of 2-hydroxyfluorene and 3-hydroxyfluorene) showed inverse associations with percentage DNA methylation of F2RL3 and AHRR in chimney sweeps (B (95% CI)=-2.7 (-3.9 to -1.5) for F2RL3_cg03636183, and -7.1 (-9.6 to -4.7) for AHRR_cg05575921: adjusted for age and smoking), but not in creosote-exposed workers. In addition, ∑OH-fluorene showed a 42% mediation effect on the inverse association between being a chimney sweep and DNA methylation of AHRR CpG2. CONCLUSIONS: Chimney sweeps and creosote-exposed workers were occupationally exposed to low-molecular-weight PAHs. Increasing fluorene exposure, among chimney sweeps, was associated with lower DNA methylation of F2RL3 and AHRR, markers for increased lung cancer risk. These findings warrant further investigation of fluorene exposure and toxicity.

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

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

Liquid chromatography coupled with hybrid ion trap time-of-flight mass spectrometry method for the determination of caulophine in rat bio-samples and its pharmacokinetic study after intragastric and intraperitoneal administration.

A rapid and precise liquid chromatography coupled with hybrid ion trap/time-of-flight mass spectrometry method to detect and quantify caulophine and its possible active metabolites in rat plasma and urine was developed. Samples were prepared by plasma protein precipitation combined with a liquid-liquid extraction method. The separation was carried out on an InertSustain® C18 column with a mobile phase comprising methanol and 0.1% aqueous formic acid solution. The analysis was complete in 20 min with a flow rate of 0.4 mL/min. Taspine was used as the internal standard. Mass spectrometric detection was conducted with hybrid ion trap/time-of-flight equipped with electrospray ionization in the positive ion mode. The calibration curves of caulophine were linear over the concentration ranges of 0.002-0.20 µg/mL for plasma and 0.005-0.50 µg/mL for urine with the correlation coefficients greater than 0.998 in both cases. The method was successfully used to investigate the pharmacokinetics and bioavailability in rat plasma and urine samples after intragastric and intraperitoneal administration of caulophine sodium salt.

Comparison of gaseous polycyclic aromatic hydrocarbon metabolites according to their specificity as biomarkers of occupational exposure: Selection of 2-hydroxyfluorene and 2-hydroxyphenanthrene.

Exposure to Polycyclic Aromatic Hydrocarbons (PAHs) occurs by respiratory, digestive and dermal absorption. Biomonitoring takes all pathways into account but sensitive and specific biomarkers are required. Different gaseous PAHs metabolites were used due to their abundance in the atmospheric mixtures but none of them were selected as better biomarker than the others. To identify the best candidates for assessing occupational airborne exposure, relation between atmospheric levels of Naphtalene, Fluorene and Phenanthrene and urinary metabolites concentrations was studied in a carbon electrode workers group. Linear mixed effects models were built to select explanatory variables and estimate variance component. Urinary creatinine was a predictor of metabolites levels confirming the importance of diuresis for interpreting results. High significance of pre-shift sampling time combined with positive coefficients of post-shift indicated that urine should be sampled at the end of the workday in association with pre-shift urine to avoid misinterpretations. Among the 10 metabolites studied, urinary 2-hydroxyfluorene and 2-hydroxyphenanthrene showed the highest increase of variance explained by models after inclusion of individual atmospheric levels as explanatory variable. Priority could be given to 2-hydroxyfluorene due to higher excretion levels than 2-hydroxyphenanthrene.

Effects of profession on urinary PAH metabolite levels in the US population.

PURPOSE: Although exposure to polycyclic aromatic hydrocarbons (PAHs) is common in both environmental and occupational settings, few studies have compared PAH exposure among people with different professions. The purpose of this study was to investigate the variations in recent PAH exposure among different occupational groups over time using national representative samples. METHOD: The study population consisted of 4162 participants from the 2001 to 2008 National Health and Nutrition Examination Survey, who had both urinary PAH metabolites and occupational information. Four corresponding monohydroxy-PAH urine metabolites: naphthalene (NAP), fluorene (FLUO), phenanthrene (PHEN), and pyrene (PYR) among seven broad occupational groups were analyzed using weighted linear regression models, adjusting for creatinine levels, sociodemographic factors, smoking status, and sampling season. RESULTS: The overall geometric mean concentrations of NAP, FLUO, PHEN, and PYR were 6927, 477, 335, and 87 ng/L, respectively. All four PAH metabolites were elevated in the "extractive, construction, and repair (ECR)" group, with 21-42 % higher concentrations than those in the reference group of "management." Similar trends were seen in the "operators, fabricators, and laborers (OFL)" group for FLUO, PHEN, and PYR. In addition, both "service" and "support" groups had elevated FLUO. Significant (p < 0.001) upward temporal trends were seen in NAP and PYR, with an approximately 6-17 % annual increase, and FLUO and PHEN remained relatively stable. Race and socioeconomic status show independent effects on PAH exposure. CONCLUSIONS: Heterogeneous distributions of urinary PAH metabolites among people with different job categories exist at the population level. The upward temporal trends in NAP and PYR warrant reduction in PAH exposure, especially among those with OFL and ECR occupations.

Urinary Biomarkers of Polycyclic Aromatic Hydrocarbons Are Associated with Cardiometabolic Health Risk.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAH) are both man-made and naturally occurring environmental pollutants that may be related to cardiometabolic health risk. OBJECTIVE: To determine whether PAH is associated with obesity in the adult population and to examine whether urinary concentrations of PAH metabolites are associated with differences in how obesity relates to 3 or more risk factors for the metabolic syndrome (3RFMetS), type 2 diabetes (T2D), hypertension, and dyslipidemia. METHODS: A total of 4765 adult participants from the 2001-2008 National Health and Nutrition Examination Survey were examined. The association between 8 urinary hydroxylated PAH metabolites, obesity, and health were examined using weighted logistic regressions adjusting for age, sex, ethnicity, PIR, smoking status, and urinary creatinine. RESULTS: There was a positive dose-dependent association between obesity and 2-phenanthrene quintiles (P trend <0.0001). Contrarily, higher quintiles of 1-naphthalene were associated with lower risk of obesity (P trend = 0.0004). For a given BMI, those in the highest quintile of 2-naphthalene, 2-fluorene, 3-fluorene and 2-phenanthrene had a 66-80% greater likelihood of 3RFMetS (P≤0.05) compared to low levels. Higher quintiles of 1-naphthalene, 2-naphthalene, 2-phenanthrene and 1-pyrene were associated with a 78-124% greater likelihood of T2D (P≤0.05) compared to low levels while high 1-naphthalene, 2-naphthalene, 2-fluorene, 3-fluorene and 2-phenanthrene were associated with a 38-68% greater likelihood of dyslipidemia (P≤0.05) compared to lower levels. Finally, 2-naphthalene and 2-phenanthrene were positively associated with hypertension (P trend = 0.008 and P trend = 0.02 respectively). CONCLUSIONS: PAH is related to obesity and the expression of a number of obesity-related cardiometabolic health risk factors. Future research is needed to bring to light the mechanistic pathways related to these findings.

A community study of the effect of polycyclic aromatic hydrocarbon metabolites on heart rate variability based on the Framingham risk score.

OBJECTIVES: To investigate the effects of the urinary metabolite profiles of background exposure to the atmospheric pollutants polycyclic aromatic hydrocarbon (PAH) and Framingham risk score (FRS), which assesses an individual's cardiovascular disease risk, on heart rate variability (HRV). METHODS: The study conducted from April to May 2011 in Wuhan, China, included 1978 adult residents with completed questionnaires, physical examinations, blood and urine samples, and 5-min HRV indices (including SD of all normal to normal intervals (SDNN), root mean square successive difference (rMSSD), low frequency (LF), high frequency (HF) and their ratio (LF/HF), and total power) obtained from 3-channel Holter monitor. 12 urinary PAH metabolites were measured by gas chromatography-mass spectrometry. FRS was calculated by age, sex, lipid profiles, blood pressure, diabetes and smoking status. Linear regression models were constructed after adjusting for potential confounders. RESULTS: Elevated total concentration of hydroxynaphthalene (ΣOHNa) was significantly associated, in a dose-responsive manner, with decreased SDNN and LF/HF (ptrend=0.014 and 0.007, respectively); elevated total concentration of hydroxyfluorene (ΣOHFlu) was significantly associated with reduced SDNN, LF and LF/HF (ptrend=0.027, 0.003, and <0.0001, respectively); and elevated total concentration of all PAH metabolites (ΣOH-PAHs) was associated with decreased LF and LF/HF (ptrend=0.005 and <0.0001, respectively). Moreover, increasing quartiles of FRS were significantly associated with decreased HRV indices, except LF/HF (all ptrend<0.0001). Interestingly, individuals in low-risk subgroups had greater decreases in SDNN, LF and LF/HF in relation to ΣOH-PAHs, ΣOHNa and ΣOHFlu than those in high-risk subgroups (all p<0.05). CONCLUSIONS: Environmental PAH exposure may differentially affect HRV based on individual coronary risk profiles.

Personal exposure levels of PAHs in the general population in northern rural area of Jiangsu Province, China.

Polycyclic aromatic hydrocarbons (PAHs) are a group of compounds that are produced by incomplete combustion of organic matters. Studies in humans have shown associations between PAHs exposure and development of cancers. Urinary monohydroxy polycyclic aromatic hydrocarbons (OH-PAHs) are a class of PAH metabolites used as biomarkers for estimating human exposure to PAHs. We collected 332 urinary samples from a nonoccupational population in northern rural area of Jiangsu. Levels of 2-hydroxynathalene (2-OHN), 2-hydroxyfluorene (2-OHF) and 1-hydroxypyrene (1-OHP) were measured as biomarkers to assess body PAHs burdens. Three PAH metabolites were detected in more than 80% of urinary samples. After being adjusted with urinary creatinine concentration, the urinary concentrations were determined as 2-OHF > 1-OHP > 2-OHN in terms. The medians of 2-OHN, 2-OHF, 1-OHP for the general population were 1.74, 30.01, 25.24 µmoL/moL creatinine, respectively. The results demonstrated that nonoccupational populations in northern rural area of Jiangsu were exposed to extremely high PAHs. The urinary concentration (median and geometric mean) of 2-OHN,2-OHF,1-OHP in males (1.90, 0.37 ± 0.46; 34.90, 1.53 ± 0.41; 27.84, 1.52 ± 0.29 µmoL/moL creatinine, respectively) was slightly higher than in females (1.56, 0.32 ± 0.42; 29.60, 1.48 ± 0.40; 23.13, 1.49 ± 0.32 µmoL/moL creatinine, respectively). However, only 2-OHN was different significantly between males and females.

Exposure to polycyclic aromatic hydrocarbons and serum inflammatory markers of cardiovascular disease.

Polycyclic aromatic hydrocarbons (PAHs) are environmental and occupational carcinogens produced by the incomplete combustion of organic materials, such as coal and petroleum product combustion, tobacco smoking, and food cooking, that may be significant contributors to the burden of cardiovascular disease in human populations. The purpose of this study was to investigate associations between ten monohydroxy urinary metabolites of four PAHs and three serum biomarkers of cardiovascular disease (fibrinogen, homocysteine, and white blood cell count). Using data on 3219 participants aged 20 years and older from the National Health and Nutrition Examination Survey (NHANES) 2001-2004 dataset, the associations between PAH metabolites and serum inflammatory markers were analyzed using the Spearman correlations and multiple linear regression modeling. The PAH metabolites of naphthalene, fluorene, phenanthrene, and pyrene each showed both positive and negative correlations with homocysteine, fibrinogen, and white blood cell count (correlation coefficient range: -0.077-0.143) in nonsmoking participants. Using multiple linear regression models adjusted for age, gender, race/ethnicity, and body mass index, estimates of weighted geometric means of inflammatory marker levels were not significantly different between high and low levels (75th vs. 25th percentiles) for all PAH metabolites in nonsmoking subjects. The results of this study do not provide evidence for a relationship between PAH exposure (as measured by urinary levels of PAH metabolites) and serum biomarkers of cardiovascular disease after controlling for tobacco use.

Personal exposure to PM(2.5) and urinary hydroxy-PAH levels in bus drivers exposed to traffic exhaust, in Trujillo, Peru.

Public transport vehicle drivers, especially in highly polluted or trafficked areas, are exposed to high levels of air pollutants. In this study, we assessed the influence of traffic on levels of hydroxy polycyclic aromatic hydrocarbons (OH-PAHs) in commercial bus drivers in Trujillo, Peru, by measuring the within-shift changes in the urinary whole weight and creatinine-corrected concentrations of the PAH metabolites. We measured personal PM(2.5) as a proxy of exposure to traffic emission. Urine samples were collected daily from two bus drivers and three minivan drivers in Trujillo, pre-, mid-, post-work shift and on days when the drivers were off work (total n = 144). Ten OH-PAH metabolites were measured in the urine samples. Drivers were also monitored for exposure to PM(2.5) (n = 41). Daily work shift (mean = 13.1 ± 1.3 hr) integrated PM(2.5) was measured in the breathing zones of the drivers for an average of 10.5 days per driver. The differences across shift in OH-PAH concentrations were not statistically significant except for urinary 2-hydroxyfluorene (2-FLU) (p = 0.04) and 4-hydroxyphenanthrene (4-PHE) (p = 0.01) and creatinine-corrected 4-hydroxyphenanthrene (p = 0.01). Correlation between pairs of hydroxy-PAHs (ρ = 0.50 to 0.93) were highest for mid-shift samples. Concentrations of PM(2.5) (geometric mean = 64 µg/m(3); 95% confidence limits = 52 µg/m(3), 78 µg/m(3)) is similar to those measured in many other studies of traffic exposure. There was significant change across work shift for concentrations of only two of the OH-PAHs (2-FLU and 4-PHE). Results indicate that the drivers may have had limited time for clearance of PAH exposure from the body between work shifts. Comparisons of the concentrations of creatinine-corrected hydroxy-PAH to those reported in other studies indicate that exposure of public transport drivers to PAH could be similar. By following the subjects over multiple days, this study gives an indication of appropriate exposure situations for the use of hydroxy-PAHs and will be beneficial in designing future occupational studies of PAH exposure.

Identification of phase I and phase II metabolites of benfluron and dimefluron in rat urine using high-performance liquid chromatography/tandem mass spectrometry.

Biotransformation products of two potential antineoplastic agents, benfluron and dimefluron, are characterized using our integrated approach based on the combination of high-performance liquid chromatography (HPLC) separation of phase I and phase II metabolites followed by photodiode-array UV detection and electrospray ionization tandem mass spectrometry (MS/MS). High mass accuracy measurement allows confirmation of an elemental composition and metabolic reactions according to exact mass defects. The combination of different HPLC/MS/MS scans, such as reconstructed ion current chromatograms, constant neutral loss chromatograms or exact mass filtration, helps the unambiguous detection of low abundance metabolites. The arene oxidation, N-oxidation, N-demethylation, O-demethylation, carbonyl reduction, glucuronidation and sulfation are typical mechanisms of the metabolite formation. The interpretation of their tandem mass spectra enables the distinction of demethylation position (N- vs. O-) as well as to differentiate N-oxidation from arene oxidation for both phase I and phase II metabolites. Two metabolic pathways are rather unusual for rat samples, i.e., glucosylation and double glucuronidation. The formation of metabolites that lead to a significant change in the chromophoric system of studied compounds, such as the reduction of carbonyl group in 7H-benzo[c]fluorene-7-one chromophore, is reflected in their UV spectra, which provides valuable complementary information to MS/MS data.

A liquid chromatography/tandem mass spectrometry (LC-MS/MS) method for the determination of phenolic polycyclic aromatic hydrocarbons (OH-PAH) in urine of non-smokers and smokers.

Polycyclic aromatic hydrocarbons (PAH) are products of the incomplete combustion of organic materials and, therefore, occur ubiquitously in the environment and also in tobacco smoke. Since some PAH have been classified as carcinogens, it is important to have access to suitable analytical methods for biomarkers of exposure to this class of compounds. Past experience has shown that measuring a profile of PAH metabolites is more informative than metabolites of a single PAH. Assessment of environmental and smoking-related exposure levels requires analytical methods with high sensitivity and specificity. In addition, these methods should be fast enough to allow high throughput. With these pre-conditions in mind, we developed and validated a high-performance liquid chromatographic method with tandem mass spectrometric detection (LC-MS/MS) for the determination of phenolic metabolites of naphthalene, fluorene, phenanthrene and pyrene in urine of smokers and non-smokers. Sample work-up comprised enzymatic hydrolysis of urinary conjugates and solid-phase extraction on C18 cartridges. The method showed good specificity, sensitivity, and accuracy for the intended purpose and was also sufficiently rapid with a sample throughput of about 350 per week. Application to urine samples of 100 smokers and 50 non-smokers showed significant differences between both groups for all measured PAH metabolites, and strong correlations with markers of daily smoke exposure in smoker urine. Urinary levels were in good agreement with previously reported data using different methodologies. In conclusion, the developed LC-MS/MS method is suitable for the quantification of phenolic PAH metabolites of naphthalene, fluorene, phenanthrene, and pyrene in smoker and non-smoker urine.

Environmental and biological monitoring of exposures to PAHs and ETS in the general population.

The objective of this study was to analyse environmental tobacco smoke (ETS) and PAH metabolites in urine samples of non-occupationally exposed non-smoker adult subjects and to establish relationships between airborne exposures and urinary concentrations in order to (a) assess the suitability of the studied metabolites as biomarkers of PAH and ETS, (b) study the use of 3-ethenypyridine as ETS tracer and (c) link ETS scenarios with exposures to carcinogenic PAH and VOC. Urine samples from 100 subjects were collected and concentrations of monophenolic metabolites of naphthalene, fluorene, phenanthrene, and pyrene and the nicotine metabolites cotinine and trans-3'-hydroxycotinine were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to assess PAH and ETS exposures. Airborne exposures were measured using personal exposure samplers and analysed using GC-MS. These included 1,3-butadiene (BUT), 3-ethenylpyridine (3-EP) (a tobacco-specific tracer derived from nicotine pyrolysis) and PAHs. ETS was reported by the subjects in 30-min time-activity questionnaires and specific comments were collected in an ETS questionnaire each time ETS exposure occurred. The values of 3-EP (>0.25 microg/m(3) for ETS) were used to confirm the ETS exposure status of the subject. Concentrations as geometric mean, GM, and standard deviation (GSD) of personal exposures were 0.16 (5.50)microg/m(3) for 3-EP, 0.22 (4.28)microg/m(3) for BUT and 0.09 (3.03)ng/m(3) for benzo(a)pyrene. Concentrations of urinary metabolites were 0.44 (1.70)ng/mL for 1-hydroxypyrene and 0.88 (5.28)ng/mL for cotinine. Concentrations of urinary metabolites of nicotine were lower than in most previous studies, suggesting very low exposures in the ETS-exposed group. Nonetheless, concentrations were higher in the ETS population for cotinine, trans-3'hydroxycotinine, 3-EP, BUT and most high molecular weight PAH, whilst 2-hydroxyphenanthrene, 3+4-hydroxyphenanthrene and 1-hydroxyphenanthrene were only higher in the high-ETS subpopulation. There were not many significant correlations between either personal exposures to PAH and their urinary metabolites, or of the latter with ETS markers. However, it was found that the urinary log cotinine concentration showed significant correlation with log concentrations of 3-EP (R=0.75), BUT (R=0.47), and high molecular weight PAHs (MW>200), especially chrysene (R=0.55) at the p=0.01 level. On the other hand, low correlation was observed between the PAH metabolite 2-naphthol and the parent PAH, gas-phase naphthalene. These results suggest that (1) ETS is a significant source of inhalation exposure to the carcinogen 1,3-butadiene and high molecular weight PAHs, many of which are carcinogenic, and (2) that for lower molecular weight PAHs such as naphthalene, exposure by routes other than inhalation predominate, since metabolite levels correlated poorly with personal exposure air sampling.

Rapid simultaneous analysis of 1-hydroxypyrene, 2-hydroxyfluorene, 9-hydroxyphenanthrene, 1- and 2-naphthol in urine by first derivative synchronous fluorescence spectrometry using Tween-20 as a sensitizer.

A novel method of first derivative synchronous fluorescence was developed for the rapid simultaneous analysis of trace 1-hydroxypyrene (1-OHP), 1-naphthol (1-NAP), 2-naphthol (2-NAP), 9-hydroxyphenanthrene (9-OHPe) and 2-hydroxyfluorene (2-OHFlu) in human urine. Only one single scan was needed for quantitative determination of five compounds simultaneously when Deltalambda=10 nm was chosen. In the optimal experimental conditions, there was a linear relationship between the fluorescence intensity and the concentration of 1-OHP, 1-NAP, 2-NAP, 9-OHPe and 2-OHFlu in the range of 1.75 x 10(-9) to 4.50 x 10(-6) mol L(-1), 3.64 x 10(-8) to 2.20 x 10(-4) mol L(-1), 8.18 x 10(-9) to 1.20 x 10(-4) mol L(-1), 3.26 x 10(-9) to 8.50 x 10(-5) mol L(-1) and 4.88 x 10(-9) to 5.50 x 10(-6) mol L(-1), respectively. The limits of detection (LOD) were found to be 5.25 x 10(-10) mol L(-1) for 1-OHP, 1.10 x 10(-8) mol L(-1) for 1-NAP, 2.46 x 10(-9) mol L(-1) for 2-NAP, 9.77 x 10(-10) mol L(-1) for 9-OHPe and 1.46 x 10(-9) mol L(-1) for 2-OHFlu. The proposed method is reliable, selective and sensitive, and has been used successfully in the determination of traces of 1-OHP, 1-NAP, 2-NAP, 9-OHPe and 2-OHFlu in human urine samples, whose results were in good agreement with those gained by the HPLC method.

Reproductive hormones in relation to polycyclic aromatic hydrocarbon (PAH) metabolites among non-occupational exposure of males.

A limited number of studies have suggested that exposure to PAHs may affect reproductive hormones. Subjects (n=642) in this study were from the affiliated hospitals of Nanjing Medical University. Individual exposures to PAHs were measured as spot urinary concentrations of four PAH metabolites, including 1-naphthol (1-N), 2-naphthol (2-N), 2-hydroxyfluorene (2-OF) and 1-hydroxypyrene (1-OP), which were adjusted by urinary creatinine (CR). Blood samples were collected to measure serum levels of reproductive hormones, including follicle-stimulating hormone (FSH), luteotrophic hormone (LH), estradiol (E2), testosterone (T) and prolactin (PRL). All of the subjects had detectable levels of the four metabolites of PAHs in their urine samples. The median concentrations of 1-N, 2-N, 2-OF and 1-OP were 2.440, 4.176, 2.843 and 1.148 microg/g of CR. There were significant P-values between increased CR-adjusted 1-N tertiles and E2 concentration, 2-OF tertiles and LH, FSH level, 1-OP and E2 level. The multivariate linear regression results also showed significant correlation between the levels of serum LH and 1-OP (the adjusting P-value was 0.048), but no correlations were found between other hormones and the level of PAH metabolites. These observed correlations between levels of hydroxy-PAH and some altered hormones indicated slight endocrine effects on adult men with PAH exposure.

Urinary metabolites of polycyclic aromatic hydrocarbons in relation to idiopathic male infertility.

BACKGROUND: Limited studies have suggested that male reproductive function might be associated with exposure to polycyclic aromatic hydrocarbons (PAHs). METHODS: Five hundred and thirteen idiopathic infertile male subjects and 273 fertile males as controls were recruited in this study, through eligibility screening procedures. Individual exposures to PAHs were measured as spot urinary concentrations of four PAH metabolites, including 1-hydroxynaphthalene (1-N), 2-hydroxynaphthalene (2-N), 1-hydroxypyrene (1-OHP) and 2-hydroxyfluorene (2-OHF), which were adjusted by urinary creatinine (CR). Subjects with idiopathic infertility were further divided into 'normal' and 'abnormal' semen quality groups based on their semen volume, sperm concentration, sperm number per ejaculum and sperm motility. RESULTS: The median CR-adjusted urinary concentrations of 1-N, 2-N, 1-OHP, 2-OHF and Sum PAH metabolites (sum of all four metabolites) of control group were lower than those found in case groups. Subjects with higher urinary concentrations of 1-OHP, 2-OHF and Sum PAH metabolites (assessed as tertiles) were more likely to have idiopathic male infertility (P-value for trend = 0.034, 0.022 and 0.022, respectively). Comparing the two groups of idiopathic infertile subjects with different semen quality, a higher idiopathic infertility risk was found in the group with abnormal semen quality. CONCLUSIONS: Increased urinary concentrations of 1-OHP, 2-OHF and Sum PAH metabolites were associated with increased male idiopathic infertility risks, while the idiopathic infertile subjects with abnormal semen might be at higher risk.

Development of a gas chromatography/mass spectrometry method to quantify several urinary monohydroxy metabolites of polycyclic aromatic hydrocarbons in occupationally exposed subjects.

The aim of this study was the development of a method for the determination of 12 urinary monohydroxy metabolites of PAHs, namely 1-hydroxynaphthalene, 2-hydroxynaphthalene, 2-hydroxyfluorene, 9-hydroxyfluorene, 1-hydroxyphenanthrene, 2-hydroxyphenanthrene, 3-hydroxyphenanthrene, 4-hydroxyphenanthrene, 9-hydroxyphenanthrene, 1-hydroxypyrene, 6-hydroxychrysene, and 3-hydroxybenzo[a]pyrene. Analytes were determined in the presence of deuterated analogues as internal standards, by GC/MS operating in the electron impact mode. Sample preparation was performed by enzymatic hydrolysis of glucoronate and sulphate conjugates of hydroxy metabolites of PAHs, liquid-liquid extraction with n-hexane, and derivatization with a silylating reagent. The method is very specific, limits of quantification are in the range 0.1-1.4 microg/l, and range of linearity is from limit of detection to 208 microg/l. Within- and between-run precision, expressed as coefficient of variation, are <20%; accuracy for most analytes is within 20% of the theoretical value. An application of the proposed method to the analysis of 10 urine samples from coke-oven workers shows that 1-hydroxynaphthalene and 2-hydroxyfluorene were the most abundant compounds (median 61.4 and 69.7 microg/l, respectively), while 6-hydroxychrysene, and 3-hydroxybenzo[a]pyrene were always below the quantification limit.

Urinary hydroxylated metabolites of polycyclic aromatic hydrocarbons as biomarkers of exposure in asphalt workers.

BACKGROUND: Fumes and vapours released during laying of hot asphalt mix have been recognised as a major source of exposure for asphalt workers. OBJECTIVES: We investigated the relationships between inhalation exposure to asphalt emissions and urinary biomarkers of polycyclic aromatic hydrocarbons (PAHs) in asphalt workers (AW, n=75) and in ground construction workers (CW, n=37). METHODS: Total polyaromatic compounds (PAC) and 15 priority PAHs in inhaled air were measured by personal sampling. Hydroxylated PAH metabolites (OH-PAHs) (2-naphthol, 2-hydroxyfluorene, 3-hydroxyphenanthrene, 1-hydroxypyrene, 6-hydroxychrysene and 3-hydroxybenzo[a]pyrene) were determined in urine spot samples collected in three different times during the work week. RESULTS: Median vapour-phase PAC (5.5 microg m(-3)), PAHs (