Naphthalene Metabolites Research Articles

Renal excretion of 1,2-dihydroxynaphthalene (DHN) in firefighting instructors after exposure to polycyclic aromatic hydrocarbons (PAHs) during live fire training

Exposure of firefighting instructors to polycyclic aromatic hydrocarbons (PAHs) such as naphthalene is unavoidable during live fire training. The study aimed to investigate naphthalene uptake by measuring the urinary excretion of the naphthalene metabolite 1,2-dihydroxynaphthalene (DHN), to describe the DHN elimination kinetics and to evaluate the results by comparison to further biomarkers of PAH exposure. N = 6 male non-smoking firefighting instructors completed five training sessions each in a residential fire simulation unit under respiratory protection. All participants provided two urine samples before and another seven samples within an 18-h-interval after each session. DHN was detected by gas chromatography/tandem mass spectrometry (GC–MS/MS) in all samples (n = 237) with median concentrations ranging from 3.3 µg/g crea. (range 0.9–10.2) before exposure to 134.2 µg/g crea. (43.4–380.4) post exposure. Maximum elimination found 3.3 h (median) after onset of exposure decreased with a mean half-life of 6.6 h to 27.1 µg/g crea. (15.7–139.5) 18 h after training. DHN sensitively indicated a presumed dermal naphthalene intake during training, showing similar elimination kinetics like other naphthalene metabolites. Internal exposure of the participants transiently exceeded exposures determined for non-smokers in the general population, but was lower than at other workplaces with PAH exposure. Despite limited uptake, accumulation is possible with daily exposure.

Differential eco-toxicological responses toward Eisenia fetida exposed to soil contaminated with naphthalene and typical metabolites.

Naphthalene (NAP) was frequently detected in polycyclic aromatic hydrocarbons (PAHs)-contaminated soil, and its residues may pose an eco-toxicological threat to soil organisms. The toxic effects of NAP were closely tied to phenolic and quinone metabolites in biological metabolism. However, the present knowledge concerning the eco-toxicological impacts of NAP metabolites at the animal level is scanty. Here, we assessed the differences in the eco-toxicological responses of Eisenia fetida (E. fetida) in NAP, 1-naphthol (1-NAO) or 1,4-naphthoquinone (1,4-NQ) contaminated soils. NAP, 1-NAO, and 1,4-NQ exposure triggered the onset of oxidative stress as evidenced by the destruction of the antioxidant enzyme system. The lipid peroxidation and DNA oxidative damage levels induced by 1-NAO and 1,4-NQ were higher than those of NAP. The elevation of DNA damage varied considerably depending on differences in oxidative stress and the direct mode of action of NAP or its metabolites with DNA. All three toxicants induced different degrees of physiological damage to the body wall, but only 1, 4-NQ caused the shedding of intestinal epithelial cells. The integrated biomarker response for different exposure times illustrated that the comprehensive toxicity at the animal level was 1,4-NQ > 1-NAO > NAP, and the time-dependent trends of oxidative stress responses induced by the three toxicants were similar. At the initial stage, the antioxidant system of E. fetida responded positively to the provocation, but the ability of E. fetida to resist stimulation decreased with the prolongation of time resulting in provocation oxidative damage. This study would provide new insights into the toxicological effects and biohazard of PAHs on soil animals.

Evaluation of exposure to multiple organic pollutants in riparian communities of the Brazilian Amazon: Screening levels and potential health risks

Organic pollutants are widely distributed in the environment. Due to their physical and chemical characteristics, they tend to be biomagnified in food chains, mainly in aquatic organisms. Therefore, food consumption is a significant route of lifelong exposure. Although the Amazon River basin contains the highest freshwater biodiversity on Earth, there is scarce literature focusing on the levels of organic pollutants in the local population. The present study was aimed at assessing the levels of several environmental pollutants (polycyclic aromatic hydrocarbons, bisphenols, parabens, and benzophenones) in urine samples from riverside communities along the Tapajós and Amazon Rivers in the Brazilian Amazon region. The results show a 100 % detection of naphthalene metabolites (namely, 1-hydroxy-naphthalene (1OH-NAP), 2-hydroxy-naphthalene (2OH-NAP)), with the highest levels belonging to benzylparaben (BzP) (17.3 ng/mL). Gender-specific analysis revealed that women had significantly higher levels of certain PAH metabolites (i.e., 1OH-NAP and 2-hydroxy-fluorene (2OH-FLU)) than men. In turn, most of the evaluated compounds were higher in urine samples from people living near the Amazon River, which presents increased traffic of boats and ships than the Tapajós River. On the other hand, the human health risk assessment suggested that all communities are at risk of suffering non-carcinogenic effects from exposure to PAHs. At the same time, they are also at risk of carcinogenic effects from exposure to benzo[a]pyrene metabolites. Thus, further studies are needed in order to evaluate the potential health effects of exposure to a mixture of these organic pollutants and other contaminants present in the area, such as mercury.

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

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

Disturbance of OH-PAH metabolites in urine induced by single PAH lab exposure.

Due to the high exposure toxicity and individual variability of polycyclic aromatic hydrocarbons (PAHs), it is difficult to accurately characterize the actual exposure of exposed individuals through external exposure detection. In this study, the monohydroxyl metabolites of naphthalene, phenanthrene, pyrene, and 9-fluorenone were identified in the urine of low-dose PAH-exposed individuals based on ultra-performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS), and their concentrations were monitored for 15 consecutive days after exposure. The results showed that the metabolite concentrations of naphthalene, phenanthrene, and pyrene were basically the same, and all of them reached the maximum value at day 8. In contrast, the metabolite of 9-fluorenone reached its maximum value on day 2. This study showed that the four metabolites were strongly correlated with their parent PAH exposure, with a wide detection window, and their assays were specific, sensitive, and reliable, while the sampling difficulty was low, so the four hydroxylated PAHs may be potential low-dose biomarkers of PAH internal exposure. This study will provide methodological and data support for further health risk studies involving internal exposure to organic pollutants such as PAHs.

Evaluating Exposure to VOCs and Naphthalene for Firefighters Wearing Different PPE Configurations through Measures in Air, Exhaled Breath, and Urine.

Firefighters are at an increased risk of cancer due to their occupational exposure to combustion byproducts, especially when those compounds penetrate the firefighter personal protective equipment (PPE) ensemble. This has led to questions about the impact of base layers (i.e., shorts vs. pants) under PPE ensembles. This study asked 23 firefighters to perform firefighting activities while wearing one of three different PPE ensembles with varying degrees of protection. Additionally, half of the firefighters unzipped their jackets after the scenario while the other half kept their jackets zipped for five additional minutes. Several volatile organic compound (VOC) and naphthalene air concentrations outside and inside of hoods, turnout jackets, and turnout pants were evaluated; biological (urinary and exhaled breath) samples were also collected. VOCs and naphthalene penetrated the three sampling areas (hoods, jackets, pants). Significant (p-value < 0.05) increases from pre- to post-fire for some metabolites of VOCs (e.g., benzene, toluene) and naphthalene were found. Firefighters wearing shorts and short sleeves absorbed higher amounts of certain compounds (p-value < 0.05), and the PPE designed with enhanced interface control features appeared to provide more protection from some compounds. These results suggest that firefighters can dermally absorb VOCs and naphthalene that penetrate the PPE ensemble.

Effect of polycyclic aromatic hydrocarbons on cancer risk causally mediated via vitamin D levels.

Polycyclic aromatic hydrocarbons (PAHs) widely exist in environmental substrates and are closely related to individual circulating vitamin D levels and tumorigenesis. Therefore, we proposed to evaluate the relationship between PAH exposure, vitamin D, and the risks for 14 cancer types via a causal inference framework underlying the mediation analysis. We evaluated seven urine monohydroxylated PAH (OH-PAH) and serum vitamin D concentrations of 3306 participants from the National Health and Nutrition Examination Survey between the 2013 and 2016 survey cycles and measured PAH concentrations in 150 subjects from the Nanjing cohort. We observed a significant negative dose-response relationship between increased OH-PAH levels and vitamin D deficiency. Each unit increase in ∑OH-PAHs could lead to a decrease in vitamin D levels (βadj = -0.98, Padj = 2.05 × 10-4 ). Body mass index could have interaction effects with ∑OH-PAHs and affect vitamin D levels. Coexposure to naphthalene and fluorene metabolites mutually affected vitamin D levels. Notably, vitamin D could causally mediate the relationship between OH-PAHs and nine types of cancer (e.g., colorectal cancer, liver cancers, etc.). This study first emphasizes the causal cascade of individual OH-PAHs, vitamin D, and cancer risk, providing insights into prevention via the environment.

Internal exposure risk based on urinary metabolites of PAHs of occupation and non-occupation populations around a non-ferrous metal smelting plant

The emission of various metals from non-ferrous metal smelting activities is well known. However, relative investigations on potential occupational exposure of organic pollutants are still limited. Herein, total of 619 human urine samples were collected from workers engaged in smelting activities and residents living near and/or far from the smelting sites, and ten mono-hydroxylated metabolites of polycyclic aromatic hydrocarbons (OH-PAHs) in human urine were determined. The median levels of Σ10OH-PAHs in smelting workers (25.6 ng/mL) were significantly higher (p < 0.01) than that of surrounding residents (9.00 ng/mL) and rural residents as the control (8.17 ng/mL), indicating an increase in occupational PAH exposure in non-ferrous metal smelting activities. The composition profiles of OH-PAH congeners were similar in three groups, in which naphthalene metabolites accounted for 76–82% of the total. The effects of smoking, drinking, gender, BMI, and occupational categories on urinary OH-PAHs were considered. The partial correlation analysis showed an insignificant effect of non-ferrous metal smelting activities on PAH exposure for surrounding residents. In the health risk assessments, almost all smelting workers had cancer risks exceeded the acceptable level of 10−6. This study provides a reference to occupational PAH exposure and reinforce the necessary of health monitoring among smelting workers.

The association between internal polycyclic aromatic hydrocarbons exposure and risk of Obesity—A systematic review with meta-analysis

Exposure to polycyclic aromatic hydrocarbons (PAHs) is emerging as a risk factor for obesity, but with conflicting findings. The aim of this systematic review is to investigate and summarize the current evidence towards the associations between PAHs exposure and risk of obesity. We conducted a systematic search of online databases, including PubMed, Embase, Cochrane Library, and Web of Science up to April 28, 2022. Eight cross-sectional studies with data from 68,454 participants were included. The present study illustrated that there was a significant positive association between naphthalene (NAP), phenanthrene (PHEN), and total OH-PAH metabolites and risk of obesity, the pooled OR (95% CI) was estimated at 1.43 (1.07, 1.90), 1.54 (1.18, 2.02), and 2.29 (1.32, 3.99), respectively. However, there was no significant association between fluorene (FLUO) and1-hydroxypyrene (1-OHP) metabolite and risk of obesity. Subgroup analyses showed that associations between PAHs exposure and risk of obesity were more apparent in children, female, smokers and developing regions.

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.

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 urinary monohydroxylated polycyclic aromatic hydrocarbons and unexplained recurrent spontaneous abortion and health risk assessment in a large case-control study in China

Polycyclic aromatic hydrocarbons (PAHs) are a group of environmental endocrine disruptors with known carcinogenic, reproductive, and developmental toxicity. Important knowledge gaps remain regarding the relationship between PAH exposure and unexplained recurrent spontaneous abortion (URSA). In the present study, twelve monohydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) were measured in the urine of 413 URSA cases and 434 controls. The main OH-PAHs measured in this study were monohydroxy metabolites of naphthalene, followed by fluorene and phenanthrene. After the creatinine correction, the median concentration of urinary OH-PAHs in the control group (17.4 μg/g Creatinine) was higher than that in the case group (14.2 μg/g Creatinine). There was no positive relationship between PAH exposure and URSA using binary logistic regression analysis. Among 847 Chinese women of childbearing age, residential environment, type of drinking water, and education level were the influencing factors of PAH exposure. The health risk assessment showed that over 98% of women had a carcinogenic risk with carcinogenic risk values above the acceptable level (10−6). Although this large-scale case-control study did not observe an association between PAH exposure and URSA, more attention should be paid to the high carcinogenic risk due to PAH exposure in women of reproductive age.

Characteristics of exposure to 10 polycyclic aromatic hydrocarbon metabolites among pregnant women: cohort of pregnant women in Zunyi, southwest China

ObjectiveOur aim was to elucidate the polycyclic aromatic hydrocarbon (PAH) metabolites exposure levels of pregnant women in the underdeveloped region of Zunyi, southwest China.MethodsSociodemographic information was collected via questionnaires, and...

Chemical mixture exposure patterns and obesity among U.S. adults in NHANES 2005–2012

BackgroundThe effect of chemical exposure on obesity has raised great concerns. Real-world chemical exposure always imposes mixture impacts, however their exposure patterns and the corresponding associations with obesity have not been fully evaluated. ObjectivesTo discover obesity-related mixed chemical exposure patterns in the general U.S. population. MethodsSparse Decompositional Regression (SDR), a model adapted from sparse representation learning technique, was developed to identify exposure patterns of chemical mixtures with exclusion (non-targeted model) and inclusion (targeted model) of health outcomes. We assessed the relationships between the identified chemical mixture patterns and obesity-related indexes. We also conducted a comprehensive evaluation of this SDR model by comparing to the existing models, including generalized linear regression model (GLM), principal component analysis (PCA), and Bayesian kernel machine regression (BKMR). ResultsEight core exposure patterns were identified using the non-targeted SDR model. Patterns of high levels of MEP, high levels of naphthalene metabolites (ΣOH-Nap), and a pattern of high exposure levels of MCOP, MCNP, and MCPP were positively associated with obesity. Patterns of high levels of BP3, and a pattern of higher mixed levels of MPB, PPB, and MEP were found to have negative associations. Associations were strengthened using the targeted SDR model. In the single chemical analysis by GLM, BP3, MBP, PPB, MCOP, and MCNP showed significant associations with obesity or body indexes. The SDR model exceeded the performance of PCA in pattern identification. Both SDR and BKMR identified a positive contribution of ΣOH-Nap and MCOP, as well as a negative contribution of BP3 and PPB to obesity. ConclusionOur study identified five core exposure patterns of chemical mixtures significantly associated with obesity using the newly developed SDR model. The SDR model could open a new avenue for assessing health effects of environmental mixture contaminants.

Responses of Wild Finescale Dace (Phoxinus neogaeus) to Experimental Spills of Cold Lake Blend Diluted Bitumen at the International Institute for Sustainable Development-Experimental Lakes Area, Northwestern Ontario.

Pipelines carrying diluted bitumen (dilbit) traverse North America and may result in dilbit release into sensitive freshwater ecosystems. To better understand the potential effects of a freshwater oil release, the Boreal-lake Oil Release Experiment by Additions to Limnocorrals project at the International Institute for Sustainable Development-Experimental Lakes Area (Ontario, Canada) modeled seven dilbit spills contained within a 10-m diameter of littoral limnocorrals in a boreal lake. Wild finescale dace (Phoxinus neogaeus) were released in the limnocorrals 21 days after oil addition and remained there for 70 days. Dilbit volumes covered a large range representing a regression of real spill sizes and total polycyclic aromatic compounds (TPAC) between 167 ng L-1 day-1 and 1989 ng L-1 day-1 . We report the effects of chronic exposure on reproductive potential as well as physiological responses in the gallbladder and liver. In exposures >1000 ng L-1 day-1 , there was a significant decrease in fish retrieval, culminating in zero recapture from the three highest treatments. Among the fish from the limnocorrals with lower levels of TPAC (<500 ng L-1 day-1 ), effects were inconsistent. Gallbladder bile fluorescence for a naphthalene metabolite was significantly different in fish from the oil-exposed limnocorrals when compared to the lake and reference corral, indicating that fish in these lower exposures were interacting with dilbit-derived polycyclic aromatic compounds. There were no significant differences in condition factor, somatic indices, or hepatocyte volume indices. There were also no significant changes in the development of testes or ovaries of exposed dace. The results from the present study may serve to orient policymakers and emergency responders to the range of TPAC exposures that may not significantly affect wild fish. Environ Toxicol Chem 2022;41:2745-2757. © 2022 SETAC.

The longitudinal biomonitoring of residents living near the waste incinerator of Turin: Polycyclic Aromatic Hydrocarbon metabolites after three years from the plant start-up

The waste-to-energy (WTE) incinerator plant located in the Turin area (Italy) started to recover energy from the combustion of municipal solid waste in 2013. A health surveillance program was implemented to evaluate the potential health effects on the population living near the plant. This program included a longitudinal biomonitoring to evaluate temporal changes of some environmental pollutants, including polycyclic aromatic hydrocarbons (PAHs), in residents living in areas near the Turin incinerator (exposed group, E) compared to those observed in subjects living far from the plant (not exposed group, NE). Ten monohydroxy-PAHs (OH-PAHs), consisting in the principal metabolites of naphthalene, fluorine, phenanthrene, and pyrene, were analyzed in urines collected from the E and NE subjects after one (T1) and three years (T2) of plant activity and compared with those determined in the same cohort established before the plant start-up (T0). Spearman correlation analysis was undertaken to explore possible associations between OH-PAHs and personal characteristics, lifestyle variables, and dietary habits. A linear mixed model (LMM) approach was applied to determine temporal trends of OH-PAHs observed in the E and NE subjects and to evaluate possible differences in trend between the two groups. Temporal trends of OH-PAHs determined by LMM analysis demonstrated that, at all times, the E group had concentrations lower than those assessed in the NE group, all other conditions being equal. Moreover, no increase in OH-PAH concentrations was observed at T1 and T2 either in E or in NE group. Significant positive correlations were found between all OH-PAHs and smoking habits. Regarding variables associated to outdoor PAH exposure, residence near high traffic roads and daily time in traffic road was positively correlated with 1-hydroxynaphthalene and 1-hydroxypyrene, respectively. In conclusion, no impact of the WTE plant on exposure to PAHs was observed on the population living near the plant.

Polycyclic aromatic hydrocarbon exposure and DNA oxidative damage of workers in workshops of a petrochemical group.

The petrochemical industry has promoted the development of economy, while polycyclic aromatic hydrocarbons (PAHs) produced by the industry become the threat for environment and humans. Data on human occupational exposure in petrochemical industry are limited. In the present study, urinary hydroxylated PAH metabolites (OH-PAHs) and a biomarker of DNA oxidative damage (8-hydroxy-2'-deoxyguanosine (8-OHdG)) were measured in 546 workers of a petrochemical group in Northeast China, to investigate PAH exposure and related potential health risk. The concentrations of ∑9OH-PAH in all workers were 0.25-175μg/g Cre with a median value of 4.41μg/g Cre. Metabolites of naphthalene were the predominant compounds. The levels of PAH metabolites were significantly different for workers with different jobs, which were the highest for recycling workers (13.7μg/g Cre) and the lowest for agency managers (5.12μg/g Cre). Besides, higher levels of OH-PAHs were usually found in males and older workers. There was a dose-response relationship between levels of 8-OHdG and ∑9OH-PAHs (p<0.01). No difference was observed in concentrations of 8-OHdG for workers of different gender or ages, work history as well as noise. Furthermore, workers simultaneously exposed to other potential pollutants and higher levels of ∑9OH-PAH had significantly higher levels of 8-OHdG compared with those in the corresponding subgroups. Our results suggested that exposure to PAHs or co-exposure to PAHs and potential toxics in the petrochemical plant may cause DNA damage. We call for more researches on the associations among noise, chemical pollution and oxidative stress to workers in the real working environment.

Biliary Polycyclic Aromatic Hydrocarbon Metabolite Equivalents Measured in Fish and Subtidal Invertebrates Following the Refugio Beach Oil Spill.

Monterey formation crude oil spilled from an onshore pipeline and entered the surf zone near Refugio State Beach, Santa Barbara County, CA, USA on 19 May 2015. Exposure to nearshore fish was evaluated by measuring biliary polycyclic aromatic hydrocarbon (PAH) metabolite concentrations in surfperch (Embiotocidae), collected near the release point, at a lesser oiled area, Gaviota State Beach, and near the Coal Oil Point oil seep, Campus Point, at both four days and approximately one year after the oil spill. Three to four weeks after the spill, fish, invertebrates, and kelp were collected near the same three sites for PAH analysis of edible tissues to support the fishery closure assessment. Additionally, thirteen days after the spill, vegetation, and invertebrate tissue samples from the seafloor near Refugio State Beach were analyzed for PAHs. In surfperch bile, mean naphthalene, phenanthrene and benzo(a)pyrene metabolite equivalents were significantly higher at Refugio State Beach, compared to Gaviota State Beach or Campus Point in 2015. One year later, there was no significant difference between the three sites. Spatial and depth zone patterns of PAH tissue concentrations from composited invertebrate, vegetation and fish showed highest concentrations were measured in invertebrates collected near Refugio State Beach. Overall, results show elevated PAH levels in nearshore organisms and provide a useful reference for potential PAH exposures in fish and subtidal invertebrates following a large nearshore oil spill.

In vitro airway models from mice, rhesus macaques, and humans maintain species differences in xenobiotic metabolism and cellular responses to naphthalene.

The translational value of high-throughput toxicity testing will depend on pharmacokinetic validation. Yet, popular in vitro airway epithelia models were optimized for structure and mucociliary function without considering the bioactivation or detoxification capabilities of lung-specific enzymes. This study evaluated xenobiotic metabolism maintenance within differentiated air-liquid interface (ALI) airway epithelial cell cultures (human bronchial; human, rhesus, and mouse tracheal), isolated airway epithelial cells (human, rhesus, and mouse tracheal; rhesus bronchial), and ex vivo microdissected airways (rhesus and mouse) by measuring gene expression, glutathione content, and naphthalene metabolism. Glutathione levels and detoxification gene transcripts were measured after 1-h exposure to 80 µM naphthalene (a bioactivated toxicant) or reactive naphthoquinone metabolites. Glutathione and glutathione-related enzyme transcript levels were maintained in ALI cultures from all species relative to source tissues, while cytochrome P450 monooxygenase gene expression declined. Notable species differences among the models included a 40-fold lower total glutathione content for mouse ALI trachea cells relative to human and rhesus; a higher rate of naphthalene metabolism in mouse ALI cultures for naphthalene-glutathione formation (100-fold over rhesus) and naphthalene-dihydrodiol production (10-fold over human); and opposite effects of 1,2-naphthoquinone exposure in some models-glutathione was depleted in rhesus tissue but rose in mouse ALI samples. The responses of an immortalized bronchial cell line to naphthalene and naphthoquinones were inconsistent with those of human ALI cultures. These findings of preserved species differences and the altered balance of phase I and phase II xenobiotic metabolism among the characterized in vitro models should be considered for future pulmonary toxicity testing.

The Association between Urinary Polycyclic Aromatic Hydrocarbons Metabolites and Type 2 Diabetes Mellitus

Polycyclic aromatic hydrocarbons (PAHs) are considered to be endocrine disruptors. In this study, the evidence on the association between PAHs and diabetes was systematically reviewed. PubMed, EMBASE, and ISI Web of Science were systematically searched for studies reporting the association between PAHs and diabetes. Of the 698 articles identified through the search, nine cross-sectional studies were included. Seven were conducted in the general population and two in coke oven workers. Fixed-effects and random-effects models were used to calculate the total effect. Subgroup analysis was further carried out according to the types of PAH metabolites. The results showed that the odds of diabetes were significantly higher for the highest category of urinary naphthalene (NAP), fluorine (FLU), phenanthrene (PHEN), and total mono-hydroxylated (OH-PAH) metabolites compared to the lowest category. The pooled odds ratios (OR) and 95% confidence intervals (CI) were 1.52 (95%CI: 1.19, 1.94), 1.53 (95%CI: 1.36, 1.71), 1.43 (95%CI: 1.28, 1.60), and 1.49 (95%CI: 1.07, 2.08), respectively. In coke oven workers, 4-hydroxyphenanthrene (4-OHPh) was significantly correlated with an increased risk of diabetes. Exposure measurements, outcome definitions, and adjustment for confounders were heterogeneous between studies. The results of the current study demonstrate a potentially adverse effect of PAHs on diabetes. Further mechanistic studies and longitudinal studies are needed to confirm whether PAH metabolite levels are causative, and hence associative, with increased diabetes incidences.