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To investigate the mediating effect of oxidative stress on the relationships between low-concentration benzene, toluene, and xylene (BTX) exposure and blood pressure in workers. A cross-sectional study involving 841 workers from a petroleum refining enterprise in Hainan, China, was conducted. Among the workers, 615 workers were exposed to low-concentration BTX, and 216 workers were in the control group. S-phenylmercapturic acid (S-PMA), hippuric acid (HA), and methyl hippuric acid (MHA, including the three isomers 2-MHA, 3-MHA, and 4-MHA) were measured in the urine of workers via high-performance liquid chromatography‒tandem triple quadrupole mass spectrometry to assess the internal BTX burden. Oxidative stress markers, blood pressure, and their correlations were analysed in both the exposed and control groups of workers. Mediation analysis was used to investigate the potential role of oxidative stress in the relationship between BTX exposure and blood pressure. The concentrations of BTX at the sampling points in the enterprise were all below the limits stipulated in China's national occupational health criteria: occupational exposure limits for hazardous agents. With respect to the internal burden of BTX, the concentrations of the benzene metabolite S-PMA, the toluene metabolite HA, and the xylene metabolites 3-MHA and 4-MHA in the urine samples in the exposure group were greater than those in the control group (P < 0.05). The correlation analysis results revealed that the concentration of the benzene metabolite S-PMA in workers' urine was positively correlated with diastolic blood pressure (DBP) (r = 0.265, P < 0.05). Compared with those in the control group, DBP was greater (β = 1.363, 95% CI 0.088 -2.639), serum superoxide dismutase (SOD) activity was lower (β = - 0.037, 95% CI - 0.060 to - 0.013), and the serum malondialdehyde (MDA) concentration was greater (β = 0.066, 95% CI 0.022-0.110) in the exposure group. Partial correlation analysis revealed a positive correlation between DBP and MDA (r s = 0.115, P < 0.01). The results of the mediation analysis indicated that MDA was a complete mediator between low BTX exposure and DBP (P < 0.05). Occupational exposure to low concentrations of BTX elevates blood pressure and oxidative stress among workers. A positive correlation between DBP and MDA was observed, with MDA acting as a complete mediator between low-concentration BTX exposure and DBP elevation., (© 2024. The Author(s).)

Aging petrochemical landfills serve as reservoirs of inorganic and organic contaminants, posing potential risks of contamination to the surrounding environment. Identifying the pollution characteristics and elucidating the translocation/ transformation processes of typical contaminants in aging petrochemical landfills are crucial yet challenging endeavors. In this study, we employed a combination of chemical analysis and microbial metagenomic technologies to investigate the pollution characteristics of benzene, toluene, ethylbenzene, and xylene (BTEX) as well as metal(loid)s in a representative aging landfill, surrounding soils, and underlying groundwater. Furthermore, we aimed to explore their transformations driven by microbial activity. Our findings revealed widespread distribution of metal(loid)s, including Cd, Ni, Cu, As, Mn, Pb, and Zn, in these environmental media, surpassing soil background values and posing potential ecological risks. Additionally, microbial processes were observed to contribute significantly to the degradation of BTEX compounds and the transformation of metal(loid)s in landfills and surrounding soils, with identified microbial communities and functions playing key roles. Notably, co-occurrence network analysis unveiled the coexistence of functional genes associated with BTEX degradation and metal(loid) transformation, driven primarily by As, Ni, and Cd. These results shed light on the co-selection of resistance traits against BTEX and metal(loid) contaminants in soil microbial consortia under co-contamination scenarios, supporting microbial adaptive evolution in aging petrochemical landfills. The insights gained from this study enhance our understanding of characteristic pollutants and microbial transformation processes in aging landfills, thereby facilitating improved landfill management and contamination remediation strategies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The presence of BTEX (Benzene, Toluene, Ethylbenzene, and Xylene) compounds in beauty salons has raised concerns about potential health risks. This study aimed to measure the levels of BTEX compounds in the air of beauty salons in Lahijan, Iran and assess the associated health risks. Air samples were collected from 15 beauty salons, and the concentrations of BTEX compounds were measured according to 1501 NIOSH standard method. The results showed that the mean concentrations of benzene (20.62 µg/m 3 ), toluene (18.3 µg/m 3 ), ethylbenzene (38.36 µg/m 3 ), and O and P-xylene (27.35, 23.6 µg/m 3 ) were above the recommended levels. The indoor to outdoor ratios for benzene, toluene, ethylbenzene, O and P-xylene were 3.04, 2.36, 3.75, 4.89, and 6.54, respectively. Also, the toluene/benzene (T/B) ratio in indoor and outdoor was 20.9 and 2.68 respectively. Almost half of the technicians (49.12%) reported adverse health effects, including joint pain, itchy eyes and nose, and respiratory allergies. The IARC guideline suggests that there is a potential risk of cancer development for individuals in all salons with LCR values exceeding 10 -6 , but the HQ index values indicate no non-carcinogenic risk. The findings suggest that beauty salon workers and customers are at risk of developing health problems from exposure to BTEX compounds. Effective risk management strategies, such as proper ventilation, use of personal protective equipment, and substitution of harmful chemicals with safer alternatives, to minimize exposure and protect the health of salon workers and customers recommended., (© 2024. The Author(s).)

The heterotrophic nitrification-aerobic denitrification (HNAD) strain Exiguobacterium H1 (H1) was isolated in this study. The changes in nitrogen metabolism functions of H1 strain were discussed in presence of disinfectants chloroxylenol (PCMX) and benzethonium chloride (BEC) alone and combined pollution (PCMX+BEC). The H1 strain could use NH 4 + -N, NO 2 - -N and NO 3 - -N as nitrogen sources and had good nitrogen removal performance under conditions of C/N ratio 25, pH 5-8, 25-35  o C and sodium acetate as carbon. PCMX and BEC alone exhibited hormesis effects on H1 strain which promoted the growth of H1 strain at low concentrations but inhibited it at high concentrations, and combined pollution showed synergistic inhibitory on H1 strain. H1 strain owned a full nitrogen metabolic pathway according to functional genes quantification. PCMX encouraged nitrification process of H1, while BEC and combined pollution mostly blocked nitrogen removal. PCMX, but not BEC, mainly led to the enrichment of resistance genes. These findings will aid in systematic assessment of contaminant tolerance characteristics of HNAD strain and its application prospects., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The potential maternal and foetal toxicity resulting from exposure to xylene at or below the allowable limit of 100 ppm during gestation is not thoroughly studied. The aim of this study was to investigate maternal and foetal outcomes following prenatal exposure to xylene during organogenesis. Pregnant Sprague Dawley (SD) rats were administered intraperitoneal (IP) corn oil (vehicle), 100, 500, and 1000 parts per million (ppm) of xylene from gestational day (GD) 6 until GD17. Clinical signs, maternal weight gain, and food consumption were recorded daily. A caesarean hysterectomy was performed on GD21 to assess the reproductive and foetal outcomes. Exposure to 1000 ppm of xylene caused a significant decrease in the maternal body weight and food consumption, and an increase in intrauterine foetal deaths. Foetal assessment revealed a significant decrease in foetal weight in both male and female foetuses of female rats treated with 500 and 1000 ppm. Male placental weight was significantly decreased in all xylene-treated groups, while 1000 ppm xylene significantly decreased female placental weight. Histologically, marked uterine inflammatory lesions, fibrosis of the liver and renal tissues, as well as increased placental glycogen content were observed. Immunohistochemistry revealed a significant increase in lipid peroxidation and apoptotic markers. Thus, the foeto-maternal toxicities of xylene have been shown to be mediated by a systemic inflammatory response that exacerbates intrauterine oxidative stress and impairs foeto-placental transfer, leading to an increase in foetal mortality., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Volatile organic compounds, such as BTEX, have been the subject of numerous debates due to their detrimental effects on the environment and human health. Human beings have had a significant role in the emergence of this situation. Even though US EPA, WHO, and other health-related organizations have set standard limits as unhazardous levels, it has been observed that within or even below these limits, constant exposure to these toxic chemicals results in negative consequences as well. According to these facts, various studies have been carried out all over the world - 160 of which are collected within this review article, so that experts and governors may come up with effective solutions to manage and control these toxic chemicals. The outcome of this study will serve the society to evaluate and handle the risks of being exposed to BTEX. In this review article, the attempt was to collect the most accessible studies relevant to risk assessment of BTEX in the atmosphere, and for the article to contain least bias, it was reviewed and re-evaluated by all authors, who are from different institutions and backgrounds, so that the insights of the article remain unbiased. There may be some limitations to consistency or precision in some points due to the original sources, however the attempt was to minimize them as much as possible., Competing Interests: Declaration of competing interest We confirm that all of the authors of this manuscript have no pecuniary or other personal interest, direct or indirect, in any matter that raises or my raise a conflict in this manuscript., (Copyright © 2023. Published by Elsevier Ltd.)

Objectives. The present study aimed to assess whether occupational exposure to low concentrations of benzene, toluene, ethylbenzene and xylene (BTEX) is associated with color vision impairment. Methods. We queried PubMed, Scopus, Embase, Web of Science and ProQuest as the main databases, as well as gray literature such as Google Scholar. A random-effects model was used to assess relative risk. A funnel plot was created to assess publication bias. Meta-regression analysis was applied to identify variables that explain the between-study variation in the reported risk estimate. Results. An overall standardized mean difference of 0.529 (95% confidence interval [0.269, 0.788]; p  < 0.0001) was obtained in the random-effects model, which corresponded to a medium-size effect. Duration and the levels of exposure to benzene, toluene and xylene were the significant predictors of the magnitude of the combined risk estimate. Chronic exposure to low levels of BTEX was associated with dyschromatopsia determined by the color confusion index. Conclusions . The impairments can occur even at exposures lower than the occupational exposure limits of BTEX. However, there are several flaws in the determination of workers' exposure, which did not allow to establish how low a level of these chemicals can cause color vision impairment.

Objective: Benzene, ethylbenzene, meta/para-xylene, and ortho-xylene, collectively referred to as benzene, ethylbenzene, and xylene (BEX), constitute the main components of volatile organic aromatic compounds (VOACs) and can have adverse effects on human health. The relationship between exposure to BEX and hearing loss (HL) in the adult U.S. population was aimed to be assessed., Methods: Cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) for the years 2003-2004, 2011-2012, and 2015-2016 were analyzed. This dataset included complete demographic characteristics, pure-tone audiometry measurements, and volatile organic compound detection data from the NHANES database. A weighted multivariate logistic regression model was employed to investigate the associations between blood BEX concentrations HL, low-frequency hearing loss (SFHL), and high-frequency hearing loss (HFHL)., Results: 2174 participants were included, with weighted prevalence rates of HL, SFHL, and HFHL being 46.81%, 25.23%, and 45.86%, respectively. Exposure to benzene, ethylbenzene, meta/para-xylene, and ortho-xylene, and cumulative BEX concentrations increased the risk of hearing loss (odds ratios [ORs] were 1.36, 1.22, 1.42, 1.23, and 1.31, respectively; all P < 0.05). In the analysis with SFHL as the outcome, ethylbenzene, m-/p-xylene, o-xylene, benzene, and overall BEX increased the risk (OR 1.26, 1.21, 1.28, 1.20, and 1.25, respectively; all P < 0.05). For HFHL, exposure to ethylbenzene, m-/p-xylene, o-xylene, benzene, and overall BEX increased the risk (OR 1.36, 1.22, 1.42, 1.22, and 1.31, respectively; all P < 0.05)., Conclusion: Our study indicated that a positive correlation between individual or cumulative exposure to benzene, ethylbenzene, meta/para-xylene, and ortho-xylene and the risk of HL, SFHL, and HFHL. Further research is imperative to acquire a more comprehensive understanding of the mechanisms by which organic compounds, notably BEX, in causing hearing loss and to validate these findings in longitudinal environmental studies., (© 2024. The Author(s).)

African American women in the United States have a high risk of adverse pregnancy outcomes. DNA methylation is a potential mechanism by which exposure to BTEX (benzene, toluene, ethylbenzene, and xylenes) may cause adverse pregnancy outcomes. Data are from the Maternal Stress Study, which recruited African American women in the second trimester of pregnancy from February 2009 to June 2010. DNA methylation was measured in archived DNA from venous blood collected in the second trimester. Trimester-specific exposure to airshed BTEX was estimated using maternal self-reported addresses and geospatial models of ambient air pollution developed as part of the Geospatial Determinants of Health Outcomes Consortium. Among the 64 women with exposure and outcome data available, 46 differentially methylated regions (DMRs) were associated with BTEX exposure (FDR adjusted p -value < 0.05) using a DMR-based epigenome-wide association study approach. Overall, 89% of DMRs consistently exhibited hypomethylation with increasing BTEX exposure. Biological pathway analysis identified 11 enriched pathways, with the top 3 involving gamma-aminobutyric acid receptor signaling, oxytocin in brain signaling, and the gustation pathway. These findings highlight the potential impact of BTEX on DNA methylation in pregnant women.

Benzene, toluene, ethyl benzene, and xylene (BTEX) are prevalent pollutants in shoe industry-related workplaces. The aim of this study was to assess exposure to BTEX and their carcinogenic and non-carcinogenic risks in shoe-industry-related workplaces. This study was carried out at different shoe manufactures, small shoe workshop units, shoe markets, and shoe stores in Tabriz, Iran in 2021. Personal inhalation exposure to BTEX was measured using the National Institute for Occupational Safety and Health (NIOSH) 1501 method. Carcinogenic and non-carcinogenic risks due to inhalation exposure to BTEX were estimated by United States Environmental Protection Agency (U.S. EPA) method based on Mont Carlo simulation. Results showed that the concentrations of benzene and toluene were higher than the threshold limit value (TLV) in both gluing and non-gluing units of shoe manufactures. The total carcinogenic risk (TCR) due to exposure to benzene and ethyl benzene was considerable in all shoe industry-related workplaces. Also, the hazard index (HI) as a non-carcinogenic index was higher than standard levels in all shoe industry-related workplaces. Therefore, shoe industry-related workers are at cancer and non-cancer risks due to exposure to BTEX. Prevention measures need to be implemented to reduce the concentration of BTEX in shoe industry-related workplaces., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The Expert Panel for Cosmetic Ingredient Safety reviewed updated information that has become available since their original assessment from 1985, along with updated information regarding product types, and frequency and concentrations of use, and reaffirmed their original conclusion that Chloroxylenol is safe as a cosmetic ingredient in the practices of use and concentration as described in this report., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The articles in this supplement were sponsored by the Cosmetic Ingredient Review.

Background: Benzene, toluene, ethylbenzene, and xylenes, collectively known as BTEX, are hazardous chemical mixtures, and their neurological health effects have not been thoroughly evaluated. We examined the association between BTEX exposure and neurological hospital admissions., Methods: This was a multicity time-series study conducted in five major Taiwanese cities. Daily hospital admission records for diseases of the nervous system from January 1, 2016, to December 31, 2017, were collected from the National Health Insurance Research Database. Ambient BTEX and criteria pollutant concentrations and weather factors were collected from Photochemical Assessment Monitoring Stations. We applied a Poisson generalized additive model (GAM) and weighted quantile sum regression to calculate city-specific effect estimates for BTEX and conducted a random-effects meta-analysis to pool estimates., Results: We recorded 68 neurological hospitalizations per day during the study period. The daily mean BTEX mixture concentrations were 22.5 µg/m 3 , ranging from 18.3 µg/m 3 in Kaohsiung to 27.0 µg/m 3 in Taichung, and toluene (13.6 µg/m 3 ) and xylene (5.8 µg/m 3 ) were the dominant chemicals. Neurological hospitalizations increased by an average of 1.6 % (95 % CI: 0.6-2.6 %) for every interquartile range (15.8 µg/m 3 ) increase in BTEX at lag 0 estimated using a GAM model. A quartile increase in the weighted sum of BTEX exposure was associated with a 1.7 % (95 % CI: 0.6-2.8 %) increase in daily neurological hospitalizations., Conclusion: We found consistent acute adverse effects of BTEX on neurological hospitalizations in Taiwan, with toluene and xylene as the dominant chemicals. These findings aid the development of more targeted public health interventions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Xylenes and propylbenzenes (PBZs) are volatile aromatic hydrocarbons with high aquatic toxicity. Xylenes can be present in three isomers: o-xylene (OX), m-xylene (MX), and p-xylene (PX), while PBZs include two isomers: n-propylbenzene (n-PBZ) and isopropylbenzene (i-PBZ). Their accidental spills and improper discharges from petrochemical industries can cause severe contamination in water bodies posing potential ecological risks. In this study, the published acute toxicity data of these chemicals for aquatic species were collected to calculate hazardous concentrations protecting 95% species (HC 5 ) using a species sensitivity distribution (SSD) approach. The acute HC 5 values for OX, MX, PX, n-PBZ, and i-PBZ were estimated to be 1.73, 3.05, 1.23, 1.22, and 1.46 mg/L, respectively. The risk quotient (RQ) values calculated based on HC 5 indicated their high risk (RQ: 1.23 ∼ 21.89) in groundwater, but low risk (RQ < 0.1) in natural seawater, river water, and lake water. When xylenes or PBZs leaked into the sea, they were expected to pose a high risk (RQ > 1) at the start and then a low risk (RQ < 0.1) after 10 days due to natural attenuation. These results may help to derive more reliable protection thresholds for xylenes and PBZs in aquatic environment and provide a basis for evaluating their ecological risks., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Daniellia oliveri (Rolfe) Hutch. & Dalziel (Fabaceae) is used for the treatment of inflammatory diseases and pains (chest pain, toothache and lumbago) and rheumatism., Aim of the Study: The study investigates the anti-inflammatory and antinociceptive properties of D. oliveri and possible mechanism of antiinflammatory action., Materials and Methods: Acute toxicity of the extract was evaluated in mice using the limit test. The anti-inflammatory activity was assessed in xylene-induced paw oedema and carrageenan-induced air-pouch models at doses of 50, 100 and 200 mg/kg, p.o. Volume of exudate, total protein, leukocyte counts, myeloperoxidase (MPO) and concentration of cytokines (TNF-α and IL-6) were measured in the exudate of rats in the carrageenan-induced air-pouch model. Other parameters include lipid peroxidation (LPO), nitric oxide (NO) and antioxidant indices (SOD, CAT and GSH). Histopathology of the air pouch tissue was also carried out. The antinociceptive effect was assessed using acetic acid-induced writhing, tail flick and formalin tests. Locomotor activity was done in the open field test. The extract was analysed with HPLC-DAD-UV technique., Results: The extract showed significant anti-inflammatory effect (73.68 and 75.79%, inhibition) in xylene-induced ear oedema test at the dose of 100 and 200 mg/kg, respectively. In carrageenan air pouch model, the extract significantly reduced exudate volume, protein concentration, the migration of leukocytes and MPO production in the exudate. The concentrations of cytokines TNF-α (12.25 ± 1.80 pg/mL) and IL-6 (21.12 pg/mL) in the exudate at the dose of 200 mg/kg were reduced compared to carrageenan alone group (48.15 ± 4.50 pg/mL; 82.62 pg/mL) respectively. The extract showed significant increase in the activities of CAT and SOD and GSH concentration. The histopathological assessment of the pouch lining revealed reduction of immuno-inflammatory cell influx. Nociception was significantly inhibited by the extract in acetic acid-induced writhing model and the second phase of formalin test indicating a peripheral mechanism of action. The open field test showed that D. oliveri did not alter locomotor activity. The acute toxicity study did not cause mortality or signs of toxicity at 2000 mg/kg, p.o. We identified and quantified caffeic acid, p-coumaric acid, ferulic acid, rutin, apigenin-7-glucoside, quercetin and kaempferol in the extract., Conclusion: The results of our study showed that the stem bark extract of D. oliveri possesses anti-inflammatory and antinociceptive activities thereby supporting its traditional use in the treatment of some inflammatory and painful disorders., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Benzene (B), toluene (T), ethylbenzene (E), and xylenes (X) are petrochemicals vital in various industrial and commercial processing but identified as priority pollutants due to their high toxicity. The objective of this study was to investigate the toxicological nature of BTEX mixtures under controlled laboratory aquatic conditions using sulfur-oxidizing bacteria (SOB). Results from individual BTEX tests demonstrated that the order of toxicity among BTEX was X ≥ E > T > B. Comparisons of dose-effect curves for BTEX suggest that the biochemical mode of action of B in SOB was different from those of T, E, and X. Toxicological interactions of BTEX in mixtures were studied using concentration addition (CA), independent action (IA), and combination index (CI)-isobologram models. The CI model approximated the actual toxicity of BTEX mixtures better than the CA and IA models. In most cases, BTEX induced synergistic interactions in mixtures. However, in some B-containing mixtures, antagonism was observed at low effective levels. The effective level (fa)-CI plots and polygonograms illustrate that synergistic interactions of BTEX became stronger with an increase in effective levels. In addition, ternary and quaternary mixtures were found to provoke stronger synergism than binary mixtures. The present study suggests that the CI-isobologram model is a suitable means to evaluate diverse toxicological interactions of contaminants in mixtures., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Children in the affected area were exposed to large amounts of volatile organic compounds (VOCs) from the Hebei Spirit oil spill accident., Objectives: We investigated the lung function loss from the exposure to VOCs in a longitudinal panel of 224 children 1, 3, and 5 years after the VOC exposure event., Methods: Atmospheric estimated concentration of total VOCs (TVOCs), benzene, toluene, ethylbenzene, and xylene for 4 days immediately after the accident were calculated for each village (n = 83) using a modeling technique. Forced expiratory volume in 1 s (FEV 1 ) as an indicator of airway status was measured 1, 3, and 5 years after the exposure in 224 children 4~9 years of age at the exposure to the oil spill. Multiple linear regression and linear mixed models were used to evaluate the associations, with adjustment for smoking and second-hand smoke at home., Results: Among the TVOCs (geometric mean: 1319.5 mg/m 3 ·4 d), xylene (9.4), toluene (8.5), ethylbenzene (5.2), and benzene (2.0) were dominant in the order of air concentration level. In 224 children, percent predicted FEV 1 (ppFEV 1 ), adjusted for smoking and second-hand smoke at home, was 100.7% after 1 year, 96.2% after 3 years, and 94.6% after 5 years, and the loss over the period was significant ( p < 0.0001). After 1 and 3 years, TVOCs, xylene, toluene, and ethylbenzene were significantly associated with ppFEV 1 . After 5 years, the associations were not significant. Throughout the 5 years' repeated measurements in the panel, TVOCs, xylene, toluene, and ethylbenzene were significantly associated with ppFEV 1 ., Conclusions: Exposure to VOCs from the oil spill resulted in lung function loss among children, which remained significant up to 5 years after the exposure.

The oil pollutant in the Sava River aquifer in the residential area of Belgrade, Serbia was investigated in order to analyze the extent, origin and spatial distribution of the pollution, with the aim to estimate potential human health risks from exposure to the compounds detected. Analytical methods indicated that the dominant compounds in this oil pollutant were gasoline range organic compounds. Benzene, toluene, ethylbenzene and xylenes (BTEX) were identified as compounds of concern and quantified by headspace gas chromatography. The concentrations of benzene measured at all sampling points were higher than the remediation value while the maximum concentrations of BTEX quantified were among the highest concentrations of these compounds reported in the petroleum-contaminated aquifers in the world. The assessment of the human health risks from exposure to BTEX-covered industrial scenario for adult receptors and residential scenario for adult receptors and children. The exposure routes analyzed were dermal contact with and ingestion of contaminated water, considering both cancer and non-cancer effects. The analysis of the lifetime incremental cancer risk indicated the potential for adverse health effects for human exposure at the investigated location, and because of that it was interpreted as an unacceptable risk level or risks of high priority which required immediate consideration for remedial measures at this location. A complete set of mitigation measures was proposed including: groundwater decontamination treatment, installation of filters for tap water, development of the system for monitoring of BTEX in the groundwater and development of the emergency response capacities at this location., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Lung is one of the primary target organs of benzene, toluene, ethylbenzene, xylene, and styrene (BTEXS). Small airways dysfunction (SAD) might be a sensitive indicator of early chronic respiratory disease. Here, we explored the relationships between exposure to BTEXS and small airways function, and identified the priority control pollutants in BTEXS mixtures., Methods: 635 petrochemical workers were recruited. Standard spirometry testing was conducted by physicians. The cumulative exposure dose (CED) of BTEXS for each worker was estimated. The peak expiratory flow (PEF), forced expiratory flow between 25 and 75% of forced vital capacity (FEF25∼75%), and the expiratory flow rate found at 25%, 50%, and 75% of the remaining exhaled vital capacity (MEF25%, MEF50%, and MEF75%) were measured. SAD was also evaluated based on measured parameters. The associations between exposure to BTEXS individuals or mixtures and small airways function were evaluated using generalized linear regression models (GLMs) and quantile g-computation models (qgcomp). Meanwhile, the weights of each homolog in the association were estimated., Results: The median CED of BTEXS are 9.624, 19.306, 24.479, 28.210, and 46.781 mg/m 3 ·years, respectively. A unit increase in ln-transformed styrene CED was associated with a decrease in FEF25∼75% and MEF50% based on GLMs. One quartile increased in BTEXS mixtures (ln-transformed) was significantly associated with a 0.325-standard deviation (SD) [95% confidence interval (CI): -0.464, -0.185] decline in FEF25∼75%, a 0.529-SD (95%CI: -0.691, -0.366) decline in MEF25%, a 0.176-SD (95%CI: -0.335, -0.017) decline in MEF75%, and increase in the risk of abnormal of SAD [risk ratios (95%CI): 1.520 (95%CI: 1.143, 2.020)]. Benzene and styrene were the major chemicals in BTEXS for predicting the overall risk of SAD., Conclusion: Our novel findings demonstrate the significant association between exposure to BTEXS mixture and small airways function decline and the potential roles of key homologs (benzene and styrene) in SAD., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Benzene, Toluene, Ethylbenzene, and Xylenes (BTEXs) are a group of aromatic air pollutants from fossil fuels. There is no research on associations of the BTEXs mixture with telomere length (TL), a marker of cellular aging, in the general population., Methods: We analyzed a subsample of 549 US adults aged 20-59 years from the National Health and Nutrition Examination Survey 1999-2000. BTEXs samples were collected by passive exposure badges worn by participants for 48-72 h. Levels of BTEXs were measured with gas chromatography/mass spectrometry. Leukocyte TL was measured with qPCR. We used Bayesian Kernel Machine Regression (BKMR) to examine the effect of the BTEXs mixture on TL adjusting for potential confounders. Analyses were stratified by tobacco smoking status (serum cotinine≥10 ng/mL vs. <10 ng/mL)., Results: Levels of personal exposure to BTEXs were detectable in most participants and were relatively higher in the 150 smokers than in the 399 nonsmokers. The BTEXs were moderately or strongly intercorrelated (0.5 < r ≤ 0.9, P < 0.05). All chemicals had weak, inverse correlations with TL (-0.1 0.05). In BKMR models among the nonsmokers, the BTEXs mixture was significantly inversely associated with TL at a low range of the BTEXs (20th-65th percentile) but was not associated with TL at a higher range (>65th percentile). Also, we found a U-shape association of benzene and a positive association of ethylbenzene with TL independent of other BTEXs. Among smokers, neither the BTEXs mixture nor any individual BTEXs were significantly associated with TL., Conclusion: Within a low-to-middle range, exposure to the BTEXs mixture may be associated with shorter telomere length in the general nonsmoking population., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Environmental exposure to toxicants is a major health issue and a leading risk factor for premature mortality worldwide, including environmental exposures to volatile organic compounds (VOCs), specifically Benzene, Toluene, Ethylbenzene, and Xylene (BTEX). While exposure to these compounds individually has shown behavioral and neurochemical effects, this investigation examined the impact of exposure to combined BTEX using a preclinical model. Male Swiss Webster mice were exposed to BTEX vapors designed to approximate environmental levels in urban communities. Animals were exposed to one of four treatment conditions: a 0-ppm (air control), two BTEX groups representing levels of environmental-like exposure, and a fourth group modeling occupational-like exposure. These exposures were conducted in 1.5-h sessions, 2 sessions/day, 5 days/week, for 3 weeks. Effects on coordination (i.e., rotarod and inverted screen test), learning and memory (i.e., Y-maze), and locomotor behavior (i.e., movement during exposure) were assessed during and after exposure. Monoamine levels in the medial prefrontal cortex and nucleus accumbens were assessed immediately following exposure. Effects of BTEX exposure were found on the variance of locomotor activity but not in other behavioral or neurochemical assessments. These results indicate that the combination of inhaled BTEX at environmentally representative concentrations has demonstrable, albeit subtle, effects on behavior., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Frying is one of the cooking methods which generates mono aromatic hydrocarbons, including benzene, toluene, ethylbenzene, and xylene (BTEX); subsequently, it affects health through carcinogenic (CR) and non-carcinogenic risks (n-CR). However, their environmental effects known by secondary organic aerosols (SOA) and ozone formation potential (OFP) were also attended by many scientists. Therefore, this study quantified the BTEX emissions from 4 types of most commonly used edible oils (canola, corn, sunflower, and blend) under various frying conditions of temperatures and food additives. Furthermore, the effects of the chemicals in the light of health (CR and n-CR) and environment (SOA and OFP) were also investigated. The study results showed that higher temperatures could significantly increase the emissions, while the addition of food ingredients significantly reduces the emissions. The rank order of emitted chemical was obtained as T > B > E > X. The blend had the most emission among oils, followed by, in descending order, corn, sunflower, and canola. In association with environmental effects, the orders of X > T > E > B and T ∼ E > X > B were obtained for OFP and SOA, respectively. THQ for blend, corn, canola, and sunflower oils was higher than 1 (1.76, 1.35, 1.27, and 1.002, respectively), showing a considerable n-CR when the hood was off. In this respect, TCR for the oils (1.78 × 10 -4 , 1.45 × 10 -4 , 1.39 × 10 -4 , and 1.05 × 10 -4 , respectively) shown the probable risk for all oils. Moreover, hood switching reduced the risk by about 11-81%., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: The root of Embelia laeta (L.) Mez., which is called Suanjifeng in Chinese ethnic Yao medicine, is traditionally for inflammation-related diseases, such as oral ulcer, sore throat, enteritis, and rheumatoid arthritis. However, the biological properties and the underlying mechanisms of Embelia laeta still need further studies., Aim of This Study: The present study aims to investigate the anti-inflammatory effect and its underlying mechanisms of Embelia laeta., Materials and Methods: In this study, except acute toxicity experiments, Kunming (KM) mice of either sex were enrolled to establish inflammatory model induced by xylene, acetic acid and carrageenan, respectively. Mice were randomly divided into different groups and pretreated by oral gavage with different doses of Embelia laeta aqueous extract (ELAE) (2.5, 5, 10 g/kg) and 10 mg/kg of Indo for 7 days. Ear edema, vascular permeability, abdominal writhing, and paw edema degree were detected in related experiments. Moreover, in the carrageenan-induced paw edema mice model, histological changes were detected by H&E staining. MDA, MPO and NO were detected by assay kit. Proinflammatory cytokines of IFN-γ, TNF-α, IL-1β, IL-6 and PGE 2 were detected by ELISA. Additionally, COX-2, iNOS and NF-κB pathway-related proteins were detected by Western blotting., Results: Results showed that the ELAE evoked an obvious dose-dependent inhibition of ear edema induced by xylene, paw edema induced by carrageenan, as well as suppressing the increase of vascular permeability and writhing times elicited by acetic acid. Histopathological analysis indicated that ELAE could significantly decrease the cellular infiltration in paw tissue. ELAE showed antioxidant property through markedly decrease the MDA level and MPO activity in edema paw. In addition, ELAE decreased the proinflammatory cytokines IFN-γ, TNF-α, IL-1β, IL-6, PGE 2 and NO that induced by carrageenan. Western blotting results also showed that ELAE could obviously downregulate the COX-2 and iNOS expression. Further analysis revealed that ELAE also inhibited NF-κB from the cytoplasm to the nucleus and stabilize the conversion of IκBα., Conclusion: ELAE had powerful anti-inflammatory property, which might be had a close relationship with mediating proinflammatory cytokines production, decreasing the COX-2 and iNOS expression, and inhibiting the activation of NF-κB signaling pathway., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Gasoline is a complex mixture of substances, including aromatic hydrocarbons such as benzene, toluene, ethylbenzene, and xylenes (BTEX). These compounds are emitted into the air, with the special relevance of benzene since it is provenly carcinogenic. The study aimed to assess BTEX concentrations in filling stations in the city of Rio de Janeiro, Brazil, and to calculate the cancer risk associated with such exposures. Two types of sampling were performed (stationary and mobile), adapted from methodology n. 1,501 (U.S. National Institute for Occupational Safety and Health) for aromatic hydrocarbons, in six filling stations in the West Zone of Rio de Janeiro. Stationary sampling was done near the fuel pumps, while mobile sampling was done in the breathing zone of the workers (station attendants) as they moved around the station. The samples were analyzed with gas chromatography flame ionization detector. The sampling results were used to calculate the health risk, using the indicators Hazard quotient (HQ) and Cancer risk (CR) to assess the possible non-carcinogenic and carcinogenic effects, respectively, in filling station workers. Environmental concentrations for the most of the BTEX compounds were below the recommended limits, except for benzene, a carcinogenic compound, which displayed concentrations far above the limits, leading to high cancer risk values. The results showed that there are health risks for filling station attendants, especially the risk of developing cancer from excessive exposure to benzene.

A lot of phenolic compounds are widespread in industrial effluents and they are considerable environmental pollutants. Being a compound commercially available, the effect of a bearing-wastewater phenolic compound 3,4-dimethylphenol (3,4-DMP) on Ca 2+ homeostasis and its related physiology has not been explored in cultured human kidney cell models. The aim of this study was to explore the effect of 3,4-DMP on [Ca 2+ ] i and viability in HK-2 human proximal renal tubular epithelial cells. In terms of Ca 2+ signaling, 3,4-DMP (5-100 μM) induced [Ca 2+ ] i rises only in HK-2 cells and Ca 2+ removal reduced the signal by 40%. In Ca 2+ -containing medium, 3,4-DMP-induced Ca 2+ entry was inhibited by 20% by a modulator of store-operated Ca 2+ channels (2-APB), and by a PKC activator (PMA) and inhibitor (GF109203X). Moreover, 3,4-DMP-induced Mn 2+ influx suggesting of Ca 2+ entry. In Ca 2+ -free medium, inhibition of PLC with U73122 abolished 3,4-DMP-induced [Ca 2+ ] i rises. Furthermore, treatment with the endoplasmic reticulum Ca 2+ pump inhibitor thapsigargin abolished 3,4-DMP-evoked [Ca 2+ ] i rises. Conversely, treatment with 3,4-DMP abolished thapsigargin-evoked [Ca 2+ ] i rises. Regarding to cell viability, 3,4-DMP (60-140 μM) killed cells in a concentration-dependent fashion in HK-2 cells. Chelation of cytosolic Ca 2+ with BAPTA-AM partially reversed cytotoxicity of 3,4-DMP. Collectively, our data suggest that in HK-2 cells, 3,4-DMP-induced [Ca 2+ ] i rises by evoking Ca 2+ entry via PKC-sensitive store-operated Ca 2+ entry and PLC-dependent Ca 2+ release from the endoplasmic reticulum. 3,4-DMP also caused cytotoxicity that was linked to preceding [Ca 2+ ] i rises. Our findings provide new insight into the cytotoxic effects of 3,4-DMP and the possible mechanisms underlying these effects.

Argania spinosa (L.) plays an important role in the Moroccan agroeconomy, providing both employment and export revenue. Argan oil production generates different by-products with functionalities that are not yet investigated, in particular, the shell fruit. The present study aims, for the first time, at evaluating the acute and subacute toxicity, anti-inflammatory, and antioxidant effects of argan fruit shell ethanol extract (AFSEE). The LD 50 of AFSEE was determined to be greater than the 5000 mg/kg body weight of mice. No significant variation in the body and organ weights was observed after 28 days of AFSEE treatment compared to that of the control group. Biochemical parameters and histopathological examination revealed no toxic effects of AFSEE. The AFSEE produced a significant inhibition of xylene-induced ear edema in mice. AFSEE reduced significantly the paw edema in mice after carrageenan injection. The chemical characterization showed that AFSEE contains a high level of total phenol content, flavonoids, condensed tannins, and flavanols. The obtained IC 50 of DPPH, ABTS, reducing power, and β -carotene demonstrates that AFSEE has a potential antioxidant effect. The results indicate that AFSEE was safe and nontoxic to mice even at higher doses. Furthermore, the present findings demonstrate that AFSEE has potential anti-inflammatory and antioxidant activities., Competing Interests: All co-authors declare no conflict of interest., (Copyright © 2021 Rachida Makbal et al.)

In order to reduce exposure to toxic chemicals, the European REACH regulation (1907/2006) recommends substituting toxic molecules with compounds that are less harmful to human health and the environment. Toluene is one of the most frequently used solvents in industries despite its toxicity. The objective of this study is to better understand and compare the toxicity of toluene and its homologues in a bronchial cell model. Thus, human bronchial BEAS-2B cells were exposed to steams of toluene, m-xylene, mesitylene (1,3,5-trimethylbenzene), and benzene (20 and 100 ppm). Exposure was carried out using an air-liquid interface (ALI) system (Vitrocell) during 1 h/day for 1, 3, or 5 days. Cytotoxicity, xenobiotic metabolism enzyme gene expression, and inflammatory response were evaluated following cell exposures. BEAS-2B cell exposure to toluene and its homologues revealed the involvement of major (CYP2E1) and minor metabolic pathways (CYP1A1). A late induction of genes (EPHX1, DHDH, ALDH2, and ALDH3B1) was measured from Day 3 and can be linked to the formation of metabolites. An increase in the secretion level of inflammatory markers (TNF-α, IL-6, IL-8, MCP-1, and GM-CSF) was also observed. In parallel, regulation between inflammatory mediators and the expression of transmembrane glycoprotein mucin MUC1 was also studied. This in vitro approach with ALI system points out the relevance of conducting repeated exposures to detect potential late effects. The difference recorded after cell exposure to toluene and its homologues highlights the importance of substitution principle., (© 2020 John Wiley & Sons, Ltd.)

Ethnopharmacological Relevance: Salvia species are known to have anti-inflammatory properties, and are traditionally used for healing purposes. Salvia verbenaca is an Algerian plant used for healing wounds and ulcers., Aim of the Study: This work aims to assess the acute and subacute safety of S. verbenaca and its possible anti-inflammatory activity as a mechanism contributing to its traditional applications., Materials and Methods: Lethal toxicity of S. verbenaca hydromethanolic extract was evaluated against Artemia salina larvae, while acute and subacute toxicity were orally tested on mice. The anti-inflammatory activity was screened ex vivo using membrane stabilization and in vivo using xylene induced ear edema as an acute inflammation model. The antiradical, reducing power and iron chelating activities of S. verbenaca were also investigated in vitro, and phenolic compounds were determined using UHPLC-DAD-ESI-MS n . RESULTS: Salvia verbenaca extract contained high amounts of phenolic compounds (206 μg GAE/mg extract). The in vitro antioxidant activity showed promising radical scavenging ability, iron chelating (IC 50 : 189 μg/mL), reducing power and strong anti-lipid-peroxidation effect (IC 50 : 111 μg/mL). The extract had potential cytotoxic effect against Artemia salina larvae (LC 50 : 30 μg/mL), but did not exhibit any acute/subacute toxicity effect on mice. Salvia verbenaca inhibited hypotonic and heat induced hemolysis and also reduced 50% of xylene induced ear edema at 600 mg/kg bw. Rosmarinic acid and caffeoylmalic acid were identified as the major compounds., Conclusion: Salvia verbenaca hydromethanolic extract was found to be safe at acute and subacute levels. Its in vitro/in vivo antioxidant activity, membrane stabilizing properties and anti-inflammatory activity may be an important aspect of its wound healing and anti-ulcer traditional use., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Epidemiological and experimental studies indicate that a number of aromatic solvents widely used in the industry can affect hearing and balance following chronic exposure. Animal studies demonstrated that long-term exposure to aromatic solvents directly damages the auditory receptor within the inner ear: the cochlea. However, no information is available on their effect on the vestibular receptor, which shares many structural features with the cochlea and is also localized in inner ear. The aim of this study was to use an in vitro approach to assess and compare the vestibular toxicity of different aromatic solvents (toluene, ethylbenzene, styrene and ortho-, meta-, para-xylene), all of which have well known cochleotoxic properties. We used a three-dimensional culture model of rat utricles ("cysts") with preserved functional sensory and secretory epithelia, and containing a potassium-rich (K + ) endolymph-like fluid for this study. Variations in K + concentrations in this model were considered as biomarkers of toxicity of the substances tested. After 72 h exposure, o-xylene, ethylbenzene and styrene decreased the K + concentration by 78 %, 37 % and 28 %, respectively. O- xylene and styrene both caused histopathological alterations in secretory and sensory epithelial areas after 72 h exposure, whereas no anomalies were observed in ethylbenzene-exposed samples. These in vitro results suggest that some widely used aromatic solvents might have vestibulotoxic properties (o-xylene, styrene and ethylbenzene), whereas others may not (p-xylene, m-xylene, toluene). Our results also indicate that variations in endolymphatic K + concentration may be a more sensitive marker of vestibular toxicity than histopathological events. Finally, this study suggests that cochleotoxic solvents might not be necessarily vestibulotoxic, and vice versa., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Xylene is a cyclic hydrocarbon, which is commonly used as a solvent in dyes, paints, polishes, and industrial solutions. It is a potential environmental pollutant. Here, we report the effect of xylene exposure on Leydig cell development in male rats during puberty. Xylene (0, 150, 750, and 1500 mg/kg) was gavaged to 35-day-old male Sprague Dawley rats for 21 days. Xylene significantly reduced serum testosterone levels at 750 and 1500 mg/kg without affecting serum luteinizing hormone and follicle-stimulating hormone levels. Xylene reduced the number of HSD11B1-positive Leydig cells at the advanced stage at 1500 mg/kg. At 750 and 1500 mg/kg, xylene also reduced the cell size and cytoplasm size. It down-regulated the expression of Leydig cell-specific genes (Lhcgr, Scarb1, Star, Cyp11a1, Hsd3b1, Cyp17a1, and Hsd11b1) and proteins. In addition, xylene significantly reduced the ratio of phosphorus-GSK-3β (pGSK-3β/GSK-3β), phosphorus-ERK1/2 (pERK)/ERK1/2, and phosphorus-AKT1 (pAKT1)/AKT1, and SIRT1 levels in the testes. In vitro Leydig cell culture showed that xylene induced oxidative stress by increasing the production of reactive oxygen species and lowing antioxidant (Sod2), and inhibited the production of testosterone, and down-regulated the expression of genes related to steroidogenesis, while vitamin E reversed the xylene-mediated effect as an antioxidant. In conclusion, xylene exposure may disrupt the development of pubertal Leydig cells by increasing reactive oxygen species production and reducing the expression of GSK-3β, ERK1/2, AKT1, and SIRT1., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Nymphaea hybrida Peck is used as a traditional medicinal herb for treating pain and inflammatory diseases, and known for its ornamental value and as a hot drink. However, the effects of N. hybrida polar fractions on lipopolysaccharide (LPS)-induced in vitro inflammation model and acute inflammation murine models have yet to be evaluated., Aim of the Study: The aim of this study was to elucidate the anti-inflammatory effects of N. hybrida ethanol extract (NHE) and its polar fractions: petroleum ether (PE), methylene chloride (MC), ethyl acetate (EA), methanol (ME), and water (WA). The underlying molecular mechanisms of active fraction in LPS-stimulated RAW 264.7 murine macrophages were further investigated., Material and Methods: Fractions with potential anti-inflammatory effects were screened using direct nitric oxide (NO) radical scavenging and cyclooxygenase (COX)-2 inhibition assays in vitro. The anti-inflammatory properties of potential fraction were evaluated in LPS-stimulated RAW264.7 cells, xylene-induced ear edema, carrageenan-induced paw edema and xylene-induced Evans blue exudation of acute inflammation murine models. The regulation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways were investigated using western blotting and immunofluorescence., Results: Compared to other polar fractions, NHE-EA displayed higher phenol and flavonoid content, and exerted greater activity in direct NO radical scavenging and COX-2 inhibition assay in vitro. NHE-EA markedly decreased the levels of inflammatory mediators, NO and prostaglandin E 2 (PGE 2 ), by suppressing the over-expression of inducible nitric oxide synthase (iNOS) and COX-2 in LPS-stimulated RAW264.7 cells. The NHE-EA fraction dose-dependently alleviated over-elevation of LPS-associated intracellular calcium and decreased the abnormal secretion of pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and interferon-γ (IFN-γ). The combination with NHE-EA effectively attenuated the activation and nuclear translocation of NF-κB p65, and the phosphorylation of extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinases (JNK), and p38 kinases of MAPK pathways. NHE-EA could significantly ameliorate the degree of swelling of the mice ear and paw, the skin exudation of Evans blue and the excessive secretion of inflammatory cytokines., Conclusion: Our results demonstrated that NHE-EA was the most active polar fraction of N. hybrida extracts. It inhibited the LPS-associated inflammatory response by blocking the activation of NF-κB and MAPKs pathways in RAW264.7 cells. It also effectively alleviated the inflammatory response of acute inflammation. These results indicated the role of NHE-EA as adjuvants and their potential role in alternative strategy for the treatment of inflammatory diseases., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aim: Xylenes are aromatic hydrocarbons used for industrial applications such as the production of petrochemicals and plastics. Acute xylene exposures can negatively impact health through neurotoxicity and irritation of respiratory and dermal tissues. We quantified urinary biomarkers of xylene exposure [2-methylhippuric acid (2MHA) and a mixture of 3- and 4-methylhippuric acids (34MH)] in a representative sample of the U.S. population. Methods: Spot urine obtained during the National Health and Nutrition Examination Survey 2005-2006 and 2011-2016 was analysed using ultra-high-performance liquid chromatography/tandem mass spectrometry. Exclusive smokers were distinguished from non-users using a combination of self-report and serum cotinine data. Results: The median 2MHA and 34MH levels were higher for exclusive smokers (100 µg/g and 748 µg/g creatinine, respectively) than for non-users (27.4 µg/g and 168 µg/g creatinine, respectively). Participants who smoked cigarettes had significantly higher 2MHA and 34MH levels ( p  < 0.0001) than unexposed participants. Smoking 1-10, 11-20, and >20 cigarettes per day (CPD) was significantly associated with 181%, 339% and 393% higher 2MHA levels, respectively. For 34MH, smoking 1-10, 11-20, and >20 CPD was significantly associated with 201%, 398%, and 471% higher 34MH levels, respectively. Conclusion: We confirm that tobacco smoke is a significant source of xylene exposure as measured by urinary 2MHA and 34MH levels.

Combined environmental exposures to the volatile organic compounds (VOCs) Benzene, Toluene, Ethylbenzene, and Xylene (BTEX) pose clear risks to public health. Research into these risks is under-studied even as BTEX levels in the atmosphere are predicted to rise. This review focuses on the available literature using single- and combined-BTEX component inhaled solvent exposures in animal models, necessarily also drawing on findings from models of inhalant abuse and occupational exposures. Health effects of these exposures are discussed for multiple organ systems, but with particular attention on neurobehavioral outcomes such as locomotor activity, impulsivity, learning, and psychopharmacological responses. It is clear that animal models have significant differences in the concentrations, durations and patterns of exposure. Experimental evidence of the deleterious health and neurobehavioral consequences of exposures to the individual components of BTEX were found, but these effects were typically assessed using concentrations and exposure patterns not characteristic of environmental exposure. Future studies with animal models designed appropriately to explore combined BTEX will be necessary and advantageous to discovering health outcomes and more subtle neurobehavioral impacts of long-term environmental exposures., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: The present study deals with the effect of Nectaroscordum koelzi fruit extract on acute and chronic inflammation., Methods: A total of 84 NMRI mice were used in this study. The effect of the extract on acute inflammation was analyzed by increasing vascular permeability via acetic acid and xylene induced ear edema among mice. The extract was evaluated in terms of effects on chronic inflammation by means of the cotton pellet test among mice. For the assessment of inflammation degree, the mice paw edema volume was measured by the plethysmometric test., Results: The findings showed that the extract was effective on acute inflammation induced by acetic acid in mice. In the xylene ear edema, N. koelzi extract indicated a significant activity in mice. In the cotton pellet method, the methanol extract produced a significant reduction in comparison with the control and dexamethasone. Mice paw edema volume decreased with the extract., Conclusion: In general, the data from the experiments indicated that the methanol extract of N. koelzi has an anti-inflammatory effect on acute and chronic inflammation. However, the exact contributing mechanisms have not been investigated for the pharmacological effects., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Uncontrolled inflammation is associated with many major diseases, and there is still an urgent need to develop new anti-inflammatory drugs. 3α-Angeloyloxy- ent -kaur-16-en-19-oic acid (WT-25) is an ent -kaurane dieterpenoid extracted from Wedelia trilobata , a medicinal plant with potential anti-inflammatory activity. The anti-inflammatory activity of WT-25 is better than that of its analog kaurenoic acid, but the underlying mechanism is still unknown. In this study, our aim was to study the anti-inflammatory effect of WT-25. In xylene-induced edema in mice, WT-25 produced 51% inhibition. WT-25 suppressed nitric oxide (NO) and prostaglandin E2 (PGE 2 ) production in LPS-stimulated RAW264.7 cells by downregulating the expression of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). WT-25 reduced expression and secretion of TNF-α and IL-6. Moreover, WT-25 inhibited NF-κB activation and its upstream signaling, decreasing phosphorylation IKK and p65 levels. WT-25 also inhibited the phosphorylation of the mitogen-activated protein kinases (MAPKs) family. Additionally, it reduced LPS-induced excessive release of reactive oxygen species (ROS) and maintained mitochondrial integrity in RAW264.7 cells. All these results indicate that WT-25 is a bioactive molecule with the potential to be developed as a novel structured anti-inflammatory drug.

In this study, human exposure to benzene, toluene, ethylbenzene, xylenes (BTEX), along with their respective risk assessment is studied in four major units (n = 14-point sources) of the largest municipal solid waste management facilities (MSWF) in Iran. The results were compared with four urban sites in Tehran, capital of Iran. Workers at the pre-processing unit are exposed to the highest total BTEX (151 μg m -3 ). In specific, they were exposed to benzene concentrations of 11 μg m -3 . Moreover, the total BTEX (t-BTEX) concentrations measured over the conveyor belt was 198 μg m -3 at most, followed by trommel (104), and active landfills (43). The mean concentration of ambient t-BTEX in Tehran is 100 μg m -3 . On average, xylenes and toluene have the highest concentrations in both on-site and urban environments, with mean values of 24 and 21, and 41 and 37 μg m -3 , respectively. Even though the non-carcinogenic risk of occupational exposure is negligible, BTEX is likely to increase the chance of carcinogenic risks (1.7E-05) for workers at the pre-processing unit. A definite carcinogenic risk of 1.3E-04, and non-carcinogenic effect, of HI = 1.6 were observed in one urban site. With the exception of the pre-processing unit, the citizens of Tehran had higher exposure to BTEX. Overall, BTEX concentrations in the largest MSWF of Iran remains an issue of public health concern., (Copyright © 2020 Elsevier Inc. All rights reserved.)

This study aimed to evaluate occupational exposure to a styrene and xylene mixture through environmental exposure assessment and identify the potential genotoxic effects through biological monitoring. Secondly, we also exposed human peripheral blood cells in vitro to both xylene and styrene either alone or in mixture at concentrations found in occupational settings in order to understand their mechanism of action. The results obtained by air monitoring were below the occupational exposure limits for both substances. All biomarkers of effect, except for nucleoplasmic bridges, had higher mean values in workers (N = 17) compared to the corresponding controls (N = 17). There were statistically significant associations between exposed individuals and the presence of nuclear buds and oxidative damage. As for in vitro results, there was no significant influence on primary DNA damage in blood cells as evaluated by the comet assay. On the contrary, we did observe a significant increase of micronuclei and nuclear buds, but not nucleoplasmic bridges upon in vitro exposure. Taken together, both styrene and xylene have the potential to induce genomic instability either alone or in combination, showing higher effects when combined. The obtained data suggested that thresholds for individual chemicals might be insufficient for ensuring the protection of human health., (Copyright © 2020 Elsevier Inc. All rights reserved.)

We examined the effects of metabolic hormones leptin and ghrelin, and the oil-related environmental contaminants toluene and xylene on the release of ovarian hormones by gravid and non-gravid cats, as well as the functional interrelationships between metabolic hormones and contaminants. Ovarian fragments of non-gravid cats were cultured with and without leptin and toluene. Next, ovarian fragments of either non-gravid or gravid animals were cultured with and without ghrelin and xylene. Oxytocin (OT) and prostaglandin F (PGF) release was measured using ELISA. We confirm ovarian OT and PGF production by feline ovary, demonstrate the involvement of leptin and ghrelin in controlling OT and PGF release, show the direct influence of toluene and xylene on feline ovarian secretory activity, indicate the ability of leptin and ghrelin to mimic and promote the main contaminant effects, demonstrate that oil-related contaminants can prevent and even invert the effects of leptin and ghrelin on the ovary, and suggest the gravidity-associated changes in ability of ghrelin to promote xylene action on PGF (but not to OT), but not in basic ovarian OT and PGF release and their response to ghrelin or xylene., Competing Interests: Declaration of Competing Interest The authors confirm lack of potential conflicts of interest, (Copyright © 2020 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier B.V. All rights reserved.)

Introduction: Exposures to volatile organic compounds and metals have previously been associated with liver diseases including steatohepatitis, although more data are needed. Benzene, toluene, ethylbenzene, xylenes, styrene (BTEXS) and metals were measured in blood samples collected between May 2012-July 2013 from volunteers participating in home visits for the Gulf Long-term Follow-up (GuLF) Study. This cross-sectional analysis evaluates associations of exposure biomarkers with serum liver injury and adipocytokine biomarkers in a sample of 214 men., Methods: Adult nonsmoking men without a history of liver disease or heavy alcohol consumption were included. The serologic disease biomarkers evaluated were the hepatocellular injury biomarker, cytokeratin 18 [whole (CK18 M65) and caspase-cleaved fragment (CK18 M30)]; and adipocytokines. Confounder-adjusted beta coefficients were determined using linear regression models for the overall sample (primary endpoints) and for obesity-classified sub-groups (secondary endpoints). A product interaction term between the exposure of interest and a dichotomized indicator of obesity was included to determine the disease modifying effects of obesity on the biomarker associations., Results: The study sample was 57% white and 51% obese. In the overall sample, lead was positively associated with CK18 M30 (β = 21.7 ± 6.0 (SE), p = 0.0004); IL-1β (β = 32.8 ± 5.2, p < 0.0001); IL-6 (β = 72.8 ± 18.3, p = 0.0001); and IL-8 (β = 140.8 ± 42.2, p = 0.001). Cadmium exposures were associated with increased IL-1β (β = 77.8 ± 26.3, p = 0.003) and IL-8 (β = 419.5 ± 201.2, p = 0.04). There were multiple significant interactions between obesity and exposure to lead, cadmium, benzene and toluene in relation to outcome biomarkers. Among obese participants (n = 108), benzene, lead, and cadmium were each positively associated with CK18 M30, IL-1β, IL-6, and IL-8. In obese subjects, lead was also inversely associated with leptin, and toluene was positively associated with IL-1β., Conclusion: For the overall sample, heavy metal exposures were associated with liver injury (lead only) and/or systemic inflammation (lead and cadmium). Obesity modified the associations between BTEXS and heavy metal exposures on several of the outcome variables. In the obesity subgroup, liver injury was positively associated with lead, cadmium and benzene exposures; systemic inflammation was increased with lead, cadmium, benzene, and toluene exposures; and leptin was inversely associated with lead exposures. The cross-sectional design of this study makes it difficult to determine causality, and all results should be interpreted cautiously. Nonetheless, the potential impact of exposures to lead, cadmium, benzene and toluene in steatohepatitis, an obesity-associated inflammatory liver disease, warrants further investigation., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Cave previously received a contract from Lakeside Life Sciences related to the clinical development of the cytokeratin 18 biomarker for alcoholic hepatitis. That contract is not directly related to this work., (Published by Elsevier Ltd.)

Despite the extensive use of Polygonum chinense (PC) as a detoxifying ingredient of Chinese cool tea, the efficacy of different PC varieties remains underexplored. Herein, we compare the chemical profiles and antioxidant/anti-inflammatory activities of the aqueous extracts of two PC varieties, namely P. chinense var. chinense (PCC) and P. chinense var. hispidum (PCH). Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MSMS) and multivariate analysis are used to rapidly identify extract components, while DPPH radical scavenging and xylene-induced mice ear edema assays are used to evaluate antioxidant and anti-inflammatory activities, respectively. Correlation analysis reveals that ellagic acid and quercitrin contents are positively correlated with the magnitude of the anti-inflammatory effect, and the adopted technique is concluded to allow for the rapid discrimination of PC varieties used in Chinese cool tea formulations., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Benzene homologues have significant toxic effects to aquatic organisms. In this study, the acute toxicity data of benzene, toluene, ethylbenzene and xylene (BTEX) were collected and screened, and the toxicity extrapolation model of paired BTEX was established. The results showed that except the correlation between benzene and xylene was not strong due to insufficient data, the linear correlation of the other five paired BTEX was good (p < 0.01), and R 2 fitted by the four out of five paired BTEX was greater than 0.85. The cross validation showed that ethylbenzene-xylene model was optimal, and for most species (81.8%), the established five BTEX models had a prediction error of less than 10%. Also, these extrapolation models were validated by experimental results of Pseudorasbora parva. The difference between the predicted and measured values of the acute toxicity of BTEX was less than 1 fold, which indicated that the extrapolation model had high accuracy., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Xylene and its derivatives are known to be neurotoxic to the central nervous system of animals. Our previous work has shown that para-xylene (PX) can cause an increase in apoptotic cells and abnormal avoidance behavior in Xenopus laevis. However, the mechanism underlying the impact of PX on neuronal structural and functional plasticity is less clear. Here, we examined the effects of PX on neuronal development and plasticity in the developing optic tectum. We found that HuC/D-positive neurons were more vulnerable than SOX2-positive progenitor cells or BLBP-positive radial glial cells after exposure to PX at 1 mM for 48 h. The further measurement of postsynaptic receptors and synaptic vesicle proteins showed that the expression levels of GluA1 and GluA2, but not Rab3a and SNAP25, were significantly decreased in the tectal brain. In vivo time-lapse images and electrophysiological recordings showed that PX exposure resulted in significant deficits in neuronal structure, particularly in the total dendritic branch length (TDBL), and visual stimulation-induced excitatory compound synaptic currents (eCSCs) without altering neurotransmitter release probability. Strikingly, coexposure to d-glucuronolactone (GA) and PX rescued the structural and functional deficits caused by PX exposure alone. Furthermore, we found that visual experience-induced structural, functional and behavioral plasticity was blocked by PX exposure, which was also rescued by the simultaneous administration of GA and PX . Thus, our findings indicate that PX is neurotoxic to brain development and plasticity and that GA may be considered a promising candidate to treat PX-induced defects in neural circuits., (Copyright © 2019 Elsevier B.V. All rights reserved.)

This study aims to determine the composition of BTEX (benzene, toluene, ethylbenzene and xylene) and assess the risk to health at different sites in Malaysia. Continuous monitoring of BTEX in Kuala Lumpur City Centre, Kuala Terengganu, Kota Kinabalu and Fraser Hill were conducted using Online Gas Chromatograph. For comparison, BTEX at selected hotspot locations were determined by active sampling method using sorbent tubes and Thermal Desorption Gas Chromatography Mass Spectrometry. The hazard quotient (HQ) for non-carcinogenic and the life-time cancer risk (LTCR) of BTEX were calculated using the United States Environmental Protection Agency (USEPA) health risk assessment (HRA) methods. The results showed that the highest total BTEX concentrations using continuous monitoring were recorded in the Kuala Lumpur City Centre (49.56 ± 23.71 μg/m 3 ). Toluene was the most dominant among the BTEX compounds. The average concentrations of benzene ranged from 0.69 ± 0.45 μg/m 3 to 6.20 ± 3.51 μg/m 3 . Measurements using active sampling showed that BTEX concentrations dominated at the roadside (193.11 ± 114.57 μg/m 3 ) in comparison to petrol station (73.08 ± 30.41 μg/m 3 ), petrochemical industry (32.10 ± 13.13 μg/m 3 ) and airport (25.30 ± 6.17 μg/m 3 ). Strong correlations among BTEX compounds (p<0.01, r>0.7) at Kuala Lumpur City Centre showed that BTEX compounds originated from similar sources. The values of HQ at all stations were <1 indicating the non-carcinogenic risk are negligible and do not pose threats to human health. The LTCR value based on benzene inhalation (1.59 × 10 -5 ) at Kuala Lumpur City Centre were between 1 × 10 -4 and 1 × 10 -5 , representing a probable carcinogenic risk., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Inflammation and insomnia are medical problems that may severely affect work and health, thereby necessitating strategies for their effective treatment. Icartin (ICT) is a major active monomeric component of icariin  . Studies have revealed that ICT possesses several pharmacological properties such anti-inflammatory, anti-tumor, anti-fibrotic, anti-osteoporotic and neuroprotective effects. The present research was carried out to investigate the anti-inflammatory, analgesic and sedative/hypnotic effects of ICT. The results obtained revealed that ICT exerted a good anti-inflammatory effect related to the downregulations of inflammatory cytokines and the inhibition of COX-2 signaling pathway. Moreover, ICT enhanced Cl- influx in mouse cortical cells in a concentration-dependent manner. These data suggest that ICT exerts a hypnotic effect in mice through a mechanism associated with increased Cl- influx in cortical cells.

The toxic effects of p-xylene, 4-methylbenzyl alcohol, p-methyl benzaldehyde, and p-toluic acid on two marine microalgae (Phaeodactylum tricornutum Bohlin, and Skeletonema costatum) were investigated. p-Xylene was the most toxic to Pha. tricornutum with a 96 h EC 50 value of 6.76 mg L -1 . Based on the 96 h EC 50 values for two microalgae, the toxicity of the four chemicals, in descending order, was: p-xylene, p-methyl benzaldehyde, 4-methylbenzyl alcohol, then p-toluic acid. The results showed that the toxicity of the transformed products of p-xylene was lower than that of p-xylene.

Objective: To assess neuropsychological performance among workers at a paint factory in Mexico City., Materials and Methods: During 2004 and 2005 we assessed the neuropsychological performance of 208 workers who were exposed to organic solvents at a paint factory, mainly toluene and xylene. We categorized workers into low and high exposure groups using a cumulative index for toluene, based on times spent in different tasks. We evaluated cognitive and motor functions with 13 neuropsychological tests., Results: We found lower attention, longer time to complete the test β=5.5 (R2=12.3%), and a lower score in the motor-cognitive test β=-15.7 (R2=19.5%) in the high exposure group through multiple linear regression model analysis, with adjustment for age and education., Conclusions: Our results are similar to the ones reported in the literature, but the effects are less severe, probably due to lower exposure to organic solvents., Competing Interests: Declaration of conflict of interests. The authors declare that they have no conflict of interests.

Toluene is a widely misused solvent that causes a variety of behavioral effects in both humans and animals. Preclinical and clinical research has provided evidence that toluene inhalation produces psychoactive effects similar to those caused by other Central Nervous System depressant drugs, but little is known about the consequences of inhaling solvents other than toluene that are also present in commercial products. As part of this research project, we studied the effects of hydrocarbon solvents chemically related to toluene on anxiety-like behavior, passive-avoidance learning, nociception, motor coordination and social interaction. We tested independent groups of adolescent male Wistar rats in the burying behavior task, step through avoidance learning task, hot plate test, shock threshold test, social interaction or rotarod tests after a 30 min exposure to either cyclohexane, benzene, toluene or m-xylene (2000 to 8000 ppm). Control animals breathed only air. Benzene, toluene and m-xylene produced anxiolytic-like actions, impaired learning, caused antinociception and decreased social interaction in a concentration-dependent manner. Locomotor coordination was impaired only with 8000 ppm m-xylene and 8000 ppm toluene. Cyclohexane had no effect on any of the behavioral tasks. Our data suggest that the aromatic ring is critical for solvents to produce a wide variety of behavioral effects., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The ubiquitous presence of fragrance-associated synthetic musk is cause for serious concern due to their transformation and environmental impacts. In particular, nitro-musks are frequently detected in various matrices, including water, even though they were restricted because of carcinogenicity. Thus, using musk xylene as a model compound, the mechanism, eco-toxicity and health effects during OH-initiated transformation process were systematically studied using quantum chemistry and computational toxicology. Results indicate that musk xylene can be exclusively transformed via H-abstraction pathways from its methyl group, with total rate constants of 5.65 × 10 8 -8.79 × 10 9  M -1  s -1 , while the contribution of other pathways, including single-electron transfer and OH-addition pathways, were insignificant. The subsequent dehydrogenation intermediates (MX(H)) could further transform into cyclic, aldehyde and demethylation products. Based on toxicity assessments, all the transformation products exhibited decreased aquatic toxicity to fish in comparison with the parent musk xylene but they were still classified at toxic or very toxic levels, especially the cyclic products. More importantly, these products still exhibited carcinogenic activity during OH-initiated transformation and increased carcinogenicity relative to the parent musk xylene. This is the first time that the transformation mechanism and environmental impacts of nitro-musks have been explored through theoretical calculations., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Water contamination by emerging organic pollutants, such as pharmaceuticals and personal care products (PPCPs), is becoming more and more serious. Porous aromatic frameworks (PAFs) are considered as promising adsorbents to remove the PPCPs. To overcome the limitation of PAFs in their powder forms for large-scale applications, herein, we proposed a strategy to covalently anchor PAFs onto electrospun polymer fiber membranes. Polyaniline (PANI) played the role of aromatic seed layer, which was coated on the electrospun polyacrylonitrile (PAN) fiber membrane first. Then, PAF-45 modification was in situ synthesized in the presence of the PANI-coated electrospun PAN fiber membrane. This study could make the PAF-based materials be handled more easily and improve the surface area of electrospun fiber membrane. The obtained composite adsorbent (PAF-45-PP FM) was applied for the adsorption of three PPCPs: ibuprofen (IBPF), chloroxylenol (CLXN), and N, N-diethyl-meta-toluamide (DEET), which exhibited high adsorption capacity and good recycling ability. According to the Langmuir model, the maximum adsorption capacities of PAF-45-PP FM toward IBPF, CLXN and DEET were 613.50, 429.18, and 384.61 mg/g, respectively. In addition, after ten adsorption-desorption cycles, the adsorption capacities toward the three PPCPs decreased slightly. Through an adsorption comparison test, the adsorption capacity of PAF-45-PP FM almost attributed to the loading PAF-45. The adsorption mechanism analysis illustrated that there were pore capture, hydrophobic interaction and π-π interaction between PPCPs and PAF-45-PP FM. Therefore, the PAF-45-PP FM can be potential adsorbents to purify water contaminated with PPCPs.

Few studies have examined the effects of environmental concentrations of benzene, toluene, ethylbenzene, and xylene (BTEX) on the hematologic system of residents near a petrochemical complex. This study evaluated the potential effects of blood BTEX concentrations on the hematologic parameters of residents in a community near a petrochemical complex (contaminated group) and another community free of known petrochemical pollution (control group). Volunteer residents were randomly recruited. Each participant completed a questionnaire and donated blood samples to evaluate blood BTEX concentrations and hematologic parameters. We found the mean concentrations of blood BTEX of the contaminated group were 1.2 to 6.7 times higher than the control group. Multiple hematologic parameters of participants were significantly different between the two study groups. Inverse associations were found for ln-transformed blood benzene concentrations with mean corpuscular hemoglobin concentration (MCHC) (β = - 2.75) and platelet counts (β = -8.18). Several weaker associations were also observed between other compounds and multiple hematologic parameters. Our results suggest that the residents living near petrochemical complexes have higher blood BTEX concentrations. Furthermore, the increased blood BTEX levels in residents are associated with the reduction in RBC counts, hemoglobin concentration, hematocrit, MCHC, and platelet counts. This study provided particularly important information for the health risk assessment of residents living near petrochemical complexes.