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This case report describes the first identification in Israel of the mesoparasitic copepod Pennella balaenoptera, in the carcass of a marine mammal. A Fin whale (Balaenoptera physalus) washed ashore on the Israeli coast was autopsied in contiguity to a large oil spill that occurred along Israel's coastline. At the external examination, a large number of Pennella balaenopterae were embedded within the whale's blubber on its ventral and lateral sides. Further toxicological analyses of lung and bronchus samples, revealed the presence of higher-thanacceptable levels of toluene without any evidence of other above-normal petroleum components, suggesting the inhalation of the substance. This paper proposes to consider toluene toxicity as a possible etiological factor affecting the host's immunity and consequently increasing the parasitic pressure. [ABSTRACT FROM AUTHOR]

The potential of microRNAs to protect the female reproductive system from the toxic influence of oil-related environmental contaminants has not yet been examined. The aim of the present study was to examine the ability of the microRNA miR-152 to prevent the toxic effects of toluene on ovarian cells. Porcine ovarian granulosa cells transfected or not transfected with miR-152 mimics were cultured with or without toluene (0, 10 and 100 ng/ml). The expression of miR-152; cell viability; proliferation (accumulation of PCNA, cyclin B1 and BrdU); cytoplasmic/mitochondrial apoptosis (accumulation of bax and caspase 3); and release of progesterone, testosterone and estradiol were quantified via RT-qPCR, the Trypan blue exclusion test, quantitative immunocytochemistry, the BrdU assay and ELISA. The addition of toluene reduced cell viability, decreased the levels of all the measured markers of proliferation and the release of all the measured steroid hormones, and promoted the expression of apoptosis markers. Transfection of cells with miR-152 mimics increased the expression of miR-152, cell proliferation, and progesterone release but reduced apoptosis and the release of testosterone and estradiol. Moreover, miR-152 prevented or inhibited all the toluene effects in addition to its inhibitory effect on testosterone and estradiol release. The present results demonstrate that miR-152 can protect ovarian cells from the harmful influence of toluene.

Inhalation toxicity assessment is a crucial tool for the identification and classification of hazardous materials like volatile organic carbons, aerosols, and particulate matter. Unlike traditional acute inhalation toxicity studies that use mortality as an endpoint, the Fixed Concentration Procedure (FCP) emphasizes "evident toxicity" by monitoring behavior, weight, and food intake. This reduces reliance on mortality but doesn't directly address respiratory system impact. The present study introduced a respirometer-based inhalation toxicity and respiratory status assessment method. The toxicity evaluation system integrated a respirometric system with an animal exposure chamber, enabling real-time monitoring of oxygen consumption. The ICR mice were exposed to various concentrations of benzene (10, 20, 40, and 80 mg/L of air), toluene (7.5, 15, 30, and 60 mg/L of air), and xylene (7.5, 15, 30, and 60 mg/L of air). The respiration rate decreased by 70 % and 69 % for benzene (80 mg/L of air) and toluene (60 mg/L of air), respectively, with EC 50 values of 32.5 mg/l and 21.2 mg/L based on oxygen consumption. Xylene did not exhibit EC 50 values at the tested concentrations. However, the oxygen consumption rate significantly decreased (46 %) at high concentrations (60 mg/L of air), indicating sub-lethal toxicological effects. Furthermore, the present study was also validated in the bleomycin-induced idiopathic pulmonary fibrosis (IPF) model, demonstrating its reliability as a respiratory impairment marker. The results exhibited a strong correlation between weight loss and less oxygen consumption in the BLM group (bleomycin-induced) as compared to the SHAM group (control), which was confirmed by histological examination and protein marker analysis. The results suggest the potential use of oxygen consumption as an endpoint measurement in inhalation toxicity assessment tests without animal sacrifice, and the present study could be useful for providing valuable insights into disease progression and pharmacological 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 © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Produced water (PW) is a significant byproduct of offshore oil and gas production, constituting a major waste stream in the North Sea. Existing regulations address only the dispersed aliphatic hydrocarbon content in PW, and limited attention is given to other potentially hazardous compounds, including benzene, toluene, ethyl benzene and xylene (BTEX), polycyclic aromatic hydrocarbons (PAHs), phenols, water-soluble petroleum constituents as well as production-related chemicals. In this study, Danish oil production PW samples were subjected to purge and trap extraction on granular activated carbon for volatile compounds identification and quantification by GC-MS analysis. The obtained analytical data correlate with toxicity assessments conducted on three trophic levels, bacteria (Aliivibrio fischeri), algae (Skeletonema costatum) and copepods (Acartia tonsa) on the whole effluent as well as on treated samples. The removal of the PW volatile fraction by purging experiments resulted in a decrease in toxicity response from 37% ± 23-65% ± 16 across the tested species. The chemicals identified in this study and their toxicity response enhance the comprehension of the PW effluent composition and inform the development of strategies for offshore reservoir wastewater., Competing Interests: Declaration of competing interest This research was funded by the Danish Offshore Technology Centre and the Danish Underground Consortium (Total Energies, Blue Nord, and Nordsøfonden) under the Produced Water Management program. These entities provided the samples and data materials used in this study. The private entities had no role in the study design, data collection, analysis, or decision to publish the results. Due to a confidential disclosure agreement with the funding entities, we cannot disclose detailed information about the provenance of the produced water (PW) samples, except for the general area of origin. We are also restricted from sharing confidential raw data on the mass spectroscopy composition of produced water. Despite these restrictions, the funding entities did not interfere with or influence the content or conclusions of this manuscript. The authors do not hold any patents or copyrights relevant to the work presented in this manuscript. There are no other activities or affiliations that the authors believe may merit disclosure in relation to this manuscript., (Copyright © 2024. Published by Elsevier Ltd.)

This study aimed to investigate the effects of combined exposure to noise (85 dB(A)) and inhaled Toluene (300 ± 10 ppm) on rat lung health. It also aimed to assess the potential therapeutic effects of Olea europaea L. leaves extract (OLE) (40 mg/kg/day) using biochemical, histopathological, and immunohistochemical (IHC) analyses, as well as determination of pro-inflammatory cytokines (TNF-α and IL-1β), and in silico Docking studies. The experiment involved forty-two male Wistar rats divided into seven groups, each exposed to a 6-week/6-hour/day regimen of noise and Toluene. The groups included a control group, rats co-exposed to noise and Toluene, and rats co-exposed to noise and Toluene treated with OLE for different durations. The results indicated that noise and Toluene exposure led to structural damage in lung tissue, oxidative harm, and increased levels of pro-inflammatory cytokines (TNF-α and IL-1β). However, the administration of OLE extract demonstrated positive effects in mitigating these adverse outcomes. OLE treatment reduced lipid peroxidation and enhanced the activities of catalase and superoxide dismutase, indicating its anti-oxidant properties. Furthermore, OLE significantly decreased the levels of pro-inflammatory cytokines compared to the groups exposed to noise and Toluene without OLE treatment. Moreover, the in silico investigation substantiated a robust affinity between COX-2 and OLE components, affirming the anti-inflammatory activity. Overall, our findings suggest that OLE possesses anti-inflammatory and anti-oxidative properties that mitigate the adverse effects of concurrent exposure to noise and Toluene.

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.)

Demand for unconventional crude oils continues to drive the production of diluted bitumen (dilbit) within Western Canada, promoting increased transport volumes across the extensive 700,000 km pipeline system of Canada and the USA. Despite this vast extent of terrestrial transport, the current understanding of the behavior and fate of spilled dilbit within shallow groundwater systems is limited. To this end, oil spill experiments with a dilbit (Cold Lake Blend) and a physicochemically similar conventional heavy crude oil (Conventional Heavy Blend) were conducted for 104 days in large soil columns (1 m height × 0.6 m diameter) engineered to model contaminant transport in the unsaturated (vadose) zone. Around two-fold greater concentrations and 6-41 % faster rates of vadose zone transport of benzene, toluene, ethylbenzene and xylenes (BTEX) and polycyclic aromatic compounds (PACs) were observed in the dilbit- compared to conventional heavy crude-contaminated columns. As determined by Orbitrap mass spectrometry, the O x S x species abundances in the acid extractable organics (AEOs) fraction of column leachate from both oil types increased over time, ostensibly due to microbial degradation of petroleum. Bioaccumulation of petroleum constituents in fathead minnow (Pimephales promelas) larvae exposed to contaminated leachate was confirmed through the induction of developmental malformations lasting up to 34 days and increased abundance of cyp1a mRNA observed throughout the experiment. Toxicity was comparable between the two oils but could not be fully attributed to metals, BTEX, PACs or AEOs, implying the presence of uncharacterized teratogens capable of being transported within the vadose zone following terrestrial dilbit and conventional heavy crude oil surface spills., 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., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Workers in occupational settings often face simultaneous exposure to multiple risk factors, including noise and chemicals. This study aimed to investigate the effects of combined exposure to noise and toluene on the cardiac health of rats, with a focus on assessing the potential mitigating effects of Olea europaea L. (OLE) leaf extract (40 mg/kg/day). The evaluation involved scrutinizing biochemical and hematological markers, quantifying oxidative stress levels, determining proinflammatory cytokines in the serum, and conducting an in silico Docking studies. Forty-two male Wistar rats were divided into eight groups-(n = 6/group):-Control-group-(C),-OLE-group-(Rats administered OLE), NT-group (rats co-exposed to noise and toluene), NT-4 group-(rats co-exposed to noise and toluene four weeks after the exposure period), NT + OLE1-group (rats co-exposed to noise and toluene treated with OLE for one week), NT + OLE2-group-(rats co-exposed to noise and toluene treated with OLE for two weeks), NT + OLE3-group-(rats co-exposed to noise and toluene treated with OLE for three weeks), and NT + OLE4-group (rats co-exposed to noise and toluene treated with OLE for four weeks). The results revealed that combined exposure to noise and toluene led to oxidative damage and increased serum levels of proinflammatory cytokines. However, OLE treatment attenuated these effects by reducing lipid peroxidation and enhancing catalase and superoxide dismutase activities. Additionally, OLE treatment significantly decreased proinflammatory cytokine levels compared to the noise and toluene co-exposed group. The study highlighted the potential of OLE to attenuate the adverse effects of combined exposure to noise and toluene, attributed to its anti-inflammatory and antioxidant properties., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Environmental factors can modify addictive responses induced by drugs of abuse; however, little is known about the impact of environmental conditions on behavioral responses induced by inhalants. In this study, we analyzed the effects of housing conditions, considering environmental enrichment (EE; n = 10), social isolation (SI; n = 10), and standard housing (STD; n = 10), as positive, negative, and control environments, respectively, on the development and persistence of behavioral sensitization induced by toluene. Mice exposed to air were used as a comparative control groups for each housing condition (EE: n = 11, SI: n = 10 and STD: n = 11). Results showed that a history of toluene exposure induced the development of locomotor sensitization in mice, independent of their housing conditions. However, SI increased the expression of behavioral sensitization to toluene after a drug-free period., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nayeli Paez-Martinez reports financial support was provided by Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz and Instituto Politécnico Nacional. If there are other authors, they 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 B.V. All rights reserved.)

In day-to-day living, individuals are exposed to various environmentally hazardous substances that have been associated with diverse diseases. Exposure to air pollutants can occur during breathing, posing a considerable risk to those with environmental health vulnerabilities. Among vulnerable individuals, maternal exposure can negatively impact the mother and child in utero. The developing fetus is particularly vulnerable to environmentally hazardous substances, with potentially greater implications. Among air pollutants, toluene is neurotoxic, and its effects have been widely explored. However, the impact of low-level toluene exposure in daily life remains unclear. Herein, we evaluated 194 mothers and infants from the Growing children's health and Evaluation of Environment (GREEN) cohort to determine the possible effects of early-life toluene exposure on the nervous system. Using Omics experiments, the effects of toluene were confirmed based on epigenetic changes and altered mRNA expression. Various epigenetic changes were identified, with upregulated expression potentially contributing to diseases such as glioblastoma and Alzheimer's, and downregulated expression being associated with structural neuronal abnormalities. These findings were detected in both maternal and infant groups, suggesting that maternal exposure to environmental hazardous substances can negatively impact the fetus. Our findings will facilitate the establishment of environmental health policies, including the management of environmentally hazardous substances for vulnerable groups.

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.

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.

Many workers can be exposed simultaneously to heat and volatile chemicals. In a controlled human exposure study, it was observed that an increase in ambient temperature was associated with increased blood concentrations for acetone and toluene. Based on the expected changes in physiological parameters that occur with an increase in ambient temperature, we aimed to develop a PBPK model for acetone and toluene that could account for the impact of temperature on the kinetics of these solvents. Changes in temperature-dependent physiological parameters (i.e. blood flows, cardiac output, alveolar ventilation) based on recent measurements in volunteers were introduced in the PBPK models to simulate observed blood concentrations for different temperature exposure conditions. Because initial simulations did not adequately predict solvent kinetics at any temperature, the most sensitive parameter (alveolar ventilation; Qp) was, therefore, optimized on experimental acetone blood concentrations to obtain a relationship with temperature. The new temperature-dependent Qp relationship gave Qp values consistent with the literature and estimated a mean increase of 19% at 30 °C (wet bulb globe temperature) compared to 21 °C. The integration of a new temperature-dependent Qp relationship in the PBPK toluene model yielded adequate simulations of the experimental data for toluene in blood, exhaled air and urine. With further validation with other solvents, the temperature-dependant PBPK model could be a useful tool to better assess the risks of simultaneous exposure to volatile chemicals and heat stress and interpret biomonitoring data in workers as well as in the general population. TRN: NCT02659410, Registration date: January 15, 2016., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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.

Currently, there is a gap in understanding the neurobiological impact early adolescent toluene exposure has on subsequent actions of other drugs. Adolescent (PND 28-32) male Swiss-Webster mice (N = 210) were exposed to 0, 2000, or 4000 ppm of toluene vapor for 30 min/day for 5 days. Immediately following the last toluene exposure (PND 32; n = 15) or after a short delay (PND 35; n = 15), a subset of subjects' brains was collected for monoamine analysis. Remaining mice were assigned to one of two abstinence periods: a short 4-day (PND 36) or long 12-day (PND 44) delay after toluene exposure. Mice were then subjected to a cumulative dose response assessment of either cocaine (0, 2.5, 5, 10, 20 mg/kg; n = 60), ethanol (0, 0.5, 1, 2, 4 g/kg; n = 60), or saline (5 control injections; n = 60). Toluene concentration-dependently increased locomotor activity during exposure. When later challenged, mice exposed previously to toluene were significantly less active after cocaine (10 and 20 mg/kg) compared to air-exposed controls. Animals were also less active at the highest dose of alcohol (4 g/kg) following prior exposure to 4000 ppm when compared to air-exposed controls. Analysis of monoamines and their metabolites using High Pressure Liquid Chromatography (HPLC) within the medial prefrontal cortex (mPFC), nucleus accumbens (NAc), dorsal striatum (dSTR), and ventral tegmental area (VTA) revealed subtle effects on monoamine or metabolite levels following cumulative dosing that varied by drug (cocaine and ethanol) and abstinence duration. Our results suggest that early adolescent toluene exposure produces behavioral desensitization to subsequent cocaine-induced locomotor activity with subtle enhancement of ethanol's depressive effects and less clear impacts on levels of monoamines., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Cameron J. Davidson reports financial support was provided by Wayne State University (GRA). Scott E. Bowen reports financial support was provided by Wayne State University (Betty J. Neitzel Award). Shane A. Perrine reports equipment, drugs, or supplies was provided by National Institute on Drug Abuse (DA042057)., (Copyright © 2023. Published by Elsevier Inc.)

Misused volatile solvents typically contain toluene (TOL) as the main psychoactive ingredient. Cyclohexane (CHX) can also be present and is considered a safer alternative. Solvent misuse often occurs at early stages of life, leading to permanent neurobehavioral impairment and growth retardation. However, a comprehensive examination of the effects of TOL and CHX on stress regulation and energy balance is lacking. Here, we compared the effect of a binge-pattern exposure to TOL or CHX (4,000 or 8,000 ppm) on body weight, food intake, the hypothalamus-pituitary-adrenal (HPA) and hypothalamus-pituitary-thyroid (HPT) axes in male adolescent Wistar rats. At 8,000 ppm, TOL decreased body weight gain without affecting food intake. In addition, TOL and CHX altered the HPA and HPT axes' function in a solvent- and concentration-dependent manner. The highest TOL concentration produced HPA axis hyperactivation in animals not subjected to stress, which was evidenced by increased corticotropin-releasing-factor (CRF) release from the median eminence (ME), elevated adrenocorticotropin hormone (ACTH) and corticosterone serum levels, and decreased CRF mRNA levels in the hypothalamic paraventricular nucleus (PVN). TOL (8,000 ppm) also increased triiodothyronine (T 3 ) serum levels, decreased pro-thyrotropin-releasing-hormone (pro-TRH) mRNA transcription in the PVN, pro-TRH content in the ME, and serum thyroid stimulating hormone (TSH) levels. CHX did not affect the HPA axis. We propose that the increased HPT axis activity induced by TOL can be related to the impaired body weight gain associated with inhalant misuse. These findings may contribute to a better understanding of the effects of the misused solvents TOL and CHX., 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.)

The action of buckwheat, rooibos and vitex on healthy female reproductive systems, as well as their ability to mitigate the reproductive toxicity of environmental contaminant toluene have not yet been examined. We analysed the influence of toluene (0, 10, 100 or 1000 ng/mL) with and without these plant extracts (10 μg/mL) on cultured porcine ovarian granulosa cells. Cell viability, proliferation (PCNA accumulation), apoptosis (accumulation of bax) and release of progesterone (P) and oestradiol (E) were measured. Toluene reduced ovarian cell viability and proliferation, increased apoptosis and suppressed E but not P release. Plant extracts, given alone, were also able to directly suppress some ovarian cell functions. The addition of buckwheat promoted toluene action on cell viability, proliferation and P release, but it did not modify other toluene effects. Rooibos mitigated toluene action on cell viability, proliferation and apoptosis but promoted its action on P and E. The addition of vitex mitigated all the tested toluene effects. These observations: (1) demonstrate the direct toxic influence of toluene on ovarian cells, (2) demonstrate the ability of food/medicinal plants to either promote or mitigate toluene effects and (3) suggest that vitex could be a natural protector against the suppressive effect of toluene on female reproduction., (© 2023 Wiley-VCH GmbH. Published by John Wiley & Sons Ltd.)

Exposure to numerous pollutants is prevalent in workplaces. Examination of combined exposure to different harmful physical factors and chemicals has offered new insights into toxicology in recent years. This study aimed to investigate the hematological alterations caused by exposure to noise and toluene. Twenty-four New Zealand white rabbits were exposed to 1000 ± 50 ppm toluene and/or 100 ± 5 dB noise for 14 consecutive days. Exposure to noise and toluene changed a number of parameters of white blood cells (WBC), red blood cells (RBC), and platelets on different days after the exposure. Simultaneous exposure to noise and toluene increased WBC, and exposure to noise and toluene alone decreased RBC. Exposure to noise and toluene alone increased basophile, monocyte, and neutrophil counts. The coefficient of variation of red blood cell distribution width (RDW-CV) and the standard deviation of red blood cell distribution width (RDW-SD) significantly increased after co-exposure to noise and toluene. Platelet levels increased in the noise-exposed and the co-exposed groups and decreased in the toluene-exposed group. Furthermore, co-exposure to noise and toluene induced dissimilar synergistic and antagonistic effects on the hematological indices. According to the results of this study, simultaneous exposure to toluene and noise can aggravate some hematotoxic effects compared to exposure to noise or toluene alone. The results also demonstrated the vital role of the modulatory mechanisms of the body in controlling the detrimental effects of stressors.

The Lower Olefins and Aromatics (LOA) REACH Consortium, which includes toluene registrants in the EU, established a Working Group (WG) to conduct a review of the occupational exposure limit (OEL) for toluene. The review focussed on CNS and neuro-behavioural toxicity, ototoxicity, effects on colour vision, reproductive and developmental effects, as safety signals for these effects were identified. The WG also examined the need for a skin notation and/or a short-term exposure limit (STEL). The WG critically reviewed and discussed the strengths and weaknesses of the available published information describing the effects of toluene in animals and humans, to assess its adequacy as a potential point of departure for the establishment of an OEL for toluene and to derive an OEL. As a result, the WG recommendation for a toluene OEL is 20 ppm 8-h TWA, with a 15-min STEL of 100 ppm and a skin notation., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Martijn Rooseboom is employed by Shell including stock ownership but was totally free to design and conduct the research and express his own scientific opinion without any obligation to either Shell or CEFIC. He is a member of the Dutch Expert Committee on Occupational Safety (DECOS) of the Health Council of the Netherlands. Colin M. North is an employee of BASF Corporation and owns shares of publicly traded companies involved in the manufacture, use, or sale of toluene. Neslihan Aygun Kocabas is an employee of TotalEnergies and owns shares of a publicly traded company involved in the manufacture, use, or sale of toluene. Richard James Radcliffe is an employee of Penman Consulting Ltd (Wantage UK), who manage and provide scientific support to the Lower Olefins and Aromatics (LOA) REACH Consortium, which includes toluene registrants in the EU. Lawrence Segal is a freelance contractor to Penman Consulting BVBA (Brussels Belgium), who manage and provide scientific support to the Lower Olefins and Aromatics (LOA) REACH Consortium, which includes toluene registrants in the EU. He is a member of the Workplace Environmental Exposure Level (WEEL) Committee., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Addiction to toluene-containing volatile inhalants is of significant medical and social concern, particularly among youth. These concerns are underscored by the fact that the majority of adult abusers of toluene started as teenagers. Surprisingly, however, the lasting effects of chronic toluene exposure, especially in various age groups, have not been well investigated. Recently, we reported that adolescent and adult male Wistar rats show differential responses to chronic toluene exposure in recognition memory tasks. Since different cognitive functions may be differentially affected by drugs of abuse, we used the same model to evaluate the short- and long-term effects of chronic toluene on spatial learning and memory using Morris water maze. Daily exposure to toluene (2000 ppm) for 40 days (5 min/day) resulted in age-dependent behavioral changes. For example, only adolescent animals showed a decrease in time and distance travelled to find the hidden platform 24 h after the last toluene exposure. In contrast, only adult rats exhibited a decrease in acquisition time and distance travelled at 90 days' post toluene exposure. Our data provide further support for the contention that age-dependent responses should be taken into consideration in interventional attempts to overcome specific detrimental consequences of chronic toluene exposure., 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. Published by Elsevier B.V.)

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.)

In this study, we aimed to investigate the potential hazards of volatile organic compounds (VOCs) on the development of zebrafish. To this end, zebrafish embryos were exposed in two different windows, either alone or in a mixture with VOCs (benzene, toluene, and formaldehyde) [EW1: 4 ± 2 h post-fertilization (hpf) to 24 hpf and EW2: 24 ± 2 hpf to 48 hpf]. Alterations in global DNA methylation and related gene expression, behavioral responses, and stress-related gene expression were observed. In addition to these endpoints, non-targeted NMR-based global metabolomics followed by pathway analysis showed significant changes in the metabolism of various amino acids during VOC exposure. Regardless of the analyzed endpoints, toluene was the most toxic chemical when exposed individually and possibly played the most pivotal role in the mixture treatment conditions. In conclusion, our data show that exposure to VOCs at embryonic developmental stages causes physiological perturbations and adverse outcomes at later life stages., 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. Published by Elsevier B.V.)

The present in vitro experiments aimed to examine the effects of the plant polyphenol quercetin and the environmental contaminant toluene on basic ovarian cell functions, including the ability of quercetin to be a natural protector against the adverse effects of toluene. The influence of toluene, quercetin, and their combination on proliferation (accumulation of PCNA), apoptosis (accumulation of bax) and release of progesterone, testosterone and insulin-like growth factor I (IGFI) by cultured porcine ovarian granulosa cells was investigated. Toluene stimulated cell proliferation and inhibited progesterone, IGF-I and testosterone release but did not affect apoptosis. Quercetin, when administered alone, inhibited cell proliferation, apoptosis, IGF-I and testosterone release and stimulated progesterone output. When administered in combination with toluene, quercetin mitigated toluene's effects on proliferation and on progesterone release and induced toluene to exhibit a pro-apoptotic effect. These observations demonstrate the direct effects of both quercetin and toluene on basic ovarian functions and a protective effect of quercetin against the effects of toluene. Therefore, quercetin-containing plants could be regulators of porcine reproduction and natural protectors against the adverse effects of the environmental contaminant toluene., (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.

Abuse of toluene-containing volatile inhalants, particularly among youth, is of significant medical and social concern worldwide. Teenagers constitute the most abundant users of toluene and the majority of adult abusers of toluene started as teenagers. Although the euphoric and neurotoxic effects of acute toluene have been widely studied, lasting effects of chronic toluene exposure, especially in various age groups, have not been well investigated. In this study, we used adolescent and adult male Wistar rats to evaluate the short- and long-term effects of chronic toluene on various behaviors including cognitive function. Daily exposure to toluene (2000 ppm) for 40 days (5 min/day) resulted in age-dependent behavioral impairments. Specifically, adolescent animals showed recognition memory impairment the day after the last exposure, which had normalized by day 90 post- exposure, whereas such impairment in adult animals was still evident at day 90 post-exposure. Our data suggest that age-dependent responses should be taken into consideration in interventional attempts to overcome specific detrimental consequences of chronic toluene exposure., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

Influence of oil-related product toluene and herbal remedy puncturevine Tribulus terrestris L. (TT) on female reproduction is known. Yet, mechanisms of their action on ovaries in different species and potential protective effect of TT against adverse toluene action remain to be established. We studied the effect of toluene, TT, and their combination on ovarian granulosa cells from two mammalian species (cows and horses). Viability, markers of proliferation (PCNA) and apoptosis (bax), steroid hormones, IGF-I, oxytocin, and prostaglandin F (PGF) release were analyzed by trypan blue exclusion test, quantitative immunocytochemistry, and EIA/ELISA. Toluene suppressed all analyzed parameters. In both species, TT stimulated proliferation and reduced progesterone, oxytocin, and PGF. In horses, TT inhibited testosterone and IGF-I. In both species, TT supported toluene effect on viability, steroids, IGF-I, and PGF, and inverted its action on apoptosis. In cows, TT promoted toluene effect on proliferation. In horses, TT supported toluene effect on oxytocin but suppressed its influence on proliferation. In both species, toluene induced inhibitory action of TT on viability, steroids, IGF-I, and PGF, and prevented its stimulatory action on proliferation. In cows, toluene supported inhibitory action of TT on oxytocin and prevented its stimulatory action on apoptosis. In horses, toluene induced stimulatory effect of TT on apoptosis. Our results indicate potential toxic toluene effect on farm animal ovaries, applicability of TT as a biostimulator of farm animal reproduction and as a protector against the adverse influence of toluene on female reproduction., (© 2022 Wiley-VCH GmbH.)

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.)

Benzene, toluene, ethylbenzene, and xylene (BTEX) can be released during extensive activities associated with the disposal of electronic waste (e-waste), which might pose deleterious health effects on workers. In this study, pollution profiles of BTEX in air and their urinary excretive profiles in occupational workers were investigated in a typical e-waste recycling industrial park. The results showed that the workers in the park were generally exposed to high levels of BTEX. The median levels of urinary metabolites were approximately 6-orders of magnitude higher than those of unmetabolized BTEX, indicating that pollutants efficiently metabolize at those occupational levels. The analytes presented differential profiles in external and internal exposure. Among the metabolites, significant correlation (p < 0.05) was observed between N-acetyl-S-benzyl-L-cysteine (S-BMA) concentration and atmospheric individual BTEX derived from the e-waste recycling area, suggesting that S-BMA is a potential marker for BTEX exposure to e-waste occupational workers. Notably, 95.2 % of all the workers showed a cumulative carcinogenic risk induced by BTEX exposure via inhalation, with 99.9 % of the carcinogenic risk distribution based on concentration of benzene metabolite (N-acetyl-S-(phenyl)-L-cysteine) exceeding 1.0E-6. This study holds potential in providing valuable inferences for the development of remediation strategies focusing on BTEX exposure reduction to protect workers' health at e-waste recycling industries., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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.)

Toluene is an aromatic hydrocarbon commonly abused by young adolescents for its central nervous system depressant effects. Although toluene's pharmacological effects at high concentrations are relatively well-known, few studies have assessed toluene's effects on lung and brain tissues. The present study characterized the pathological effects of acute inhaled toluene exposure in the lungs and brains of male Swiss-Webster mice (N = 68). Using a static vapor exposure chamber, mice (PND 28) received a single 30-min toluene administration (0, 1000, 2000, or 4000 ppm). Lung and brain tissues were extracted 24-h post-exposure. Histology results revealed significant changes in the morphology of lung tissue (e.g., irregular cellular architecture) with the 2000- and 4000-ppm exposures expressing greater signs of pathology than control 0-ppm exposure. Markers of immune system activity (F4/80 and Ly-6G) and cellular proliferation (Ki-67) in the lung revealed no significant differences. Additionally, brain tissues were analyzed for changes of astrogliosis (glial fibrillary acidic protein [GFAP]) and oxidative stress (glutathione peroxidase [GPx]). GFAP showed increased astrogliosis in the striatum with 2000-ppm toluene showing significantly higher expression than control (p < 0.05) and a marginal effect in the hippocampus. No other markers showed significant changes. The increased signs of inflammation and cellular damage suggest that exposure to a single high concentration of toluene, typical of abuse, is capable of producing pathology in both lung and brain tissue., (© 2022 John Wiley & Sons, Ltd.)

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.)

Long-term exposure to organic solvents is known to affect human health posing serious occupational hazards. Organic solvents are genotoxic, and they can cause genetic changes in the exposed employees' somatic or germ cells. Chemicals such as benzene, toluene, and gasoline induce an excessive amount of genotoxicity results either in genetic polymorphism or culminates in deleterious mutations when concentration crosses the threshold limits. The impact of genotoxicity is directly related to the time of exposure, types, and quantum of solvent. Genotoxicity affects almost all the physiological systems, but the most vulnerable ones are the nervous system, reproductive system, and blood circulatory system. Based on the available literature report, we propose to evaluate the outcomes of such chemicals on the exposed humans at the workplace. Attempts would be made to ascertain if the long-term exposure makes a person resistant to such chemicals. This may seem to be a far-fetched idea but has not been studied. The health prospect of this study is envisaged to complement the already existing data facilitating a deeper understanding of the genotoxicity across the population. This would also demonstrate if it correlates with the demographic profile of the population and contributes to comorbidity and epidemiology., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Printing workers (PWs) are exposed to a mixture of solvents, yet the health risks associated with such exposuer are unknown. This study aimed to compare the serum levels of selected biomarkers of oxidative stress among occupationally exposed PWs to low-level of toluene and xylenes and unexposed controls. Associations between levels of such biomarkers and occupational exposures to toluene and xylene were also investigated. Urinary levels of hippuric acid (HA) and methyl hippuric acids (MHAs) as exposure biomarkers of toluene and xylenes, respectively, and serum levels of oxidative stress biomarkers, including total antioxidant capacity (TAC), malondialdehyde (MDA), and the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), were measured among the 84 subjects, comprising 44 PWs and 40 unexposed subjects. Mean concentrations of urinary HA and MHAs of PWs showed a significant increase compared with the unexposed controls. Although levels of urinary biomarkers of exposure to toluene (HA) and xylenes (MHAs) were well below the biological exposure indices (BEIs; ACGHI), PWs presented significantly increased serum levels of MDA, and significantly decreased serum activities of SOD and GPx compared to the unexposed controls. However, for serum TAC and CAT activity, no significant difference was observed between the two groups. Correlation analyses indicated that urinary levels of HA and MHAs were positively correlated with MDA levels and negatively correlated with GPx and SOD. Our study suggested that the alterations evidenced in serum levels of MDA, SOD, and GPx could be involved in the oxidative stress caused by co-exposure to low levels of toluene and xylene. Further investigation is needed to clarify the effect of low-level occupational exposure to solvents among PWs.

Noise and toluene can have significant adverse effects on different systems in the human body, but little is known about their combination. The aim of this study was to see how their combined action reflects on serum levels of inflammatory cytokines tumour necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β), body weight, and pathological changes in the heart, lung, stomach, and spleen tissues. To do that we exposed New Zealand rabbits to 1000 mg/L toluene and 100 dB of white noise in a chamber specifically designed for the purpose over two consecutive weeks. Serum levels of TNF-α and IL-1β were measured with the enzyme-linked immunosorbent assay (ELISA), whereas Bax and Bcl-2 expressions in tissues were determined with real-time polymerase chain reaction (PCR). Noise and toluene changed TNF-α and IL-1β serum levels on different days following the end of exposure and significantly increased the Bax/Bcl-2 ratio in the lung and spleen. In addition, they induced different pathological changes in the heart, lung, spleen, and stomach tissues. This study has confirmed that exposure to noise and toluene can induce a range of toxicopathological changes, probably by inducing inflammatory pathways and apoptosis, but their combined effects look weaker than those of its components, although histopathological findings suggest the opposite., (© 2022 Amirreza Abouee-Mehrizi, Yahya Rasoulzadeh, Tohid Kazemi, Ahmad Mehdipour, Mehran Mesgari-Abbasi, published by Sciendo.)

Toluene is an air pollutant widely used as an organic solvent in industrial production and emitted by fossil fuel combustion, in addition to being used as a drug of abuse. Its toxic effects in the central nervous system have not been well established, and how and which neurons are affected remains unknown. Hence, this study aimed to fill this gap by investigating three central questions: 1) How does toluene induce neurotoxicity? 2) Which neurons are affected? And 3) What are the long-term effects induced by airborne exposure to toluene? To this end, a Caenorhabditis elegans model was employed, in which worms at the fourth larval stage were exposed to toluene in the air for 24 h in a vapor chamber to simulate four exposure scenarios. After the concentration-response curve analysis, we chose scenarios 3 (E3: 792 ppm) and 4 (E4: 1094 ppm) for the following experiments. The assays were performed 1, 48, or 96 h after removal from the exposure environments, and an irreversible reduction in neuron fluorescence and morphologic alterations were observed in different neurons of exposed worms, particularly in the dopaminergic neurons. Moreover, a significant impairment in a dopaminergic-dependent behavior was also associated with negative effects in healthspan endpoints, and we also noted that mitochondria may be involved in toluene-induced neurotoxicity since lower adenosine 5'-triphosphate (ATP) levels and mitochondrial viability were observed. In addition, a reduction of electron transport chain activity was evidenced using ex vivo protocols, which were reinforced by in silico and in vitro analysis, demonstrating toluene action in the mitochondrial complexes. Based on these findings model, it is plausible that toluene neurotoxicity can be initiated by complex I inhibition, triggering a mitochondrial dysfunction that may lead to irreversible dopaminergic neuronal death, thus impairing neurobehavioral signaling., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Crinum jagus ( C. jagus ; J. Thomps.) Dandy (Liliaceae) is a pantropical plant known for its medicinal values and pharmacological properties. The study assessed the protective effects and changes in oxidative stress indices due to C. jagus leaf extracts on the toluene-induced liver and kidney injuries in rats. The study was conducted on 8-week-old male Wistar rats (n = 80), weighing 243.3 ± 1.42 g. Group I, 1 ml/kg distilled water for 7 days; Group II, 4.5 ml/kg toluene once, 1 ml/kg distilled water for 7 days; Group III, 4.5 ml/kg toluene once, 500 mg/kg methanolic extract for 7 days; Group IV, 4.5 ml/kg toluene once, 500 mg/kg aqueous extract for 7 days; Group V, 500 mg/kg methanolic extract for 7 days; Group VI, 500 mg/kg aqueous extract for 7 days; Group VII, 500 mg/kg of vitamin C for 7 days; Group, VIII, 4.5 ml/kg toluene once, 500 mg/kg vitamin C for 7 days, all administrations were given by oral gavage. The phytochemical contents, absolute and relative organ weights of liver and kidneys, liver and kidney function tests, antioxidant status, as well as histological tests were analyzed using standard protocols. The tannins, flavonoids, and polyphenols were in highest concentration in both extracts, content in methanol extract (57.04 ± 1.51 mgg -1 , 35.43 ± 1.03 mgg -1 , 28.2 ± 0.34 mgg -1 respectively) > aqueous extract (18.74 ± 1.01 mgg -1 , 13.43 ± 0.47 mgg -1 , 19.65 ± 0.21 mgg -1 respectively). In the negative control group (II), bodyweights significantly (P < 0.05) reduced by 22%, liver weight and kidney weight significantly (P < 0.05) increased by 42% and 83% respectively, liver-to-bodyweight and kidney-to-bodyweight ratios increased significantly (P < 0.05); serum liver function tests (LFTs) i.e., bilirubin, alkaline phosphatase (ALP), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma-glutamyl transferase (GGT), and serum kidney function tests (creatinine and urea) were significantly (P < 0.05) elevated; oxidant status (tissue malondialdehyde; MDA) was significantly (P < 0.05) elevated, antioxidant status i.e., tissue superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels was significantly (P < 0.05) reduced; with markedly visible renal and hepatic histopathological findings, compared to the normal control group. In C. jagus extract test groups (III and IV), the parameters were significantly (P < 0.05) alleviated and reversed to normal/near normal compared to the negative control. The LFTs, kidney function tests, and antioxidant status were significantly (P < 0.05) more improved with the methanol extract test and standard control groups compared to the aqueous extract test group; Also, the methanol extract test group showed better histological features than the aqueous extract test and standard control groups. The methanolic extract shows better antioxidant potential due to the availability of more nonenzymatic antioxidants (tannins, flavonoids, and polyphenols). The findings showed that toluene is a very aggressive xenobiotic due to the promotion of oxidative stress and peroxidation of cellular lipids, but C. jagus leaves provide significant protection through the reducing power of nonenzymatic antioxidants and their ability to induce endogenous antioxidant enzymes (SOD, CAT, and glutathione reductase or GR) causing reduced cellular lipid peroxidation and tissue damages, quickened tissue repair, and improved cell biology of liver and kidneys during toluene toxicity. The methanol leaf extract provides better protection and should be advanced for more experimental and clinical studies to confirm its efficacy in alleviating oxidative stress tissue injuries, specifically due to toluene., Competing Interests: 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., (© 2022 The Authors.)

The aim of this study is to investigate the concentration of Benzene, Toluene, Ethylbenzene, and Xylene (BTEX) compounds in the indoor air of residential-commercial complexes and to compare it with other residential buildings (control) as well as to assess the carcinogenicity and non-carcinogenicity risk of these pollutants. BTEX concentration was investigated in the indoor air of 30 ground floor restaurants, 30 upper residential units of the complexes, 20 adjacent residential units (control), and their corridors. The mean BTEX concentration measured in the upper residential units was reported higher than in the control residential units, though they were not significantly different. The lifetime cancer risk (LTCR) value calculated for benzene in the upper residential units was lower than 10 -4 and higher than 10 -6 across all ages, indicating a carcinogenicity risk. Furthermore, the mean hazard quotient (HQ) for all compounds was obtained lower than 1, suggesting no concern about the non-carcinogenicity risk of these compounds in the studied region. Nevertheless, considering the sources of benzene production in the indoor air as well as the carcinogenicity of these pollutants and the risk they pose in human health, application towards the reduction of the sources and concentration of benzene in the indoor air are necessary.

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.

Toluene is a highly flammable and commonly used industrial chemical with severe health consequences on humans upon exposure and ingestion. In this study, multispecies bioassays were conducted using a species sensitivity distribution approach to determine acute and chronic hazardous concentrations of toluene in soil. Acute and chronic toluene toxicity tests were conducted with seven soil species from four taxonomic groups. The results from the toxicity tests were used to estimate the acute and chronic HC 5 (hazardous concentration for 5 % of species) of toluene in the terrestrial environment at 58.9 (5.4-639.6) mg kg -1 and 2.2 (0.2-19.8) mg kg -1 , respectively. To the best of our knowledge, this is the first study to estimate the hazardous concentration of toluene in soil by conducting a battery of bioassays. These values can be used as references for the environmental risk assessment of chemical accidents involving toluene and estimating its impact on soil to protect the terrestrial environment., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Real-time BTEX(including benzene, toluene, ethylbenzene, m -, p -, and o -xylenes) were measured continuously in Tianjin urban site in July 2019 and January 2020 using a Syntech Spectras GC955 analyzer. The BTEX concentration levels, composition, and evolutionary mechanisms during typical pollution episodes were investigated. The potential sources of BTEX were analyzed qualitatively using the diagnostic ratios method. Finally, the BTEX health risk was evaluated by using the human exposure analysis and evaluation method according to US EPA. The averaged total mixing ratio of BTEX were 1.32×10 -9 and 4.83×10 -9 during ozone pollution and haze episodes, respectively. Benzene was the most abundant species, followed by toluene. The mixing ratio of BTEX was largely affected by short southwestern distance transportation in January, while local emissions in July. In addition, the BTEX mixing ratio depended on the influence of temperature and relative humidity(RH) in July, while the concentration was more sensitive to changes in RH when the temperature was low in January. Diagnostic ratios and source implications suggested that the BTEX was affected mainly by biomass/biofuel/coal burning during haze episodes. The traffic related emissions also had an impact except for the influence of biomass/biofuel/coal burning in July. The averaged hazard quotient(HQ) values were 0.072 and 0.29 during ozone pollution and haze episodes, respectively, which were in the upper safety range limit recommended by the US EPA. The carcinogenic risk posed by benzene in both cleaning and pollution processes was higher than the safety threshold set by the US EPA, which should be monitored carefully.