The Impact of Environmental Benzene, Toluene, Ethylbenzene, and Xylene Exposure on Blood-Based DNA Methylation Profiles in Pregnant African American Women from Detroit.

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.

Abuse-like toluene exposure during early adolescence alters subsequent ethanol and cocaine behavioral effects and brain monoamines in male mice.

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.

Health risk assessment of exposure to benzene, toluene, ethyl benzene, and xylene in shoe industry-related workplaces.

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.

Modeling the impact of heat stress on the toxicokinetics of toluene and acetone.

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.

Repeated toluene and cyclohexane inhalation produces differential effects on HPA and HPT axes in adolescent male rats.

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 (T3) 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.

Can some food/medicinal plants directly affect porcine ovarian granulosa cells and mitigate the toxic effect of toluene?

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.

Hematotoxicity induced by simultaneous exposure to noise and toluene in New Zealand white rabbits: Synergistic and antagonistic effects.

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.

Recommendation for an occupational exposure limit for toluene.

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.

Short- and long-term effects of chronic toluene exposure on spatial memory in adolescent and adult male Wistar rats.

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.

Evaluation of joint toxicity of BTEX mixtures using sulfur-oxidizing bacteria.

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.

Quercetin can affect porcine ovarian cell functions and to mitigate some of the effects of the environmental contaminant toluene.

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.

Mixture and individual effects of benzene, toluene, and formaldehyde in zebrafish (Danio rerio) development: Metabolomics, epigenetics, and behavioral approaches.

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.

Exposure to Crude Oil-Related Volatile Organic Compounds Associated with Lung Function Decline in a Longitudinal Panel of Children.

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 (FEV1) 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/m3·4 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 FEV1 (ppFEV1), 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 ppFEV1. 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 ppFEV1. 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.

Short- and long-term effects of chronic toluene exposure on recognition memory in adolescent and adult male Wistar rats.

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.

Tribulus terrestris can suppress the adverse effect of toluene on bovine and equine ovarian granulosa cells.

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.

Human exposure to BTEX emitted from a typical e-waste recycling industrial park: External and internal exposure levels, sources, and probabilistic risk implications.

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.

Association between exposure to a mixture of benzene, toluene, ethylbenzene, xylene, and styrene (BTEXS) and small airways function: A cross-sectional study.

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/m3·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.

Blood serum levels of selected biomarkers of oxidative stress among printing workers occupationally exposed to low-levels of toluene and xylene.

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.

Toxicopathological changes induced by combined exposure to noise and toluene in New Zealand White rabbits.

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-1ß), 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-1ß 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-1ß 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.

A novel preclinical model of environment-like combined benzene, toluene, ethylbenzene, and xylenes (BTEX) exposure: Behavioral and neurochemical findings.

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.