Benzene Exposure Research Articles

Health Risk Assessment of Ambient Air Benzene Among Primary School Children in Urban and Rural Areas in Johor, Malaysia

Introduction: It is a fact that children are vulnerable, and are at risk from benzene, a volatile, carcinogenic organic compound. The aim of our study is to determine the levels of ambient air benzene and examine the non-carcinogenic and carcinogenic risks involved Methods: A cross-sectional study was conducted in two urban and two rural primary schools in Johor, Malaysia. Benzene concentrations were measured using BUCK Libra L-4 pumps and analyzed in the gas chromatography-mass spectrometry (GC-MS). Data were collected from 334 10-12 year old children, to calculate the exposure levels based on their body weights and heights. The hazard quotient (HQ) served to evaluate the non-carcinogenic risks, whereas the lifetime cancer risk (LCR) was determined with the aid of the United States Environmental Protection Agency (USEPA). Results and Discussion: Benzene concentrations were higher in rural than urban areas, surpassing the European Union (EU) standard of 5 μg/m³. It was also established that the highest average levels recorded were 6.89 ± 6.68 μg/m³. The HQ values, nonetheless, had indicated no immediate non-carcinogenic risk, while LCR estimates were found to be within a tolerable range across all sites. Findings showed that although the immediate risk from benzene exposure is low, long-term exposure still poses a significant cancer risk to children; even low levels of chronic exposure can heighten the likelihood of children to develop cancers. Conclusion: This study has produced a revelation that there are elevated benzene levels in rural areas in Johor. Despite the low, immediate non-carcinogenic risks, further investigation on the potential for long-term cancer risks is warranted. These risks can be addressed by conducting stricter air quality monitoring, enhancing vehicle emission standards, and introducing educational programs that can raise awareness about benzene exposure.

Mediating effect of oxidative stress on blood pressure elevation in workers exposed to low concentrations of benzene, toluene, and xylene (BTX).

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 (rs = 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.

Accurate low-dose exposure assessment of benzene and monoaromatic compounds by diffusive sampling: Sampling and analytical method validation according to ISO 23320 for radiello® samplers packed with graphitised charcoal and suitable for thermal desorption

This research was aimed at providing an accurate low-dose benzene exposure assessment method, prospectively suitable to exposure limit values in the low ppb range, such as in the present-day chemical, petrochemical, foundry and pharmaceutical industry. The project addresses the need for a robust and fully validated method of personal exposure measurements considering that the Occupational Exposure Limit Value for benzene will be significantly lowered in the next few years. Diffusive sampling offers a reliable alternative to pumped sampling methods, intrinsic safety in potentially explosive atmospheres, lightness and ease of use. The tested diffusive sampler is radiello® with the RAD145 adsorption substrate. This configuration is packed with graphitised charcoal suitable for thermal desorption and analysis by HRGC-FID or HRGC-MS.The experiments have been conducted following the ISO 23320 standard in the range from 0.005 to 0.1 ppm (16 to 320 µg/m3), yielding a full validation of the sampling and analytical method. The sampler performances have fulfilled all requisites of the ISO 23320 standard, in particular: bias due to the selection of a non-ideal sorbent is lower than 10 % (no significant back diffusion of benzene due to concentration change in the atmosphere); bias due to storage of samples for up to 2 months is lower than 10 %; nominal uptake rate for benzene on RAD145 is 32.3 mL/min; expanded uncertainty of the sampling and analytical method is 22.1 % in the concentration range from 80 to 320 µg/m³. The sampling and analytical method is therefore fit-for-purpose for the personal exposure measurements aimed at testing compliance with lowered occupational exposure limit values for benzene. The method is also fit for short duration exposure monitoring related to specific tasks, and other volatile organic compounds, usually found in the same workplaces, such as aliphatic and aromatic hydrocarbons and some oxygenated compounds, have been also studied. In particular, n-hexane and isopropyl benzene (also known as cumene), whose classification is currently under revision, can be efficiently monitored by this technique.

Considerations for using tree-based machine learning to assess causation between demographic and environmental risk factors and health outcomes.

Evaluation of the heterogeneous treatment effect (HTE) allows for the assessment of the causal effect of a therapy or intervention while considering heterogeneity in individual factors within a population. Machine learning (ML) methods have previously been employed for HTE evaluation, addressing the limitations associated with modelling complex systems. In this work, three tree-based ML algorithms, causal random forest (CRF), causal Bayesian additive regression trees (CBART), and causal rule ensemble (CRE), are used to analyze the potential causation of benzene exposure to cause childhood acute myeloid leukemia (AML). Data for this analysis is generated by drawing samples from a previously developed model that estimates AML probability given as input demographic information and benzene exposure. Comparison is drawn between the three tree-based algorithms in terms of the predicted average treatment effect (ATE), the regression coefficient of determination, and the computational time of each algorithm. Minimal difference is reported between the three tree-based algorithms in terms of the ATE, as well as the regression coefficient of determination. However, CRF outperforms CBART in terms of algorithm computational time. Moreover, CRF allows for both continuous and binary treatment variables, as opposed to CBART and CRE, making it better suited to environmental health studies, where exposure levels of pollutants shall be considered continuous. Following the comparison of all three algorithms, the influence of adding Gaussian noise to the treatment and outcome variables, as well as outliers, is investigated using CRF. A set of considerations is drawn to guide researchers in using these algorithms. These considerations detail the simulation settings, applications, and results interpretation and aim to provide prompt information in decision-making surrounding the establishment of pollutant exposure thresholds in environmental risk assessments.

Pipeline-Related Residential Benzene Exposure and Groundwater Natural Attenuation Capacity in the Eastern Niger Delta, Nigeria

This study was conducted to investigate the presence of benzene in the ground and drinking water in the eastern Niger Delta, where multiple oil and gas production facilities are present. Samples from drinking water wells were collected for measurements of benzene, toluene, ethylbenzene, and xylenes (BTEX). Additionally, the dissolved organic carbon (DOC) concentration was determined for the first time to establish the groundwater’s total hydrocarbon and non-hydrocarbon load. The groundwater BTEX and benzene levels were up to 3904 µg/L and 3500 µg/L, respectively. DOC concentrations were up to 49 mg/L. The highest benzene concentrations were detected in wells near an underground petroleum pipeline. However, the concentrations decreased with distance from the pipeline to levels less than 0.1 µg/L. Despite benzene contamination, the aquifer has shown promising aerobic attenuation potential, having up to a 7.5 (95%) mg/L DO level and 2.11 mg/L BTEX biodegradation capacity for DO. However, the high groundwater temperature of up to 32.5 °C may weaken attenuation. The benzene and BTEX point attenuation rates ranged from 0.128 to 0.693 day−1 and 0.086 to 0.556 day−1, respectively. Hence, by natural attenuation alone, up to 66.5 and 85 years would be required to reach Nigeria’s groundwater benzene and BTEX remediation goals, respectively.

Combined effects of benzene, toluene, xylene, ethylbenzene, and styrene exposure on hearing loss mediated by oxidative stress at realistic low levels

The link between benzene, toluene, ethylbenzene, xylene, and styrene (BTEXS) exposure and hearing loss (HL) is not well-established. This study investigated 1694 petrochemical workers in southern China to examine the effects of BTEXS urinary metabolites on auditory function, considering oxidative stress (OS) as a potential cause. Using generalized linear models, elastic net regression, and quantile g-computation, we evaluated the single and combined effects of BTEXS, OS indicators, and HL. Subgroup analysis explored interactions between BTEXS and cumulative noise exposure (CNE), while mediation analysis assessed OS's role in BTEXS-related HL. Positive associations were found between hippuric acid (HA) and HL (OR = 1.20, P < 0.05) and high-frequency hearing loss (HFHL) (OR = 1.22, P < 0.05). The ENET model linked 3&4-methylhippuric acid (3&4-MHA) with increased HFHL risk. The qgcomp model showed a 23% increased HL risk and a 20% increased HFHL risk per quartile increase in BTEXS exposure. Toluene metabolites (SBMA and HA) were significant contributors to HL, HFHL, and speech-frequency hearing loss (SFHL). Higher BTEXS SBMA, MA and HA levels exacerbated HL risk in workers exposed to CNE. Interaction analysis revealed synergistic effects between tt-MA and other metabolites on HFHL risk. Total SOD (TSOD) significantly mediated the BTEXS-HL relationship. These findings highlight a dose-effect association between BTEXS exposure and HL due to oxidative damage, with toluene metabolites being critical pollutants. BTEXS exposure also synergistically increased HL risk with noise.

Evaluation of Benzene Presence and Formation in Benzoyl Peroxide Drug Products

The potent carcinogen, benzene, is a known degradation product of benzoyl peroxide (BPO) and was recently reported to form when BPO drug products, used for acne and rosacea treatment, are incubated at body temperature and elevated temperatures expected during storage and transportation. This study provides evidence for a wide range of benzene concentrations (0.16 ppm to 35.30 ppm) detected by GC-MS in 111 over-the-counter BPO drug products tested and maintained at room temperature. A prescription encapsulated BPO drug product was stability tested at cold (2°C) and elevated temperature (50°C), resulting in no apparent benzene formation at 2°C, and high levels of benzene formation at 50°C, suggesting that encapsulation technology may not stabilize BPO drug products but cold storage may greatly reduce benzene formation. Face model experiments where BPO drug product was applied to PolyMethyl MethAcrylate (PMMA) photoprotection test skin plates and benzene was detected in surrounding air by SIFT-MS, showed detectable benzene through evaporation and substantial benzene formation when exposed to UV light at levels below peak sunlight. Results suggest that potential benzene exposure from formation during BPO drug product use poses significant risks independent of the starting benzene concentration.

LncRNA TUG1 regulates mir-34a-5p / SIRT6 to participate in benzene-induced hematotoxicity through PI3K / AKT /mTOR signaling pathway

LncRNA TUG1 plays pivotal roles in various diseases. However, its exact roles in benzene - induced hematotoxicity remain unclear. Herein, we aimed to investigate the role and mechanism of TUG1 in hematoxic injuries caused by benzene. In the current study, TUG1 was found dramatically decreased in WBCs of benzene exposure workers and negatively correlated with benzene exposure duration and urine SPMA. In vitro assays demonstrated that TUG1 overexpression attenuated 1,4-BQ-caused suppression of cell viability and proliferation, and promotion of ROS generation and apoptosis via PI3K/AKT/mTOR pathway. Bioinformatic prediction and molecular assay validated miR-34a-5p was negatively regulated by TUG1. The miR-34a-5p was upregulated in 1,4-BQ treated cells and downregulated in TUG1 overexpression cells. Moreover, miR-34a-5p upregulation partially reversed the protective effects of TUG1 overexpression on 1,4-BQ - caused cytotoxicity. Furthermore, SIRT6 was a downstream target gene of miR-34a-5p, whose expression was reduced in miR-34a-5p upregulation cells and elevated in TUG1 overexpression cells. Upregulated SIRT6 could counteract accelerated cytotoxicity mediated by miR-34a-5p upregulation after 1,4-BQ treatment. Taken together, our study revealed that the critical role of the TUG1/miR-34a-5p/SIRT6 axis in benzene-caused hematotoxicity, and provided scientific basis for further understanding the epigenetic regulatory mechanisms underlying benzene hematotoxicity.

Microglia Mediate Metabolic Dysfunction from Common Air Pollutants through NF-κB Signaling.

The prevalence of Type 2 Diabetes (T2D) poses a significant health challenge yet the contribution of air pollutants to T2D epidemics remains understudied. Several studies demonstrated a correlation between exposure to volatile organic compounds (VOCs) in indoor/outdoor environments, and T2D. Here, we conducted the first meta-analysis, establishing a robust association between exposure to benzene, a prevalent airborne VOC, and insulin resistance in humans across all ages. We utilized a controlled benzene exposure system, continuous glucose monitoring (CGM) approach and indirect calorimetry in mice, to investigate the underlying mechanisms. Following exposure, disruptions in energy homeostasis, accompanied by modifications in the hypothalamic transcriptome and alterations in insulin and immune signaling, were observed exclusively in males, leading to a surge in blood glucose levels. In agreement, RNA-sequencing of microglia reveals increased expression of genes associated with immune response and NF-κB signaling. Selective ablation of IKKβ in immune cells (Cx3cr1GFPΔIKK) or exclusively in microglia (Tmem119ERΔIKK) in adult mice alleviated benzene-induced gliosis, restored energy homeostasis, hypothalamic gene expression, and protected against hyperglycemia. We conclude that the microglial NF-κB pathway plays a critical role in chemical-induced metabolic disturbances, revealing a vital pathophysiological mechanism linking exposure to airborne toxicants and the onset of metabolic diseases.

Biological monitoring of exposure to benzene in water pipe smokers of rural Western Uttar Pradesh (India)

Aim: Present study was performed to investigate the possible human exposure to benzene through water pipe smoking, if any, in the selected rural population of Western Uttar Pradesh. Methodology: Urine samples from water pipe smokers of both the sexes were collected and analyzed for urinary concentration of phenol, creatinine and malondialdehyde employing standard methods. Results: The results showed that tobacco used by selected rural population contained traces of benzene in the range of 2.75 to 9.682µl ml-1. Analysis of urine samples for phenol, a major metabolite of benzene, showed its increased concentrations in water pipe smokers than non smokers. Further, the effects of age and gender differences on the excretion of phenol were also recorded. Female water pipe smokers were found to be more vulnerable to benzene exposure than male smokers. Intriguingly, alcoholic water pipe smokers were less vulnerable than the non-alcoholic smokers. Interpretation: It is concluded that respiratory, cardiac and haematological disorders caused by water pipe smoking might be attributed to long term benzene exposure amongst water pipe smokers. Large scale epidemiological studies are warranted in Indian rural population considering WHO (Framework Convention on Tobacco Control) regulations of water pipe smoking and tobacco products. Key words: Biological monitoring, Benzene, Oxidative stress, Phenol, Tobacco, Waterpipe smoking

4D label-free proteome analysis of the liver damage mechanism in mice with chronic benzene exposure

4D label-free proteome analysis of the liver damage mechanism in mice with chronic benzene exposure

Global, regional, and national burden of acute myeloid leukemia, 1990–2021: a systematic analysis for the global burden of disease study 2021

BackgroundAcute myeloid leukemia (AML), as the most common subtype of leukemia in adults, is characterised by rapid progression and poor prognosis. In the context of the rapid development of medical technology and the complexity of social factors, a detailed report describing the latest epidemiological patterns of AML is important for decision makers to allocate healthcare resources effectively.MethodsOur research utilized the latest data sourced from the Global Burden of Disease (GBD) 2021. To delineate the burden of AML, we comprehensively described the incidence, deaths, disability-adjusted life years (DALYs), and the associated age-standardized rates per 100,000 persons (ASR) spanning from 1990 to 2021 stratifies according to age, sex, socio-demographic index (SDI), and nationality. Additionally, we extracted and analyzed data about the risk factors that contribute to AML-related deaths and DALYs.ResultsAccording to our study, the incidence of AML has continued to rise globally from 79,372 in 1990 to 144,645 in 2021 and AML affected the male and the elderly populations disproportionately. Furthermore, there was a significant positive correlation between the burden of AML and the SDI value. Developed nations generally exhibited higher age-standardized incidence rate, age-standardized death rate, and age-standardized disability-adjusted life year rate than the developing nations. We also analyzed the prevalence of smoking, high body mass index, and occupational benzene and formaldehyde exposure in the AML population in different SDI regions. Moreover, smoking and high body mass index were more prevalent in developed countries, whereas occupational exposure to these chemicals was the predominant risk factor in developing countries.ConclusionThe global burden of AML has increased over the past 32 years, with rising morbidity and mortality. The incidence of AML is differentially distributed across different SDI countries or regions. AML incidence is higher in the elderly and in men. The proportions of smoking, high body mass index, and occupational exposure to benzene and formaldehyde varied by region. The findings highlight the need for region-specific prevention and call for future research on preventive strategies and new treatments to lower AML incidence and improve patient outcomes.

Unveiling BTX dynamics, source identification, and health implications during COVID-19 lockdown

The COVID-19 pandemic of 2020, marked by stringent lockdowns and reduced human activity, resulted in a significant decrease in air pollutant emissions. This study investigates the impact of these altered atmospheric conditions on human health by focusing on Volatile Organic Compounds (VOCs) such as benzene, toluene, and meta-xylene (BTX), comparing data from before, during, and after the pandemic lockdowns. The objectives were to assess changes in Total VOC (TVOC) concentrations and to evaluate the associated health risks, particularly Lifetime Cancer Risk (LCR) from benzene exposure. Analysis of the data revealed a notable reduction in TVOCs during the 2020 lockdown, with average concentrations of 12.15 ± 20.49 µg/m3 in 2019, 8.08 ± 5.50 µg/m3 in 2020, and 5.12 ± 7.56 µg/m3 in 2021. LCR values also fluctuated, with averages of 1.12 × 10−5, 1.23 × 10−5, and 6.91 × 10−6 or pre-pandemic, during-pandemic, and post-pandemic periods, respectively. The findings highlight the potential effectiveness of lockdowns in reducing air pollution and underscore the need for continued, targeted environmental policies to improve public health.

Occupational exposure to benzene and risk of non-Hodgkin lymphoma in an extended follow-up of two population-based prospective cohorts of Chinese men and women.

The carcinogenicity of benzene was reevaluated by the International Agency for Research on Cancer in 2017, with the Working Group reaffirming positive yet inconclusive associations with non-Hodgkin lymphoma (NHL). To extend our previous observation of a significant exposure-response for cumulative occupational benzene exposure and NHL risk among Chinese women in a population-based cohort in Shanghai, we extended follow-up of this cohort and pooled the data with a similarly designed population-based cohort of men in Shanghai. Cumulative exposure estimates were derived for 134,449 participants in the pooled analysis by combining ordinal job-exposure matrix intensity ratings with quantitative benzene measurements from an inspection database of Shanghai factories. Associations between benzene exposure metrics and NHL (n = 363 cases including multiple myeloma [MM]) were assessed using Cox proportional hazard models. Ever occupational exposure to benzene in the pooled population was associated with NHL risk (HR = 1.5, 95% CI = 1.2-2.0), and exposure-response relationships were observed for increasing duration (ptrend = .003) and cumulative exposure (ptrend = .003). Associations with ever exposure, duration, and cumulative exposure were similar for NHL with and without MM in the case definition, including lifetime cumulative exposures in the highest quartile (HR = 1.6, 95% CI = 1.1-2.4 with MM included; HR = 1.7, 95% CI = 1.1-2.7 with MM excluded). An elevated risk of the chronic lymphocytic leukemia subtype was suggested in the pooled analyses (HR for ever vs. never exposure = 2.3, 95% CI = 0.9-5.6). These observations provide additional support for a plausible association between occupational benzene exposure and risk of NHL.

In utero benzene exposure alters the expression of reactive oxygen species protective genes in mouse placentas, which is dependent on intra-litter variables

In utero benzene exposure alters the expression of reactive oxygen species protective genes in mouse placentas, which is dependent on intra-litter variables

Occupational benzene exposure and risk of kidney and bladder cancers: a systematic review and meta-analysis.

Benzene is recognized as leukemogenic. However, the association between it and solid cancers has been the subject of less investigation. We aim to conduct a systematic review and meta-analysis to evaluate the association between occupational exposure to benzene and the risk of urinary tract cancer, including kidney and bladder. We included 41 cohort and case-control studies listed in the most recent International Agency for Research on Cancer (IARC) Monograph on benzene exposure and the result of a literature review to identify more recent studies. Forest plots of relative risk (RR) were constructed for kidney, bladder, and urinary tract cancer overall. A random-effects model was used to address heterogeneity between studies. Stratified analyses were conducted to explore effect modification. Our findings revealed an association between exposure to occupational benzene and kidney and unspecified urinary tract cancers (RR = 1.20, 95% confidence interval = 1.03-1.39), and an association of borderline statistical significance with bladder cancer (RR = 1.07, 95% confidence interval = 0.97-1.18). Publication bias was excluded for both kidney (P = 0.809) and bladder cancer (P = 0.748). Stratification analysis according to the selected study characteristics showed no difference except regarding the industry for kidney cancer (P < 0.000), with a stronger association in the chemical industry. An analysis by exposure level did not reveal any trend for kidney cancer, whereas there was a trend (P = 0.01) for bladder cancer. Our study found an association between occupational benzene exposure and kidney cancer and a dose-effect association between benzene exposure and bladder cancer.

Occupational Benzene Exposure and Cancer Risk among Chinese Men: A Report from the Shanghai Men's Health Study.

Benzene exposure has been associated with increased risk of leukemia and other cancers; however, epidemiologic evidence is inconsistent for the latter, and confounding from smoking and alcohol was rarely adjusted. We investigated associations between occupational benzene exposure and risk of leukemia, lymphoma, myeloma, and lung, stomach, liver, and kidney cancers in a population-based cohort of 61,377 men, ages 40 to 74 years. A job-exposure matrix, constructed by industrial hygienists specifically for the study population, was used to derive cumulative benzene exposure from all jobs held. Cox regressions were performed to estimate adjusted HRs (aHR) and 95% confidence intervals (CI) for benzene-cancer risk associations with adjustment for potential confounders. Over 15 years of follow-up, 1,145 lung cancer, 656 stomach cancer, 445 liver cancer, 243 kidney cancer, 100 leukemia, 124 lymphoma, and 46 myeloma cases were identified. Benzene exposure >550 mg/m3 was associated with an increased risk of leukemia (aHR = 2.3; 95% CI, 1.1-4.5), lung cancer (aHR = 1.2; 95% CI, 1.0-1.6), and stomach cancer (aHR = 1.4; 95% CI, 1.0-1.9); benzene exposure was associated with early cancer diagnosis age. The benzene-leukemia and benzene-stomach cancer associations followed a linear dose-response pattern (Plinear = 0.016 and 0.023), whereas the benzene-lung cancer association was evident at higher exposure levels (Pnonlinear = 0.027). Alcohol consumption modified the benzene-leukemia association (aHR = 3.0; 95% CI, 1.1-8.3 for drinkers and aHR = 0.9; 95% CI, 0.4-2.0 for nondrinkers, Pinteraction = 0.047). Benzene exposure was associated with an increased risk of leukemia, stomach cancer, and lung cancer. Alcohol consumption may modify the benzene-leukemia association, although estimates are imprecise. Our study provides additional evidence that benzene exposure increases cancer risk beyond leukemia, information important for policymakers to develop programs to mitigate cancer risk among benzene-exposed workers.

Hydroquinone impairs trophoblast migration and invasion via AHR-twist-IFITM1 axis

IntroductionEmbryo implantation is a tightly regulated process, critical for a successful pregnancy. After attachment of the blastocyst to the surface epithelium of the endometrium trophoblast migrate from the trophectoderm and invade into the stromal component of endometrium. Alterations on either process will lead to implantation failure or miscarriage. Volatile organic compounds (VOCs) such as benzene induce pregnancy complications, including preterm birth and miscarriages. The mechanism of this effect is unknown. The objective of this study was to elucidate the impact of benzene metabolite, Hydroquinone, on trophoblast function. We tested the hypothesis that Hydroquinone activates the Aryl hydrocarbon receptor (AhR) pathway modulating trophoblast migration and invasion. MethodsFirst-trimester trophoblast cells (Sw.71) were treated with hydroquinone (6 and 25 μM). Trophoblast migration and invasion was evaluated using a 3D invasion/migration model. Gene expression was quantified by q-PCR and Western blot analysis. ResultsHydroquinone impairs trophoblast migration and invasion. This loss is associated with the activation of the AhR pathway which reduced the expression of Twist1and IFITM1. IFITM1 overexpression can rescue impaired trophoblast migration. DiscussionOur study highlights that hydroquinone treatment induces the activation of the AhR pathway in trophoblast cells, which impairs trophoblast invasion and migration. We postulate that activation of the AhR pathway in trophoblast suppress Twist1 and a subsequent IFITM1. Thus, the AhR-Twist1-IFITM1 axis represent a critical pathway involved in the regulation of trophoblast migration and it is sensitive to benzene exposure. These findings provide crucial insights into the molecular mechanisms underlying pregnancy complications induced by air pollution.

Integrated transcriptomic and proteomic analyses reveal the effects of chronic benzene exposure on the central nervous system in mice

Benzene exposure is known to cause serious damage to the human hematopoietic system. However, recent studies have found that chronic benzene exposure may also cause neurological damage, but there were few studies in this issue. The aim of this study was to investigate the mechanism of damage to the central nervous system (CNS) by chronic benzene exposure with a multi-omics analysis. We established a chronic benzene exposure model in C57BL/6J mice by gavage of benzene-corn oil suspension, identified the differentially expressed proteins (DEPs) and differentially expressed genes (DEGs) in mice brain using 4D Label-free proteomic and RNA-seq transcriptomic. We observed that the benzene exposure mice had a significant loss of body weight, reduction in complete blood counts, abnormally high MRI signals in brain white matter, as well as extensive brain edema and neural demyelination. 162 DEPs were identified by the proteome, including 98 up-regulated and 64 down-regulated proteins. KEGG pathway analysis of DEPs showed that they were mainly involved in the neuro-related signaling pathways such as metabolic pathways, pathways of neurodegeneration, chemical carcinogenesis, Alzheimer disease, and autophagy. EPHX1, GSTM1, and LIMK1 were identified as important candidate DEGs/DEPs by integrated proteomic and transcriptomic analyses. We further performed multiple validation of the above DEGs/DEPs using fluorescence quantitative PCR (qPCR), parallel reaction monitoring (PRM), immunohistochemistry, and immunoblotting to confirm the reliability of the multi-omics study. The functions of these DEGs/DEPs were further explored and analyzed, providing a theoretical basis for the mechanism of nerve damage caused by benzene exposure.

Cancer incidence in Swedish oil refinery workers exposed to benzene

BackgroundOil refinery workers are exposed to benzene, which is a well-known cause of leukaemia, but results on leukaemia in oil refinery workers have been mixed, and the data on workers’ exposure is limited. Oil refinery workers are also exposed to asbestos and several studies have shown increased risk of mesothelioma. AimThe objective was to investigate cancer incidence, especially leukaemia, at low to moderate exposure to benzene in an update of a previous study of employees at three Swedish oil refineries. MethodsCancer incidence was followed up in 2264 men (1548 refinery operators) employed at three oil refineries in Sweden for at least one year. Job types and employment times were collected from complete company files. A retrospective assessment of the benzene exposure was performed by occupational hygienists in collaboration with the refineries using historic measurements as well as detailed information on changes in the industrial hygiene and technological developments. Cases of cancer were retrieved by a linkage with the Swedish Cancer Register through 35–47 years of follow-up and standardized incidence ratios (SIR) with 95% confidence intervals (CI) were calculated. ResultsIn total, 258 tumors had occurred versus 240 expected (SIR 1.07; 95% CI 0.95–1.21). There were 10 cases of leukaemia, all in refinery operators (SIR 2.4; 95% CI 1.18–4.51). There were three cases of pleural mesothelioma, two of which in refinery operators. The mean estimated cumulative benzene exposure for the cases of leukaemia was 7.9 ppm-years (median 4.9, range 0.1–31.1). DiscussionThe study suggests that low to moderate average cumulative benzene exposure increases the risk of leukaemia. Limitations include the modest number of cases and potential misclassification of exposure. ConclusionThe present study indicated an increased risk of leukaemia in male oil refinery workers with low to moderate exposure to benzene.