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Critical Reviews in Toxicology Nov 2022Historically, benzene has been widely used in a large variety of applications. Occupational exposure limits (OELs) were set for benzene as it was found to be acutely... (Review)
Review
Historically, benzene has been widely used in a large variety of applications. Occupational exposure limits (OELs) were set for benzene as it was found to be acutely toxic, causing central nervous system depression at high exposures. OELs were lowered when it was discovered that chronic exposure to benzene could cause haematotoxicity. After confirmation that benzene is a human carcinogen causing acute myeloid leukaemia and possibly other blood malignancies, OEL were further lowered. The industrial application of benzene as solvent is almost completely discontinued but it is still used as feedstock for the production of other materials, such as styrene. Occupational exposure to benzene may also occur since it is present in crude oil, natural gas condensate and a variety of petroleum products and because benzene can be formed in combustion of organic material. In the past few years, lower OELs for benzene in the range of 0.05-0.25 ppm have been proposed or were already established to protect workers from benzene-induced cancer. The skin is an important potential route of exposure and relatively more important at lower OELs. Consequently, human biomonitoring - which integrates all exposure routes - is routinely applied to control overall exposure to benzene. Several potential biomarkers have been proposed and investigated. For compliance check of the current low OELs, urinary S-phenylmercapturic acid (S-PMA), urinary benzene and blood benzene are feasible biomarkers. S-PMA appears to be the most promising biomarker but proper validation of biomarker levels corresponding to airborne benzene concentrations below 0.25 ppm are needed.
Topics: Humans; Benzene; Biological Monitoring; Occupational Exposure; Petroleum; Biomarkers; Environmental Monitoring
PubMed: 36880454
DOI: 10.1080/10408444.2023.2175642 -
American Journal of Respiratory and... Apr 2024
Topics: Humans; Benzene; Environmental Exposure; Air Pollutants
PubMed: 38301235
DOI: 10.1164/rccm.202401-0005ED -
Nature Chemistry May 2022
Topics: Benzene
PubMed: 35513569
DOI: 10.1038/s41557-022-00948-7 -
Journal of Molecular Microbiology and... 2016Aromatic hydrocarbons such as benzene and polycyclic aromatic hydrocarbons (PAHs) are very slowly degraded without molecular oxygen. Here, we review the recent advances... (Review)
Review
Aromatic hydrocarbons such as benzene and polycyclic aromatic hydrocarbons (PAHs) are very slowly degraded without molecular oxygen. Here, we review the recent advances in the elucidation of the first known degradation pathways of these environmental hazards. Anaerobic degradation of benzene and PAHs has been successfully documented in the environment by metabolite analysis, compound-specific isotope analysis and microcosm studies. Subsequently, also enrichments and pure cultures were obtained that anaerobically degrade benzene, naphthalene or methylnaphthalene, and even phenanthrene, the largest PAH currently known to be degradable under anoxic conditions. Although such cultures grow very slowly, with doubling times of around 2 weeks, and produce only very little biomass in batch cultures, successful proteogenomic, transcriptomic and biochemical studies revealed novel degradation pathways with exciting biochemical reactions such as for example the carboxylation of naphthalene or the ATP-independent reduction of naphthoyl-coenzyme A. The elucidation of the first anaerobic degradation pathways of naphthalene and methylnaphthalene at the genetic and biochemical level now opens the door to studying the anaerobic metabolism and ecology of anaerobic PAH degraders. This will contribute to assessing the fate of one of the most important contaminant classes in anoxic sediments and aquifers.
Topics: Anaerobiosis; Bacteria, Anaerobic; Batch Cell Culture Techniques; Benzene; Biodegradation, Environmental; Metabolic Networks and Pathways; Polycyclic Aromatic Hydrocarbons
PubMed: 26960214
DOI: 10.1159/000441358 -
International Journal of Environmental... Sep 2022The concentrations of benzene and 1,3-butadiene in urban, suburban, and rural sites of the U.K. were investigated across 20 years (2000-2020) to assess the impacts of...
The concentrations of benzene and 1,3-butadiene in urban, suburban, and rural sites of the U.K. were investigated across 20 years (2000-2020) to assess the impacts of pollution control strategies. Given the known toxicity of these pollutants, it is necessary to investigate national long-term trends across a range of site types. We conclude that whilst legislative intervention has been successful in reducing benzene and 1,3-butadiene pollution from vehicular sources, previously overlooked sources must now be considered as they begin to dominate in contribution to ambient pollution. Benzene concentrations in urban areas were found to be ~5-fold greater than those in rural areas, whilst 1,3-butadiene concentrations were up to ~10-fold greater. The seasonal variation of pollutant concentration exhibited a maximum in the winter and a minimum in the summer with summer: winter ratios of 1:2.5 and 1:1.6 for benzene and 1,3-butadiene, respectively. Across the period investigated (2000-2020), the concentrations of benzene decreased by 85% and 1,3-butadiene concentrations by 91%. A notable difference could be seen between the two decades studied (2000-2010, 2010-2020) with a significantly greater drop evident in the first decade than in the second, proving, whilst previously successful, legislative interventions are no longer sufficiently limiting ambient concentrations of these pollutants. The health impacts of these pollutants are discussed, and cancer impact indices were utilized allowing estimation of cancer impacts across the past 20 years for different site types. Those particularly vulnerable to the adverse health effects of benzene and 1,3-butadiene pollution are discussed.
Topics: Air Pollutants; Benzene; Butadienes; Environmental Monitoring; Humans; Neoplasms; United Kingdom
PubMed: 36231204
DOI: 10.3390/ijerph191911904 -
Frontiers in Endocrinology 2022Benzene is a ubiquitous pollutant and mainly accumulates in adipose tissue which has important roles in metabolic diseases. The latest studies reported that benzene...
Benzene is a ubiquitous pollutant and mainly accumulates in adipose tissue which has important roles in metabolic diseases. The latest studies reported that benzene exposure was associated with many metabolic disorders, while the effect of benzene exposure on adipose tissue remains unclear. We sought to investigate the effect using and experiments. Male adult C57BL/6J mice were exposed to benzene at 0, 1, 10 and 100 mg/kg body weight by intragastric gavage for 4 weeks. Mature adipocytes from 3T3-L1 cells were exposed to hydroquinone (HQ) at 0, 1, 5 and 25 μM for 24 hours. Besides the routine hematotoxicity, animal experiments also displayed significant body fat content decrease from 1 mg/kg. Interestingly, the circulating non-esterified fatty acid (NEFA) level increased from the lowest dose < 0.05). Subsequent analysis indicated that body fat content decrease may be due to atrophy of white adipose tissue (WAT) upon benzene exposure. The average adipocyte area of WAT decreased significantly even from 1 mg/kg with no significant changes in total number of adipocytes. The percentages of small and large adipocytes in WAT began to significantly increase or decrease from 1 mg/kg (all < 0.05), respectively. Critical genes involved in lipogenesis and lipolysis were dysregulated, which may account for the disruption of lipid homeostasis. The endocrine function of WAT was also disordered, manifested as significant decrease in adipokine levels, especially the leptin. cell experiments displayed similar findings in decreased fat content, dysregulated critical lipid metabolism genes, and disturbed endocrine function of adipocytes after HQ treatment. Pearson correlation analysis showed positive correlations between white blood cell (WBC) count with WAT fat content and plasma leptin level ( = 0.330, 0.344, both < 0.05). This study shed light on the novel aspect that benzene exposure could induce lipodystrophy and disturb endocrine function of WAT, and the altered physiology of WAT might in turn affect benzene-induced hematotoxicity and metabolic disorders. The study provided new insight into understanding benzene-induced toxicity and the relationship between benzene and adipose tissue.
Topics: Adipose Tissue, White; Animals; Benzene; Leptin; Lipodystrophy; Male; Mice; Mice, Inbred C57BL
PubMed: 35909554
DOI: 10.3389/fendo.2022.937281 -
Human & Experimental Toxicology May 2020Benzene is a known hematotoxic and leukemogenic agent with hematopoietic stem cells (HSCs) niche being the potential target. Occupational and environmental exposure to... (Review)
Review
Benzene is a known hematotoxic and leukemogenic agent with hematopoietic stem cells (HSCs) niche being the potential target. Occupational and environmental exposure to benzene has been linked to the incidences of hematological disorders and malignancies. Previous studies have shown that benzene may act via multiple modes of action targeting HSCs niche, which include induction of chromosomal and micro RNA aberrations, leading to genetic and epigenetic modification of stem cells and probable carcinogenesis. However, understanding the mechanism linking benzene to the HSCs niche dysregulation is challenging due to complexity of its microenvironment. The niche is known to comprise of cell populations accounted for HSCs and their committed progenitors of lymphoid, erythroid, and myeloid lineages. Thus, it is fundamental to address novel approaches via lineage-directed strategy to elucidate precise mechanism involved in benzene-induced toxicity targeting HSCs and progenitors of different lineages. Here, we review the key genetic and epigenetic factors that mediate hematotoxicological effects by benzene and its metabolites in targeting HSCs niche. Overall, the use of combined genetic, epigenetic, and lineage-directed strategies targeting the HSCs niche is fundamental to uncover the key mechanisms in benzene-induced hematological disorders and malignancies.
Topics: Animals; Benzene; Carcinogens; Epigenesis, Genetic; Hematopoiesis; Hematopoietic Stem Cells; Humans; Neoplasms; Stem Cell Niche
PubMed: 31884827
DOI: 10.1177/0960327119895570 -
International Journal of Environmental... May 2023(1) Background: Benzene, toluene, and xylene isomers (BTX) are present in gasoline. Exposure to benzene may lead to the appearance of a series of signs, symptoms, and...
(1) Background: Benzene, toluene, and xylene isomers (BTX) are present in gasoline. Exposure to benzene may lead to the appearance of a series of signs, symptoms, and complications, which are characterized by benzene poisoning, which is an occupational disease. This study evaluated the presence of signs and symptoms related to occupational exposure and whether occupational exposure to BTX is associated with the development of hematological changes. (2) Material and Methods: This cross-sectional epidemiological study included 542 participants, in which 324 were gas station workers (GSWs) and 218 were office workers (OWs) with no occupational exposure to benzene. To characterize the type of exposure (exposed and not exposed), trans,trans-Muconic acid (tt-MA), Hippuric acid (HA), and Methylhippuric acid (MHA) were used as exposure biomarkers. The tt-MA analysis revealed that the GSWs had 0.29 mg/g of urinary creatinine and the OWs had 0.13 mg/g of urinary creatinine. For HA, the GSWs presented 0.49 g/g of creatinine while the OWs presented 0.07. MHA analysis revealed that the GSWs had 1.57 g/g creatinine and the OWs had 0.01 g/g creatinine. Occupation habits and clinical symptoms were collected by questionnaire and blood samples were analyzed for hematological parameters. The persistence of hematological changes was evaluated with three serial blood collections every 15 days followed by laboratory hematological analysis. A descriptive analysis by the Chi-square test method was performed to evaluate the association between occupational exposure to fuels and the occurrence of changes in hematological parameters. (3) Results: In the GSWs, the most described signs and symptoms were somnolence (45.1%), headache (38.3%), dizziness (27.5%), tingling (25.4%), and involuntary movement (25%). Twenty GSWs that presented hematological alterations performed serial collections fifteen days apart. In addition, these workers presented total leukocyte counts above the upper limit and lymphocyte counts close to the lower limit. Leukocytosis and lymphopenia are hematological alterations present in chronic benzene poisoning. (4) Conclusions: The results found an initial change in different hematological parameters routinely used in clinics to evaluate health conditions. These findings reveal the importance of valuing clinical changes, even in the absence of disease, during the health monitoring of gas station workers and other groups that share the same space.
Topics: Humans; Benzene; Environmental Monitoring; Creatinine; Cross-Sectional Studies; Occupational Exposure
PubMed: 37239622
DOI: 10.3390/ijerph20105896 -
Environmental Pollution (Barking, Essex... May 2022Single-chemical thresholds cannot comprehensively evaluate the risk of chemical mixture exposure in indoor air. Moreover, a large number of researches have focused on...
Single-chemical thresholds cannot comprehensively evaluate the risk of chemical mixture exposure in indoor air. Moreover, a large number of researches have focused on short-term and high-concentration co-exposure scenarios related to different species, based on diverse endpoints, which hampers the application and improvement of existing risk evaluation models of chemical mixture exposures. More importantly, current risk evaluation models are not user-friendly for construction practitioners who do not have sufficient toxicological knowledge. Therefore, in this study, an inhalation experiment system and a hazard index (HI) were developed to investigate the risks associated with low-concentration and long-term inhalation exposure scenarios of formaldehyde and benzene, individually and combined, based on Drosophila melanogaster mortality. The results showed that the system exhibited good reproducibility in providing stable exposure concentrations during D. melanogaster life cycle. Furthermore, in a range of experimental concentrations, the interaction between formaldehyde and benzene was additive or synergistic, which was concentration- and ratio-dependent. This study is of great significance in harmonising and providing toxicity data under long-term and low-concentration exposure scenarios, which is beneficial for establishing a new user-friendly risk evaluation model for indoor chemical mixture exposures. It should be noted that the proposed HI value could indicate the hazard degrees of long-term inhalation exposures of formaldehyde and benzene, individually and combined, to D. melanogaster. However, the applicability of this index requires further experiments to evaluate the exposure risks of other volatile organic compounds (VOCs) to D. melanogaster.
Topics: Air Pollutants; Air Pollution, Indoor; Animals; Benzene; Drosophila melanogaster; Formaldehyde; Reproducibility of Results; Volatile Organic Compounds
PubMed: 35104555
DOI: 10.1016/j.envpol.2022.118924 -
Epigenetics Dec 2022Sufficient evidence supports a relationship between certain myeloid neoplasms and exposure to benzene or formaldehyde. DNA methylation could underlie benzene- and...
Sufficient evidence supports a relationship between certain myeloid neoplasms and exposure to benzene or formaldehyde. DNA methylation could underlie benzene- and formaldehyde-induced health outcomes, but data in exposed human populations are limited. We conducted two cross-sectional epigenome-wide association studies (EWAS), one in workers exposed to benzene and another in workers exposed to formaldehyde. Using HumanMethylation450 BeadChips, we investigated differences in blood cell DNA methylation among 50 benzene-exposed subjects and 48 controls, and among 31 formaldehyde-exposed subjects and 40 controls. We performed CpG-level and regional-level analyses. In the benzene EWAS, we found genome-wide significant alterations, i.e., FWER-controlled -values <0.05, in the mean and variance of methylation at 22 and 318 CpG sites, respectively, and in mean methylation of a large genomic region. Pathway analysis of genes corresponding to benzene-associated differential methylation sites revealed an impact on the AMPK signalling pathway. In formaldehyde-exposed subjects compared to controls, 9 CpGs in the gene promoter had genome-wide significant decreased methylation variability and a large region of the promoter with 44 CpGs was hypomethylated. Our findings suggest that DNA methylation may contribute to the pathogenesis of diseases related to benzene and formaldehyde exposure. Aberrant expression and methylation of previously has been shown to be clinically significant in myeloid leukaemias. The tumour suppressor gene is a potential biomarker of exposure to formaldehyde, and irregularities have been associated with multiple exposures and diseases.
Topics: Humans; Benzene; DNA Methylation; Epigenome; Cross-Sectional Studies; Occupational Exposure; Formaldehyde; Genome-Wide Association Study; CpG Islands
PubMed: 36017556
DOI: 10.1080/15592294.2022.2115604