-
Ecotoxicology and Environmental Safety Nov 2022Benzene is a common industrial chemical and environmental pollutant. However, the mechanism of hematotoxicity caused by exposure to low doses of benzene is unknown....
Benzene is a common industrial chemical and environmental pollutant. However, the mechanism of hematotoxicity caused by exposure to low doses of benzene is unknown. Let-7e-5p pathway regulatory networks were constructed by bioinformatics analysis using a benzene-induced aplastic anemia (BIAA) mouse model. The MTT assay, EdU staining, flow cytometric analysis, dual luciferase reporter gene assay, and RIP assay were utilized to evaluate the effects of benzoquinone (1,4-BQ) on let-7e-5p pathway. This study consisted of 159 workers with a history of low-level benzene exposure and 159 workers with no history of benzene exposure. After the confounding factors were identified, the associations between let-7e-5p expression and hematotoxicity were assessed by multiple linear regression. Furthermore, we used four machine learning algorithms (decision trees, neural network, Bayesian network, and support vector machines) to construct a predictive model for detecting benzene-causing hematotoxicity in workers. In this study, compared with respective controls, let-7e-5p expression was decreased in BIAA mice and benzene-exposed workers. After 1,4-BQ exposure, let-7e-5p overexpression negatively regulated caspase-3 and p21 expression, protected cells from apoptosis, and facilitated cell proliferation. RIP assays, and dual luciferase reporter gene assays confirmed that let-7e-5p could target p21 and caspase-3 and regulate the cell cycle and apoptosis. The support vector machines classifier achieved the best prediction of benzene-induced hematotoxicity (prediction accuracy = 88.27, AUC = 0.83) by statistically characterizing the internal dose of benzene exposure and the oxidative stress index, as well as the expression levels of let-7e-5p pathway-related genes in benzene-exposed workers. Let-7e-5p may be a potential therapeutic target of benzene-induced hematotoxicity, provide a basis for evaluating the health hazards of long-term and low-dose benzene exposure in workers, and supply a reference for revising occupational health standards.
Topics: Animals; Mice; Bayes Theorem; Benzene; Biomarkers; Caspase 3; MicroRNAs
PubMed: 36193590
DOI: 10.1016/j.ecoenv.2022.114142 -
Environmental Health Perspectives Dec 1996Benzene, an important industrial solvent, is also present in unleaded gasoline and cigarette smoke. The hematotoxic effects of benzene in humans are well documented and... (Review)
Review
Benzene, an important industrial solvent, is also present in unleaded gasoline and cigarette smoke. The hematotoxic effects of benzene in humans are well documented and include aplastic anemia, pancytopenia, and acute myelogenous leukemia. However, the risks of leukemia at low exposure concentrations have not been established. A combination of metabolites (hydroquinone and phenol, for example) may be necessary to duplicate the hematotoxic effect of benzene, perhaps due in part to the synergistic effect of phenol on myeloperoxidase-mediated oxidation of hydroquinone to the reactive metabolite benzoquinone. Because benzene and its hydroxylated metabolites (phenol, hydroquinone, and catechol) are substrates for the same cytochrome P450 enzymes, competitive interactions among the metabolites are possible. In vivo data on metabolite formation by mice exposed to various benzene concentrations are consistent with competitive inhibition of phenol oxidation by benzene. In vitro studies of the metabolic oxidation of benzene, phenol, and hydroquinone are consistent with the mechanism of competitive interaction among the metabolites. The dosimetry of benzene and its metabolites in the target tissue, bone marrow, depends on the balance of activation processes such as enzymatic oxidation and deactivation processes such as conjugation and excretion. Phenol, the primary benzene metabolite, can undergo both oxidation and conjugation. Thus the potential exists for competition among various enzymes for phenol. Zonal localization of phase I and phase II enzymes in various regions of the liver acinus also impacts this competition. Biologically based dosimetry models that incorporate the important determinants of benzene flux, including interactions with other chemicals, will enable prediction of target tissue doses of benzene and metabolites at low exposure concentrations relevant for humans.
Topics: Animals; Benzene; Bone Marrow; Cytochrome P-450 CYP2E1; Humans; Liver; Mice; Models, Biological; Phenols
PubMed: 9118926
DOI: 10.1289/ehp.961041399 -
The Lancet. Planetary Health Nov 2023High-level exposure to indoor air pollutants (IAPs) and their corresponding adverse health effects have become a public concern in China in the past 10 years. However,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
High-level exposure to indoor air pollutants (IAPs) and their corresponding adverse health effects have become a public concern in China in the past 10 years. However, neither national nor provincial level burden of disease attributable to multiple IAPs has been reported for China. This is the first study to estimate and rank the annual burden of disease and the financial costs attributable to targeted residential IAPs at the national and provincial level in China from 2000 to 2017.
METHODS
We first did a systematic review and meta-analysis of 117 articles from 37 231 articles identified in major databases, and obtained exposure-response relationships for the candidate IAPs. The exposure levels to these IAPs were then collected by another systematic review of 1864 articles selected from 52 351 articles. After the systematic review, ten IAPs with significant and robust exposure-response relationships and sufficient exposure data were finally targeted: PM, nitrogen dioxide, sulphur dioxide, ozone, carbon monoxide, radon, formaldehyde, benzene, toluene, and p-dichlorobenzene. The annual exposure levels in residences were then evaluated in all 31 provinces in mainland China continuously from 2000 to 2017, using the spatiotemporal Gaussian process regression model to analyse indoor originating IAPs, and the infiltration factor method to analyse outdoor originating IAPs. The disability-adjusted life-years (DALYs) attributable to the targeted IAPs were estimated at both national and provincial levels in China, using the population attributable fraction method. Financial costs were estimated by an adapted human capital approach.
FINDINGS
From 2000 to 2017, annual DALYs attributable to the ten IAPs in mainland China decreased from 4620 (95% CI 4070-5040) to 3700 (3210-4090) per 100 000. Nevertheless, in 2017, IAPs still ranked third among all risk factors, and their DALYs and financial costs accounted for 14·1% (95% CI 12·3-15·6) of total DALYs and 3·45% (3·01-3·82) of the gross domestic product. Specifically, the rank of ten targeted IAPs in order of their contribution to DALYs in 2017 was PM, carbon monoxide, radon, benzene, nitrogen dioxide, ozone, sulphur dioxide, formaldehyde, toluene, and p-dichlorobenzene. The DALYs attributable to IAPs were 9·50% higher than those attributable to outdoor air pollution in 2017. For the leading IAP, PM, the DALYs attributable to indoor origins are 18·3% higher than those of outdoor origins.
INTERPRETATION
DALYs attributed to IAPs in China have decreased by 20·0% over the past two decades. Even so, they are still much higher than those in the USA and European countries. This study can provide a basis for determining which IAPs to target in various indoor air quality standards and for estimating the health and economic benefits of various indoor air quality control approaches, which will help to reduce the adverse health effects of IAPs in China.
FUNDING
The National Key Research and Development Program of China and the National Natural Science Foundation of China.
Topics: Humans; Air Pollutants; Carbon Monoxide; Sulfur Dioxide; Benzene; Nitrogen Dioxide; Formaldehyde; Cost of Illness; Particulate Matter; Radon; Ozone; Toluene
PubMed: 37940210
DOI: 10.1016/S2542-5196(23)00215-2 -
Pituitary Jun 2017Endocrine disruptors are known to modulate a variety of endocrine functions and increase the risk for neoplasia. Epidemiological data reported increased prevalence of...
PURPOSE
Endocrine disruptors are known to modulate a variety of endocrine functions and increase the risk for neoplasia. Epidemiological data reported increased prevalence of pituitary tumors in high industrial areas while genotyping studies showed that mutations in the aryl hydrocarbon receptor (AhR) interacting protein (AIP)-chaperone to the dioxin ligand AhR-gene are linked to predisposition to pituitary tumor development. Aim of the present study was to establish whether endocrine pollutants can induce cell proliferation in normal rat pituitary cells.
METHODS
Pituitary primary cultures were incubated with 250, 650 and 1250 pM benzene or 2-ethyl-phthalate for up to 96 h and viability, energy content and cell proliferation assessed. Expression of pituitary tumor transforming gene (PTTG), cyclin D1 (Ccnd1), AhR and AIP was quantified by RT-qPCR.
RESULTS
Incubation with benzene or 2-ethyl-phthalate increased viability and energy content in pituitary cells. The endocrine disruptors also increased cell proliferation as well as Ccnd1 and PTTG expression. Increased AhR and AIP expression was observed after incubation with the two pollutants.
CONCLUSIONS
Our findings indicate that benzene and 2-ethyl-phthalate activate AhR/AIP expression and stimulate proliferation in normal rat pituitary cells. This study is the first demonstration that pollutants can induce normal pituitary cells to proliferate and provides a link between epidemiological and genomic findings in pituitary tumors.
Topics: Animals; Apoptosis; Benzene; Cell Proliferation; Cell Survival; Male; Phthalic Acids; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction
PubMed: 27853917
DOI: 10.1007/s11102-016-0777-3 -
International Journal of Environmental... Sep 2021This cross-sectional study examined the risk factors affecting adverse health effects from benzene exposure among gasoline station workers in Khon Kean province,...
This cross-sectional study examined the risk factors affecting adverse health effects from benzene exposure among gasoline station workers in Khon Kean province, Thailand. An interview questionnaire of adverse symptoms relating to benzene toxicity was administered to 151 workers. Area samplings for benzene concentration and spot urine for tt-muconic acid (tt-MA), a biomarker of benzene exposure, were collected. The factors associated with adverse symptoms were analysed by using multiple logistic regression. It was found that these symptoms mostly affected fuelling workers (77.5%), and the detected air benzene reached an action level or higher than 50% of NIOSH REL (>50 ppb). The top five adverse symptoms, i.e., fatigue, headache, dizziness, nasal congestion, and runny nose, were reported among workers exposed to benzene. More specific symptoms of benzene toxicity were chest pain, bleeding/epistaxis, and anaemia. The detected tt-MA of workers was 506.7 ug/g Cr (IQR), which was a value above the BEI and higher than that of asymptomatic workers. Risk factors significantly associated with adverse symptoms, included having no safety training experience (OR = 5.22; 95% CI: 2.16-12.58) and eating during work hours (OR = 16.08; 95% CI: 1.96-131.74). This study urges the tightening of health and safety standards at gasoline stations to include training and eating restrictions while working in hazardous areas.
Topics: Air Pollutants, Occupational; Benzene; Cross-Sectional Studies; Gasoline; Humans; National Institute for Occupational Safety and Health, U.S.; Occupational Exposure; United States
PubMed: 34639318
DOI: 10.3390/ijerph181910014 -
Environmental Health Perspectives Dec 1993Acute and chronic exposure to benzene vapors poses a number of health hazards to humans. To evaluate the probability that a specific degree of exposure will produce an... (Comparative Study)
Comparative Study Review
Acute and chronic exposure to benzene vapors poses a number of health hazards to humans. To evaluate the probability that a specific degree of exposure will produce an adverse effect, risk assessment methods must be used. This paper reviews much of the published information and evaluates the various risk assessments for benzene that have been conducted over the past 20 years. There is sufficient evidence that chronic exposure to relatively high concentrations of benzene can produce an increased incidence of acute myelogenous leukemia (AML). Some studies have indicated that benzene may cause other leukemias, but due to the inconsistency of results, the evidence is not conclusive. To predict the leukemogenic risk for humans exposed to much lower doses of benzene than those observed in most epidemiology studies, a model must be used. Although several models could yield plausible results, to date most risk assessments have used the linear-quadratic or conditional logistic models. These appear to be the most appropriate ones for providing the cancer risk for airborne concentrations of 1 ppb to 10 ppm, the range most often observed in the community and workplace. Of the seven major epidemiology studies that have been conducted, there is a consensus that the Pliofilm cohort (rubber workers) is the best one for estimating the cancer potency because it is the only one with good exposure and incidence of disease data. The current EPA, OSHA, and ACGIH cancer potency estimates for benzene are based largely on this cohort. A retrospective exposure assessment and an analysis of the incidence of disease in these workers were completed in 1991. All of these issues are discussed and the implications evaluated in this paper. The range of benzene exposures to which Americans are commonly exposed and the current regulatory criteria are also presented.
Topics: Animals; Benzene; Dose-Response Relationship, Drug; Environmental Pollution; Evaluation Studies as Topic; Female; Forecasting; Humans; Male; Occupational Diseases; Risk Factors
PubMed: 8020442
DOI: 10.1289/ehp.93101s6177 -
International Archives of Occupational... Nov 2016Petroleum refinery workers' exposure to the carcinogens benzene and 1,3-butadiene has decreased during normal operations. However, certain occupational groups or events...
PURPOSE
Petroleum refinery workers' exposure to the carcinogens benzene and 1,3-butadiene has decreased during normal operations. However, certain occupational groups or events at the refineries still involve a risk of higher exposures. The aim of this study was to examine the personal exposure to benzene and 1,3-butadiene at refinery turnarounds and during work in the oil harbour.
METHODS
Personal exposure measurements of benzene and 1,3-butadiene were taken during work shifts, with a priori assumed higher benzene exposure, using PerkinElmer diffusive samplers filled with Carbopack X. Mean exposure levels were calculated, and repeated exposure measurements, when available, were assessed using mixed effect models. Group and individual compliance with the Swedish occupational exposure limit (OEL) was tested for the different exposure groups.
RESULTS
Mean benzene exposure levels for refinery workers during the three measured turnarounds were 150, 610 and 960 µg/m, and mean exposures for oil harbour workers and sewage tanker drivers were 310 and 360 µg/m, respectively. Higher exposures were associated with handling benzene-rich products. Most occupational groups did not comply with the Swedish OEL for benzene nor did the individuals within the groups. The exposure to 1,3-butadiene was very low, between <1 and 3 % of the Swedish OEL.
CONCLUSIONS
Work within the petroleum refinery industry, with potential exposure to open product streams containing higher fractions of benzene, pose a risk of personal benzene exposures exceeding the OEL. Refinery workers performing these work tasks frequently, such as contractors, sewage tanker drivers and oil harbour workers, need to be identified and protected.
Topics: Adult; Benzene; Butadienes; Environmental Monitoring; Humans; Occupational Exposure; Oil and Gas Industry; Sweden
PubMed: 27568022
DOI: 10.1007/s00420-016-1163-1 -
International Journal of Environmental... Jul 2019This paper presents a spatial analysis of the association between industrial benzene emissions and the 10-year incidence rates of cancers likely to be associated with...
This paper presents a spatial analysis of the association between industrial benzene emissions and the 10-year incidence rates of cancers likely to be associated with benzene exposure (Lymphohematopoietic, lung and lip cancers) at the county level in Texas. The spatial distribution of incident cases of the above cancers between 2004 and 2013 was assessed at the county level and found to have positive spatial auto-correlation. Subsequently, point pattern analysis was performed on industrial emissions of benzene reported to the Toxic Release Inventory (TRI), revealing a non-random spatial pattern. Universal kriging was performed using the industrial emissions data to derive estimates of ambient benzene levels at the county level. An ordinary linear regression model was fitted using the incidence rates as the outcome and the estimated benzene level along with chosen covariates and the residuals were assessed for lingering spatial auto-correlation. As the residuals showed that spatial auto-correlation persists, a spatial conditional auto-regression (CAR) model was fitted instead. In the spatial CAR linear regression model, estimated levels of ambient benzene were not found to be significantly associated with the 10-year incidence rates of lymphohematopoietic, lung and lip cancers at the county level.
Topics: Air Pollutants; Benzene; Humans; Incidence; Industry; Linear Models; Neoplasms; Spatial Analysis; Texas
PubMed: 31344779
DOI: 10.3390/ijerph16152627 -
Nature Communications Jul 2021Benzene is a widely used commodity chemical, which is currently produced from fossil resources. Lignin, a waste from lignocellulosic biomass industry, is the most...
Benzene is a widely used commodity chemical, which is currently produced from fossil resources. Lignin, a waste from lignocellulosic biomass industry, is the most abundant renewable source of benzene ring in nature. Efficient production of benzene from lignin, which requires total transformation of C-C/C-O into C-H bonds without side hydrogenation, is of great importance, but has not been realized. Here, we report that high-silica HY zeolite supported RuW alloy catalyst enables in situ refining of lignin, exclusively to benzene via coupling Bronsted acid catalyzed transformation of the C-C bonds on the local structure of lignin molecule and RuW catalyzed hydrogenolysis of the C-O bonds using the locally abstracted hydrogen from lignin molecule, affording a benzene yield of 18.8% on lignin weight basis in water system. The reaction mechanism is elucidated in detail by combination of control experiments and density functional theory calculations. The high-performance protocol can be readily scaled up to produce 8.5 g of benzene product from 50.0 g lignin without any saturation byproducts. This work opens the way to produce benzene using lignin as the feedstock efficiently.
Topics: Benzene; Catalysis; Hydrogen; Hydrogen Bonding; Lignin; Metal Nanoparticles; Metals; Models, Chemical; Molecular Structure; Oxidation-Reduction; Water; Zeolites
PubMed: 34312395
DOI: 10.1038/s41467-021-24780-8 -
Environmental Health Perspectives Dec 1996An overall hypothesis for benzene-induced leukemia is proposed. Key components of the hypothesis include a) activation of benzene in the liver to phenolic metabolites;... (Review)
Review
An overall hypothesis for benzene-induced leukemia is proposed. Key components of the hypothesis include a) activation of benzene in the liver to phenolic metabolites; b) transport of these metabolites to the bone marrow and conversion to semiquinone radicals and quinones via peroxidase enzymes; c) generation of active oxygen species via redox cycling; d) damage to tubulin, histone proteins, topoisomerase II, other DNA associated proteins, and DNA itself; and e) consequent damage including DNA strand breakage, mitotic recombination, chromosome translocations, and aneuploidy. If these effects take place in stem or early progenitor cells a leukemic clone with selective advantage to grow may arise, as a result of protooncogene activation, gene fusion, and suppressor gene inactivation. Epigenetic effects of benzene metabolites on the bone marrow stroma, and perhaps the stem cell itself, may then foster development and survival of the leukemic clone. Evidence for this hypothesis is mounting with the recent demonstration that benzene induces gene-duplicating mutations in human bone marrow and chromosome-specific aneuploidy and translocations in peripheral blood cells. If this hypothesis is correct, it also potentially implicates phenolic and quinonoid compounds in the induction of "spontaneous" leukemia in man.
Topics: Aneuploidy; Animals; Benzene; Carcinogens; Humans; Leukemia; Liver; Models, Biological; Phenols; Recombination, Genetic; Translocation, Genetic
PubMed: 9118896
DOI: 10.1289/ehp.961041219