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International Journal of Environmental... Aug 2012Excessive exposure to benzene has been known for more than a century to damage the bone marrow resulting in decreases in the numbers of circulating blood cells, and... (Review)
Review
Excessive exposure to benzene has been known for more than a century to damage the bone marrow resulting in decreases in the numbers of circulating blood cells, and ultimately, aplastic anemia. Of more recent vintage has been the appreciation that an alternative outcome of benzene exposure has been the development of one or more types of leukemia. While many investigators agree that the array of toxic metabolites, generated in the liver or in the bone marrow, can lead to traumatic bone marrow injury, the more subtle mechanisms leading to leukemia have yet to be critically dissected. This problem appears to have more general interest because of the recognition that so-called "second cancer" that results from prior treatment with alkylating agents to yield tumor remissions, often results in a type of leukemia reminiscent of benzene-induced leukemia. Furthermore, there is a growing literature attempting to characterize the fine structure of the marrow and the identification of so called "niches" that house a variety of stem cells and other types of cells. Some of these "niches" may harbor cells capable of initiating leukemias. The control of stem cell differentiation and proliferation via both inter- and intra-cellular signaling will ultimately determine the fate of these transformed stem cells. The ability of these cells to avoid checkpoints that would prevent them from contributing to the leukemogenic response is an additional area for study. Much of the study of benzene-induced bone marrow damage has concentrated on determining which of the benzene metabolites lead to leukemogenesis. The emphasis now should be directed to understanding how benzene metabolites alter bone marrow cell biology.
Topics: Animals; Benzene; Bone Marrow; Environmental Exposure; Hematopoiesis; Hematopoietic Stem Cells; Humans; Leukemia; Neoplastic Stem Cells; Signal Transduction
PubMed: 23066403
DOI: 10.3390/ijerph9082875 -
International Journal of Environmental... Feb 2022Sex-related biological differences might lead to different effects in women and men when they are exposed to risk factors. A scoping review was carried out to understand... (Review)
Review
Sex-related biological differences might lead to different effects in women and men when they are exposed to risk factors. A scoping review was carried out to understand if sex could be a discriminant in health outcomes due to benzene. Studies on both animals and humans were collected. In vivo surveys, focusing on genotoxicity, hematotoxicity and effects on metabolism suggested a higher involvement of male animals (mice or rats) in adverse health effects. Conversely, the studies on humans, focused on the alteration of blood parameters, myeloid leukemia incidence and biomarker rates, highlighted that, overall, women had significantly higher risk for blood system effects and a metabolization of benzene 23-26% higher than men, considering a similar exposure situation. This opposite trend highlights that the extrapolation of in vivo findings to human risk assessment should be taken with caution. However, it is clear that sex is a physiological parameter to consider in benzene exposure and its health effects. The topic of sex difference linked to benzene in human exposure needs further research, with more numerous samples, to obtain a higher strength of data and more indicative findings. Sex factor, and gender, could have significant impacts on occupational exposures and their health effects, even if there are still uncertainties and gaps that need to be filled.
Topics: Benzene; Female; Humans; Incidence; Male; Occupational Exposure; Risk Assessment; Sex Characteristics; Sex Factors
PubMed: 35206525
DOI: 10.3390/ijerph19042339 -
Environmental Health Perspectives Apr 1993Benzene is metabolized, primarily in the liver, to a series of phenolic and ring-opened products and their conjugates. The mechanism of benzene-induced aplastic anemia... (Review)
Review
Benzene is metabolized, primarily in the liver, to a series of phenolic and ring-opened products and their conjugates. The mechanism of benzene-induced aplastic anemia appears to involve the concerted action of several metabolites acting together on early stem and progenitor cells, as well as on early blast cells, such as pronormoblasts and normoblasts to inhibit maturation and amplification. Benzene metabolites also inhibit the function of microenvironmental stromal cells necessary to support the growth of differentiating and maturing marrow cells. The mechanism of benzene-induced leukemogenesis is less well understood. Benzene and its metabolites do not function well as mutagens but are highly clastogenic, producing chromosome aberrations, sister chromatid exchange, and micronuclei. Benzene has been shown to be a multi-organ carcinogen in animals. Epidemiological studies demonstrate that benzene is a human leukemogen. There is need to better define the lower end of the dose-response curve for benzene as a human leukemogen. The application of emerging methods in biologically based risk assessment employing pharmacokinetic and mechanistic data may help to clarify the uncertainties in low-dose risk assessment.
Topics: Animals; Benzene; Chromosome Aberrations; Hematopoiesis; Humans; Mutagens; Neoplasms
PubMed: 8354177
DOI: 10.1289/ehp.93100293 -
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 -
Environmental Science & Technology Jul 2023Exposure pathways to the carcinogen benzene are well-established from tobacco smoke, oil and gas development, refining, gasoline pumping, and gasoline and diesel...
Exposure pathways to the carcinogen benzene are well-established from tobacco smoke, oil and gas development, refining, gasoline pumping, and gasoline and diesel combustion. Combustion has also been linked to the formation of nitrogen dioxide, carbon monoxide, and formaldehyde indoors from gas stoves. To our knowledge, however, no research has quantified the formation of benzene indoors from gas combustion by stoves. Across 87 homes in California and Colorado, natural gas and propane combustion emitted detectable and repeatable levels of benzene that in some homes raised indoor benzene concentrations above well-established health benchmarks. Mean benzene emissions from gas and propane burners on high and ovens set to 350 °F ranged from 2.8 to 6.5 μg min, 10 to 25 times higher than emissions from electric coil and radiant alternatives; neither induction stoves nor the food being cooked emitted detectable benzene. Benzene produced by gas and propane stoves also migrated throughout homes, in some cases elevating bedroom benzene concentrations above chronic health benchmarks for hours after the stove was turned off. Combustion of gas and propane from stoves may be a substantial benzene exposure pathway and can reduce indoor air quality.
Topics: Air Pollution, Indoor; Benzene; Propane; Gasoline; Household Products; Cooking; Air Pollutants
PubMed: 37319002
DOI: 10.1021/acs.est.2c09289 -
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 -
Environment International Aug 2023Recent population and animal studies have revealed a correlation between fat content and the severity of benzene-induced hematologic toxicity. However, the precise...
Recent population and animal studies have revealed a correlation between fat content and the severity of benzene-induced hematologic toxicity. However, the precise impact of lipid deposition on benzene-induced hematotoxicity and the underlying mechanisms remain unclear. In this study, we established a mouse model with moderate lipid accumulation by subjecting the mice to an 8-week high-fat diet (45% kcal from fat, HFD), followed by 28-day inhalation of benzene at doses of 0, 1, 10, and 100 ppm. The results showed that benzene exposure caused a dose-dependent reduction of peripheral white blood cell (WBC) counts in both diet groups. Notably, this reduction was less pronounced in the HFD-fed mice, suggesting that moderate lipid accumulation mitigates benzene-related hematotoxicity. To investigate the molecular basis for this effect, we performed bioinformatics analysis of high-throughput transcriptome sequencing data, which revealed that moderate lipid deposition alters mouse metabolism and stress tolerance towards xenobiotics. Consistently, the expression of key metabolic enzymes, such as Cyp2e1 and Gsta1, were upregulated in the HFD-fed mice upon benzene exposure. Furthermore, we utilized a real-time exhaled breath detection technique to monitor exhaled benzene metabolites, and the results indicated that moderate lipid deposition enhanced metabolic activation and increased the elimination of benzene metabolites. Collectively, these findings demonstrate that moderate lipid deposition confers reduced susceptibility to benzene-induced hematotoxicity in mice, at least in part, by accelerating benzene metabolism and clearance.
Topics: Mice; Animals; Benzene; Leukocytes; Acceleration; Lipids; Lipid Metabolism
PubMed: 37506515
DOI: 10.1016/j.envint.2023.108113 -
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 -
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 -
British Journal of Industrial Medicine Jul 1991Benzene, a common industrial chemical and a component of gasoline, is radiomimetic and exposure may lead progressively to aplastic anaemia, leukaemia, and multiple... (Review)
Review
Benzene, a common industrial chemical and a component of gasoline, is radiomimetic and exposure may lead progressively to aplastic anaemia, leukaemia, and multiple myeloma. Although benzene has been shown to cause many types of genetic damage, it has consistently been classified as a non-mutagen in the Ames test, possibly because of the inadequacy of the S9 microsomal activation system. The metabolism of benzene is complex, yielding glucuronide and sulphate conjugates of phenol, quinol, and catechol, L-phenylmercapturic acid, and muconaldehyde and trans, trans-muconic acid by ring scission. Quinol is oxidised to p-benzoquinone, which binds to vital cellular components or undergoes redox cycling to generate oxygen radicals; muconaldehyde, like p-benzoquinone, is toxic through depletion of intracellular glutathione. Exposure to benzene may also induce the microsomal mixed function oxidase, cytochrome P450 IIE1, which is probably responsible for the oxygenation of benzene, but also has a propensity to generate oxygen radicals. The radiomimetic nature of benzene and its ability to induce different sites of neoplasia indicate that formation of oxygen radicals is a major cause of benzene toxicity, which involves multiple mechanisms including synergism between arylating and glutathione-depleting reactive metabolites and oxygen radicals. The occupational exposure limit in the United Kingdom (MEL) and the United States (PEL) was 10 ppm based on the association of benzene exposure with aplastic anaemia, but recently was lowered to 5 ppm and 1 ppm respectively, reflecting a concern for the risk of neoplasia. The American Conference of Governmental Industrial Hygienists (ACGIH) has even more recently recommended that, as benzene is considered an A1 carcinogen, the threshold limit value (TLV) should be decreased to 0.1 ppm. Only one study in man, based on nine cases of benzene associated fatal neoplasia, has been considered suitable for risk assessment. Recent re-evaluation of these data indicated that past assessments may have overestimated the risk, and different authors have considered that lifetime exposure to benzene at 1 ppm would result in an excess of leukaemia deaths of 9.5 to 1.0 per 1000. Although in this study, deaths at low levels of benzene exposure were associated with multiple myeloma and a long latency period, instead of leukaemia, which might justify further lowering of the exposure limit, the risk assessment model has been found to be non-significant for response at low levels of exposure. The paucity of data for man, the complexity of the metabolic activation of benzene, the interactive and synergistic mechanisms of benzene toxicity and carcinogenicity, the different disease endpoints (aplastic anaemia, leukaemia, and multiple myeloma), and different individual susceptibilities, all indicate that in such a complex scenario, regulators should proceed with caution before making further changes to the exposure limit for this chemical.
Topics: Anemia, Aplastic; Animals; Benzene; Bone Marrow; Chemical Phenomena; Chemistry; Humans; Leukemia; Maximum Allowable Concentration; Multiple Myeloma; Neoplasms; Occupational Exposure; Risk
PubMed: 1854646
DOI: 10.1136/oem.48.7.437