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Benzene is associated with diverse occupational and public health hazards. It exhibits an ability to rapidly permeate the skin and contaminate water and food sources, leading to dermal and ingestion exposures. Despite numerous studies examining the associations between benzene and various indicators of harm, the findings have yielded inconsistent results. Furthermore, relying solely on air concentration as a measure of benzene exposure is limited, as it fails to account for internal exposure dose and individual susceptibility. This study aimed to conduct a comprehensive review in order to present current knowledge on benzene biomarkers and their significance in evaluating exposure levels and associated health hazards. The search methodology adhered to the PRISMA guidelines and involved the application of specific inclusion and exclusion criteria across multiple databases including PubMed, Embase, and Web of Science. Two researchers independently extracted and evaluated the relevant data based on predetermined criteria. Following the screening process, a total of 80 articles were considered eligible out of the initially retrieved 1053 articles after undergoing screening and assessment for inclusion. As the level of exposure decreased, specific biomarkers demonstrated a gradual increase in limitations, including heightened background concentrations and vulnerability to confounding factors. The advancement of sampling and analysis techniques will yield new biomarkers. Additionally, when conducting practical work, it is crucial to employ a comprehensive utilization of diverse biomarkers while excluding individual metabolic variations and combined exposure factors. [ABSTRACT FROM AUTHOR]

Benzene, a common industrial solvent, poses significant health risks including poisoning and hematopoietic diseases. However, its precise toxicity mechanisms remain unclear. To assess the health impact of prolonged benzene exposure through metabolomic analyses of exposed workers and benzene-poisoned mice, aiming to identify biomarkers and minimize occupational hazards. This study compared 18 benzene-exposed workers with 18 non-exposed workers, matching for age, lifestyle, and BMI. The metabolites in the workers' samples were analyzed using ultra-high-performance liquid chromatography and mass spectrometry. A larger study included 118 exposed and 158 non-exposed workers, incorporating surveys and routine blood and urine tests with differential metabolites targeted via an enzyme-linked immunosorbent assay. The animal studies consisted of two 15- and 60-day benzene staining and control experiments on 28 C57BL/6J mice, followed by sample collection and organ analysis. The data analysis employed eXtensible Computational Mass Spectrometry (XCMS), Python, MetaboAnalyst 6.0, and SPSS24.0. The exposed workers exhibited altered metabolites indicating external benzene exposure, lower glucose levels, and changes in white blood cell counts and urinary ketone bodies. The plasma metabolomics revealed disturbances in energy and lipid metabolism. The benzene-exposed mice displayed reduced weight gain, behavioral changes, and organ damage. Oxidative stress and abnormal purine and lipid metabolism were observed in both the long-term benzene-exposed workers and benzene-exposed mice. Metabolic markers for the early detection of benzene exposure hazards were identified, underscoring the need to mitigate occupational risks. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Benzene is one of the major carcinogenic factors that can affect liver, kidneys, and lungs. Chronic inhalation of benzene vapor by petrol stations workers has been shown to have an impact on hematological parameters; thus, the present study aimed to investigate the effect of benzene exposure on petrol station workers. SUBJECTS AND METHODS: The study involved 99 participants, 50 of whom have been exposed to benzene and 49 of whom have not (control). A 5 ml blood sample in an ethylenediaminetetraacetic acid (EDTA) anticoagulant tube was collected from each subject, and a complete blood count test was used to test hematological parameters. RESULTS: The current study showed a significant decrease in red blood cells, packed cell volume, and hemoglobin in the exposed group compared to the control group. However, the amount of white blood cells was significantly increased (p < 0.0001) in the exposed group compared to the control group. Notably, there was no significant difference in platelet counts between the two groups. In terms of exposure time, subjects who have been exposed to benzene for more than a year and fewer than 10 years showed a significant decrease (p < 0.05) in RBCs indices and a significant increase (p < 0.0001) in WBCs compared to those in the control group CONCLUSIONS: Thus, the findings indicated that significant differences in hematological parameters were found in workers who were exposed to benzene compared to those who had not been exposed. [ABSTRACT FROM AUTHOR]

Background. Benzene is a known human carcinogen. Human exposure to benzene can be assessed by measuring trans, trans-muconic acid (MUCA) in urine. Golestan Province in northeastern Iran has been reported to have high incidence of esophageal cancer linked to the use of tobacco products. This manuscript evaluates the urinary MUCA concentrations among the participants of the Golestan Cohort Study (GCS). Methods. We analyzed MUCA concentration in 177 GCS participants' urine samples and performed nonparametric pairwise multiple comparisons to determine statistically significant difference among six different product use groups. Mixed effects model was fitted on 22 participants who exclusively smoked cigarette and 51 participants who were classified as nonusers. The urinary MUCA data were collected at the baseline and approximately five years later, and intraclass correlation coefficient (ICC) was calculated from the model. Results. Compared with nonusers, tobacco smoking was associated with higher urinary MUCA concentrations. Based on the nonparametric test of pairwise multiple comparisons, MUCA concentrations among participants who smoked combusted tobacco products were statistically significantly higher compared to nonusers. Urinary MUCA collected five years apart from the same individuals showed moderate reliability (ICC = 0.41), which was expected given the relatively short half-life (∼6 h) of MUCA. Conclusion. Our study revealed that tobacco smoke was positively associated with increased levels of urinary MUCA concentration, indicating that it is a significant source of benzene exposure among GCS participants. [ABSTRACT FROM AUTHOR]

Benzene, a common industrial solvent, poses significant health risks including poisoning and hematopoietic diseases. However, its precise toxicity mechanisms remain unclear. To assess the health impact of prolonged benzene exposure through metabolomic analyses of exposed workers and benzene-poisoned mice, aiming to identify biomarkers and minimize occupational hazards. This study compared 18 benzene-exposed workers with 18 non-exposed workers, matching for age, lifestyle, and BMI. The metabolites in the workers’ samples were analyzed using ultra-high-performance liquid chromatography and mass spectrometry. A larger study included 118 exposed and 158 non-exposed workers, incorporating surveys and routine blood and urine tests with differential metabolites targeted via an enzyme-linked immunosorbent assay. The animal studies consisted of two 15- and 60-day benzene staining and control experiments on 28 C57BL/6J mice, followed by sample collection and organ analysis. The data analysis employed eXtensible Computational Mass Spectrometry (XCMS), Python, MetaboAnalyst 6.0, and SPSS24.0. The exposed workers exhibited altered metabolites indicating external benzene exposure, lower glucose levels, and changes in white blood cell counts and urinary ketone bodies. The plasma metabolomics revealed disturbances in energy and lipid metabolism. The benzene-exposed mice displayed reduced weight gain, behavioral changes, and organ damage. Oxidative stress and abnormal purine and lipid metabolism were observed in both the long-term benzene-exposed workers and benzene-exposed mice. Metabolic markers for the early detection of benzene exposure hazards were identified, underscoring the need to mitigate occupational risks.

Benzene exposure in humans has significant negative health consequences and may be linked to an increased risk of blood biochemical changes. Therefore, the goal of this study was to determine the level of lead in blood of fuel station workers at various petroleum stations in holly Makkah city and look into its effects on specific blood biochemical parameters. Blood samples were collected from 63 individuals, including 44 samples from gasoline station workers (exposed group) and 19 samples from women who were not subjected to any kind of benzene exposure (nonexposed group). Socio-demographic data were collected using a structured questionnaire and 10 ml of venous blood was collected for the determination of lead and biochemical parameters. Data obtained were analyzed using Statistical Package for the Social Sciences (SPSS). The median (range) of blood lead level among exposed group 40.5 (4.0-90.0) 5µg/dL was significantly higher (P = 0.00) than non-exposed group 3.2 (2.7-15.0) µg/dL). Exposed workers had decreased level in albumin, glucose, total protein, and hemoglobin when compared with normal level in human blood (p<0.0001). The results also confirmed that, there was significant relation between exposure to benzene and increase in blood cholesterol (p<0.01). The correlation between benzene exposure and the blood lead level was confirmed by comparing with the non-exposed group (p<0.01). The outcomes from the exposure call upon increased concern for policy action to avoid the adverse effects of benzene on gasoline stations workers' health. [ABSTRACT FROM AUTHOR]

Urinary benzene metabolites trans, trans-muconic acid (t, t-MA), and S-phenyl mercapturic acid (S-PMA) are often used as biomarkers of internal exposure to benzene. However, there are few reports on using urinary benzene metabolites to estimate airborne benzene concentrations in individuals exposed to benzene. In this study, t, t-MA, and S-PMA were analyzed by UPLC-MS/MS, and a simple pharmacokinetic model was used to calculate the daily intake (DI) of benzene based on the levels of urinary t, t-MA, and S-PMA in occupational individuals. The back-calculated airborne benzene levels (BCABL) were obtained from the DI of benzene. Among the exposed subjects (n = 84), the median BCABL (3.67 mg/m3) based on t, t-MA was very close to the median level of measured airborne benzene (3.27 mg/m3, p = 0.171), and there was no effect of smoking or dietary habits on t, t-MA-based BCABL. In the control subjects (n = 49), the levels of measured airborne benzene were all below the quantitation limit (0.024 mg/m3), and the BCABL (0.002–0.25 mg/m3) calculated by S-PMA was close to this background level. Our study suggests that the t, t-MA-based BCABL can reflect the actual airborne benzene level in a range of 1.10–86.91 mg/m3 and that the S-PMA-based BCABL is more reliable for non-professional benzene exposure. [ABSTRACT FROM AUTHOR]

Abstract Background Ubiquitously distributed benzene is a known hematotoxin. Increasing evidence has suggested that erythroid-related hematologic parameters may be sensitive to benzene exposure. Fat content, which is also closely associated with erythroid-related hematologic parameters, may affect the distribution and/or metabolism of benzene, and eventually benzene-induced toxicity. Methods To explore the influence of benzene exposure, fat content, and their interactions on erythroid-related hematologic parameters, we recruited 1669 petrochemical workers and measured their urinary S-phenylmercapturic acid (SPMA) concentration and erythroid-related hematological parameters. Indices for fat content included body fat percentage (BF%), plasma total cholesterol (TC) and triglycerides (TG), and occurrence of fatty liver. Results The dose-response curve revealed U-shaped nonlinear relationships of SPMA with hematocrit (HCT) and mean corpuscular hemoglobin concentration (MCHC) (P-overall

Our aim was to analyze the effects of benzene exposure on hematotoxicity in workers, with a focus on gender differences. The study was divided into three parts, and the survey included 218,061 workers. Since 2017, some workers are selected from the total workers each year to explore the possible influencing factors (age, duration of benzene exposure, TWA (8-h time-weighted average) of benzene, SPMA (S-phenylmercapturic acid), MDA (malondialdehyde), 8-OHdG (8-hydroxy-2′-deoxyguanosine) of different hematotoxicity of different genders). The abnormal rate of WBC (white blood cell), ANC (absolute neutrophil count), and platelets of female workers in the benzene exposure group was higher than that of males in the benzene exposure group and also higher than that of the female workers in the control group. Research results in 2019 showed increased SPMA as well as increases their DNA damage including 8-OHdG and MDA in benzene-exposed female workers compared to those in the control female group (all p < 0.05. SPMA, 8-OHdG, and MDA in benzene exposure female workers increased 555%, 183%, and 33.3%, respectively). Female workers are at significantly higher risk for blood system effects of benzene exposure. Therefore, more stringent standards and guidelines may be needed to protect the changing professional population, especially for females. [ABSTRACT FROM AUTHOR]

Urinary benzene metabolites trans, trans-muconic acid (t, t-MA), and S-phenyl mercapturic acid (S-PMA) are often used as biomarkers of internal exposure to benzene. However, there are few reports on using urinary benzene metabolites to estimate airborne benzene concentrations in individuals exposed to benzene. In this study, t, t-MA, and S-PMA were analyzed by UPLC-MS/MS, and a simple pharmacokinetic model was used to calculate the daily intake (DI) of benzene based on the levels of urinary t, t-MA, and S-PMA in occupational individuals. The back-calculated airborne benzene levels (BCABL) were obtained from the DI of benzene. Among the exposed subjects (n = 84), the median BCABL (3.67 mg/m3) based on t, t-MA was very close to the median level of measured airborne benzene (3.27 mg/m3, p = 0.171), and there was no effect of smoking or dietary habits on t, t-MA-based BCABL. In the control subjects (n = 49), the levels of measured airborne benzene were all below the quantitation limit (0.024 mg/m3), and the BCABL (0.002–0.25 mg/m3) calculated by S-PMA was close to this background level. Our study suggests that the t, t-MA-based BCABL can reflect the actual airborne benzene level in a range of 1.10–86.91 mg/m3 and that the S-PMA-based BCABL is more reliable for non-professional benzene exposure.

Benzene exposure leads to hematotoxicity, and epigenetic modification is considered to be a potential mechanism of benzene pathogenesis. As a newly discovered post-transcriptional modification, the roles of N6-methyladenosine (m6A) in benzene hematotoxicity are still unclear. m6A can only exert its gene regulatory function after being recognized by m6A reading proteins. In this study, we found that the expression of m6A reader IGF2BP1 decreased in benzene poisoning workers and in 20 μM benzene metabolite 1,4-BQ-treated AHH-1 cells. Further overexpression of IGF2BP1 in mice alleviated 50 ppm benzene-induced hematopoietic damage, suggesting that IGF2BP1 plays a critical role in benzene hematotoxicity. Next, we examined transcriptome-wide m6A methylation in vitro to search for target genes of IGF2BP1. We found that benzene metabolite 1,4-BQ treatment altered the m6A methylation levels of various genes. The comprehensive analysis of mRNA expression and m6A methylation uncovered that the hypomethylated Ribosomal Protein L36 (RPL36) and its consequent reduced expression impaired cell proliferation. Mechanically, m6A modification reduced RNA stability to down-regulate RPL36 expression. Moreover, overexpression of IGF2BP1 relieved RPL36 reduction and cell proliferation inhibition caused by benzene in vitro and in vivo by directly binding with RPL36 mRNA. In conclusion, the m6A reader IGF2BP1 attenuates the stability of RPL36 and cell proliferation to mediate benzene hematotoxicity by recognizing m6A modification. IGF2BP1 and RPL36 may be key molecules and potential therapeutic targets for benzene hematotoxicity. [Display omitted] • The m6A reader IGF2BP1 mediates benzene hematotoxicity. • IGF2BP1 overexpression attenuates benzene hematotoxicity in mice. • m6A-methylated RPL36 is a key molecule of benzene hematotoxicity. • IGF2BP1 enhances RPL36 stability and cell proliferation by recognizing m6A sites. [ABSTRACT FROM AUTHOR]

Environmental chemicals play a significant role in the development of metabolic disorders, especially when exposure occurs early in life. We have recently demonstrated that benzene exposure, at concentrations relevant to cigarette smoke, induces a severe metabolic imbalance in a sex-specific manner affecting male but not female mice. However, the roles of benzene in the development of aberrant metabolic outcomes following gestational exposure, remain largely unexplored. In this study, we exposed pregnant C57BL/6JB dams to benzene at 50 ppm or filtered air for 6 h/day from gestational day 0.5 (GD0.5) through GD21 and studied male and female offspring metabolic phenotypes in their adult life. While no changes in body weight or body composition were observed between groups, 4-month-old male and female offspring exhibited reduced parameters of energy homeostasis (VO2, VCO2, and heat production). However, only male offspring from benzene-exposed dams were glucose intolerant and insulin resistant at this age. By 6 months of age, both male and female offspring exhibited marked glucose intolerance however, only male offspring developed severe insulin resistance. This effect was accompanied by elevated insulin secretion and increased beta-cell mass only in male offspring. In support, Homeostatic Model Assessment for Insulin Resistance, the index of insulin resistance was elevated only in male but not in female offspring. Regardless, both male and female offspring exhibited a considerable increase in hepatic gene expression associated with inflammation and endoplasmic reticulum stress. Thus, gestational benzene exposure can predispose offspring to increased susceptibility to the metabolic imbalance in adulthood with differential sensitivity between sexes. [ABSTRACT FROM AUTHOR]

Background: Low benzene exposure leads to hematotoxicity, but we still lack sensitive early monitoring and early warning markers. Benzene is associated with inflammation, which is mainly mediated by cytokines network. However, until now few studies have conducted high-throughput detection of multi-cytokines to get a global view of cytokine changes and screen for markers of benzene-induced toxicity. We hypothesized that cytokine profiles mediate benzene-induced hematotoxicity. Methods: 228 subjects consisting of 114 low benzene exposed workers and 114 healthy controls were recruited at Research Center of Occupational Medicine, Peking University Third Hospital, Beijing. The serum concentrations of 27 cytokines were detected by cytokinomics array, urinary benzene series metabolites were measured by UPLC-MS/MS, and peripheral blood cell counts were observed by basic blood test. Results: Among 27 cytokines, IL-9 and MIP1-α were significantly lower, but IL-4, IL-10, IL-15, MCP-1, TNF-α and VEGF were significantly higher in benzene exposure group than controls. Urinary benzene metabolite S-phenylmercapturic acid (S-PMA) was significantly higher in benzene exposure group and had a negative linear relationship with WBC count. S-PMA was only significantly associated with IL-9, meanwhile IL-9, IL-15 and VEGF had a positive linear relationship with WBC count. The bootstrapping mediation models showed that the effect of S-PMA on WBC count was partially explained by IL-9 for 10.11%. Conclusion: This study suggests that exposure to benzene was associated with alternation of blood cell count and cytokine profiles in workers exposed to low levels of benzene, especially decreases of WBC count and IL-9. We also found IL-9 partially mediated the effect of low benzene exposure on WBC count, which may be a potential and promising early monitoring and early warning marker of benzene hematotoxicity.

This study aims to determine BTEX concentrations in the Metropolitan Region of Rio de Janeiro (MRRJ, Brazil) and evaluate potential health risks of benzene and ethylbenzene exposure based on the collected data, in 2015, the year before the Rio 2016 Olympic Games. Samples were collected and analyzed following method TO-15 (U.S.EPA). Toluene was the most abundant compound in all samples (mean concentration 16.72 ± 15.70 µg m−3). The average benzene concentration in ambient air (3.44 ± 3.14 µg m−3) was slightly lower than the yearly average "upper assessment threshold", 3.5 µg m−3, established by EU Directive 2008/50/EC. The calculated cancer risk values were > 1 × 10−6 for all samples, clearly indicating a potential cancer risk and the importance of fixed measurements by the monitoring stations to assess ambient air quality in the urban areas of the MRRJ. Calculated ratios for the BTEX species indicate that these compounds are predominantly emitted from vehicular sources with a contribution from industrial sources. [ABSTRACT FROM AUTHOR]

Background: Manufacture of paints using benzene in large quantities in the products they produce. Workers in the paint industry may face an increased risk of high health complications. The purpose of this study was to determine the levels of safe concentration of benzene for workers in the Paint Manufacturing Industry in Sidoarjo East Java, Indonesia. Methods: This research was conducted using a cross sectional method. The sample in this study were 24 respondents. The variables that became the data of this study included benzene concentration (C) time of daily exposure (tE), frequency of annual exposure (fE), duration of exposure (Dt), height (cm), weight (kg), age, respiration rate (BR), body surface area, weight of white rat, body surface of white rat, highest dose of toxin without effect on experimental animals (NOAEL), Km factor in animal (Animal Km), Km factor on workers (Human Km), safe limits for toxin doses for workers (SHD), and benzene concentrations in safe air for workers (C is safe). Data analysis in this study was carried out by using quantitative data analysis manually to determine the safe concentration of benzene for workers in the Paint Manufacturing Industry in Sidoarjo East Java, Indonesia. Results: Based on the results of measurements carried out, the concentration of benzene in the work environment of the Sidoarjo Paint Industry in the mixing solvent section is 2 ppm and in the packing section is 0.4 ppm, the safe concentration is 0.028 ppm. Conclusion: The recommended safe concentration of benzene exposure is 0.028 ppm. The safe concentration value exceeds the set value of 0.009 ppm daily for acute effects and 0.003 ppm daily for chronic effects, so control measures are needed to protect against the adverse effects of benzene on the health of workers. Control recommendations are to provide a good exhaust ventilation system at the paint manufacturing. [ABSTRACT FROM AUTHOR]

Background: Ubiquitously distributed benzene is a known hematotoxin. Increasing evidence has suggested that erythroid-related hematologic parameters may be sensitive to benzene exposure. Fat content, which is also closely associated with erythroid-related hematologic parameters, may affect the distribution and/or metabolism of benzene, and eventually benzene-induced toxicity.Methods: To explore the influence of benzene exposure, fat content, and their interactions on erythroid-related hematologic parameters, we recruited 1669 petrochemical workers and measured their urinary S-phenylmercapturic acid (SPMA) concentration and erythroid-related hematological parameters. Indices for fat content included body fat percentage (BF%), plasma total cholesterol (TC) and triglycerides (TG), and occurrence of fatty liver.Results: The dose-response curve revealed U-shaped nonlinear relationships of SPMA with hematocrit (HCT) and mean corpuscular hemoglobin concentration (MCHC) (P-overall < 0.001, and P-nonlinear < 0.015), as well as positive linear associations and r-shaped nonlinear relationships of continuous fat content indices with erythroid-related hematological parameters (P-overall ≤0.005). We also observed modification effects of fat content on the associations between benzene exposure and erythroid-related hematological parameters, with workers of lower or higher BF% and TG more sensitive to benzene-induced elevation of MCHC (Pinteraction = 0.021) and benzene-induced decrease of HCT (Pinteraction = 0.050), respectively. We also found that some erythroid-related hematologic parameters differed between subgroups of workers with different SPMA levels and fat content combination.Conclusions: Our study suggested that benzene exposure, fat content, and their interactions may affect erythroid-related hematological parameters in petrochemical workers in a complex manner that are worthy of further investigation. [ABSTRACT FROM AUTHOR]

Highlights • SPMA was confirmed as the best biomarker of benzene, even at very low levels of exposure. • Cigarette smoking was confirmed as an important confounding factor for the benzene biomarkers. • The GSTT1 but not GSTM1 genotype significantly modulates the urinary levels of SPMA. • Toluene exposure, even at low concentrations, inhibits benzene metabolism to SPMA. Abstract The aim of the study was to investigate the effect of various factors that modulate the metabolism of benzene, including smoking habits, metabolic genotype of GST and co-exposure to toluene, on the levels of three biomarkers, i.e. urinary benzene (UB), S-phenylmercapturic acid (SPMA) and t,t -muconic acid (t,t -MA), in 146 refinery workers exposed to low levels of air benzene (AB) in the range <1.5–529.2 μg/m3 (mean value 32.6 μg/m3). The study confirmed the validity of SPMA as a good biomarker of benzene exposure even at low levels of exposure. It was also confirmed that cigarette smoking is the main confounding factor when assessing biological monitoring data of occupational exposure to AB. Our data indicate that the GSTT1, but not the GSTM1 genotype, significantly increases the urinary levels of SPMA, even at low levels of exposure. It is not known, though, whether subjects with a GSTT1 "null" genotype may be more susceptible to the effects of benzene. Finally, environmental toluene appears to inhibit the metabolism of benzene to SPMA even at low concentrations, also resulting in an underestimation by SPMA levels of the actual exposure of workers to benzene. [ABSTRACT FROM AUTHOR]

Health risk characterization of exposure to benzene in service stations and petroleum refineries has been carried out in previous studies using guideline values set by various agencies. In this work, health risk was characterized with the exposure data as cumulative probability distribution (CPD) plots but using human epidemiological data. This was achieved by using lowest observable adverse effects levels (LOAEL) data plotted as cumulative probability lowest effects distribution (CPLED). The health risk due to benzene was characterized by using probabilistic methods of hazard quotient (HQ50/50 and HQ95/5), Monte-Carlo simulation (MCS) and overall risk probability (ORP). CPD relationships of adverse health effects relationships and exposure data were in terms of average daily dose (ADD) and lifetime average daily dose (LADD) for benzene. For service station environments HQ50/50 and HQ95/5 were in a range of 0.000071–0.055 and 0.0049–21, respectively. On the other hand, the risk estimated for petroleum refinery environments suggests higher risk with HQ50/50 and HQ95/5 values ranging from 0.0012 to 77 and 0.17 to 560, respectively. The results of Monte-Carlo risk probability (MRP) and ORP indicated that workers in petroleum refineries (MRP of 2.9–56% and ORP of 4.6–52% of the affected population) were at a higher risk of adverse health effects from exposure to benzene as compared to exposure to benzene in service station environments (MRP of 0.051 –3.4% and ORP of 0.35–2.7% affected population). The adverse effect risk probabilities estimated by using the Monte-Carlo simulation technique and the ORP method were found to be generally consistent.

Objectives The main aim of this study was to assess the biological uptake of benzene and polycyclic aromatic hydrocarbons (PAHs) for subjects exposed to fresh crude oil released at sea. Methods The study included 22 subjects participating in an 'oil-on-water' field trial in the North Sea. Over 2 consecutive days, there were six releases with two different types of fresh crude oils. Exposed subjects (n = 17) were either located in small, open-air boats downwind and close to the released oil (<50 m) or on the main deck of two large vessels further from the released oil (100–200 m). Subjects assumed to be unexposed (n = 5) were located indoors on the command bridge of either vessel. Full-shift personal benzene exposure was monitored with passive thermal desorption tubes (ATD-tubes) packed with Tenax TA and subsequent gas chromatographic analysis. Urine samples were collected before and after work-shift on both days and analyzed for urinary markers of benzene [(S-phenylmercapturic acid (SPMA)] and PAHs [1-hydroxypyrene (1-OH)]. Information about the use of personal protective equipment, smoking habits, location, work tasks, and length of work-shift were recorded by a questionnaire. Results Subjects located in the small boats downwind and close to the released oil were exposed to relatively high concentrations of benzene (arithmetic mean = 0.2 ppm, range 0.002–1.5 ppm) compared to the occupational exposure limits (OELs) for 8 h (1 ppm) and 12 h (0.6 ppm). Although respirators were available to all exposed subjects, SPMA was detected in post-shift urine (0.5–3.3 µmol mol−1) of five exposed subjects reporting not wearing respirators, all located in the small boats downwind and close to the released oil. For exposed subjects wearing respirators (n = 12), the post-shift urinary SPMA was below the detection limit (0.8 µmol mol−1) even when the benzene exposure exceeded the OELs. Urinary levels of PAH were within the reference range of what is considered as background levels (<0.4 µmol mol−1). Conclusions During the initial stages of a bulk oil spill at sea, when the evaporation of benzene is at its highest, it is important to use appropriate respirators to prevent biological uptake of benzene. [ABSTRACT FROM AUTHOR]

Exposure to benzene results in peripheral blood cell reduction, aplastic anemia, and leukemia. We previously observed that the lncRNA OBFC2A was upregulated significantly in benzene-exposed workers and correlated with reduced blood cell counts. However, the role of lncRNA OBFC2A in benzene hematotoxicity remains unclear. In this study, we discovered that lncRNA OBFC2A was regulated by oxidative stress and played roles in cell autophagy and apoptosis caused by the benzene metabolite 1,4-Benzoquinone (1,4-BQ) in vitro. Mechanistically, protein chip, RNA pull-down, and FISH colocalization uncovered that lncRNA OBFC2A directly bound to LAMP2, a regulator of chaperone-mediated autophagy (CMA), and upregulated its expression in 1,4-BQ-treated cells. LncRNA OBFC2A knockdown alleviated LAMP2 overexpression caused by 1,4-BQ, which confirmed their regulatory relationship. In conclusion, we demonstrate that lncRNA OBFC2A mediates 1,4-BQ-induced apoptosis and autophagy by interacting with LAMP2. LncRNA OBFC2A could serve as a biomarker for hematotoxicity caused by benzene. [Display omitted] • LncRNA OBFC2A was upregulated in benzene-exposed workers and in vitro. • LncRNA OBFC2A knockdown inhibited 1,4-BQ-induced apoptosis and autophagy. • LncRNA OBFC2A interacted with LAMP2 to mediate benzene hematotoxicity. [ABSTRACT FROM AUTHOR]

Objectives: Characterize personal exposure to airborne hydrocarbons, particularly carcinogenic benzene, during spill of two different fresh crude oils at sea. Methods: The study included 22 participants taking part in an «oil on water» field trial in the North Sea. Two types of fresh crude oils (light and heavy) were released six times over two consecutive days followed by different oil spill response methods. The participants were distributed on five boats; three open sampling boats (A, B, and C), one release ship (RS), and one oil recovery (OR) vessel. Assumed personal exposure was assessed a priori, assuming high exposure downwind and close to the oil slick (sampling boats), low exposure further downwind (100-200 m) and upwind from the oil slick (main deck of RS and OR vessel), and background exposure indoors (bridge of RS/OR vessel). Continuous measurements of total volatile organic compounds in isobutylene equivalents were performed with photoionization detectors placed in all five boats. Full-shift personal exposure to benzene, toluene, ethylbenzene, xylenes, naphthalene, and n-hexane was measured with passive thermal desorption tubes. Results: Personal measurements of benzene, averaged over the respective sample duration, on Day 1 showed that participants in the sampling boats (A, B, and C) located downwind and close to the oil slick were highest exposed (0.14-0.59 ppm), followed by participants on the RS main deck (0.02-0.10 ppm) and on the bridge (0.004-0.03 ppm). On Day 2, participants in sampling boat A had high benzene exposure (0.87-1.52 ppm) compared to participants in sampling boat B (0.01-0.02 ppm), on the ships (0.06-0.10 ppm), and on the bridge (0.004-0.01 ppm). Overall, the participants in the sampling boats had the highest exposure to all of the compounds measured. The light crude oil yielded a five times higher concentration of total volatile organic compounds in air in the sampling boats (max 510 ppm) than the heavy crude oil (max 100 ppm) but rapidly declined to <20 ppm within 24 min after release of oil, indicating short periods of exposure. Conclusions: The personal exposure to benzene downwind and close to the oil slick during spills of light crude oil was relatively high, with concentration levels approaching the occupational exposure limits for several participants. For bulk spill scenarios like in this study, cleanup should not be initiated the first 30-60 min to allow for evaporation, while appropriate personal protective equipment should be used in continuous spills when working downwind and close to the oil slick. [ABSTRACT FROM AUTHOR]

The objective of the current study was the development of a reliable modeling platform to calculate in real time the personal exposure and the associated health risk for filling station employees evaluating current environmental parameters (traffic, meteorological and amount of fuel traded) determined by the appropriate sensor network. A set of Artificial Neural Networks (ANNs) was developed to predict benzene exposure pattern for the filling station employees. Furthermore, a Physiology Based Pharmaco-Kinetic (PBPK) risk assessment model was developed in order to calculate the lifetime probability distribution of leukemia to the employees, fed by data obtained by the ANN model. Bayesian algorithm was involved in crucial points of both model sub compartments. The application was evaluated in two filling stations (one urban and one rural). Among several algorithms available for the development of the ANN exposure model, Bayesian regularization provided the best results and seemed to be a promising technique for prediction of the exposure pattern of that occupational population group. On assessing the estimated leukemia risk under the scope of providing a distribution curve based on the exposure levels and the different susceptibility of the population, the Bayesian algorithm was a prerequisite of the Monte Carlo approach, which is integrated in the PBPK-based risk model. In conclusion, the modeling system described herein is capable of exploiting the information collected by the environmental sensors in order to estimate in real time the personal exposure and the resulting health risk for employees of gasoline filling stations.

Benzene is a group I carcinogen determined by IARC. The prevalence of benzene in occupational and general environments increases the risk of acute myeloid leukemia (AML) among workers and childhood leukemia. However, the mechanism of hematotoxicity induced by benzene remains unclear. Recently, the gut microbiota has been regarded as a pivotal part of normal and malignant hematopoiesis. Therefore, in this study, we explored the function of gut microbiota in hematopoietic injury induced by benzene by 16S rRNA sequencing. We found that benzene exposure caused bone marrow damage, hematopoietic stem and progenitor cells (HSPCs) dysfunction, and peripheral blood cell reduction. Moreover, intestinal barrier damage and gut microbiota dysbiosis were also observed in benzene-exposed mice. Interestingly, two gut flora, Lachnospiraceae_NK4A136_group and unclassified_Muribaculaceae, were significantly up-regulated and associated with hematopoietic indicators, suggesting that gut-host crosstalk might mediate benzene hematotoxicity. Microbiota-derived metabolites, such as short-chain fatty acids (SCFAs), bile acids, and tryptophan metabolites, are the primary mediators of the gut-host crosstalk. Therefore, we conducted absolute quantitative metabolomics to investigate the impact of benzene exposure on these metabolites in mice. The results showed that the concentration of SCFA butyrate, t ryptophan metabolites kynurenine, and Indole-3-propionic acid (IPA) were significantly altered after benzene exposure. However, no difference was found in bile acids. Significant correlations were found between altered metabolites and hematopoietic indicators. We then investigated the flora that derived these metabolites. Lachnospiraceae_NK4A136_group and unclassified_Muribaculaceae were enriched in the butyrate metabolism and tryptophan metabolism pathways. Correlation analysis further suggested that unclassified_Muribaculaceae was positively associated with butyrate (r = 0.588, P < 0.05) and IPA (r = 0.59, P < 0.05). The above results demonstrated that unclassified_Muribaculaceae and microbiota-derived butyrate and IPA were involved in hematopoietic toxicity caused by benzene. This study provides insight into gut microbiota-derived metabolites-host crosstalk in benzene hematopoietic toxicity. [Display omitted] • Benzene exposure damaged hematopoiesis and intestinal barrier of mice. • Benzene exposure altered gut microbiota and their derived metabolites in mice. • Unclassified_muribaculaceae, butyrate, and IPA were involved in hematotoxicity. [ABSTRACT FROM AUTHOR]

Exposure to benzene causes damage to the hematopoietic system, but the mechanisms are still unclear. Competitive endogenous RNAs (ceRNAs) are the epigenetic regulatory axis of long non-coding RNA (lncRNA)-microRNA-mRNA, which are shown to play roles in benzene-induced hematotoxicity. Ferroptosis, a lipid peroxidation-dependent cell death, has been reported to be regulated by ceRNAs. We hypothesized that ceRNAs regulated ferroptosis to participate in benzene hematotoxicity. In this study, we observed that the expression of lncRNA TC (Lnc-TC) and CUL4B were increased, but miR-142-5p was decreased in benzene-exposed workers. Correlation analysis suggested that the ceRNAs had co-expression relationships, and were associated with blood cell counts. We further explored the role of ceRNA in vitro, and discovered that 1,4- benzoquinone (1,4-BQ) stimulated ferroptosis in AHH-1 cells by inhibiting the expression of GPX4 and SLC7A11 , which was partially relieved by knockdown of Lnc-TC and CUL4B. Finally, by interfering with Lnc-TC and miR-142-5p expression, we confirmed that Lnc-TC acted as a microRNA sponge to reduce the accessibility and inhibition of miR-142-5p to CUL4B , thus increasing the expression of CUL4B. In summary, Lnc-TC / miR-142-5p / CUL4B signaling axis promoted cell ferroptosis to participate in benzene hematotoxicity, and was a potential biomarker for risk screening and health surveillance of benzene-exposed workers. [Display omitted] • Benzene induced aberrant expression of Lnc-TC/miR-142-5p/CUL4B network. • Ferroptosis was involved in hematotoxicity of benzene. • Lnc-TC/miR-142-5p/CUL4B network mediated benzene-induced ferroptosis. • Lnc-TC acted as a sponge for miR-142-5p to increase CUL4B expression. [ABSTRACT FROM AUTHOR]

The near field/far field (NF/FF) model is a contaminant dispersion construct that permits making airborne contaminant exposure estimates for an individual located close to an emission source. In the present analysis, chemical emission involves a constant mass rate of chemical application to surfaces, denoted I (mg/min), and an exponentially decreasing rate of emission of the chemical from the surfaces with rate constant α (min-1). The time-dependent emission rate function is: G(t), mg/min = I -- I exp(-- at), where time t is in minutes. The exact time-dependent equations for the contaminant concentration in the NF and the FF are presented. These equations are used to revise a previous analysis of a study in which a penetrant liquid containing benzene was applied to parts on a work table in a test room. The previous analysis assumed that the benzene was applied as a bolus at the start of a 15-min use period, whereas the present analysis assumes the same total benzene mass was applied at a uniform rate over the 15-min use period, but with the same evaporation rate constant α. The new G(t) function leads to a lower 15-min time weighted average NF benzene concentration that better matches the experimental data. It is also shown that the exact equation for the NF concentration is well approximated by combining two well-mixed single-zone equations. The approximation method is mathematically simpler and obviates the need to derive the exact NF equation. [ABSTRACT FROM AUTHOR]

This study examined the health effects of benzene exposure among children from a flaring incident at the British Petroleum (BP) refinery in Texas City, Texas. A total of 899 children (benzene exposed, n = 641 and unexposed, n = 258), aged <17 years, were included. Hematological analysis showed that white blood cell (×103/µL) counts were significantly decreased in the exposed children compared with the unexposed children (7.1 ± 2.2 versus 7.6 ± 2.1, P = .001). Similarly, the hemoglobin (g/dL) levels were decreased significantly in the exposed group compared with the unexposed group (12.7 ± 1.3 vs 13.1 ± 1.5, P = .001). Conversely, platelet (×103/µL) counts were increased significantly in the exposed group compared with the unexposed group (318.6 ± 79.8 versus 266.9 ± 58.8, P = .001). Hepatic enzymes were also significantly elevated among exposed children compared with the unexposed children. These findings suggest that children exposed to benzene are at a higher risk of developing both hepatic and bone marrow–related disorders. [ABSTRACT FROM AUTHOR]

DNA damage and cellular repair capacity were studied in 18 male fuel tanker drivers and 13 male filling-station attendants exposed to low and very low concentrations of benzene, respectively, and compared to 20 males with no occupational exposure (controls). Exposure to airborne benzene was measured using passive personal samplers, and internal doses were assayed through the biomarkers t,t-muconic acid, S-phenylmercapturic acid and urinary benzene. DNA damage was evaluated using tail intensity (TI) determined by the comet assay in peripheral lymphocytes. Urinary 7-hydro-8-oxo-2'-deoxyguanosine (8-oxodG) was measured as a biomarker of oxidative damage. DNA repair kinetics were assessed using the comet assay in lymphocytes sampled 20 and 60 min post H2O2 exposure. Benzene exposure differed significantly between the drivers (median 246.3 µg/m3), attendants (median 13.8 µg/m3), and controls (median 4.1 µg/m3). There were no differences in TI and 8-oxodG among the three groups, or between smokers and non-smokers. DNA repair kinetics were similar among the drivers, attendants and controls, although the comet assay on H2O2-damaged lymphocytes after 60 min revealed significantly lower levels of TI only in drivers. The DNA repair process in smokers was similar to that observed in drivers. In conclusion, this study found no relationship between low levels of benzene exposure and DNA damage, although there was evidence that exposure interferes with DNA repair kinetics. The biological impact of this finding on the onset of genotoxic effects in exposed workers has still to be ascertained. Environ. Mol. Mutagen. 57:151-158, 2016. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

For the first time, hollow-fiber liquid-phase microextraction combined with high-performance liquid chromatography-ultraviolet was used to extract trans, trans-muconic acid, in urine samples of workers who had been exposed to benzene. The parameters affecting the metabolite extraction were optimized as follows: the volume of sample solution was 11 mL with pH 2, liquid membrane containing dihexyl ether as the supporter, 15% (w/v) of trioctylphosphine oxide as the carrier, the time of extraction was 120 minutes, and stirring rate was 500 rpm. Organic phase impregnated in the pores of a hollow fiber was extracted into 24 µL solution of 0.05 mol L-1 Na2CO3 located inside the lumen of the fiber. Under optimized conditions, a high enrichment factor of 153-182 folds, relative recovery of 83%-92%, and detection limit of 0.001 µg mL-1 were obtained. The method was successfully applied to the analysis of ttMA in real urine samples. [ABSTRACT FROM AUTHOR]

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The aim of this work was to evaluate the oxidative damage to nucleic acids in children (5–11 years) associated with exposure to environmental pollutants and tobacco smoke (ETS). For each subject, urinary sampling was done twice (evening and next morning) to measure by tandem LC–MS–MS such oxidated products of nucleic acids as 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodGuo), 8-oxo-7,8-dihydroguanosine (8-oxoGuo), and 8-oxo-7,8-dihydroguanine (8-oxoGua). Methyl tert- butyl ether (U-MTBE), benzene (U-Benz), and its metabolites ( t,t -muconic and S -phenylmercapturic acids, t,t -MA and S -PMA, respectively) were determined as biomarkers of exposure to air pollution, and cotinine as a biomarker of exposure to ETS. Biomarkers of exposure ( S -PMA and U-MTBE) and of DNA oxidation (8-oxodGuo) were dependent on the urbanization and industrialization levels and increased in the evening sample as compared to next morning ( p <0.05). In both evening and next morning samples, 8-oxodGuo and 8-oxoGuo correlated with each other ( r =0.596 and r =0.537, respectively, p <0.01) and with biomarkers of benzene exposure, particularly S -PMA ( r =0.59 and r =0.45 for 8-oxodGuo and r =0.411 and r =0.383 for 8-oxoGuo, p <0.01). No such correlations were observed for U-MTBE and cotinine. Multiple linear regression analyses showed that 8-oxodGuo was positively associated with S -PMA at both sampling times ( β =0.18 and β =0.14 for evening and next morning sampling, respectively; p <0.02) and weakly with U-MTBE ( β =0.07, p =0.020) only in the evening urines. These results suggest that the selected biomarkers of exposure to benzene, particularly S -PMA, are good tracers of exposure to complex mixtures of oxidative pollutants and that the associated oxidative damage to nucleic acids is detectable even at very low levels of exposure. [ABSTRACT FROM AUTHOR]

Volatile organic compounds (VOCs) are ubiquitous pollutants known to be present in both indoor and outdoor air arising from various sources. Indoor exposure has increasingly become a major cause of concern due to the effects that such pollutants can have on health. Benzene, along with toluene, is one of the main components of the VOC mixture and is a known carcinogen due to its genotoxic effects. The aim of this study was to test the feasibility of an in vitro model to study the short-term effects of exposure of lung cells to airborne benzene. We studied the effects of exposure on DNA and the production of reactive oxygen species (ROS) in A549 cells, exposed to various concentrations of benzene (0.03; 0.1; 0.3 ppm) in gaseous form using a custom designed cell exposure chamber. Results showed a concentration-dependent increase of DNA breaks and an increase of ROS production, confirming the feasibility of the experimental procedure and validating the model for further in vitro studies of exposure to other VOCs. [ABSTRACT FROM AUTHOR]

This study investigated the effect of polymorphic genes GSTT1, GSTM1, GSTA1, EHPX1, NQO1, CYP2E1, CYP1A and MPO on the urinary concentrations and ratio ( R ) of the benzene metabolites trans , trans -muconic acid ( t , t -MA) and S -phenyl mercapturic acid ( S -PMA) in 301 oil refinery workers. The metabolites’ concentrations are lower and R is higher (100.66) in non-smokers ( n = 184) than in smokers ( n = 117, R = 36.54). Non-smokers have lower S -PMA and a higher R in GSTT1 null genotypes than in positive, and a higher S -PMA and a lower R in GSTA1 wild type genotypes. In smokers the GSTT1 null genotype effect on both S -PMA and R is confirmed, and is also shown in GSTM1 null, but not in GSTA1 wild type genotypes. GSTT1 null polymorphism reduces the conjugation rate of benzene epoxide with GSH, and to a lesser extent also GSTTA1 mutant, GSTM1 null and NQO1 mutant genotypes. The activity of one GST is compensated by another in GSTM1 and GSTA1 defective subjects, but not in GSTT1 null genotypes, whose average S -PMA excretion is about 50% with respect to the positive ones, for the same benzene exposure. R showed to be a more sensitive marker for these effects than the metabolite levels. [ABSTRACT FROM AUTHOR]

Long-term exposure to benzene has been associated with several blood malignancies, including aplastic anemia, myeloproliferative neoplasms, and different leukemias. We present a case of primary myelofibrosis in a 59-year-old woman who worked as a cleaner at a car dealership and automobile mechanic shop. For 25 years, she used gasoline as a degreaser and solvent to clean engine parts, floors and work desks on a daily basis. She was referred by her primary care provider to the Occupational Health Unit of Barcelona to assess whether her illness was work-related. Review of her job history and working conditions revealed chronic exposure to benzene in the absence of adequate preventive measures. An association between benzene exposure and myeloproliferative disease was established, suspicious for an occupational disease. [ABSTRACT FROM AUTHOR]

Highlights: [•] Benzene designated as environmental and occupational carcinogen. [•] Benzene is hematotoxin and leukemogenic agent. [•] Secondary form of acute myeloid leukemia (AML) is a consequence of conventional therapeutic exposure for controlling the primary one. [•] Toxicokinetic studies of benzene can provide the information of physico-biochemical changes related to this secondary form of AML. [ABSTRACT FROM AUTHOR]

A community and personal exposure assessment was performed to evaluate the benzene concentrations on the St. Regis Mohawk Tribe (SRMT) reservation at Akwesasne. The reservation is divided by the USA-Canada border. Located to the west of the reservation is a large aluminum smelter that routinely emits approximately 29,000 pounds of benzene per year. The objective of the campaign was to determine the benzene, toluene, ethyl benzene, and xylenes (BTEX) concentrations in ambient air on the reservation and characterize the benzene sources. These emissions, given the prevailing winds, could impact the SRMT community and may be a significant source of benzene on the reservation. However, the reservation has approximately 15 gas stations, a casino, and a major roadway (State Route 37) transecting it. Prior work has shown that traffic was the predominant source of benzene, and the smelter was not a significant contributor to airborne benzene. To asses exposure across the reservation, BTEX samples were collected at nine locations distributed across the reservation using 6-L stainless steel silonite canisters for 24 h every 6th day between May 2007 and July 2008. In addition, personal sampling using miniature canisters was conducted for 20 subjects selected from workers in the following microenvironments: restaurants, gas filling stations, solid waste collection, day care centers, casinos, offices (smoking and non-smoking) as well as vehicle repair shops. The samples were concentrated using a cryogenic preconcentrator and analyzed by GC/MS/FID. Moderate seasonal variability in BTEX concentrations was observed at all the sampling locations with fall and winter having higher concentrations than summer and spring. The sampling locations near busy roads and intersections had the highest BTEX concentrations. The highest BTEX personal exposures were observed at the gas stations and at the repair shop. [ABSTRACT FROM AUTHOR]

Abstract: The aims of the study were to evaluate the feasibility of urinary trans, trans-muconic acid (u-t,t-MA) and urinary S-phenylmercapturic acid (u-SPMA) as markers of exposure to urban benzene pollution for biomonitoring studies performed on children and to investigate the impact that creatinine correction may have on the classification of children exposure status. U-t,t-MA, u-SPMA, u-cotinine, and u-creatinine levels were measured in urine samples of 396 Italian children (5–11years) living in three areas with different degrees of urbanisation (very, fairly and non-urban). The median u-SPMA levels significantly increased with increased urbanisation: non-urban (0.19μg/L; 0.22μg/g creatinine)

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