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1.
Article En | MEDLINE | ID: mdl-38541258

African American women in the United States have a high risk of adverse pregnancy outcomes. DNA methylation is a potential mechanism by which exposure to BTEX (benzene, toluene, ethylbenzene, and xylenes) may cause adverse pregnancy outcomes. Data are from the Maternal Stress Study, which recruited African American women in the second trimester of pregnancy from February 2009 to June 2010. DNA methylation was measured in archived DNA from venous blood collected in the second trimester. Trimester-specific exposure to airshed BTEX was estimated using maternal self-reported addresses and geospatial models of ambient air pollution developed as part of the Geospatial Determinants of Health Outcomes Consortium. Among the 64 women with exposure and outcome data available, 46 differentially methylated regions (DMRs) were associated with BTEX exposure (FDR adjusted p-value < 0.05) using a DMR-based epigenome-wide association study approach. Overall, 89% of DMRs consistently exhibited hypomethylation with increasing BTEX exposure. Biological pathway analysis identified 11 enriched pathways, with the top 3 involving gamma-aminobutyric acid receptor signaling, oxytocin in brain signaling, and the gustation pathway. These findings highlight the potential impact of BTEX on DNA methylation in pregnant women.


Air Pollutants , Benzene , Black or African American , DNA Methylation , Female , Humans , Pregnancy , Air Pollutants/toxicity , Air Pollutants/analysis , Benzene/analysis , Benzene/toxicity , Benzene Derivatives/analysis , Benzene Derivatives/toxicity , Black or African American/genetics , Environmental Monitoring , Toluene/toxicity , Toluene/analysis , Xylenes/toxicity , Xylenes/analysis
2.
Arch Toxicol ; 98(1): 327-334, 2024 Jan.
Article En | MEDLINE | ID: mdl-38059960

The kinetically-derived maximal dose (KMD) is defined as the maximal external dose at which kinetics are unchanged relative to lower doses, e.g., doses at which kinetic processes are not saturated. Toxicity produced at doses above the KMD can be qualitatively different from toxicity produced at lower doses. Here, we test the hypothesis that neoplastic lesions reported in the National Toxicology Program's (NTP) rodent cancer bioassay with ethylbenzene are a high-dose phenomenon secondary to saturation of elimination kinetics. To test this, we applied Bayesian modeling on kinetic data for ethylbenzene from rats and humans to estimate the Vmax and Km for the Michaelis-Menten equation that governs the elimination kinetics. Analysis of the Michaelis-Menten elimination curve generated from those Vmax and Km values indicated KMD ranges for venous ethylbenzene of 8-17 mg/L in rats and 10-18 mg/L in humans. Those venous concentrations are produced by inhalation concentrations of around 200 ppm ethylbenzene, which is well above typical human exposures. These KMD estimates support the hypothesis that neoplastic lesions seen in the NTP rodent bioassay occur secondary to saturation of ethylbenzene elimination pathways and are not relevant for human risk assessment. Thus, ethylbenzene does not pose a credible cancer risk to humans under foreseeable exposure conditions. Cancer risk assessments focused on protecting human health should avoid endpoint data from rodents exposed to ethylbenzene above the KMD range and future toxicological testing should focus on doses below the KMD range.


Benzene Derivatives , Neoplasms , Humans , Rats , Animals , Bayes Theorem , Benzene Derivatives/toxicity , Neoplasms/chemically induced , Risk Assessment
3.
Toxicol Ind Health ; 40(1-2): 33-40, 2024.
Article En | MEDLINE | ID: mdl-37936286

Benzene, toluene, ethyl benzene, and xylene (BTEX) are prevalent pollutants in shoe industry-related workplaces. The aim of this study was to assess exposure to BTEX and their carcinogenic and non-carcinogenic risks in shoe-industry-related workplaces. This study was carried out at different shoe manufactures, small shoe workshop units, shoe markets, and shoe stores in Tabriz, Iran in 2021. Personal inhalation exposure to BTEX was measured using the National Institute for Occupational Safety and Health (NIOSH) 1501 method. Carcinogenic and non-carcinogenic risks due to inhalation exposure to BTEX were estimated by United States Environmental Protection Agency (U.S. EPA) method based on Mont Carlo simulation. Results showed that the concentrations of benzene and toluene were higher than the threshold limit value (TLV) in both gluing and non-gluing units of shoe manufactures. The total carcinogenic risk (TCR) due to exposure to benzene and ethyl benzene was considerable in all shoe industry-related workplaces. Also, the hazard index (HI) as a non-carcinogenic index was higher than standard levels in all shoe industry-related workplaces. Therefore, shoe industry-related workers are at cancer and non-cancer risks due to exposure to BTEX. Prevention measures need to be implemented to reduce the concentration of BTEX in shoe industry-related workplaces.


Air Pollutants , Benzene , Humans , Benzene/toxicity , Benzene/analysis , Xylenes/toxicity , Xylenes/analysis , Toluene/toxicity , Toluene/analysis , Shoes , Environmental Monitoring/methods , Air Pollutants/analysis , Benzene Derivatives/toxicity , Benzene Derivatives/analysis , Carcinogens , Workplace , Carcinogenesis , Risk Assessment
4.
Ecotoxicol Environ Saf ; 263: 115239, 2023 Sep 15.
Article En | MEDLINE | ID: mdl-37441946

BACKGROUND: Benzene, toluene, ethylbenzene, and xylenes, collectively known as BTEX, are hazardous chemical mixtures, and their neurological health effects have not been thoroughly evaluated. We examined the association between BTEX exposure and neurological hospital admissions. METHODS: This was a multicity time-series study conducted in five major Taiwanese cities. Daily hospital admission records for diseases of the nervous system from January 1, 2016, to December 31, 2017, were collected from the National Health Insurance Research Database. Ambient BTEX and criteria pollutant concentrations and weather factors were collected from Photochemical Assessment Monitoring Stations. We applied a Poisson generalized additive model (GAM) and weighted quantile sum regression to calculate city-specific effect estimates for BTEX and conducted a random-effects meta-analysis to pool estimates. RESULTS: We recorded 68 neurological hospitalizations per day during the study period. The daily mean BTEX mixture concentrations were 22.5 µg/m3, ranging from 18.3 µg/m3 in Kaohsiung to 27.0 µg/m3 in Taichung, and toluene (13.6 µg/m3) and xylene (5.8 µg/m3) were the dominant chemicals. Neurological hospitalizations increased by an average of 1.6 % (95 % CI: 0.6-2.6 %) for every interquartile range (15.8 µg/m3) increase in BTEX at lag 0 estimated using a GAM model. A quartile increase in the weighted sum of BTEX exposure was associated with a 1.7 % (95 % CI: 0.6-2.8 %) increase in daily neurological hospitalizations. CONCLUSION: We found consistent acute adverse effects of BTEX on neurological hospitalizations in Taiwan, with toluene and xylene as the dominant chemicals. These findings aid the development of more targeted public health interventions.


Air Pollutants , Xylenes , Humans , Xylenes/toxicity , Xylenes/analysis , Taiwan , Benzene Derivatives/toxicity , Benzene Derivatives/analysis , Toluene/analysis , Benzene/analysis , Hospitalization , Air Pollutants/analysis , Environmental Monitoring
5.
J Environ Manage ; 325(Pt A): 116435, 2023 Jan 01.
Article En | MEDLINE | ID: mdl-36270122

Benzene (B), toluene (T), ethylbenzene (E), and xylenes (X) are petrochemicals vital in various industrial and commercial processing but identified as priority pollutants due to their high toxicity. The objective of this study was to investigate the toxicological nature of BTEX mixtures under controlled laboratory aquatic conditions using sulfur-oxidizing bacteria (SOB). Results from individual BTEX tests demonstrated that the order of toxicity among BTEX was X ≥ E > T > B. Comparisons of dose-effect curves for BTEX suggest that the biochemical mode of action of B in SOB was different from those of T, E, and X. Toxicological interactions of BTEX in mixtures were studied using concentration addition (CA), independent action (IA), and combination index (CI)-isobologram models. The CI model approximated the actual toxicity of BTEX mixtures better than the CA and IA models. In most cases, BTEX induced synergistic interactions in mixtures. However, in some B-containing mixtures, antagonism was observed at low effective levels. The effective level (fa)-CI plots and polygonograms illustrate that synergistic interactions of BTEX became stronger with an increase in effective levels. In addition, ternary and quaternary mixtures were found to provoke stronger synergism than binary mixtures. The present study suggests that the CI-isobologram model is a suitable means to evaluate diverse toxicological interactions of contaminants in mixtures.


Benzene Derivatives , Xylenes , Biodegradation, Environmental , Xylenes/toxicity , Benzene Derivatives/toxicity , Toluene/toxicity , Benzene/toxicity , Sulfur , Bacteria , Oxidation-Reduction
6.
Toxicol Mech Methods ; 33(3): 222-232, 2023 Mar.
Article En | MEDLINE | ID: mdl-36042574

The Health and environmental hazards of benzene and nitrobenzene (NB) derivatives have remained a topic of interest of researchers. In silico methods for prediction of toxicity of chemicals have proved their worth in accurate forecast of environmental as well as health toxicity and are strongly recommended by regulatory authorities. Two quantitative structure-toxicity relationship (QSTR) models explaining Scenedesmus obliquus toxicity trends among 39 benzene derivatives and Tetrahymena pyriformis toxicity of 103 NB and 392 benzene derivatives are developed using semiempirical quantum chemical parameters. The best constructed QSTR models have good fitting ability (R2 = 0.8053, 0.7591, and 0.8283) and robustness (Q2LOO = 0.7507, 0.7227, and 0.8194; Q2LMO = 0.7338, 0.7153, and 0.8172). The external predictivity of all the models are quite good (R2EXT = 0.8256, 0.9349, and 0.8698). Electronegativity, Cosmo volume, total energy, and molecular weight are responsible for the increase and decrease of toxicity of benzene derivatives against S. obliquus while electronegativity, electrophilicity index, the heat of formation, total energy, hydrophobicity, and cosmo volume are responsible for modulation of toxicity of NB and benzene derivatives toward T. pyriformis. These models fulfill the requirements of all the five OECD principles.


Benzene Derivatives , Tetrahymena pyriformis , Benzene Derivatives/chemistry , Benzene Derivatives/toxicity , Quantitative Structure-Activity Relationship , Nitrobenzenes
7.
Article En | MEDLINE | ID: mdl-36497672

BACKGROUND: Children in the affected area were exposed to large amounts of volatile organic compounds (VOCs) from the Hebei Spirit oil spill accident. OBJECTIVES: We investigated the lung function loss from the exposure to VOCs in a longitudinal panel of 224 children 1, 3, and 5 years after the VOC exposure event. METHODS: Atmospheric estimated concentration of total VOCs (TVOCs), benzene, toluene, ethylbenzene, and xylene for 4 days immediately after the accident were calculated for each village (n = 83) using a modeling technique. Forced expiratory volume in 1 s (FEV1) as an indicator of airway status was measured 1, 3, and 5 years after the exposure in 224 children 4~9 years of age at the exposure to the oil spill. Multiple linear regression and linear mixed models were used to evaluate the associations, with adjustment for smoking and second-hand smoke at home. RESULTS: Among the TVOCs (geometric mean: 1319.5 mg/m3·4 d), xylene (9.4), toluene (8.5), ethylbenzene (5.2), and benzene (2.0) were dominant in the order of air concentration level. In 224 children, percent predicted FEV1 (ppFEV1), adjusted for smoking and second-hand smoke at home, was 100.7% after 1 year, 96.2% after 3 years, and 94.6% after 5 years, and the loss over the period was significant (p < 0.0001). After 1 and 3 years, TVOCs, xylene, toluene, and ethylbenzene were significantly associated with ppFEV1. After 5 years, the associations were not significant. Throughout the 5 years' repeated measurements in the panel, TVOCs, xylene, toluene, and ethylbenzene were significantly associated with ppFEV1. CONCLUSIONS: Exposure to VOCs from the oil spill resulted in lung function loss among children, which remained significant up to 5 years after the exposure.


Air Pollutants , Petroleum , Tobacco Smoke Pollution , Volatile Organic Compounds , Child , Humans , Volatile Organic Compounds/toxicity , Volatile Organic Compounds/analysis , Benzene/analysis , Benzene Derivatives/toxicity , Benzene Derivatives/analysis , Xylenes/toxicity , Xylenes/analysis , Toluene/toxicity , Toluene/analysis , Lung , Air Pollutants/analysis , Environmental Monitoring/methods
8.
J Hazard Mater ; 437: 129343, 2022 09 05.
Article En | MEDLINE | ID: mdl-35716574

Benzene, toluene, ethylbenzene, and xylene (BTEX) can be released during extensive activities associated with the disposal of electronic waste (e-waste), which might pose deleterious health effects on workers. In this study, pollution profiles of BTEX in air and their urinary excretive profiles in occupational workers were investigated in a typical e-waste recycling industrial park. The results showed that the workers in the park were generally exposed to high levels of BTEX. The median levels of urinary metabolites were approximately 6-orders of magnitude higher than those of unmetabolized BTEX, indicating that pollutants efficiently metabolize at those occupational levels. The analytes presented differential profiles in external and internal exposure. Among the metabolites, significant correlation (p < 0.05) was observed between N-acetyl-S-benzyl-L-cysteine (S-BMA) concentration and atmospheric individual BTEX derived from the e-waste recycling area, suggesting that S-BMA is a potential marker for BTEX exposure to e-waste occupational workers. Notably, 95.2 % of all the workers showed a cumulative carcinogenic risk induced by BTEX exposure via inhalation, with 99.9 % of the carcinogenic risk distribution based on concentration of benzene metabolite (N-acetyl-S-(phenyl)-L-cysteine) exceeding 1.0E-6. This study holds potential in providing valuable inferences for the development of remediation strategies focusing on BTEX exposure reduction to protect workers' health at e-waste recycling industries.


Air Pollutants , Electronic Waste , Occupational Exposure , Air Pollutants/analysis , Benzene/metabolism , Benzene Derivatives/analysis , Benzene Derivatives/toxicity , Environmental Monitoring/methods , Humans , Occupational Exposure/analysis , Toluene/analysis , Toluene/toxicity , Xylenes/analysis
9.
Environ Res ; 212(Pt D): 113488, 2022 09.
Article En | MEDLINE | ID: mdl-35597292

BACKGROUND: Lung is one of the primary target organs of benzene, toluene, ethylbenzene, xylene, and styrene (BTEXS). Small airways dysfunction (SAD) might be a sensitive indicator of early chronic respiratory disease. Here, we explored the relationships between exposure to BTEXS and small airways function, and identified the priority control pollutants in BTEXS mixtures. METHODS: 635 petrochemical workers were recruited. Standard spirometry testing was conducted by physicians. The cumulative exposure dose (CED) of BTEXS for each worker was estimated. The peak expiratory flow (PEF), forced expiratory flow between 25 and 75% of forced vital capacity (FEF25∼75%), and the expiratory flow rate found at 25%, 50%, and 75% of the remaining exhaled vital capacity (MEF25%, MEF50%, and MEF75%) were measured. SAD was also evaluated based on measured parameters. The associations between exposure to BTEXS individuals or mixtures and small airways function were evaluated using generalized linear regression models (GLMs) and quantile g-computation models (qgcomp). Meanwhile, the weights of each homolog in the association were estimated. RESULTS: The median CED of BTEXS are 9.624, 19.306, 24.479, 28.210, and 46.781 mg/m3·years, respectively. A unit increase in ln-transformed styrene CED was associated with a decrease in FEF25∼75% and MEF50% based on GLMs. One quartile increased in BTEXS mixtures (ln-transformed) was significantly associated with a 0.325-standard deviation (SD) [95% confidence interval (CI): -0.464, -0.185] decline in FEF25∼75%, a 0.529-SD (95%CI: -0.691, -0.366) decline in MEF25%, a 0.176-SD (95%CI: -0.335, -0.017) decline in MEF75%, and increase in the risk of abnormal of SAD [risk ratios (95%CI): 1.520 (95%CI: 1.143, 2.020)]. Benzene and styrene were the major chemicals in BTEXS for predicting the overall risk of SAD. CONCLUSION: Our novel findings demonstrate the significant association between exposure to BTEXS mixture and small airways function decline and the potential roles of key homologs (benzene and styrene) in SAD.


Benzene , Xylenes , Benzene/toxicity , Benzene Derivatives/toxicity , Cross-Sectional Studies , Humans , Styrene/toxicity , Toluene/toxicity , Xylenes/toxicity
10.
Neurotoxicol Teratol ; 91: 107076, 2022.
Article En | MEDLINE | ID: mdl-35167944

Environmental exposure to toxicants is a major health issue and a leading risk factor for premature mortality worldwide, including environmental exposures to volatile organic compounds (VOCs), specifically Benzene, Toluene, Ethylbenzene, and Xylene (BTEX). While exposure to these compounds individually has shown behavioral and neurochemical effects, this investigation examined the impact of exposure to combined BTEX using a preclinical model. Male Swiss Webster mice were exposed to BTEX vapors designed to approximate environmental levels in urban communities. Animals were exposed to one of four treatment conditions: a 0-ppm (air control), two BTEX groups representing levels of environmental-like exposure, and a fourth group modeling occupational-like exposure. These exposures were conducted in 1.5-h sessions, 2 sessions/day, 5 days/week, for 3 weeks. Effects on coordination (i.e., rotarod and inverted screen test), learning and memory (i.e., Y-maze), and locomotor behavior (i.e., movement during exposure) were assessed during and after exposure. Monoamine levels in the medial prefrontal cortex and nucleus accumbens were assessed immediately following exposure. Effects of BTEX exposure were found on the variance of locomotor activity but not in other behavioral or neurochemical assessments. These results indicate that the combination of inhaled BTEX at environmentally representative concentrations has demonstrable, albeit subtle, effects on behavior.


Air Pollutants , Xylenes , Animals , Benzene/analysis , Benzene/toxicity , Benzene Derivatives/analysis , Benzene Derivatives/toxicity , Male , Mice , Toluene/toxicity , Xylenes/analysis , Xylenes/toxicity
11.
Environ Res ; 209: 112810, 2022 06.
Article En | MEDLINE | ID: mdl-35101395

BACKGROUND: Benzene, Toluene, Ethylbenzene, and Xylenes (BTEXs) are a group of aromatic air pollutants from fossil fuels. There is no research on associations of the BTEXs mixture with telomere length (TL), a marker of cellular aging, in the general population. METHODS: We analyzed a subsample of 549 US adults aged 20-59 years from the National Health and Nutrition Examination Survey 1999-2000. BTEXs samples were collected by passive exposure badges worn by participants for 48-72 h. Levels of BTEXs were measured with gas chromatography/mass spectrometry. Leukocyte TL was measured with qPCR. We used Bayesian Kernel Machine Regression (BKMR) to examine the effect of the BTEXs mixture on TL adjusting for potential confounders. Analyses were stratified by tobacco smoking status (serum cotinine≥10 ng/mL vs. <10 ng/mL). RESULTS: Levels of personal exposure to BTEXs were detectable in most participants and were relatively higher in the 150 smokers than in the 399 nonsmokers. The BTEXs were moderately or strongly intercorrelated (0.5 < r ≤ 0.9, P < 0.05). All chemicals had weak, inverse correlations with TL (-0.1 0.05). In BKMR models among the nonsmokers, the BTEXs mixture was significantly inversely associated with TL at a low range of the BTEXs (20th-65th percentile) but was not associated with TL at a higher range (>65th percentile). Also, we found a U-shape association of benzene and a positive association of ethylbenzene with TL independent of other BTEXs. Among smokers, neither the BTEXs mixture nor any individual BTEXs were significantly associated with TL. CONCLUSION: Within a low-to-middle range, exposure to the BTEXs mixture may be associated with shorter telomere length in the general nonsmoking population.


Benzene , Xylenes , Adult , Bayes Theorem , Benzene/analysis , Benzene/toxicity , Benzene Derivatives/toxicity , Cross-Sectional Studies , Humans , Middle Aged , Nutrition Surveys , Telomere , Toluene/analysis , Xylenes/analysis , Xylenes/toxicity , Young Adult
12.
Article En | MEDLINE | ID: mdl-35055545

The aim of this study is to investigate the concentration of Benzene, Toluene, Ethylbenzene, and Xylene (BTEX) compounds in the indoor air of residential-commercial complexes and to compare it with other residential buildings (control) as well as to assess the carcinogenicity and non-carcinogenicity risk of these pollutants. BTEX concentration was investigated in the indoor air of 30 ground floor restaurants, 30 upper residential units of the complexes, 20 adjacent residential units (control), and their corridors. The mean BTEX concentration measured in the upper residential units was reported higher than in the control residential units, though they were not significantly different. The lifetime cancer risk (LTCR) value calculated for benzene in the upper residential units was lower than 10-4 and higher than 10-6 across all ages, indicating a carcinogenicity risk. Furthermore, the mean hazard quotient (HQ) for all compounds was obtained lower than 1, suggesting no concern about the non-carcinogenicity risk of these compounds in the studied region. Nevertheless, considering the sources of benzene production in the indoor air as well as the carcinogenicity of these pollutants and the risk they pose in human health, application towards the reduction of the sources and concentration of benzene in the indoor air are necessary.


Air Pollutants , Xylenes , Air Pollutants/analysis , Air Pollutants/toxicity , Benzene/analysis , Benzene/toxicity , Benzene Derivatives/analysis , Benzene Derivatives/toxicity , Environmental Monitoring , Humans , Iran/epidemiology , Toluene/analysis , Toluene/toxicity , Xylenes/analysis
13.
Environ Res ; 203: 111725, 2022 01.
Article En | MEDLINE | ID: mdl-34302825

Children are highly susceptible to environmental contaminants as their physiology and some metabolic pathways differ from adults. The present cross-sectional study aimed to assess whether exposure to benzene, toluene, ethylbenzene, o,p-xylene, and m-xylene (BTEX) affects oxidative DNA damage in street children using a biomonitoring approach. Thirty-five boys (7-13 years of age), exposed by working at a busy intersection, and 25 unexposed boys of similar age and living in the neighborhood near the busy intersection were recruited. Urinary un-metabolized BTEX levels were quantified by a headspace gas chromatography-mass spectrometry (GC-MS). Urinary malonaldehyde (MDA) was measured with spectrophotometry. Sociodemographic and lifestyle conditions information was collected by interviews using administered questionnaires. Exposed subjects provided urine before (BE) and after work exposure (AE), while unexposed boys gave a single morning sample. Urinary BTEX concentrations in BE samples were similar to unexposed. Concentrations in AE samples were 2.36-fold higher than observed in BE samples (p < 0.05) and higher than those in the unexposed group (p < 0.05). In addition, urinary MDA levels in AE samples were 3.2 and 3.07-times higher than in BE samples and in the unexposed group (p < 0.05). Environmental tobacco smoke (ETS) increased urinary BTEX and MDA levels in both groups. Our findings confirm that street children working at busy intersections are significantly exposed to BTEX, which is associated with oxidative stress. Implementing protective measures is crucial to reduce exposure and to improve health outcomes in this group.


Air Pollutants , Homeless Youth , Adult , Air Pollutants/analysis , Benzene/analysis , Benzene/toxicity , Benzene Derivatives/analysis , Benzene Derivatives/toxicity , Biomarkers , Child , Cross-Sectional Studies , Environmental Monitoring , Humans , Male , Oxidative Stress , Toluene/analysis
15.
Huan Jing Ke Xue ; 42(11): 5210-5219, 2021 Nov 08.
Article Zh | MEDLINE | ID: mdl-34708960

Real-time BTEX(including benzene, toluene, ethylbenzene, m-, p-, and o-xylenes) were measured continuously in Tianjin urban site in July 2019 and January 2020 using a Syntech Spectras GC955 analyzer. The BTEX concentration levels, composition, and evolutionary mechanisms during typical pollution episodes were investigated. The potential sources of BTEX were analyzed qualitatively using the diagnostic ratios method. Finally, the BTEX health risk was evaluated by using the human exposure analysis and evaluation method according to US EPA. The averaged total mixing ratio of BTEX were 1.32×10-9 and 4.83×10-9 during ozone pollution and haze episodes, respectively. Benzene was the most abundant species, followed by toluene. The mixing ratio of BTEX was largely affected by short southwestern distance transportation in January, while local emissions in July. In addition, the BTEX mixing ratio depended on the influence of temperature and relative humidity(RH) in July, while the concentration was more sensitive to changes in RH when the temperature was low in January. Diagnostic ratios and source implications suggested that the BTEX was affected mainly by biomass/biofuel/coal burning during haze episodes. The traffic related emissions also had an impact except for the influence of biomass/biofuel/coal burning in July. The averaged hazard quotient(HQ) values were 0.072 and 0.29 during ozone pollution and haze episodes, respectively, which were in the upper safety range limit recommended by the US EPA. The carcinogenic risk posed by benzene in both cleaning and pollution processes was higher than the safety threshold set by the US EPA, which should be monitored carefully.


Air Pollutants , Air Pollutants/analysis , Air Pollutants/toxicity , Benzene/analysis , Benzene/toxicity , Benzene Derivatives/analysis , Benzene Derivatives/toxicity , Environmental Monitoring , Humans , Risk Assessment , Toluene/analysis , Toluene/toxicity , Xylenes
16.
Int J Mol Sci ; 22(14)2021 Jul 17.
Article En | MEDLINE | ID: mdl-34299276

1-cyclohexyl-x-methoxybenzene is a novel psychoactive substance (NPS), first discovered in Europe in 2012 as unknown racemic mixture of its three stereoisomers: ortho, meta and para. Each of these has structural similarities with the analgesic tramadol and the dissociative anesthetic phencyclidine. In light of these structural analogies, and based on the fact that both tramadol and phencyclidine are substances that cause toxic effects in humans, the aim of this study was to investigate the in vitro and in vivo pharmacodynamic profile of these molecules, and to compare them with those caused by tramadol and phencyclidine. In vitro studies demonstrated that tramadol, ortho, meta and para were inactive at mu, kappa and delta opioid receptors. Systemic administration of the three stereoisomers impairs sensorimotor responses, modulates spontaneous motor activity, induces modest analgesia, and alters thermoregulation and cardiorespiratory responses in the mouse in some cases, with a similar profile to that of tramadol and phencyclidine. Naloxone partially prevents only the visual sensorimotor impairments caused by three stereoisomers, without preventing other effects. The present data show that 1-cyclohexyl-x-methoxybenzene derivatives cause pharmaco-toxicological effects by activating both opioid and non-opioid mechanisms and suggest that their use could potentially lead to abuse and bodily harm.


Analgesics, Opioid/toxicity , Anisoles/toxicity , Benzene Derivatives/toxicity , Hallucinogens/toxicity , Phencyclidine/toxicity , Psychotropic Drugs/toxicity , Receptors, Opioid/metabolism , Tramadol/toxicity , Analgesics, Opioid/chemistry , Animals , Anisoles/chemistry , Benzene Derivatives/chemistry , Cells, Cultured , Cricetinae , Hallucinogens/chemistry , In Vitro Techniques , Male , Mice , Mice, Inbred ICR , Models, Animal , Phencyclidine/chemistry , Psychotropic Drugs/chemistry , Tramadol/chemistry
18.
Neurotoxicology ; 84: 96-104, 2021 05.
Article En | MEDLINE | ID: mdl-33745965

Thyroid hormones (THs) are essential for normal vertebrate development and diverse environmental chemicals are hypothesized to cause developmental toxicity by disrupting TH-mediated signaling. The larval zebrafish (Danio rerio) is an emerging in vivo model of developmental TH disruption; however, the effects of TR antagonism have not yet been studied in zebrafish. NH3, generally considered a potent and specific thyroid hormone receptor (TR) antagonist, has been used in rodents and Xenopus laevis to characterize phenotypes of TR antagonism. The objective of this study is to determine the effects of NH3 on endpoints previously determined to be TH-sensitive in larval zebrafish, specifically teratology and mortality, photomotor behavior, and mRNA expression of TH signaling genes. Zebrafish embryos were exposed to NH3 via static waterborne exposure at concentrations ranging from 0.001 to 10 µM beginning at 6 h post-fertilization (hpf) through 5 days post fertilization (dpf). Significant mortality and teratogenesis was observed at 3, 4, and 5 dpf in zebrafish exposed to NH3 at 10 µM. At concentrations that did not cause significant mortality, NH3 did not exert a consistent antagonistic effect on photomotor behavior assays or mRNA expression when administered alone or in the presence of exogenous T4. Rather, depending on the NH3 concentration and larval age NH3 decreased or increased swimming triggered by transition from light to dark. Similarly, inconsistent antagonistic and agonistic effects on mRNA expression of TH signaling genes were noted following treatment with NH3 alone. NH3 did inhibit T4 (30 nM)-induced gene expression; however, this was only consistently observed at a concentration of NH3 (10 µM) that also caused significant mortality. Collectively, these results suggest that NH3 does not act solely as a TR antagonist in larval zebrafish, but instead exhibits complex modulatory effects on TR activity. These data support the hypothesis that NH3 is a selective thyroid hormone receptor modulator. Further studies of NH3 interactions with the zebrafish thyroid hormone receptor are required to characterize the activity of NH3 in target tissues of the larval zebrafish at the molecular level, highlighting the importance of characterizing NH3 effects in specific models of TH-disruption to better interpret its actions in mechanistic screens of environmental chemicals for TH action.


Benzene Derivatives/pharmacology , Larva/drug effects , Locomotion/drug effects , Receptors, Thyroid Hormone/agonists , Receptors, Thyroid Hormone/antagonists & inhibitors , Animals , Benzene Derivatives/toxicity , Dose-Response Relationship, Drug , Larva/metabolism , Locomotion/physiology , Receptors, Thyroid Hormone/metabolism , Swimming/physiology , Teratogenesis/drug effects , Teratogenesis/physiology , Thyroxine/pharmacology , Zebrafish
19.
Article En | MEDLINE | ID: mdl-33671888

Tens of millions of individuals go to gasoline stations on a daily basis in the United States. One of the constituents of gasoline is benzene, a Group 1 carcinogen that has been strongly linked to both occupational and non-occupational leukemias. While benzene content in gasoline is federally regulated, there is approximately a thirty-year data gap in United States research on benzene exposures from pumping gasoline. Using a novel self-sampling protocol with whole air canisters, we conducted a gasoline pumping exposure assessment for benzene, toluene, ethylbenzene, and xylene (BTEX) on Baltimore, MD consumers. Geometric mean exposures (geometric standard deviations) were 3.2 (2.7) ppb,9.5 (3.5) ppb, 2.0 (2.8) ppb, and 7.3 (3.0) ppb, respectively, on 32 samples. Using the benzene exposures, we conducted consumer and occupational probabilistic risk assessments and contextualized the risk with ambient benzene exposure risk. We found that the consumer scenarios did not approach the 1:1,000,000 excess risk management threshold and that the occupational scenario did not exceed the 1:10,000 excess risk management threshold. Further, in all Monte Carlo trials, the ambient risk from benzene exposure exceeded that of pumping risk for consumers, but that in approximately 30% of occupational trials, the pumping risk exceeded the ambient risk.


Neoplasms , Occupational Exposure , Baltimore , Benzene/analysis , Benzene/toxicity , Benzene Derivatives/analysis , Benzene Derivatives/toxicity , Gasoline/analysis , Humans , Occupational Exposure/analysis , Toluene/analysis , Toluene/toxicity , United States , Xylenes/analysis
20.
Nat Commun ; 12(1): 812, 2021 02 05.
Article En | MEDLINE | ID: mdl-33547279

Carbon dots (CDs) are photoluminescent nanomaterials with wide-ranging applications. Despite their photoactivity, it remains unknown whether CDs degrade under illumination and whether such photodegradation poses any cytotoxic effects. Here, we show laboratory-synthesized CDs irradiated with light degrade into molecules that are toxic to both normal (HEK-293) and cancerous (HeLa and HepG2) human cells. Eight days of irradiation photolyzes 28.6-59.8% of the CDs to <3 kilo Dalton molecules, 1431 of which are detected by high-throughput, non-target high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Molecular network and community analysis further reveal 499 cytotoxicity-related molecules, 212 of which contain polyethylene glycol, glucose, or benzene-related structures. Photo-induced production of hydroxyl and alkyl radicals play important roles in CD degradation as affected by temperature, pH, light intensity and wavelength. Commercial CDs show similar photodegraded products and cytotoxicity profiles, demonstrating that photodegradation-induced cytotoxicity is likely common to CDs regardless of their chemical composition. Our results highlight the importance of light in cytocompatibility studies of CDs.


Carbon/toxicity , Cytotoxins/toxicity , Quantum Dots/toxicity , Benzene Derivatives/chemistry , Benzene Derivatives/toxicity , Carbon/chemistry , Carbon/radiation effects , Cell Survival/drug effects , Cytotoxins/chemistry , Glucose/chemistry , Glucose/toxicity , HEK293 Cells , HeLa Cells , Humans , Hydrogen-Ion Concentration , Hydroxyl Radical/chemistry , Hydroxyl Radical/toxicity , Kinetics , Light , Photolysis , Polyethylene Glycols/chemistry , Polyethylene Glycols/toxicity , Quantum Dots/chemistry , Quantum Dots/radiation effects , Temperature
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