Heterogeneous Oxidation Products of Fine Particulate Isoprene Epoxydiol-Derived Methyltetrol Sulfates Increase Oxidative Stress and Inflammatory Gene Responses in Human Lung Cells.

Hydroxyl radical (·OH)-initiated oxidation of isoprene, the most abundant nonmethane hydrocarbon in the atmosphere, is responsible for substantial amounts of secondary organic aerosol (SOA) within ambient fine particles. Fine particulate 2-methyltetrol sulfate diastereoisomers (2-MTSs) are abundant SOA products formed via acid-catalyzed multiphase chemistry of isoprene-derived epoxydiols with inorganic sulfate aerosols under low-nitric oxide conditions. We recently demonstrated that heterogeneous ·OH oxidation of particulate 2-MTSs leads to the particle-phase formation of multifunctional organosulfates (OSs). However, it remains uncertain if atmospheric chemical aging of particulate 2-MTSs induces toxic effects within human lung cells. We show that inhibitory concentration-50 (IC50) values decreased from exposure to fine particulate 2-MTSs that were heterogeneously aged for 0 to 22 days by ·OH, indicating increased particulate toxicity in BEAS-2B lung cells. Lung cells further exhibited concentration-dependent modulation of oxidative stress- and inflammatory-related gene expression. Principal component analysis was carried out on the chemical mixtures and revealed positive correlations between exposure to aged multifunctional OSs and altered expression of targeted genes. Exposure to particulate 2-MTSs alone was associated with an altered expression of antireactive oxygen species (ROS)-related genes (NQO-1, SOD-2, and CAT) indicative of a response to ROS in the cells. Increased aging of particulate 2-MTSs by ·OH exposure was associated with an increased expression of glutathione pathway-related genes (GCLM and GCLC) and an anti-inflammatory gene (IL-10).

Acrylonitrile butadiene styrene microplastics aggravate the threat of decabromodiphenyl ethane to Eisenia fetida: Bioaccumulation, tissue damage, and transcriptional responses.

Little is known about how brominated flame retardants (NBFRs) and microplastics (MPs) co-pollution influences soil organisms. Here, we investigated the impacts of acrylonitrile butadiene styrene (ABS)-MPs in soil on the 28-d dynamic bioaccumulation, tissue damage, and transcriptional responses of decabromodiphenyl ethane (DBDPE) in Eisenia fetida by simulating different pollution scenarios (10 mg kg-1 DBDPE, 10 mg kg-1 DBDPE accompanied by 0.1 % ABS-MPs, and 10 mg kg-1 DBDPE accompanied by 0.1 % ABS-resin). The results show ABS resin did not influence DBDPE bioaccumulation or distribution, but ABS-MPs, particularly 74-187 µm size of MPs, prolonged DBDPE equilibrium time and significantly promoted DBDPE bioaccumulation in tissue (1.76-2.38 folds) and epidermis (2.72-3.34 folds). However, ABS-MPs and ABS-resin reduced DBDPE concentrations of intestines by 22.2-30.6 % and 37.3 %, respectively. DBDPE-MPs caused more serious epidermis and intestines damages than DBDPE. Additionally, compared to the control, DBDPE significantly up-regulated 1957 genes and down-regulated 2203 genes; meanwhile, DBDPE-MPs up-regulated 1475 genes and down-regulated 2231 genes. DBDPE and DBDPE-MPs both regulated lysosome, phagosome, and apoptosis as the top 3 enriched pathways, while DBDPE-MPs specifically regulated signaling pathways and compound metabolism. This study demonstrated that the presence of ABS-MPs aggravated the biotoxicity of DBDPE, providing scientific information for assessing the ecological risks of MPs and additives from e-waste in soil.

Levels, Distributions, and Potential Risks of Hexachlorobutadiene from Two Tetrachloroethylene Factories in China.

A systematic investigation was conducted on the emission of hexachlorobutadiene (HCBD) from two tetrachloroethylene factories that used the acetylene method (F1) and the tetrachloride transformation method (F2). The levels of HCBD in the air for F1 were found to be in the range of 1.46-1170 µg/m3, whereas F2 had levels in the range of 1.96-5530 µg/m3. Similarly, the levels of HCBD in the soil for F1 were found to be in the range from 42.2 to 140 µg/kg, whereas F2 had levels in the range from 4.13 to 2180 µg/kg. Samples obtained from the air, soil, and sludge in the reaction area of the tetrachloroethylene factories in China showed high levels of HCBD. The F1 method unintentionally produced more HCBD than the F2 method during tetrachloroethylene production, leading to greater harm. The results of the risk assessment suggested the presence of harmful health effects on workers in the workplace. The investigation findings highlight the need for improved management systems to ensure the safe production of tetrachloroethylene.

Aquatic toxicity of tire microplastics on marine and freshwater organisms: An in silico approach.

Tire wear particles are a notable source of tire microplastics (TMPs) in the environment. However, only a few reports have focused on the aquatic toxicity effects of composite TMPs and their additives and the mechanistic analysis at the microscopic level. Therefore, this paper study the toxic effects of tire microplastics and their additives on zebrafish based on theoretical chemical calculation method (Taguchi orthogonal experiment method, full factorial experimental design, molecular docking, and molecular dynamics computational technique). We designed five kinds of proportioning schemes of tire rubber polymers and additive components (64 groups in each). The compound toxicity effects of the tire rubber polymers and their additives on zebrafish were simulated and calculated. The simulation results indicated styrene butadiene rubber had the most significant toxic effect on zebrafish. Subsequently, taking the composition ratio scheme of styrene butadiene rubber with the lowest biotoxicity effect as an example, we analyzed the main effects, second-order interactions, and third-order interactions of styrene butadiene rubber polymer and its additive combination in terms of biotoxicity using the fixed effects model. The toxic effects (developmental toxicity, neurotoxicity, and reproductive toxicity) of styrene butadiene rubber on marine and freshwater organisms could be drastically alleviated by adjusting the ratio of rubber additives. The analysis of the interaction between amino acid residues and non-bonds during the docking process of styrene butadiene rubber and toxic receptors revealed the interaction mechanisms between the styrene butadiene rubber polymer and its additives and between the additive molecules. Hydrophobic interaction was found to be the key factor for the binding of styrene butadiene rubber additives to nonpolar amino acids in the receptor proteins. Our findings are expected to provide theoretical support for identifying and regulating the toxicity characteristics of rubber TMPs and to aid in proposing a strategy to alleviate the toxic effects on aquatic organisms.

Probabilistic human health risk assessment of 1,3-butadiene and styrene exposure using Monte Carlo simulation technique in the carpet production industry.

Chemicals containing Volatile Organic Compounds (VOCs) are commonly used in the machine carpet production. 1,3-butadiene and styrene are main components of the carpenter's glue used in carpet factories. Exposition to these chemicals can lead to a number of adverse health effects. This is the first study of the human health risk assessment due to inhalational exposure to 1,3-butadiene (BD) and styrene (ST) performed among workers in the carpet factories in Kashan city, Iran. The importance of the study was related with the fact of high popularity of carpet production in the South Asia countries. Inhalation exposure to BD and ST were measured based on the National Institute for Occupational Safety and Health (NIOSH) 1024 and 1501 methods, respectively. The cancerogenic risk (CR) and non-cancerogenic risk described as Hazard Quotient (HQ) values were calculated based on the United States Environmental Protection Agency (USEPA) method. The sensitivity and uncertainty analysis were performed by the Monte Carlo simulation (MCS) technique. The average concentration measured of BD and ST during work shifts of employees were 0.039 mg m-3 (0.017 ppm) and 12.108 mg m-3 (2.84 ppm), respectively. The mean ± SD value of estimated cancerogenic risk in inhalation exposure to BD and ST were equal to 5.13 × 10-3 ± 3.85 × 10-4 and 1.44 × 10-3 ± 2.36 × 10-4, respectively exceeding the acceptable risk level of 10-6 defined by USEPA. The average non-carcinogenic risk (HQ) values of BD and ST were equal to 8.50 × 100 and 5.13 × 100, respectively exceeding the acceptable risk level of 1. As the results of our studies exceeded both cancerogenic and non-carcinogenic risk values it indicates that adverse health effects due to inhalational exposure to BD and ST for workers in the machine carpet industry are very likely. To avoid negative health effects protective measures for employees in the factories should be introduced immediately and furher detailed research are recommended.

An updated lymphohematopoietic and bladder cancers risk evaluation for occupational and environmental exposures to 1,3-butadiene.

EPA designated 1,3-butadiene (BD) as a high priority chemical in December 2019 and is presently performing an evaluation under the Toxic Substances Control Act (TSCA). EPA's cancer dose-response assessment for BD was published in 2002 and was primarily based on a study on workers exposed to BD in the North American synthetic Styrene-Butadiene Rubber (SBR) Industry developed by the University of Alabama at Birmingham (UAB). EPA relied upon a Poisson regression of leukemia mortality data from this cohort (hereinafter referred to as the SBR study) to estimate the cancer potency of BD. At the time, the SBR cohort included more than 15,000 male workers that were followed up through 1991. The SBR cohort has undergone multiple updates over the past two decades. Most recently, Sathiakumar et al. (2021a, b) published an update, with 18 more years of follow up in addition to approximately 5,000 female workers and updated exposure concentration estimates. Recent EPA assessments (e.g., for ethylene oxide, USEPA 2016) based on epidemiological studies use Cox proportional hazards models because they offer better control of the effect of age in cancer development and are less restrictive than Poisson regression models. Here, we develop exposure-response models using standard Cox proportional hazards regression. We explore the relationship between six endpoints (all leukemia, lymphoid leukemia, myeloid leukemia, multiple myeloma, non-Hodgkin's lymphoma, and bladder cancer) and exposures to BD using the most recent exposure metrics and the most recent update of the SBR study. After adjusting for statistically significant covariates, an upper 95% confidence level on the cancer potency based on leukemia derived herein is 0.000086 per ppm, which is approximately 1,000-fold less than EPA's (2002) estimate of 0.08 per ppm and about 10-fold less than TCEQ's (2008) estimate of 0.0011 per ppm.

Use of biomarker data and metabolite relative potencies to support derivation of noncancer reference values based on the reproductive and developmental toxicity effects of 1,3-butadiene.

Subchronic and chronic reference values (RfVs) were derived for 1,3-butadiene (BD) based upon its ability to cause reproductive and developmental effects observed in laboratory mice and rats. Metabolism has been well-established as an important determinant of the toxicity of BD. A major challenge to human health risk assessment is presented by large quantitative species differences in the metabolism of BD, differences that should be accounted for when the rodent toxicity responses are extrapolated to humans. The methods of Fred et al. (2008)/Motwani and Törnqvist (2014) were extended and applied here to the noncancer risk assessment of using data-derived extrapolation factors to account for species differences in metabolism, as well as differences in cytotoxic potency of three BD metabolites. This approach made use of biomarker data (hemoglobin adducts) to quantify species differences in the internal doses of BD metabolites experienced in mice, rats and humans. Using these methods, the dose-response relationships in mice and rats exhibit improved concordance, and result in subchronic and chronic inhalation reference values of 29 and 10 ppm, respectively, for BD. Confidence in these reference values is considered high, based on high confidence in the key studies, medium-to-high confidence in the toxicity database, high confidence in the estimates of internal dose, and high confidence in the dose-response modeling.

Evaluation of Pulmonary Effects of 3-D Printer Emissions From Acrylonitrile Butadiene Styrene Using an Air-Liquid Interface Model of Primary Normal Human-Derived Bronchial Epithelial Cells.

This study investigated the inhalation toxicity of the emissions from 3-D printing with acrylonitrile butadiene styrene (ABS) filament using an air-liquid interface (ALI) in vitro model. Primary normal human-derived bronchial epithelial cells (NHBEs) were exposed to ABS filament emissions in an ALI for 4 hours. The mean and mode diameters of ABS emitted particles in the medium were 175 ± 24 and 153 ± 15 nm, respectively. The average particle deposition per surface area of the epithelium was 2.29 × 107 ± 1.47 × 107 particle/cm2, equivalent to an estimated average particle mass of 0.144 ± 0.042 µg/cm2. Results showed exposure of NHBEs to ABS emissions did not significantly affect epithelium integrity, ciliation, mucus production, nor induce cytotoxicity. At 24 hours after the exposure, significant increases in the pro-inflammatory markers IL-12p70, IL-13, IL-15, IFN-γ, TNF-α, IL-17A, VEGF, MCP-1, and MIP-1α were noted in the basolateral cell culture medium of ABS-exposed cells compared to non-exposed chamber control cells. Results obtained from this study correspond with those from our previous in vivo studies, indicating that the increase in inflammatory mediators occur without associated membrane damage. The combination of the exposure chamber and the ALI-based model is promising for assessing 3-D printer emission-induced toxicity.

Characterization of population variability of 1,3-butadiene derived protein adducts in humans and mice.

1,3-butadiene is a known human carcinogen and a chemical to which humans are exposed occupationally and through environmental pollution. Inhalation risk assessment of 1,3-butadiene was completed several decades ago before data on molecular biomarkers of exposure and effect have been reported from both human studies of workers and experimental studies in mice. To improve risk assessment of 1,3-butadiene, the quantitative characterization of uncertainty in estimations of inter-individual variability in cancer-related effects is needed. For this, we ought to take advantage of the availability of the data on 1,3-butadiene hemoglobin adducts, well established biomarkers of the internal dose of the reactive epoxides, from several large-scale human studies and from a study in a Collaborative Cross mouse population. We found that in humans, toxicokinetic uncertainty factor for 99th percentile of the population ranged from 3.27 to 7.9, depending on the hemoglobin adduct. For mice, these values ranged from less than 2 to 7.51, depending on the dose and the adduct. Quantitative estimated from this study can be used to reduce uncertainties in the parameter estimates used in the models to derive the inhalation unit risk, as well as to address possible differences in variability in 1,3-butadiene metabolism that may be dose-related.

Lung metabolome of 1,3-butadiene exposed Collaborative Cross mice reflects metabolic phenotype of human lung cancer.

1,3-Butadiene (BD) exposure is known to cause numerous adverse health effects, including cancer, in animals and humans. BD is metabolized to reactive epoxide intermediates, which are genotoxic, but it is not well know what other effects BD has on cellular metabolism. We examined the effects of exposure to BD on the mouse lung metabolome in the genetically heterogeneous collaborative cross outbred mouse model. Mice were exposed to 3 concentra-tions of BD for 10 days (2, 20, and 200 ppm), and lung tissues were analyzed using high-resolution mass spectrometry-based metabolomics. As compared to controls (0 ppm BD), BD had extensive effects on lung metabolism at all concentrations of exposure, including the lowest concentration of 2 ppm, as reflected by reprogramming of multiple metabolic pathways. Metabolites participating in glycolysis and the tricarboxylic acid cycle were elevated, with 8 out of 10 metabolites demonstrating a 2 to 8-fold increase, including the oncometabolite fumarate. Fatty acid levels, sphingosine, and sphinganine were decreased (2 to 8-fold), and fatty acyl-CoAs were significantly increased (16 to 31-fold), suggesting adjustments in lipid metabolism. Furthermore, metabolites involved in basic amino acid metabolism, steroid hormone metabolism, and nucleic acid metabolism were significantly altered. Overall, these changes mirror the metabolic alterations found in lung cancer cells, suggesting that very low doses of BD induce metabolic adaptations that may prevent or promote adverse health effects such as tumor formation.

Exploring the toxicity of the aged styrene-butadiene rubber microplastics to petroleum hydrocarbon-degrading bacteria under compound pollution system.

As a new pollutant, microplastics have increasingly drawn public attention to its toxic behavior in the environment. The aim was to investigate the effect of styrene-butadiene-rubber microplastics (mSBR) with different degrees of aging on petroleum hydrocarbon (PHC) degrading bacteria in an environment with simultaneously existing pollutants. A series of experiments were carried out to investigate the changes in the physical and chemical properties of mSBR with aging and to examine the influence of these changes on the inhibition of PHC-degrading bacteria by mSBR in the vicinity of coexisting pollutants. The results showed that in the early stage of ultraviolet aging (10d), the particle surface shows wrinkles, but the structure is intact. After reaching the late stage of aging (20d), nano-scale fragments were generated on the surface of mSBR, the average particle size decreased from 3.074 µm to 2.297 µm, and the zeta potential increased from - 25.1 mV to - 33.1 mV. The inhibitory effect of bacteria is greater. At the same time, these changes in the physicochemical properties increase the adsorption effect of Cd by 20%, and also improve the stability of mSBR in solution, whereby bacterial growth is inhibited by inhibiting the LPO activity and protein concentration of PHC degrading bacteria.

1,3-Butadiene, styrene and selected outcomes among synthetic rubber polymer workers: Updated exposure-response analyses.

OBJECTIVE: - To evaluate exposure-response relationships between 1,3-butadiene and styrene and selected diseases among synthetic rubber polymer workers. METHODS: - 21,087 workers (16,579 men; 4508 women) were followed from 1943 through 2009 to determine mortality outcomes. Cox regression models estimated rate ratios (RRs) and 95% confidence intervals (CIs) by quartile of cumulative exposure to butadiene or styrene and exposure-response trends for cancers of the bladder, lung, kidney, esophagus and pancreas, and for all nonmalignant respiratory disease (NMRD), chronic obstructive pulmonary disease (COPD) and pneumonia. RESULTS: - Bladder cancer RRs were 2.13 (95% CI = 1.03 to 4.41) and 1.64 (95% CI = 0.76 to 3.54) in the highest quartiles of cumulative exposure to butadiene and styrene, respectively, and exposure-response trends were positive for both monomers (butadiene, trend p = 0.001; styrene, trend p = 0.004). Further analyses indicated that the exposure-response effect of each monomer on bladder cancer was demonstrated clearly only in the subgroup with high cumulative exposure (at or above the median) to the other monomer. Lung cancer was not associated with either monomer among men. Among women, lung cancer RRs were above 1.0 in each quartile of cumulative exposure to each monomer, but exposure-response was not seen for either monomer. Male workers had COPD RRs slightly above 1.0 in each quartile of cumulative exposure to each monomer, but there was no evidence of exposure-response among the exposed. Monomer exposure was not consistently associated with COPD in women or with the other cancer outcomes. CONCLUSIONS: - This study found a positive exposure-response relationship between monomer exposures and bladder cancer. The independent effects of butadiene and styrene on this cancer could not be delineated. In some analyses, monomer exposure was associated with lung cancer in women and with COPD in men, but inconsistent exposure-response trends and divergent results by sex do not support a causal interpretation of the isolated positive associations.

Ethnic differences in excretion of butadiene-DNA adducts by current smokers.

1,3-Butadiene (BD) is a known human carcinogen used in the synthetic polymer industry and also found in cigarette smoke, automobile exhaust and wood burning smoke. BD is metabolically activated by cytochrome P450 monooxygenases (CYP) 2E1 and 2A6 to 3,4-epoxy-1-butene (EB), which can be detoxified by GST-catalyzed glutathione conjugation or hydrolysis. We have previously observed ethnic differences in urinary levels of EB-mercapturic acids in white, Japanese American and Native Hawaiian smokers. In the present study, similar analyses were extended to urinary BD-DNA adducts. BD-induced N7-(1-hydroxy-3-buten-2-yl) guanine (EB-GII) adducts were quantified in urine samples obtained from smokers and non-smokers belonging to three racial/ethnic groups: white, Japanese American and Native Hawaiian. After adjusting for sex, age, nicotine equivalents, body mass index and batch, we found that Japanese American smokers excreted significantly higher amounts of urinary EB-GII than whites [1.45 (95% confidence interval: 1.12-1.87) versus 0.68 (95% confidence interval: 0.52-0.85) fmol/ml urine, P = 4 × 10-5]. Levels of urinary EB-GII in Native Hawaiian smokers were not different from those in whites [0.67 (95% confidence interval: 0.51-0.84) fmol/ml urine, P = 0.938]. There were no racial/ethnic differences in urinary EB-GII adduct levels in non-smokers. Racial/ethnic differences in urinary EB-GII adduct levels in smokers could not be explained by GSTT1 gene deletion or CYP2A6 enzymatic activity. Urinary EB-GII adduct levels in smokers were significantly associated with concentrations of BD metabolite dihyroxybutyl mercapturic acid. Overall, our results reveal that urinary EB-GII adducts in smokers differ across racial/ethnic groups. Future studies are required to understand genetic and epigenetic factors that may be responsible for these differences.

An unexpected butadiene diolepoxide-mediated genotoxicity implies alternative mechanism for 1,3-butadiene carcinogenicity.

1,3-Butadiene (BD) is abundant in combustion products such as cigarette smoke. While BD has been classified as a known human carcinogen, a long-standing question is the identity of the ultimate carcinogenic metabolite in humans. We hypothesize that 3,4-epoxybutane-1,2-diol (EBD) may play a critical role in human carcinogenesis due to its high bioavailability. We utilized a differential toxicity assay for BD metabolites and newly synthesized EBD analogs in a series of isogenic chicken cells lacking specific DNA repair proteins to address the mode of action of BD genotoxicity and infer a mode of action. Surprisingly, as with the diepoxide 1,2:3,4-diepoxybutane (DEB), the monoepoxide EBD showed remarkable toxicity to cells deficient in Fanconi anemia (FANC) genes. This observation suggests that EBD may be transformed into a bifunctional metabolite and forms interstrand cross-links. EBD and its analog with a hydroxy substituent at C1 were found to be highly toxic to FANCD2-deficient chicken and human cells. The Results suggest that EBD may be transformed to a bifunctional epoxy aldehyde, perhaps by alcohol dehydrogenase, to which the observed FANC sensitivity could be attributed. The implications of this study are very important in considering mechanisms by which EBD may cause leukemia and lymphoma in humans exposed to BD.

Pulmonary and systemic toxicity in rats following inhalation exposure of 3-D printer emissions from acrylonitrile butadiene styrene (ABS) filament.

BACKGROUND: Fused filament fabrication 3-D printing with acrylonitrile butadiene styrene (ABS) filament emits ultrafine particulates (UFPs) and volatile organic compounds (VOCs). However, the toxicological implications of the emissions generated during 3-D printing have not been fully elucidated. AIM AND METHODS: The goal of this study was to investigate the in vivo toxicity of ABS-emissions from a commercial desktop 3-D printer. Male Sprague Dawley rats were exposed to a single concentration of ABS-emissions or air for 4 hours/day, 4 days/week for five exposure durations (1, 4, 8, 15, and 30 days). At 24 hours after the last exposure, rats were assessed for pulmonary injury, inflammation, and oxidative stress as well as systemic toxicity. RESULTS AND DISCUSSION: 3-D printing generated particulate with average particle mass concentration of 240 ± 90 µg/m³, with an average geometric mean particle mobility diameter of 85 nm (geometric standard deviation = 1.6). The number of macrophages increased significantly at day 15. In bronchoalveolar lavage, IFN-γ and IL-10 were significantly higher at days 1 and 4, with IL-10 levels reaching a peak at day 15 in ABS-exposed rats. Neither pulmonary oxidative stress responses nor histopathological changes of the lungs and nasal passages were found among the treatments. There was an increase in platelets and monocytes in the circulation at day 15. Several serum biomarkers of hepatic and kidney functions were significantly higher at day 1. CONCLUSIONS: At the current experimental conditions applied, it was concluded that the emissions from ABS filament caused minimal transient pulmonary and systemic toxicity.

Effect of elasticity on electrospun styrene-butadiene-styrene fibrous membrane cell culture behaviors.

In this study, elastic styrene-butadiene-styrene (SBS), non-elastic SBS and their blends at different ratios were electrospun into fibrous membranes and their cell biocompatibility was evaluated. The as-spun fibers showed an average fiber diameter of 2 µm, and the fibrous membranes had pore size of 8 ± 0.01 µm. The blending ratios of the elastic with non-elastic SBSs showed little effect on fibrous structure, but affected the mechanical properties. All SBS membrane showed no cytotoxicity on endothelial cells (ECs). ECs attached and proliferated on all the SBS fibrous membrane scaffolds regardless of their elasticity. ECs maintained their polygonal shape on the scaffolds and they tended to orient along the fiber length. The SBS fibrous samples with elastic:non-elastic SBS weight ratios of 1:1 and 2:3 showed better cell viability than that of elastic and non-elastic SBS.

Evaluation of pulmonary function and respiratory symptoms among workers exposed to 1,3-Butadiene in a petrochemical industry in Iran.

This study aimed to evaluate pulmonary function among workers exposed to 1,3-butadiene and was carried out in a petrochemical industry in Iran. The study participants consisted of fifty male workers with current respiratory exposure to 1,3-butadiene and fifty non-exposed workers as the control group. Exposure to 1,3-butadiene was measured according to the NIOSH 1024 method. Respiratory symptom histories were collected through the American Thoracic Society respiratory symptom questionnaire. Lung functions were evaluated using spirometry method. The results showed that exposed participants had significantly higher prevalence rates of all respiratory symptoms compared to the control group. Statistical tests demonstrated a significant difference between pulmonary function tests of exposed and non-exposed personnel. Ultimately, the results of the present study indicate that respiratory exposure to 1,3-butadiene can lead to negative effects on pulmonary functions.

A Review on Hexachloro-1,3-butadiene (HCBD): Sources, Occurrence, Toxicity and Transformation.

Hexachloro-1,3-butadiene (HCBD) is a persistent organic pollutant listed in Annex A and C of the Stockholm Convention. This review summarized the sources, occurrence, toxicity, and transformation of HCBD in the environment. HCBD had no natural sources, and anthropogenic sources made it frequently detected in environmental medium, generally at µg L- 1 and µg kg- 1 in water and soil (or organism) samples, respectively. HCBD posed reproductive, genetic, and potentially carcinogenic toxicity to organisms, threatening human health and the ecosystem. Upon biodegradation, photodegradation and physicochemical degradation processes, HCBD can be degraded to a different extent. Nevertheless, further studies should be focused on the potential emission sources and the impact of HCBD on human health and the environment. Additionally, exploring removal technologies based on advanced oxidation and reduction are recommended.

Acrylonitrile butadiene styrene (ABS) and polycarbonate (PC) filaments three-dimensional (3-D) printer emissions-induced cell toxicity.

During extrusion of some polymers, fused filament fabrication (FFF) 3-D printers emit billions of particles per minute and numerous organic compounds. The scope of this study was to evaluate FFF 3-D printer emission-induced toxicity in human small airway epithelial cells (SAEC). Emissions were generated from a commercially available 3-D printer inside a chamber, while operating for 1.5 h with acrylonitrile butadiene styrene (ABS) or polycarbonate (PC) filaments, and collected in cell culture medium. Characterization of the culture medium revealed that repeat print runs with an identical filament yield various amounts of particles and organic compounds. Mean particle sizes in cell culture medium were 201 ±â€¯18 nm and 202 ±â€¯8 nm for PC and ABS, respectively. At 24 h post-exposure, both PC and ABS emissions induced a dose dependent significant cytotoxicity, oxidative stress, apoptosis, necrosis, and production of pro-inflammatory cytokines and chemokines in SAEC. Though the emissions may not completely represent all possible exposure scenarios, this study indicate that the FFF could induce toxicological effects. Further studies are needed to quantify the detected chemicals in the emissions and their corresponding toxicological effects.

Synergistic effects of a cremophor EL drug delivery system and its U0126 cargo in an ex vivo model.

Neuroprotection has proven clinically unsuccessful in subarachnoid hemorrhage. We believe that this is because the major component in the early damage pathway, the vascular wall, has not been given the necessary focus. U0126 is a potent inhibitor of vascular phenotypical changes, exemplified by functional endothelin B (ETB) receptor upregulation. The current study aimed to determine the optimal dose of U0126 ex vivo and test the toxicology of this dose in vivo. To find the optimal dose and test a suitable in vivo delivery system, we applied an ex vivo model of blood flow cessation and investigated functional ETB receptor upregulation (using a specific agonist) as the primary endpoint. The secondary endpoint was depolarization-induced contractility assessed by 60 mM K+ stimuli. Furthermore, an in vivo toxicology study was performed on the optimal selected doses. U0126 (10 µM) had a strong effect on the prevention of functional ETB receptor contractility, combined with minimal effect on the depolarization-induced contractility. When cremophor EL was chosen for drug delivery, it had an inhibitory and additive effect (combined with U0126) on the ETB receptor contractility. Hence, 10 µM U0126 in 0.5% cremophor EL seems to be a dose that will be close to the maximal inhibition observed ex vivo on basilar arteries, without exhibiting side effects in the toxicology studies. U0126 and cremophor EL are well tolerated at doses that have effect on ETB receptor upregulation. Cremophor EL has an additional positive effect, preventing functional ETB receptor upregulation, making it suitable as a drug delivery system.