Sociodemographic inequities in the burden of carcinogenic industrial air emissions in the United States.

BACKGROUND: Industrial facilities are not located uniformly across communities in the United States, but how the burden of exposure to carcinogenic air emissions may vary across population characteristics is unclear. We evaluated differences in carcinogenic industrial pollution among major sociodemographic groups in the United States and Puerto Rico. METHODS: We evaluated cross-sectional associations of population characteristics including race and ethnicity, educational attainment, and poverty at the census tract level with point-source industrial emissions of 21 known human carcinogens using regulatory data from the US Environmental Protection Agency. Odds ratios and 95% confidence intervals comparing the highest emissions (tertile or quintile) to the referent group (zero emissions [ie, nonexposed]) for all sociodemographic characteristics were estimated using multinomial, population density-adjusted logistic regression models. RESULTS: In 2018, approximately 7.4 million people lived in census tracts with nearly 12 million pounds of carcinogenic air releases. The odds of tracts having the greatest burden of benzene, 1,3-butadiene, ethylene oxide, formaldehyde, trichloroethylene, and nickel emissions compared with nonexposed were 10%-20% higher for African American populations, whereas White populations were up to 18% less likely to live in tracts with the highest emissions. Among Hispanic and Latino populations, odds were 16%-21% higher for benzene, 1,3-butadiene, and ethylene oxide. Populations experiencing poverty or with less than high school education were associated with up to 51% higher burden, irrespective of race and ethnicity. CONCLUSIONS: Carcinogenic industrial emissions disproportionately impact African American and Hispanic and Latino populations and people with limited education or experiencing poverty thus representing a source of pollution that may contribute to observed cancer disparities.

1,3-Butadiene, styrene and lymphohaematopoietic cancers among North American synthetic rubber polymer workers: exposure-response analyses.

OBJECTIVE: To evaluate exposure-response between 1,3-butadiene, styrene and lymphohaematopoietic cancers in an updated cohort of workers at six North American plants that made synthetic rubber polymers. METHODS: Employees were followed from 1943 through 2009 to determine mortality outcomes. Cox regression analyses estimated rate ratios (RRs) and 95% CIs by quartile of cumulative exposure to butadiene or styrene, measured in parts per million-years (ppm-years), and exposure-response trends for all leukaemia, lymphoid leukaemia, myeloid leukaemia, acute myeloid leukaemia, non-Hodgkin's lymphoma (NHL), multiple myeloma and all B-cell malignancies. RESULTS: Among 21 087 workers, adjusted RRs for butadiene and all leukaemia (132 deaths) rose with increasing exposure, with an RR of 2.53 (95% CI 1.37 to 4.67) in the highest exposure quartile (≥363.64 ppm-years), and the exposure-response trend was statistically significant for all leukaemia (p=0.014) and for lymphoid leukaemia (52 deaths, p=0.007). Styrene exposure-response trends for all leukaemia and lymphoid leukaemia were less consistent than those for butadiene. Cumulative exposures to butadiene and styrene were not associated consistently with myeloid leukaemias or the B-cell malignancies, NHL and multiple myeloma. CONCLUSIONS: We confirmed a positive exposure-response relationship between butadiene and all leukaemia among workers, most of whom had coexposure to styrene. Results supported an association between butadiene and lymphoid leukaemia, but not myeloid leukaemia, and provided little evidence of any association of butadiene or styrene exposures with major subtypes of B-cell malignancies other than lymphoid leukaemia, including NHL and multiple myeloma.

Integrated QSAR and Adverse Outcome Pathway Analysis of Chemicals Released on 3D Printing Using Acrylonitrile Butadiene Styrene.

Additive manufacturing commonly known as 3D printing has numerous applications in several domains including material and biomedical technologies and has emerged as a tool of capabilities by providing fast, highly customized, and cost-effective solutions. However, the impact of the printing materials and chemicals present in the printing fumes has raised concerns about their adverse potential affecting humans and the environment. Thus, it is necessary to understand the properties of the chemicals emitted during additive manufacturing for developing safe and biocompatible fibers having controlled emission of fumes including its sustainable usage. Therefore, in this study, we have developed a computational predictive risk-assessment framework on the comprehensive list of chemicals released during 3D printing using the acrylonitrile butadiene styrene (ABS) filament. Our results showed that the chemicals present in the fumes of the ABS-based fiber used in additive manufacturing have the potential to lead to various toxicity end points such as inhalation toxicity, oral toxicity, carcinogenicity, hepatotoxicity, and teratogenicity. Moreover, because of their absorption, distribution in the body, metabolism, and excretion properties, most of the chemicals exhibited a high absorption level in the intestine and the potential to cross the blood-brain barrier. Furthermore, pathway analysis revealed that signaling like alpha-adrenergic receptor signaling, heterotrimeric G-protein signaling, and Alzheimer's disease-amyloid secretase pathway are significantly overrepresented given the identified target proteins of these chemicals. These findings signify the adversities associated with 3D printing fumes and the necessity for the development of biodegradable and considerably safer fibers for 3D printing technology.

Reduction of thrombotic and inflammatory complications of polystyrene-block-polyisoprene-block-polystyrene (SIS) with one-step electrospinning.

Polystyrene-block-polyisoprene-block-polystyrene (SIS) has been used as biomaterials due to its soft and stable properties under physiological conditions. However, the thrombotic and inflammatory complications caused by SIS restrain its application as blood-contacting implant. To overcome this problem, the hydrophilic core-shell structured SIS-based microfiber with antioxidant encapsulation is fabricated with one-step reactive electrospinning. We demonstrate that the phase separation of SIS and acylated Pluronic F127 (F127-DA) components and crosslinking during electrospinning renders the microfiber blood compatible and stable under physiological condition; the encapsulation of 2-O-d-glucopyranosyl-l-ascorbic acid (AA-2G) in microfiber and subsequent release of AA-2G detoxifies the excess reactive oxygen species (ROS). The microfibers are nontoxic to cells and promote the fast growth and proliferation of human umbilical vein endothelial cells (HUVECs) in the presence of ROS; the thrombotic and inflammatory complications are effectively reduced with implant evaluation in vivo. Therefore, our work paves a new way to improve the biocompatibility of SIS, making it a promising candidate for blood contact materials.

Mortality Among Men and Women in the North American Synthetic Rubber Industry, 1943 to 2009.

OBJECTIVE: To evaluate 1943 to 2009 mortality among 22,785 synthetic rubber industry employees. METHODS: Standardized mortality ratio (SMR) and internal Cox regression analyses. RESULTS: Among hourly employees with more than or equal to 10 years worked and more than or equal to 20 years since hire, SMRs were elevated for leukemia (SMR = 139, 95% confidence interval [CI] = 106 to 179), non-Hodgkin lymphoma (NHL) (SMR = 136, CI = 102 to 177), bladder cancer (SMR = 148, CI = 110 to 195) and, for women only, lung cancer (SMR = 225, CI = 103 to 427). Butadiene and styrene exposure-response trends were positive for leukemia and bladder cancer but not for NHL or for lung cancer among women. CONCLUSIONS: Results support a causal relationship between butadiene and leukemia. Interpretation of results for lung cancer among women and for bladder cancer is uncertain because of inability to control for smoking and inadequate or inconsistent support from other studies for an association between butadiene or styrene and the latter cancers.

Acute health effects of desktop 3D printing (fused deposition modeling) using acrylonitrile butadiene styrene and polylactic acid materials: An experimental exposure study in human volunteers.

3D printers are increasingly run at home. Nanoparticle emissions from those printers have been reported, which raises the question whether adverse health effects from ultrafine particles (UFP) can be elicited by 3D printers. We exposed 26 healthy adults in a single-blinded, randomized, cross-over design to emissions of a desktop 3D printer using fused deposition modeling (FDM) for 1 hour (high UFP-emitting acrylonitrile butadiene styrene [ABS] vs low-emitting polylactic acid [PLA]). Before and after exposures, cytokines (IL-1ß, IL-6, TNF-α, INF-γ) and ECP in nasal secretions, exhaled nitric oxide (FeNO), urinary 8-isoprostaglandin F2α (8-iso PGF2α ), and self-reported symptoms were assessed. The exposures had no significant differential effect on 8-iso PGF2α and nasal biomarkers. However, there was a difference (P < .05) in the time course of FeNO, with higher levels after ABS exposure. Moreover, indisposition and odor nuisance were increased for ABS exposure. These data suggest that 1 hour of exposure to 3D printer emissions had no acute effect on inflammatory markers in nasal secretions and urine. The slight relative increase in FeNO after ABS printing compared to PLA might be due to eosinophilic inflammation from inhaled UFP particles. This possibility should be investigated in further studies using additional biomarkers and longer observation periods.

Characterization of isoprene-derived secondary organic aerosols at a rural site in North China Plain with implications for anthropogenic pollution effects.

Isoprene is the most abundant non-methane volatile organic compound (VOC) and the largest contributor to secondary organic aerosol (SOA) burden on a global scale. In order to examine the influence of high concentrations of anthropogenic pollutants on isoprene-derived SOA (SOA i ) formation, summertime PM2.5 filter samples were collected with a three-hour sampling interval at a rural site in the North China Plain (NCP), and determined for SOA i tracers and other chemical species. RO2+NO pathway derived 2-methylglyceric acid presented a relatively higher contribution to the SOA i due to the high-NOx (~20 ppb) conditions in the NCP that suppressed the reactive uptake of RO2+HO2 reaction derived isoprene epoxydiols. Compared to particle acidity and water content, sulfate plays a dominant role in the heterogeneous formation process of SOA i . Diurnal variation and correlation of 2-methyltetrols with ozone suggested an important effect of isoprene ozonolysis on SOA i formation. SOA i increased linearly with levoglucosan during June 10-18, which can be attributed to an increasing emission of isoprene caused by the field burning of wheat straw and a favorable aqueous SOA formation during the aging process of the biomass burning plume. Our results suggested that isoprene oxidation is highly influenced by intensive anthropogenic activities in the NCP.

Case report of asthma associated with 3D printing.

BACKGROUND: Three-dimensional (3D) printing is being increasingly used in manufacturing and by small business entrepreneurs and home hobbyists. Exposure to airborne emissions during 3D printing raises the issue of whether there may be adverse health effects associated with these emissions. AIMS: We present a case of a worker who developed asthma while using 3D printers, which illustrates that respiratory problems may be associated with 3D printer emissions. CASE REPORT: The patient was a 28-year-old self-employed businessman with a past history of asthma in childhood, which had resolved completely by the age of eight. He started using 10 fused deposition modelling 3D printers with acrylonitrile-butadiene-styrene filaments in a small work area of approximately 3000 cubic feet. Ten days later, he began to experience recurrent chest tightness, shortness of breath and coughing at work. After 3 months, his work environment was modified by reducing the number of printers, changing to polylactic acid filaments and using an air purifier with an high-efficiency particulate air filter and organic cartridge. His symptoms improved gradually, although he still needed periodic treatment with a salbutamol inhaler. While still symptomatic, a methacholine challenge indicated a provocation concentration causing a 20% fall in FEV1 (PC20) of 4 mg/ml, consistent with mild asthma. Eventually, his symptoms resolved completely and a second methacholine challenge after symptom resolution was normal (PC20 > 16 mg/ml). CONCLUSIONS: This case indicates that workers may develop respiratory problems, including asthma when using 3D printers. Further investigation of the specific airborne emissions and health problems from 3D printing is warranted.

Differences in environmental exposure assignment due to residential mobility among children with a central nervous system tumor: Texas, 1995-2009.

In epidemiologic studies of childhood cancer, environmental exposures are often assigned based on either residence at birth or diagnosis without considering the impact of residential mobility. Therefore, we evaluated residential mobility and exposure assignment differences to hazardous air pollutants between birth and diagnosis in children with a central nervous system (CNS) tumor. Children diagnosed with CNS tumors during 1995-2009 (N=1,196) were identified from the Texas Cancer Registry. Census tract-level estimates of 1,3-butadiene and benzene were used to assign quartiles of exposure based on the maternal residence at birth and the child's residence at diagnosis. Overall, 64% of younger (0-4 years) children and 79% of older (5-14 years) children moved between birth and diagnosis. Using mixed-effects ordinal logistic regression, residence at diagnosis compared to birth did not result in a significant change in exposure assignment for younger children; however, older children were more likely to be placed in a lower 1,3-butadiene or benzene exposure quartile based on residence at diagnosis compared to birth (odds ratio (OR)=0.58, 95% confidence interval (CI)=0.45-0.76; OR=0.57, 95% CI=0.44-0.75, respectively). In conclusion, while the majority of children moved between birth and CNS tumor diagnosis, mobility did not significantly impact 1,3-butadiene and benzene exposure assessment in younger children.

1,3-Butadiene exposure and metabolism among Japanese American, Native Hawaiian, and White smokers.

BACKGROUND: We hypothesize that the differences in lung cancer risk in Native Hawaiians, whites, and Japanese Americans may, in part, be due to variation in the metabolism of 1,3-butadiene, one of the most abundant carcinogens in cigarette smoke. METHODS: We measured two biomarkers of 1,3-butadiene exposure, monohydroxybutyl mercapturic acid (MHBMA) and dihydroxybutyl mercapturic acid (DHBMA), in overnight urine samples among 584 Native Hawaiians, Japanese Americans, and white smokers in Hawaii. These values were normalized to creatinine levels. Ethnic-specific geometric means were compared adjusting for age at urine collection, sex, body mass index, and nicotine equivalents (a marker of total nicotine uptake). RESULTS: We found that mean urinary MHBMA differed by race/ethnicity (P = 0.0002). The values were highest in whites and lowest in Japanese Americans. This difference was only observed in individuals with the GSTT1-null genotype (P = 0.0001). No difference across race/ethnicity was found among those with at least one copy of the GSTT1 gene (P ≥ 0.72). Mean urinary DHBMA did not differ across racial/ethnic groups. CONCLUSIONS: The difference in urinary MHBMA excretion levels from cigarette smoking across three ethnic groups is, in part, explained by the GSTT1 genotype. Mean urinary MHBMA levels are higher in whites among GSTT1-null smokers. IMPACT: The overall higher excretion levels of MHBMA in whites and lower levels of MHBMA in Japanese Americans are consistent with the higher lung cancer risk in the former. However, the excretion levels of MHBMA in Native Hawaiians are not consistent with their disease risk and thus unlikely to explain their high risk of lung cancer.

Risk of leukemia in relation to exposure to ambient air toxics in pregnancy and early childhood.

There are few established causes of leukemia, the most common type of cancer in children. Studies in adults suggest a role for specific environmental agents, but little is known about any effect from exposures in pregnancy to toxics in ambient air. In our case-control study, we ascertained 69 cases of acute lymphoblastic leukemia (ALL) and 46 cases of acute myeloid leukemia (AML) from California Cancer Registry records of children

Protective effect of rutin on hexachlorobutadiene-induced nephrotoxicity.

Hexachlorobutadiene (HCBD) is a potent nephrotoxin which nowadays contaminates human foods and water. On the other hands, it has been reported that rutin is a chemopreventive flavonoid which exerts some protective effects on the kidney. Therefore, in this work, the possible effect of rutin on HCBD-induced nephrotoxicity was investigated in female rats. The animals were divided into five groups. Groups 1 and 2 were treated with vehicle and HCBD (100 mg/kg, i.p.), respectively. Groups 3-5 were pretreated with rutin (100, 500 and 1000 mg/kg, i.p.) 1 h before HCBD injection. The level of serum urea and creatinine as well as urinary glucose and protein were measured. Total thiol content and lipid peroxidation level were also determined in the kidney homogenate. When compared to control group, a significant increase in the level of serum creatinine and urea (p < 0.001) as well as urine glucose and protein (p < 0.001) were observed after 24 h of HCBD administration. HCBD also caused a significant decrease in total thiol content (p < 0.001) and a significant increase in lipid peroxidation level (p < 0.001). Pretreatment with rutin could decrease serum creatinine (p < 0.001) and urea (p < 0.001) as well as urine protein (p < 0.001) concentrations when compared with HCBD treated rats. No significant modification on urine glucose was seen (p > 0.05). Rutin also reversed the HCBD-induced depletion in thiol content (p < 0.001) and elevation in lipid peroxidation (p < 0.001) in the kidney. The results of present study showed that rutin clearly attenuated HCBD-induced nephrotoxicity and has the potential to be considered as a nephroprotective agent.

Environmental-sanitary risk analysis procedure applied to artificial turf sports fields.

Owing to the extensive use of artificial turfs worldwide, over the past 10 years there has been much discussion about the possible health and environmental problems originating from styrene-butadiene recycled rubber. In this paper, the authors performed a Tier 2 environmental-sanitary risk analysis on five artificial turf sports fields located in the city of Turin (Italy) with the aid of RISC4 software. Two receptors (adult player and child player) and three routes of exposure (direct contact with crumb rubber, contact with rainwater soaking the rubber mat, inhalation of dusts and gases from the artificial turf fields) were considered in the conceptual model. For all the fields and for all the routes, the cumulative carcinogenic risk proved to be lower than 10(-6) and the cumulative non-carcinogenic risk lower than 1. The outdoor inhalation of dusts and gases was the main route of exposure for both carcinogenic and non-carcinogenic substances. The results given by the inhalation pathway were compared with those of a risk assessment carried out on citizens breathing gases and dusts from traffic emissions every day in Turin. For both classes of substances and for both receptors, the inhalation of atmospheric dusts and gases from vehicular traffic gave risk values of one order of magnitude higher than those due to playing soccer on an artificial field.

Chromosomal damage and polymorphisms of metabolic genes among 1, 3-butadiene-exposed workers in a matched study in China.

1, 3-Butadiene (BD) is a high-efficiency carcinogen in rodents and was classified as a human carcinogen in 2008 by the International Agency for Research on Cancer. However, its ability to induce genetic damage and the influence of metabolic polymorphisms to such damage in humans are both controversial claims. This study was conducted to investigate the relationships between exposure to BD, the polymorphisms of metabolic genes and the chromosomal damage in 45 pairs of occupationally exposed workers in a BD product workshop and matched control workers in an administrative office and circulatory water workshop in China. Exposure to BD was evaluated by personal sampling and stationary sampling. Different chromosomal damage endpoints in peripheral blood lymphocytes were determined using the cytokinesis-blocked micronucleus (CBMN) cytome assay; polymorphisms of metabolic genes [cytochrome P450 2E1 (CYP2E1), glutathione S-transferases (GST) and microsomal epoxide hydrolase (mEH)] in BD-exposed group were detected by polymerase chain reaction (PCR) or PCR-restriction fragment length polymorphism analysis. The results show that the average BD measurements of the exposed group were significantly higher than those for the control group (a personal sampling and stationary sampling, respectively). The BD-exposed workers exhibited increased frequencies of micronuclei (MNi) (8.00 ± 3.78‰ versus 5.62 ± 2.41‰) and nucleoplasmic bridges (NPBs) (2.58 ± 2.79‰ versus 1.13 ± 1.34‰) and a decreased nuclear division index (2.20 ± 0.14 versus 2.35 ± 0.27) when compared subjects in the control group. Meanwhile, BD-exposed workers carrying CYP2E1 c1c2/c2c2 or mEH intermediate (I)/high (H) group had a significantly higher NPB frequency than those carrying CYP2E1 c1c1 [frequency ratio (FR) = 2.60, 95% confidence interval (CI) 1.72-3.93; P < 0.0001) or the mEH low(S) group (FR = 2.06, 95% CI% 1.17-3.62; P < 0.05), respectively. Our study suggests that MNi and NPB frequency in CBMN cytome assay could be potential genotoxic biomarkers for BD exposure in humans. The polymorphism of CYP2E1 and mEH could also affect the chromosomal instability of BD workers.

Serum cytokeratin 18 and cytokine elevations suggest a high prevalence of occupational liver disease in highly exposed elastomer/polymer workers.

OBJECTIVE: Cytokeratin 18 (CK18) is a novel serologic biomarker for occupational liver disease. The purpose of this study is to determine the prevalence of CK18 elevation in elastomer/polymer workers exposed to acrylonitrile, 1,3-butadiene, and styrene. METHODS: A total of 82 chemical workers were evaluated. Cytokeratin 18 was determined by enzyme-linked immunosorbent assay and proinflammatory cytokines were measured by multi-analyte chemiluminescent detection. RESULTS: Thirty-nine percent (32 of 82) had elevated CK18 levels, which were not explained by alcohol or obesity, except in potentially four cases. The pattern of CK18 elevation was consistent with toxicant-associated steatohepatitis (TASH) in the majority of cases (78%). Tumor necrosis factor α, interleukin-6, interleukin-8, monocyte chemotactic protein-1, and plasminogen activator inhibitor-1 were increased in these workers compared with those with normal CK18 levels. CONCLUSIONS: These results suggest a high prevalence of occupational liver disease and TASH in elastomer/polymer workers with elevated proinflammatory cytokines.

Antiviral activity of the MEK-inhibitor U0126 against pandemic H1N1v and highly pathogenic avian influenza virus in vitro and in vivo.

The emergence of the 2009 H1N1 pandemic swine influenza A virus is a good example of how this viral infection can impact health systems around the world in a very short time. The continuous zoonotic circulation and reassortment potential of influenza A viruses (IAV) in nature represents an enormous public health threat to humans. Beside vaccination antivirals are needed to efficiently control spreading of the disease. In the present work we investigated whether the MEK inhibitor U0126, targeting the intracellular Raf/MEK/ERK signaling pathway, is able to suppress propagation of the 2009 pandemic IV H1N1v (v=variant) as well as highly pathogenic avian influenza viruses (HPAIV) in cell culture and also in vivo in the mouse lung. U0126 showed antiviral activity in cell culture against all tested IAV strains including oseltamivir resistant variants. Furthermore, we were able to demonstrate that treatment of mice with U0126 via the aerosol route led to (i) inhibition of MEK activation in the lung (ii) reduction of progeny IAV titers compared to untreated controls (iii) protection of IAV infected mice against a 100× lethal viral challenge. Moreover, no adverse effects of U0126 were found in cell culture or in the mouse. Thus, we conclude that U0126, by inhibiting the cellular target MEK, has an antiviral potential not only in vitro in cell culture, but also in vivo in the mouse model.

A chronic reference value for 1,3-butadiene based on an updated noncancer toxicity assessment.

A chronic noncancer toxicity assessment for 1,3-butadiene (BD) has been conducted by the Texas Commission on Environmental Quality (TCEQ) using information not available to the U.S. Environmental Protection Agency (U.S. EPA) in 2002. The TCEQ developed a chronic reference value (ReV) of 33 microg/m3 (15 ppb). The chronic ReV is based on the same animal study and critical endpoint used by U.S. EPA for ovarian atrophy in B6C3F1 mice, but uses mode of action (MOA) information that indicates the diepoxide metabolite is responsible for ovarian atrophy. In addition, diepoxide-specific hemoglobin adduct data in mice, rats, and humans and other experimental data that became available after 2002 were used to support a conservative data-derived toxicokinetic animal-to-human uncertainty factor (UFA) of 0.3. The default toxicodynamic UFA of 3 was used, together with the data-derived toxicokinetic UFA of 0.3, resulting in a total UFA of 1. The necessary experimental data were not available to calculate a chemical-specific adjustment factor, although supporting data suggest the toxicokinetic UFA may range from 0.01 to 0.2. The chronic ReV value, along with a unit risk factor developed by the TCEQ, will be used to evaluate ambient air monitoring data so that the general public is protected against adverse health effects from chronic exposure to BD.