Reducing Transdermal Uptake of Semivolatile Plasticizers from Indoor Environments: A Clothing Intervention.

Models and laboratory studies suggest that everyday clothing influences the transdermal uptake of semivolatile organic compounds, including phthalate plasticizers, from indoor environments. However, this effect has not been documented in environmental exposure settings. In this pilot study, we quantified daily excretion of 17 urinary metabolites (µg/day) for phthalates and phthalate alternatives in nine participants during 5 days. On Day 0, baseline daily excretion was determined in participants' urine. Starting on Day 1, participants refrained from eating phthalate-heavy foods and using personal care products. On Days 3 and 4, participants wore precleaned clothing as an exposure intervention. We observed a reduction in the daily excretion of phthalates during the intervention; mono-n-butyl phthalate, monoisobutyl phthalate (MiBP), and monobenzyl phthalate were significantly reduced by 35, 38, and 56%, respectively. Summed metabolites of di(2-ethylhexyl)phthalate (DEHP) were also reduced (27%; not statistically significant). A similar reduction among phthalate alternatives was not observed. The daily excretion of MiBP during the nonintervention period strongly correlated with indoor air concentrations of diisobutyl phthalate (DiBP), suggesting that inhalation and transdermal uptake of DiBP from the air in homes are dominant exposure pathways. The results indicate that precleaned clothing can significantly reduce environmental exposure to phthalates and phthalate alternatives.

Feasibility of Implementing a Total Worker Health® Intervention During the COVID-19 Pandemic in Small and Medium Businesses : Results From the Carolina PROSPER Study.

OBJECTIVE: In response to the COVID-19 pandemic's disruptive effect on employers and workers, an interdisciplinary team launched the Carolina Promoting Safe Practices for Employees' Return study to assess the feasibility of providing tailored technical assistance to small and medium North Carolina businesses using a Total Worker Health (TWH) ® approach. METHODS: Feasibility of the approach was assessed via surveys and interviews of business representatives from four participating businesses ranging in size from 3 to 110 employees. RESULTS: The TWH approach is feasible, that is, in demand, practical, and acceptable to protect and promote worker safety, health, and well-being. Potential challenges include implementation cost, difficulty engaging all employees, and difficulty accessing tailored health and safety materials in a timely manner. CONCLUSIONS: Additional refinement and testing of the TWH approach postpandemic with more worksites is warranted.

Occupational exposure to PFAS: Research and protection needed.

Per- and polyfluoroalkyl substances (PFAS) have been used in a variety of consumer and industrial applications. PFAS are associated with numerous detrimental health effects, but workplace exposure to PFAS has only been studied in a small number of occupations. More research is needed to fully understand how workers may be exposed to PFAS and what health effects this may cause.

Occupational exposures to airborne per- and polyfluoroalkyl substances (PFAS)-A review.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are a group of synthetically-made chemicals with diverse functional properties that have become ubiquitous in our environment because of their widespread use. PFAS exposure has been associated with adverse health effects, and it is therefore vital to know how exposure may occur. Many studies have focused on environmental exposure from drinking water, but there is a paucity of data on inhalation exposure, especially in occupational settings. METHODS: In this study, through a comprehensive literature search, measured airborne (i.e., aerosols, volatiles, and dust) inhalation exposure and area levels were compiled for various occupations to compare reported levels of PFAS exposure. Airborne PFAS levels measured in various occupations such as ski waxing, textile manufacturing, firefighting, and floor waxing were analyzed and compared. RESULTS: Results of this review demonstrate that workers experience varying levels of PFAS exposure contingent on the workplace and industry and the work tasks performed within the workplace. Out of all occupations, ski waxing exhibited the highest total PFAS airborne concentrations when compared to all other reported occupational and residential exposures. CONCLUSIONS: Further research is recommended to estimate the risk of PFAS exposures in the occupations reviewed and to identify other potential occupations at risk of PFAS exposure. In addition, informed recommendations to implement safety measures ought to be developed to protect workers from adverse health effects.

Occupational exposure and serum levels of per- and polyfluoroalkyl substances (PFAS): A review.

BACKGROUND: Per- and polyfluoroalkyl substances, or PFAS, are a class of chemicals used in nearly all sectors of industry and many consumer products. Their resistance to degradation, however, means that PFAS are ubiquitous in the environment and bioaccumulate. PFAS exposure has also been linked to a variety of adverse health effects. Occupational PFAS exposure is of particular concern as research on PFAS exposure in worker populations has historically been limited and generally restricted to fluorochemical plant workers involved in PFAS production. METHODS: A comprehensive review of peer-reviewed scientific literature was conducted to investigate which worker populations may experience occupational exposure to PFAS. Serum PFAS levels reported in various occupations were analyzed and compared to serum PFAS levels published on the general public exposed to PFAS-contaminated drinking water and the study population of the National Health and Nutrition Examination Survey (NHANES). RESULTS: Our analysis indicates that professional ski waxers and firefighters may be exposed to several different PFAS at levels often similar to or higher than levels among fluorochemical plant workers and individuals in communities with PFAS-contaminated drinking water, and higher than levels in the general public. PFAS serum level data on other occupations were largely absent. CONCLUSIONS: Results highlight a need for additional research on occupational PFAS exposures and concomitant environmental exposures in these populations. Research on exposure levels in occupations and industries known or suspected to utilize PFAS is critically needed to foster informed recommendations for exposure mitigation measures to protect workers from adverse health effects of PFAS exposure.

The genetics of occupational asthma development among workers exposed to diisocyanates: A systematic literature review with meta-analysis.

Diisocyanates are widely used compounds that pose a safety concern for workers in occupations within the spray-paint, spray-foam insulation, and furniture varnish industries. Epidemiological studies show that only a subset of workers exposed to diisocyanates develop diisocyanate-induced occupational asthma (diisocyanate asthma, DA), indicating that genetic susceptibility may play a role. The purpose of this systematic literature review was to compile and meta-analyze the reported data on genetic susceptibility markers for DA. Three databases (Embase, Pubmed, and Scopus) were searched and 169 non-duplicate publications were identified, of which 22 relevant occupational studies were included in this review. Researchers reported prevalence odds ratios (PORs) for 943 comparisons in 82 different genes/serotypes. Protein network functions for the DA-associated genes from this review include: antigen processing, lymphocyte activation, cytokine production regulation, and response to oxidative stress. Meta-analysis of comparisons between workers with DA and controls was conducted for 23 genetic markers within: CTNNA3, GSTM1, GSTP1, GSTT1, HLA-C, HLA-DQB1, HLA-DR1, HLA-DR3, HLA-DR4, HLA-DR7, and HLA-DR8. These genes code for proteins that are involved in cell-cell adhesions (CTNNA3), glutathione conjugation for xenobiotic metabolism (GST gene family), and immune system response (HLA gene family). The most compelling pooled PORs were for two studies on CTNNA3 (increased DA risk: rs10762058 GG, rs7088181 GG, rs4378283 TT; PORs 4.38-4.97) and three studies on HLA-DR1 (decreased DA risk, POR 0.24). Bioinformatics of the predicted protein pathways for DA shows overlap with biomarker-associated pathways in workers before development of asthma, suggesting overlap in toxicokinetic and toxicodynamic pathways of diisocyanates. The control groups were also compared against each other and differences were negligible. Suggestions for improving future research are also presented. Of the highest importance, the literature was found to be profoundly publication-biased, in which researchers need to report the data for all studied markers regardless of the statistical significance level. We demonstrate the utility of evaluating the overlap in predicted protein pathway functions for identifying more consistency across the reported literature including for asthma research, biomarker research, and in vitro studies. This will serve as an important resource for researchers to use when generating new hypothesis-driven research about diisocyanate toxicology.

Lung and extrathoracic cancer incidence among underground uranium miners exposed to radon progeny in the Príbram region of the Czech Republic: a case-cohort study.

OBJECTIVES: Radon is carcinogenic, but more studies are needed to understand relationships with lung cancer and extrathoracic cancers at low exposures. There are few studies evaluating associations with cancer incidence or assessing the modifying effects of smoking. METHODS: We conducted a case-cohort study with 16 434 underground uranium miners in the Czech Republic with cancer incidence follow-up 1977-1996. Associations between radon exposure and lung cancer, and extrathoracic cancer, were estimated with linear excess relative rate (ERR) models. We examined potential modifying effects of smoking, time since exposure and exposure rate. RESULTS: Under a simple ERR model, assuming a 5-year exposure lag, the estimated ERR of lung cancer per 100 working level months (WLM) was 0.54 (95% CI 0.33 to 0.83) and the estimated ERR of extrathoracic cancer per 100 WLM was 0.07 (95% CI -0.17 to 0.72). Most lung cancer cases were observed among smokers (82%), and the estimated ERR of lung cancer per 100 WLM was larger among smokers (ERR/100 WLM=1.35; 95% CI 0.84 to 2.15) than among never smokers (ERR/100 WLM=0.12; 95% CI -0.05 to 0.49). Among smokers, the estimated ERR of lung cancer per 100 WLM decreased with time since exposure from 3.07 (95% CI -0.04 to 10.32) in the period 5-14 years after exposure to 1.05 (95% CI 0.49 to 1.87) in the period 25+ years after exposure. CONCLUSIONS: We observed positive associations between cumulative radon exposure and lung cancer, consistent with prior studies. We observed a positive association between cumulative radon exposure and extrathoracic cancers, although the estimates were small. There was evidence that the association between radon and lung cancer was modified by smoking in a multiplicative or super-multiplicative fashion.

Viability of cultured human skin cells treated with 1,6-hexamethylene diisocyanate monomer and its oligomer isocyanurate in different culture media.

The isocyanate monomer 1,6-hexamethylene diisocyanate (HDI) and one of its trimers, HDI isocyanurate, are airway and skin sensitizers contained in polyurethane paint. The toxic response of cultured skin cells to these compounds was measured by evaluating the isocyanate concentrations at which 50% of the cells die (i.e., lethal concentration 50%, LC50) because the relative toxicity of each form of HDI should be considered when exposure limits of HDI-based paints are set. By using a luminescent ATP-viability assay, we compared the cytotoxic effects of HDI monomer and HDI isocyanurate on cultured human skin cells (keratinocytes, fibroblasts, and melanocytes) after 4-h isocyanate exposures using culture media with varying levels of nutrients in order to also determine the effects of media composition on isocyanate toxicity. Before analysis, experimental wells were normalized to controls containing cells that were cultured with the same vehicle and media. The measured mean LC50 values ranged from 5 to 200 µM across the experimental conditions, in which HDI isocyanurate in protein-devoid media was the most toxic to cells, producing the lowest LC50 values. For HDI monomer, keratinocytes were the most resistant to its toxicity and melanocytes were the most susceptible. However, when exposed to HDI isocyanurate, the opposite was observed, with melanocytes being the most resilient and the keratinocytes and fibroblasts were more susceptible. Depending on the type of skin cells, dose-response data indicated that HDI isocyanurate was 2-6 times more toxic than HDI monomer when using protein-devoid media whereas HDI isocyanurate was 4-13 times more toxic than HDI monomer when protein-rich media was used. Therefore, if the protein-devoid saline medium alone were used for these experiments, then a significant under-estimation of their relative toxicities in protein-rich environments would have resulted. This difference is because HDI monomer toxicity was more attenuated by the presence of protein in the culture media than HDI isocyanurate toxicity. Thus, conclusions based on comparative toxicity studies and consequent inference applied to potential human toxicity can be affected by in vitro culture media conditions. The physiochemical difference in reactivity of the two forms of HDI to biological molecules most likely explains the observed toxicity differences and may have implications for skin penetration, adverse effects like skin sensitization, and systemic responses like asthma. Future studies are warranted to investigate differences in the biological availability, cellular toxicity, and immunologic sensitization mechanisms for HDI monomer and HDI isocyanurate.

Epigenetic Markers Are Associated With Differences in Isocyanate Biomarker Levels in Exposed Spray-Painters.

Isocyanates are respiratory and skin sensitizers that are one of the main causes of occupational asthma globally. Genetic and epigenetic markers are associated with isocyanate-induced asthma and, before asthma develops, we have shown that genetic polymorphisms are associated with variation in plasma and urine biomarker levels in exposed workers. Inter-individual epigenetic variance may also have a significant role in the observed biomarker variability following isocyanate exposure. Therefore, we determined the percent methylation for CpG islands from DNA extracted from mononuclear blood cells of 24 male spray-painters exposed to 1,6-hexamethylene diisocyanate (HDI) monomer and HDI isocyanurate. Spray-painters' personal inhalation and skin exposure to these compounds and the respective biomarker levels of 1,6-diaminohexane (HDA) and trisaminohexyl isocyanurate (TAHI) in their plasma and urine were measured during three repeated industrial hygiene monitoring visits. We controlled for inhalation exposure, skin exposure, age, smoking status, and ethnicity as covariates and performed an epigenome-wide association study (EWAS) using likelihood-ratio statistical modeling. We identified 38 CpG markers associated with differences in isocyanate biomarker levels (Bonferroni < 0.05). Annotations for these markers included 18 genes: ALG1, ANKRD11, C16orf89, CHD7, COL27A, FUZ, FZD9, HMGN1, KRT6A, LEPR, MAPK10, MED25, NOSIP, PKD1, SNX19, UNC13A, UROS, and ZFHX3. We explored the functions of the genes that have been published in the literature and used GeneMANIA to investigate gene ontologies and predicted protein-interaction networks. The protein functions of the predicted networks include keratinocyte migration, cell-cell adhesions, calcium transport, neurotransmitter release, nitric oxide production, and apoptosis regulation. Many of the protein pathway functions overlap with previous findings on genetic markers associated with variability both in isocyanate biomarker levels and asthma susceptibility, which suggests there are overlapping protein pathways that contribute to both isocyanate toxicokinetics and toxicodynamics. These predicted protein networks can inform future research on the mechanism of allergic airway sensitization by isocyanates and aid in the development of mitigation strategies to better protect worker health.

Influence of Genetic Variance on Biomarker Levels After Occupational Exposure to 1,6-Hexamethylene Diisocyanate Monomer and 1,6-Hexamethylene Diisocyanate Isocyanurate.

We evaluated the impact of genetic variance on biomarker levels in a population of workers in the automotive repair and refinishing industry who were exposed to respiratory sensitizers 1,6-hexamethylene diisocyanate (HDI) monomer and one of its trimers, HDI isocyanurate. The exposures and respective urine and plasma biomarkers 1,6-diaminohexane (HDA) and trisaminohexyl isocyanurate (TAHI) were measured in 33 workers; and genome-wide microarrays (Affymetrix 6.0) were used to genotype the workers' single-nucleotide polymorphisms (SNPs). Linear mixed model analyses have indicated that interindividual variations in both inhalation and skin exposures influenced these biomarker levels. Using exposure values as covariates and a false discovery rate < 0.10 to assess statistical significance, we observed that seven SNPs were associated with HDA in plasma, five were associated with HDA in urine, none reached significance for TAHI in plasma, and eight were associated with TAHI levels in urine. The different genotypes for the 20 significant SNPs accounted for 4- to 16-fold changes observed in biomarker levels. Associated gene functions include transcription regulation, calcium ion transport, vascular morphogenesis, and transforming growth factor beta signaling pathway, which may impact toxicokinetics indirectly by altering inflammation levels. Additionally, in an expanded analysis using a minor allele cutoff of 0.05 instead of 0.10, there were biomarker-associated SNPs within three genes that have been associated with isocyanate-induced asthma: ALK, DOCK2, and LHPP. We demonstrate that genetic variance impacts the biomarker levels in workers exposed to HDI monomer and HDI isocyanurate and that genetics can be used to refine exposure predictions in small cohorts when quantitative personal exposure and biomarker measurements are included in the models.

Human Cytomegalovirus Infections Are Associated With Elevated Biomarkers of Vascular Injury.

Background: Human cytomegalovirus (HCMV) infects ~50% of adults in the United States. HCMV infections may cause vascular inflammation leading to cardiovascular disease, but the existing evidence is inconsistent. Objective: We investigated demographic predictors of HCMV infection and explored associations between HCMV infection status, the intensity of anti-HCMV Immunoglobulin G (IgG) antibody response, and biomarkers of inflammation and endothelial function which are known predictors of cardiovascular disease. Methods: We conducted a cross-sectional study of 694 adults residing in the Raleigh-Durham-Chapel Hill, NC metropolitan area. Serum samples were tested for IgG antibody response to HCMV, and for biomarkers of vascular injury including soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1), C-reactive protein (CRP), and serum amyloid A (SAA). Associations between HCMV and biomarker levels were analyzed using two approaches with HCMV serostatus modeled as a binary variable and as an ordinal variable with five categories comprised of seronegative individuals and quartiles of anti-HCMV antibody responses in seropositive individuals. Results: HCMV seroprevalence in the study population was 56%. Increased body mass index, increased age, female gender, racial/ethnic minority status, and current smoking were significantly associated with HCMV seropositivity in a multivariate regression analysis. HCMV seropositivity was also associated with 9% (95% confidence interval 4-15%) and 20% (0.3-44%) increases in median levels of sICAM-1 and CRP, respectively, after adjusting for covariates. The association between HCMV seropositivity and median levels of sVCAM-1 and SAA were positive but not statistically significant. Significant positive associations were observed between the intensity of anti-HCMV IgG responses and levels of sICAM-1 and sVCAM-1 (p-values 0.0008 and 0.04 for linear trend, respectively). To our knowledge, this is the first epidemiological study to show a relationship between anti-HCMV IgG responses and vascular injury biomarkers sICAM-1 and sVCAM-1 in the general population. Conclusion: HCMV infections are associated with vascular injury and inflammation biomarkers in adult residents of North Carolina.

A Physiologically Based Pharmacokinetic Model for Naphthalene With Inhalation and Skin Routes of Exposure.

Naphthalene, a volatile organic compound present in moth repellants and petroleum-based fuels, has been shown to induce toxicity in mice and rats during chronic inhalation exposures. Although simpler default methods exist for extrapolating toxicity points of departure from animals to humans, using a physiologically based pharmacokinetic (PBPK) model to perform such extrapolations is generally preferred. Confidence in PBPK models increases when they have been validated using both animal and human in vivo pharmacokinetic (PK) data. A published inhalation PBPK model for naphthalene was previously shown to predict rodent PK data well, so we sought to evaluate this model using human PK data. The most reliable human data available come from a controlled skin exposure study, but the inhalation PBPK model does not include a skin exposure route; therefore, we extended the model by incorporating compartments representing the stratum corneum and the viable epidermis and parameters that determine absorption and rate of transport through the skin. The human data revealed measurable blood concentrations of naphthalene present in the subjects prior to skin exposure, so we also introduced a continuous dose-rate parameter to account for these baseline blood concentration levels. We calibrated the three new parameters in the modified PBPK model using data from the controlled skin exposure study but did not modify values for any other parameters. Model predictions then fell within a factor of 2 of most (96%) of the human PK observations, demonstrating that this model can accurately predict internal doses of naphthalene and is thus a viable tool for use in human health risk assessment.

Radon and cancer mortality among underground uranium miners in the Príbram region of the Czech Republic.

BACKGROUND: This study aims to estimate the association between radon and site-specific cancer mortality among a large contemporary cohort of male uranium miners. METHODS: Annual occupational radon exposure was estimated based on a worker's duration of underground mining in a year and estimates of potential alpha energy of radon progeny in their location of work. Cancer mortality over the period 1977-1992 was ascertained for a cohort of 16 434 male underground uranium miners employed in the Czech Republic between 1946 and 1992. Poisson regression was used to estimate relationships between cumulative radiation exposure (in working level months [WLM]) and site-specific cancer mortality. RESULTS: Radon is positively associated with lung cancer mortality (excess relative rate [ERR] per 100 WLM = 0.2; 95% confidence interval [CI]: 0.10, 0.37). The best fit of the dose-response relationship between radon and lung cancer mortality was linear and estimates of radon-lung cancer associations varied by windows of time-since-exposure. Positive associations between radon and several types of cancer other than lung cancer were identified, notably chronic lymphocytic leukemia (CLL) (ERR/100 WLM = 0.24; 95% CI: [not determined [ND], 5.10]) and extrathoracic cancer (ERR/100 WLM = 0.12; 95% CI: [ND, 0.69]). We observed no associations between radon and stomach cancer, nor between radon and several hematopoietic cancer subtypes. CONCLUSIONS: This study confirms the established radon-lung cancer association and suggests that radon may also be associated with other types of cancer mortality. Further investigations of extrathoracic and CLL cancer, with the aim of obtaining more precise estimates, are warranted to understand associations between radon and cancers other than lung.

Mortality and cancer incidence among underground uranium miners in the Czech Republic 1977-1992.

OBJECTIVES: Uranium miners in Príbram, Czech Republic were exposed to low and moderate levels of radon gas and other hazards. It is unknown whether these hazards increase the risk of mortality or cancer incidence when compared with the general Czech population. METHODS: A cohort of 16 434 male underground miners employed underground for at least 1 year between 1946 and 1976, and alive and residing in the Czech Republic in 1977, were followed for mortality and cancer incidence through 1992. We compared observed deaths and cancer incidence to expectation based on Czech rates. Standardised mortality ratios (SMRs), standardised incidence ratios (SIRs) and causal mortality ratios were calculated. RESULTS: Underground workers in the Príbram mines had higher rates of death than expected due to all causes (SMR=1.23, 95% CI 1.20 to 1.27), all cancers (SMR=1.52, 95% CI 1.44 to 1.60), lung cancer (SMR=2.12, 95% CI 1.96 to 2.28) and extrathoracic cancer (SMR=1.41, 95% CI 1.15 to 1.77). Similar excess was observed in cancer incidence analyses, with the addition of stomach cancer (SIR=1.37, 95% CI 1.11 to 1.63), liver cancer (SIR=1.70, 95% CI 1.16 to 2.25) and rectal cancer (SIR=1.41, 95% CI 1.16 to 1.66). The SIR was elevated for all leukaemias (SIR=1.51, 95% CI 1.08 to 2.07) and for lymphatic and haematopoietic cancers combined (SIR=1.31, 95% CI 1.05 to 1.61), but results for specific subtypes were imprecise. Deaths due to hazardous mining conditions resulted in 0.33 person-years of life lost per miner. CONCLUSIONS: Occupational exposure to the Príbram mines resulted in excess cancers at several sites, including sites previously linked to radon and uranium exposure. Incidence analyses showed relative excess of several additional cancer subtypes.

Animal production, insecticide use and self-reported symptoms and diagnoses of COPD, including chronic bronchitis, in the Agricultural Health Study.

BACKGROUND: Occupational exposure to animal production is associated with chronic bronchitis symptoms; however, few studies consider associations with chronic obstructive pulmonary disease (COPD). We estimated associations between animal production activities and prevalence of self-reported COPD among farmers in the Agricultural Health Study. METHODS: During a 2005-2010 interview, farmers self-reported information about: their operations (i.e., size, type, number of animals, insecticide use), respiratory symptoms, and COPD diagnoses (i.e., COPD, chronic bronchitis, emphysema). Operations were classified as small or medium/large based on regulatory definitions. Farmers were classified as having a COPD diagnosis, chronic bronchitis symptoms (cough and phlegm for ≥3 months during 2 consecutive years), or both. Polytomous logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Of 22,491 participating farmers (median age: 59 years), 922 (4%) reported a COPD diagnosis only, 254 (1%) reported a diagnosis and symptoms, and 962 (4%) reported symptoms only. Compared to raising no commercial animals, raising animals on a medium/large operation was positively associated with chronic bronchitis symptoms with (OR: 1.59; 95% CI: 1.16, 2.18) and without a diagnosis (OR: 1.69; 95% CI: 1.42, 2.01). Ever use of multiple organophosphates, carbaryl, lindane, and permethrin were positively associated with chronic bronchitis symptoms. CONCLUSION: Animal production work, including insecticide use, was positively associated with chronic bronchitis symptoms; but not consistently with COPD diagnosis alone. Our results support the need for further investigation into the role of animal production-related exposures in the etiology of COPD and better respiratory protection for agricultural workers.

Inorganic Arsenic as an Endocrine Disruptor: Modulation of the Glucocorticoid Receptor Pathway in Placental Cells via CpG Methylation.

Prenatal exposure to inorganic arsenic (iAs) has been associated with adverse developmental and reproductive outcomes. These outcomes may be tied to altered functionality of nuclear transcription factors such as the glucocorticoid receptor (GR) in the placenta and associated gene expression. The GR pathway is integral for proper fetal and placental development, and perturbations in this pathway may underlie observed associations between prenatal iAs exposure and adverse birth outcomes. We therefore set out to investigate whether iAs modulates the GR signaling pathway in placental cells. JEG-3 trophoblasts were exposed to environmentally-relevant doses of iAs, and mRNA expression assessed. To examine the links between iAs exposure, the GR signaling pathway, and epigenetic modification, DNA methylation levels were also quantified. Treatment with iAs altered the expression of 12 GR-genes that play a role in fetal and placental development. Furthermore, at a gene-specific level, mRNA abundance was associated with changes in DNA methylation patterning in JEG-3 cells, suggesting that the effects of iAs are mediated by epigenetic mechanisms. The identified target genes have been associated with prenatal iAs exposure, placental physiology, and fetal development. This study provides further evidence for iAs as an endocrine disruptor and provides insight as to the mechanisms by which prenatal iAs exposure may induce adverse birth outcomes.

Early Adoption of an Improved Household Energy System in Urban Rwanda.

Cooking with solid fuels and inefficient cookstoves has adverse consequences for health, environment, and human well-being. Despite the promise of improved cookstoves to reduce these impacts, adoption rates are relatively low. Using a 2-wave sample of 144 households from the baseline and first midline of an ongoing 4-year randomized controlled trial in Rwanda, we analyze the drivers and associations of early adoption of a household energy intervention marketed by a private sector firm. Households sign an annual contract to purchase sustainably produced biomass pellets and lease a fan micro-gasification cookstove with verified emissions reductions in laboratory settings. Using difference-in-differences and fixed effects estimation techniques, we examine the association between take-up of the improved cooking system and household fuel expenditures, health outcomes, and time use for primary cooks. Thirty percent of households adopted the pellet and improved cookstove system. Adopting households had more assets, lower per capita total expenditures and cooking fuel expenditures, and higher per capita hygiene expenditures. Households with married household heads and female cooks were significantly more likely to adopt. Adjusting for confounders, we find significant reduction in primary cooks' systolic blood pressure, self-reported prevalence of shortness of breath, an indicator of respiratory illness, time spent cooking, and household expenditures on charcoal. Our findings have implications for marketing of future clean fuel and improved cookstove programs in urban settings or where stoves and fuel are purchased. Analysis of follow-up surveys will allow for estimation of long-term impacts of adoption of interventions involving pellets and fan micro-gasification cookstoves.

Trisaminohexyl isocyanurate, a urinary biomarker of HDI isocyanurate exposure.

Biological monitoring of occupational exposure to 1,6-hexamethylene diisocyanate (HDI)-containing spray-paints is limited to analysis of metabolites of HDI monomer although polymeric HDI isocyanurate constitutes the predominant inhalation and skin exposure for workers in the automotive paint industry. A novel method using nanoflow ultra-performance liquid chromatography coupled to nano-electrospray ionization tandem mass spectrometry (nano-UPLC-ESI-MS/MS) was developed to quantify trisaminohexyl isocyanurate (TAHI), a hydrolysis product of HDI isocyanurate, in the urine of spray-painters. Analytical and internal standards were synthesized in-house and weighted linear regression calibration curves were generated using spiked control urine from non-exposed persons (0.06-7.98 µg/L; N = 13; w = x-2; r = 0.998). Urine samples collected from 15 exposed workers (N = 111) were subjected to acid hydrolysis and extracted with dichloromethane, then derivatized with acetic anhydride. The derivatized product, trisacetamidohexyl isocyanurate (TAAHI), was analyzed using nano-UPLC-ESI-MS/MS. The protocol was sensitive and specific for analysis of TAHI in the urine of exposed workers with a method detection limit at 0.03 µg/L. TAHI was detected in 33 of 111 urine samples and in 11 of 15 workers. This biomarker for HDI isocyanurate is critical to determine the relative potency and dose-relationships between the monomer and oligomer exposure on the development of diisocyanate induced health effects in future studies.

Effective Message Elements for Disclosures About Chemicals in Cigarette Smoke.

Introduction: Cigarette smoke contains at least 93 chemicals or "constituents" that the Food and Drug Administration has identified as harmful and potentially harmful constituents to human health. Our study sought to identify which constituent disclosure message elements are most effective in discouraging people from smoking. Methods: Three hundred eighty eight current smokers aged 18 and older completed an online survey in February 2015. We randomized participants to respond to one of two sets of 13 toxic products that contain cigarette constituents and 25 health effects associated with cigarette constituents. Results: Products that elicited the most discouragement were those with lower chances of exposure (e.g., explosives), followed by products with possible exposure (e.g., rat poison), and products with a high likelihood of exposure (e.g., floor cleaner). Awareness of toxic products that constituents are found in (p < .001) and low exposure products (p < .001) were associated with higher discouragement. Health effects that people had heard are caused by cigarette smoke constituents elicited higher discouragement from smoking cigarettes (p < .001). Cancer was associated with higher discouragement relative to respiratory, cardiovascular, and reproductive health effects (all p < .001). Conclusions: Cigarette smoke constituent messages may be more effective at discouraging smoking if they include information about carcinogenic health effects (e.g., mouth cancer and lung tumors) and low exposure toxic products (e.g., explosives and radioactive material) as message elements. Implications: Our study identified health effects and toxic products, especially cancers and rarely encountered toxic products, that may discourage smoking when included in disclosure messages. By constructing messages that communicate the harms associated with tobacco use by contextualizing those harms in terms of specific constituents, tobacco education messaging efforts may be increasingly successful.