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.

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.