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.
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.
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.
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%, LC
) 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 LC
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 LC
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.
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.
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.
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.
•A urine biomarker, TAHI, was established for the asthmogen HDI isocyanurate.•Standards were synthesized for specific and sensitive nano-UPLC-ESI-MS/MS analysis.•TAHI was quantified in the urine of 11 of 15 spray painters.•Linear correlation was observed between inhalation exposure and urine TAHI levels.
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.
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.
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.
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.
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.
Additional refinement and testing of the TWH approach postpandemic with more worksites is warranted.
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