The Climate Change Burden on Immune Health: Are Persons Living with HIV More at Risk?

Climate change poses one of the most significant modern threats to overall human health,especially for vulnerable populations including persons living with HIV (PLWH). In this perspective, we specifically explore the concept of immune resilience in human health and how climate change phenomena - including extreme weather events, food insecurity, pollution, and emerging diseases - may exacerbate immune dysfunction and comorbidities faced by PLWH and hinder access to HIV treatment and prevention services. Multidisciplinary, collaborative efforts are urgently needed to quantify these impacts, develop mitigation strategies, and strengthen policies and funding to bolster immune resilience for PLWH in the face of accelerating climate change.

Flame Retardant Exposure in Vehicles Is Influenced by Use in Seat Foam and Temperature.

Flame retardants (FRs) are added to vehicles to meet flammability standards, such as US Federal Motor Vehicle Safety Standard FMVSS 302. However, an understanding of which FRs are being used, sources in the vehicle, and implications for human exposure is lacking. US participants (n = 101) owning a vehicle of model year 2015 or newer hung a silicone passive sampler on their rearview mirror for 7 days. Fifty-one of 101 participants collected a foam sample from a vehicle seat. Organophosphate esters (OPEs) were the most frequently detected FR class in the passive samplers. Among these, tris(1-chloro-isopropyl) phosphate (TCIPP) had a 99% detection frequency and was measured at levels ranging from 0.2 to 11,600 ng/g of sampler. TCIPP was also the dominant FR detected in the vehicle seat foam. Sampler FR concentrations were significantly correlated with average ambient temperature and were 2-5 times higher in the summer compared to winter. The presence of TCIPP in foam resulted in ∼4 times higher median air sampler concentrations in winter and ∼9 times higher in summer. These results suggest that FRs used in vehicle interiors, such as in seat foam, are a source of OPE exposure, which is increased in warmer temperatures.

Monitoring human exposure to four parabens and triclosan: comparing silicone wristbands with spot urine samples as predictors of internal dose.

BACKGROUND: People are exposed to a variety of chemicals each day as a result of their personal care product (PCP) use. OBJECTIVE: This study was designed to determine if silicone wristbands provide a quantitative estimate of internal dose for phenols commonly associated with PCPs, with a focus on triclosan and four parabens: methyl-, ethyl-, propyl-, and butylparaben. Uptake of these compounds into wristbands and correlations with internal dose were assessed. METHODS: Ten adults from central North Carolina wore five silicone wristbands, with one wristband removed each day for 5 days. Each participant provided a 24 h urine sample and a random spot urine sample each day, in which paraben and triclosan metabolites were evaluated. RESULTS: All parabens and triclosan were detected frequently in wristbands and, except for butylparaben, in urine samples. Wristband and spot urine concentrations of parabens and triclosan were both compared to a measurement of internal dose (i.e., the total metabolite mass excreted over 5 days as a measurement of internal dose). IMPACT STATEMENT: The two most hydrophobic compounds investigated, butylparaben and triclosan, displayed significant linear uptake in wristbands over 5 days, whereas concentrations of methyl- and ethylparaben displayed a steady state concentration. In general, wristbands and spot urine samples were similarly correlated to internal dose for frequently detected parabens and triclosan.  However, wristbands have additional advantages including higher detection rates and reduced participant burden that may make them more suitable tools for assessing exposure to PCPs.

Children's exposure to brominated flame retardants in the home: The TESIE study.

Due to differences in chemical properties and half-lives, best practices for exposure assessment may differ for legacy versus novel brominated flame retardants (BFRs). Our objective was to identify the environment matrix that best predicted biomarkers of children's BFR exposures. Paired samples were collected from children aged 3-6 years and their homes, including dust, a small piece of polyurethane foam from the furniture, and a handwipe and wristband from each child. Biological samples collected included serum, which was analyzed for 11 polybrominated diphenyl ethers (PBDEs), and urine, which was analyzed for tetrabromobenzoic acid (TBBA), a metabolite of 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB). Significant positive correlations were typically observed between BFRs measured in dust, handwipes and wristbands, though wristbands and handwipes tended to be more strongly correlated with one another than with dust. PBDEs, EH-TBB and BEH-TEBP were detected in 30% of the sofa foam samples, suggesting that the foam was treated with PentaBDE or Firemaster® 550/600 (FM 550/600). PBDEs were detected in all serum samples and TBBA was detected in 43% of urine samples. Statistically significant positive correlations were observed between the environmental samples and serum for PBDEs. Urinary TBBA was 6.86 and 6.58 times more likely to be detected among children in the highest tertile of EH-TBB exposure for handwipes and wristbands, respectively (95 % CI: 2.61, 18.06 and 1.43, 30.05 with p < 0.001 and 0.02, respectively). The presence of either PentaBDE or FM 550/600 in furniture was also associated with significantly higher levels of these chemicals in dust, handwipes and serum (for PBDEs) and more frequent detection of TBBA in urine (p = 0.13). Our results suggest that children are exposed to a range of BFRs in the home, some of which likely originate from residential furniture, and that silicone wristbands are a practical tool for evaluating external exposure to both legacy and novel BFRs.

Chemical uptake into silicone wristbands over a five day period.

Silicone wristbands are a noninvasive personal exposure assessment tool. However, despite their utility, questions remain about the rate at which chemicals accumulate on wristbands when worn, as validation studies utilizing wristbands worn by human participants are limited. This study evaluated the chemical uptake rates of 113 organic pollutants from several chemical classes (i.e., polychlorinated biphenyls (PCB), organophosphate esters (OPEs), alkyl OPEs, polybrominated diphenyl ethers (PBDEs), brominated flame retardants (BFR), phthalates, pesticides, and polycyclic aromatic hydrocarbons (PAHs) over a five-day period. Adult participants (n = 10) were asked to wear five silicone wristbands and then remove one wristband each day. Several compounds were detected in all participants' wristbands after only one day. The number of chemicals detected frequently (i.e. in at least seven participants wristbands) increased from 20% of target compounds to 26% after three days and more substantially increased to 34% of target compounds after four days of wear. Chemicals detected in at least seven participants' day five wristbands (n = 24 chemicals) underwent further statistical analysis, including estimating the chemical uptake rates over time. Some chemicals, including pesticides and phthalates, had postive and significant correlations between concentrations on wristbands worn five days and concentrations of wristbands worn fewer days suggesting chronic exposure. For 23 of the 24 compounds evaluated there was a statistically significant and positive linear association between the length of time wristbands were worn and chemical concentrations in wristbands. Despite the differences that exist between laboratory studies using polydimethylsiloxane (PDMS) environmental samplers and worn wristbands, these results indicate that worn wristbands are primarily acting as first-order kinetic samplers. These results suggest that studies using different deployment lengths should be comparable when results are normalized to the length of the deployment period. In addition, a shorter deployment period could be utilized for compounds that were commonly detected in as little as one day.

Dimensional versus conceptual incommensurability in the social and behavioral sciences.

This commentary analyzes the extent to which the incommensurability problem can be resolved through the proposed alternative method of integrative experiment design. We suggest that, although one aspect of incommensurability is successfully addressed (dimensional incommensurability), the proposed design space method does not yet alleviate another major source of discontinuity, which we call conceptual incommensurability.

Cumulative environmental quality is associated with breast cancer incidence differentially by summary stage and urbanicity.

Individual environmental contaminants have been associated with breast cancer; however, evaluations of multiple exposures simultaneously are limited. Herein, we evaluated associations between breast cancer summary stages and the Environmental Quality Index (EQI), which includes a range of environmental factors across five domains. The EQI (2000-2005) was linked to county-level age-standardized incidence rates (SIRs) obtained from the North Carolina Central Cancer Registry (2010-2014). Incidence rates and SIRs of total, in situ, localized, regional, and distant breast cancers were evaluated stratified by rural-urban status. In counties with poor environmental quality compared to those with good environmental quality, total breast cancer incidence was higher by 10.82 cases per 100,000 persons (95% CI 2.04, 19.60, p = 0.02). This association was most pronounced for localized breast cancer (ß = 5.59, 95% CI 0.59, 10.58, p = 0.03). Higher incidence of early-stage disease (carcinoma in situ ß = 5.25, 95% CI 2.34, 8.16, p = 0.00 and localized breast cancer ß = 6.98, 95% CI 2.24, 11.73, p = 0.00) and total breast cancer (ß = 11.44, 95% CI 3.01, 19.87, p = 0.01) occurred in counties with poor land quality, especially urban counties. Our analyses indicate significant associations between environmental quality and breast cancer incidence, which differ by breast cancer stage and urbanicity, identifying a critical need to assess cumulative environmental exposures in the context of cancer stage.

Proximity to Swine Farming Operations as a Risk Factor for Eosinophilic Esophagitis.

We aimed to determine whether residential proximity to permitted swine facilities was associated with an increased risk of eosinophilic esophagitis (EoE) by conducting a case-control study using 2 complementary data sources: 1 from a tertiary care center (n = 401 cases and 1805 controls) and 1 from a large pathology group (n = 904 cases and 4074 controls). Addresses of the subjects and swine facilities were geocoded, and adjusted odds of EoE relative to proximity to and density of swine facilities were calculated. We observed a positive association between proximity to a permitted swine facility (<1 mile) and odds of EoE (adjusted odds ratio R, 2.56; 95% CI, 1.33-4.95) in the tertiary center data; density of farms (>10 farms/census tract) was also positively associated (adjusted odds ratio, 2.76; 95% CI, 1.30-5.84). However, this association was not observed in the pathology database. Though proximity to and density of swine operations were associated with EoE, associations were sensitive to the database used.

Characterizing azobenzene disperse dyes and related compounds in house dust and their correlations with other organic contaminant classes.

Azobenzene disperse dyes are the fastest-growing category of commercial dyestuffs and are implicated in the literature as potentially allergenic. In the indoor environment, these dyes may be shed from various textiles, including clothing and upholstery and accumulate in dust particles potentially leading to exposure in young children who have higher exposure to chemicals associated with dust due to their crawling and mouthing behaviors. Children may be more vulnerable to dye exposure due to their developing immune systems, and therefore, it is critical to characterize azobenzene disperse dyes in children's home environments. Here, we investigate azobenzene disperse dyes and related compounds in house dust samples (n = 124) that were previously analyzed for flame retardants, phthalates, pesticides and per- and polyfluoroalkyl substances (PFAS). High-resolution mass spectrometry was used to support both targeted and suspect screening of dyes in dust. Statistical analyses were conducted to determine if dye concentrations were related to demographic information. Detection frequencies for 12 target dyes ranged from 11% to 89%; of the dyes that were detected in at least 50% of the samples, geometric mean levels ranged from 32.4 to 360 ng/g. Suspect screening analysis identified eight additional high-abundance azobenzene compounds in dust. Some dyes were correlated to numerous flame retardants and several antimicrobials, and statistically higher levels of some dyes were observed in homes of non-Hispanic Black mothers than in homes of non-Hispanic white mothers. To our knowledge, this is the most comprehensive study of azobenzene disperse dyes in house dust to date. Future studies are needed to quantify additional dyes in dust and to examine exposure pathways of dyes in indoor environments where children are concerned.

Characterizing the Contribution of Indoor Residential Phthalate and Phthalate Alternative Dust Concentrations to Internal Dose in the US General Population: An Updated Systematic Review and Meta-Analysis.

Diet is the primary exposure pathway for phthalates, but relative contributions of other exposure sources are not well characterized. This study quantifies the relative contribution of indoor residential dust phthalate and phthalate alternative concentrations to total internal dose estimated from the National Health and Nutrition Examination Survey (NHANES) urinary metabolite concentrations. Specifically, median phthalate and phthalate alternative concentrations measured in residential dust were determined by updating a pre-existing systematic review and meta-analysis published in 2015 and the attributable internal dose was estimated using intake and reverse dosimetry models. Employing a predetermined search strategy, 12 studies published between January 2000 and April 2022 from Web of Science and PubMed measuring phthalates and phthalate alternatives in residential dust were identified. From the data extracted, it was estimated that dust contributed more significantly to the internal dose of low-molecular weight chemicals such as DEP and BBP when compared to high-molecular weight chemicals such as DEHTP. Additionally, findings showed that the chemical profile of residential dust is changing temporally with more phthalate alternatives being detected in the indoor environment. Future studies should seek to characterize the contribution of dust to an overall phthalate and phthalate alternative intake for individuals who have higher than normal exposures.

Measuring semi-volatile organic compound exposures during pregnancy using silicone wristbands.

Silicone wristbands were utilized as personal passive samplers in a sub-cohort of 92 women, who participated in New York University Children's Health and Environment Study, to assess exposure to semi-volatile organic compounds (SVOCs). Wristbands were analyzed for 77 SVOCs, including halogenated and non-halogenated organophosphate esters (OPEs), polychlorinated biphenyls (PCBs), pesticides, phthalates, and brominated flame retardants (BFRs) (e.g. polybrominated diphenyl ethers (PBDEs)). This study aimed to look for patterns in chemical exposure utilizing participant demographics gathered from a questionnaire, and chemical exposure data across multiple timepoints during pregnancy. Analysis focused on 27 compounds detected in at least 80% of the wristbands examined. The chemicals detected most frequently included two pesticides, eight phthalates, one phthalate alternative, seven BFRs, and nine OPEs, including isopropylated and tert-butylated triarylphosphate esters (ITPs and TBPPs). Co-exposure to different SVOCs was most prominent in compounds that were within the same chemical class or were used in similar consumer applications such as phthalates and OPEs, which are often used as plasticizers. Pre-pregnancy BMI was positively associated with multiple compounds, and there were both positive and negative associations between women's parity and SVOC exposure. Outdoor temperature was not correlated with the wristband concentrations over a five-day sampling period. Lastly, significant and moderately high Intraclass Correlation Coefficient (ICC) (0.66-0.84) values for phthalate measurementsacross pregnancy indicate chronic exposure and suggest that using wristbands during one sampling period may reliably predict exposure. However, multiple sampling periods may be necessary to accurately determine indoor exposure to other SVOCs including OPEs and BFRs.

Escherichia coli ST131 Associated with Increased Mortality in Bloodstream Infections from Urinary Tract Source.

Escherichia coli sequence type 131 (ST131) is a globally dominant multidrug-resistant clone, although its clinical impact on patients with bloodstream infection (BSI) is incompletely understood. This study aims to further define the risk factors, clinical outcomes, and bacterial genetics associated with ST131 BSI. A prospectively enrolled cohort study of adult inpatients with E. coli BSI was conducted from 2002 to 2015. Whole-genome sequencing was performed with the E. coli isolates. Of the 227 patients with E. coli BSI in this study, 88 (39%) were infected with ST131. Patients with E. coli ST131 BSI and those with non-ST131 BSI did not differ with respect to in-hospital mortality (17/82 [20%] versus 26/145 [18%]; P = 0.73). However, in patients with BSI from a urinary tract source, ST131 was associated with a numerically higher in-hospital mortality than patients with non-ST131 BSI (8/42 [19%] versus 4/63 [6%]; P = 0.06) and increased mortality in an adjusted analysis (odds ratio of 5.85; 95% confidence interval of 1.44 to 29.49; P = 0.02). Genomic analyses showed that ST131 isolates primarily had an H4:O25 serotype, had a higher number of prophages, and were associated with 11 flexible genomic islands as well as virulence genes involved in adhesion (papA, kpsM, yfcV, and iha), iron acquisition (iucC and iutA), and toxin production (usp and sat). In patients with E. coli BSI from a urinary tract source, ST131 was associated with increased mortality in an adjusted analysis and contained a distinct repertoire of genes influencing pathogenesis. These genes could contribute to the higher mortality observed in patients with ST131 BSI.

PFAS levels in paired drinking water and serum samples collected from an exposed community in Central North Carolina.

The community of Pittsboro, North Carolina has been documented to have extensive per- and polyfluoroalkyl substances (PFAS) contamination in its drinking water source, the Haw River, over the last 20 years. However, a detailed exposure assessment has never been conducted. In this study, we sought to characterize the PFAS in paired drinking water and blood samples collected from a small cohort of Pittsboro residents (n = 49). Drinking water and serum from blood were collected from adults in late 2019 and early 2020 and were analyzed to quantify 13 PFAS analytes. In order to explore potential health effects of PFAS exposure, serum was further analyzed for clinical chemistry endpoints that could be potentially associated with PFAS (e.g., cholesterol, liver function biomarkers). PFAS were detected in all serum samples, and some serum PFAS concentrations were 2 to 4 times higher than the median U.S. serum concentrations reported in the general U.S. population. Of the 13 PFAS in drinking water, perfluorohexanoic acid (PFHxA) was measured at the highest concentrations. PFAS levels in the current drinking water were not associated with current serum PFAS, suggesting that the serum PFAS in this cohort likely reflects historical exposure to PFAS with long half-lives (e.g., PFOS and PFOA). However, one PFAS with a shorter half-life (PFHxA) was observed to increase in serum, reflecting the temporal variability of PFHxA in river and drinking water. Statistical analyses indicated that serum PFOA and PFHxS were positively associated with total cholesterol and non-HDL cholesterol. No serum PFAS was associated with HDL cholesterol. In the clinical chemistry analyses, serum PFHxA was found to be negatively associated with electrolytes and liver enzymes (e.g., AST and ALT), and serum PFOS was found to be positively associated with the ratio of blood urea nitrogen to creatinine (BUN:Cre). While small in size, this study revealed extensive exposure to PFAS in Pittsboro and associations with clinical blood markers, suggesting potential health impacts in community residents.

Adipogenic and endocrine disrupting mixture effects of organic and inorganic pollutant mixtures.

Chronic health conditions are rapidly increasing in prevalence and cost to society worldwide: in the US, >42 % of adults aged 20 and older are currently classified as obese. Exposure to endocrine disrupting chemicals (EDCs) has been implicated as a causal factor; some EDCs, termed "obesogens", can increase weight and lipid accumulation and/or perturb metabolic homeostasis. This project aimed to assess the potential combination effects of diverse inorganic and organic contaminant mixtures, which more closely reflect environmentally realistic exposures, on nuclear receptor activation/inhibition and adipocyte differentiation. Herein, we focused on two polychlorinated biphenyls (PCB-77 and 153), two perfluoroalkyl substances (PFOA and PFOS), two brominated flame retardants (PBB-153 and BDE-47), and three inorganic contaminants (lead, arsenic, and cadmium). We examined adipogenesis using human mesenchymal stem cells and receptor bioactivities using luciferase reporter gene assays in human cell lines. We observed significantly greater effects for several receptor bioactivities by various contaminant mixtures relative to individual components. All nine contaminants promoted triglyceride accumulation and/or pre-adipocyte proliferation in human mesenchymal stem cells. Comparing simple component mixtures to individual components at 10 % and 50 % effect levels revealed putative synergistic effects for each of the mixtures for at least one of the concentrations relative to the individual component chemicals, some of which also exhibited significantly greater effects than the component contaminants. Our results support further testing of more realistic and complex contaminant mixtures that better reflect environmental exposures, in order to more conclusively define mixture responses both in vitro and in vivo.

Brominated flame retardants and legacy organochlorines in archived human placenta samples: Sex differences, temporal analysis and associations with infant birth weight.

Perinatal exposure to persistent organic pollutants (POPs) has been suggested to play a role in the etiology of adverse pregnancy outcomes. This study evaluated temporal changes in the accumulation of several classes of POPs, including polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs) and several organochlorine pesticides in human placenta and examined their associations with birth outcomes at delivery. Placental tissues (n = 99) previously collected and archived at the Duke University Medical Center from 2009 to 2015 were analyzed for 22 POPs using gas chromatography mass spectrometry. The mean age of mothers was 30.6 years; 8% of newborns were characterized as low birthweight (<2500 g). Of the 22 POPs targeted in the analysis, only p,p'-DDE, BDE-47 and BDE-100 were detected in more than 50% of the samples, with median concentrations of 0.110, 0.310, and 0.033 ng/g wet weight, respectively. Placental PBDE concentrations generally decreased over time, particularly BDE-47. Placental tissues associated with female infants had significantly higher levels of BDE-100 than placental tissues associated with male infants (p = 0.02) and a similar, but not statistically significant trend was observed for BDE-47 (p = 0.07). Multivariate regression models revealed that placental BDE-47 concentrations were associated with a significantly lower birthweight among male, but not female infants. A similar, although non-statistically significant, trend was observed for other POPs, further suggesting sex-specific associations between gestational exposure to POPs and birthweight.

Changes in hemoglobin and clinical outcomes drive improvements in fatigue, quality of life, and physical function in patients with paroxysmal nocturnal hemoglobinuria: post hoc analyses from the phase III PEGASUS study.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, chronic, acquired, hematologic, life-threatening disease characterized by thrombosis, impaired bone marrow function, and complement-mediated hemolysis. The PEGASUS phase III clinical trial demonstrated superiority of pegcetacoplan over eculizumab regarding improvements in hemoglobin levels in patients with suboptimal response to prior eculizumab treatment. The objective of this post hoc analysis was to compare the patient-reported outcome (PRO) response rates observed among PEGASUS participants and the relationships between their PRO scores with clinical and hematological parameters. Data from the 16-week randomized, controlled (1:1 to pegcetacoplan or eculizumab) period of the PEGASUS trial included comparisons of weekly PRO measurements taken using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) scales. A clinically meaningful FACIT-F response was defined as an increase from baseline of ≥5 points. Convergent validity was assessed using conventional threshold correlations between FACIT-F, EORTC QLQ-C30, and laboratory parameters. A clinically meaningful improvement in FACIT-F score was seen in 72.2% of pegcetacoplan-treated patients compared to 22.9% of eculizumab-treated patients. At week 16, the FACIT-F total score correlated with hemoglobin levels (r=0.47, p< 0.0001), absolute reticulocyte count (r=-0.37, p<0.01), and indirect bilirubin levels (r=-0.25, p<0.05). Clinically meaningful improvements in pegcetacoplan-treated patients were also observed for multiple EORTC scales. Fatigue and other self-reported outcomes were correlated with clinically meaningful improvements in clinical and hematological parameters. Clinical trial registration: NCT03500549.

On the Utility of ToxCast-Based Predictive Models to Evaluate Potential Metabolic Disruption by Environmental Chemicals.

BACKGROUND: Research suggests environmental contaminants can impact metabolic health; however, high costs prohibit in vivo screening of putative metabolic disruptors. High-throughput screening programs, such as ToxCast, hold promise to reduce testing gaps and prioritize higher-order (in vivo) testing. OBJECTIVES: We sought to a) examine the concordance of in vitro testing in 3T3-L1 cells to a targeted literature review for 38 semivolatile environmental chemicals, and b) assess the predictive utility of various expert models using ToxCast data against the set of 38 reference chemicals. METHODS: Using a set of 38 chemicals with previously published results in 3T3-L1 cells, we performed a metabolism-targeted literature review to determine consensus activity determinations. To assess ToxCast predictive utility, we used two published ToxPi models: a) the 8-Slice model published by Janesick et al. (2016) and b) the 5-Slice model published by Auerbach et al. (2016). We examined the performance of the two models against the Janesick in vitro results and our own 38-chemical reference set. We further evaluated the predictive performance of various modifications to these models using cytotoxicity filtering approaches and validated our best-performing model with new chemical testing in 3T3-L1 cells. RESULTS: The literature review revealed relevant publications for 30 out of the 38 chemicals (the remaining 8 chemicals were only examined in our previous 3T3-L1 testing). We observed a balanced accuracy (average of sensitivity and specificity) of 0.86 comparing our previous in vitro results to the literature-derived calls. ToxPi models provided balanced accuracies ranging from 0.55 to 0.88, depending on the model specifications and reference set. Validation chemical testing correctly predicted 29 of 30 chemicals as per 3T3-L1 testing, suggesting good adipogenic prediction performance for our best adapted model. DISCUSSION: Using the most recent ToxCast data and an updated ToxPi model, we found ToxCast performed similarly to that of our own 3T3-L1 testing in predicting consensus calls. Furthermore, we provide the full ranked list of largely untested chemicals with ToxPi scores that predict adipogenic activity and that require further investigation. https://doi.org/10.1289/EHP6779.

Infants' diminished response to DTaP vaccine is associated with exposure to organophosphate esters.

Organophosphate esters (OPEs) are commonly applied as flame retardants and plasticizers. Toxicological studies suggest exposure effects on immune endpoints, raising concerns as infants' OPE exposures are elevated compared to older children and adults due to hand-to-mouth behavior and breastfeeding. Here, we sought to evaluate the immune responsiveness of infants to a neoantigen (e.g., a newly encountered antigen) in the presence of OPE exposures. As a proxy for immune responsiveness, children were given three doses of the Diphtheria, Tetanus, and Pertussis (DTaP) vaccine as recommended, and diphtheria and tetanus antibodies were evaluated in serum samples collected when children were 12 months old (n = 84). Titers were compared, based on maximum sample overlap, to measurements of OPE metabolites in spot urine samples collected before vaccination (age 2 months, n = 73) and at the time of antibody assessment (12 months of age, n = 46). Metabolites of two chlorinated OPEs were significantly associated with diminished antibodies for diphtheria and tetanus. A metabolite of tris (1,3-dichloroisopropyl)phosphate (TDCIPP) measured at 2 months was associated with decreased diphtheria antibodies (-0.07 IU/mL per log10 increase in metabolite). One metabolite of tris(2-chloroisopropyl)phosphate (TCIPP) measured at 12 months was associated with decreased tetanus antibodies (-0.57 IU/mL per log10 increase in metabolite). These results provide some preliminary insights for OPE exposure impacts on vaccine responses in early life and may have important implications for immune health through childhood and adulthood.

Characterizing firefighter's exposure to over 130 SVOCs using silicone wristbands: A pilot study comparing on-duty and off-duty exposures.

Firefighters are occupationally exposed to an array of hazardous chemicals, and these exposures have been linked to the higher rates of some cancer in firefighters. However, additional research that characterizes firefighters' exposure is needed to fully elucidate the impacts on health risks. In this pilot study, we used silicone wristbands to quantify off-duty and on-duty chemical exposures experienced by 20 firefighters in Durham, North Carolina. By using each firefighter's off-duty wristband to represent individual baseline exposures, we assessed occupation-related exposures (i.e. on-duty exposures). We also investigated the influence of responding to a fire event while on-duty. In total, 134 chemicals were quantified using both GC-MS and LC-MS/MS targeted methods. Seventy-one chemicals were detected in at least 50% of all silicone wristbands, including 7 PFAS, which to our knowledge, have not been reported in wristbands previously. Of these, phthalates were generally measured at the highest concentrations, followed by brominated flame retardants (BFRs) and organophosphate esters (OPEs). PFAS were measured at lower concentrations overall, but firefighter PFOS exposures while on-duty and responding to fires were 2.5 times higher than off-duty exposures. Exposure to polycyclic aromatic hydrocarbons (PAH), BFRs, and some OPEs were occupationally associated, with firefighters experiencing 0.5 to 8.5 times higher exposure while on-duty as compared to off-duty. PAH exposures were also higher for firefighters who respond to a fire than those who did not while on-duty. Additional research with a larger population of firefighters that builds upon this pilot investigation may further pinpoint exposure sources that may contribute to firefighters' risk for cancer, such as those from firefighter gear or directly from fires. This research demonstrates the utility of using silicone wristbands to quantify occupational exposure in firefighters and the ability to disentangle exposures that may be specific to fire events as opposed to other sources that firefighters might experience.