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.

Online and Offline Prioritization of Chemicals of Interest in Suspect Screening and Non-targeted Screening with High-Resolution Mass Spectrometry.

Recent advances in high-resolution mass spectrometry (HRMS) have enabled the detection of thousands of chemicals from a single sample, while computational methods have improved the identification and quantification of these chemicals in the absence of reference standards typically required in targeted analysis. However, to determine the presence of chemicals of interest that may pose an overall impact on ecological and human health, prioritization strategies must be used to effectively and efficiently highlight chemicals for further investigation. Prioritization can be based on a chemical's physicochemical properties, structure, exposure, and toxicity, in addition to its regulatory status. This Perspective aims to provide a framework for the strategies used for chemical prioritization that can be implemented to facilitate high-quality research and communication of results. These strategies are categorized as either "online" or "offline" prioritization techniques. Online prioritization techniques trigger the isolation and fragmentation of ions from the low-energy mass spectra in real time, with user-defined parameters. Offline prioritization techniques, in contrast, highlight chemicals of interest after the data has been acquired; detected features can be filtered and ranked based on the relative abundance or the predicted structure, toxicity, and concentration imputed from the tandem mass spectrum (MS2). Here we provide an overview of these prioritization techniques and how they have been successfully implemented and reported in the literature to find chemicals of elevated risk to human and ecological environments. A complete list of software and tools is available from https://nontargetedanalysis.org/.

Complex Mixtures and Multiple Stressors: Evaluating Combined Chemical Exposures and Cumulative Toxicity.

The problem of chemical mixtures in the environment encompasses biological, analytical, logistical, and regulatory challenges, among others [...].

Demonstrating the Use of Non-targeted Analysis for Identification of Unknown Chemicals in Rapid Response Scenarios.

Several thousand intentional and unintentional chemical releases occur annually in the U.S., with the contents of almost 30% being of unknown composition. When targeted methods are unable to identify the chemicals present, alternative approaches, including non-targeted analysis (NTA) methods, can be used to identify unknown analytes. With new and efficient data processing workflows, it is becoming possible to achieve confident chemical identifications via NTA in a timescale useful for rapid response (typically 24-72 h after sample receipt). To demonstrate the potential usefulness of NTA in rapid response situations, we have designed three mock scenarios that mimic real-world events, including a chemical warfare agent attack, the contamination of a home with illicit drugs, and an accidental industrial spill. Using a novel, focused NTA method that utilizes both existing and new data processing/analysis methods, we have identified the most important chemicals of interest in each of these designed mock scenarios in a rapid manner, correctly assigning structures to more than half of the 17 total features investigated. We have also identified four metrics (speed, confidence, hazard information, and transferability) that successful rapid response analytical methods should address and have discussed our performance for each metric. The results reveal the usefulness of NTA in rapid response scenarios, especially when unknown stressors need timely and confident identification.

Impact of diabetes (type 2) and glycemic control on health-related outcomes of patients receiving chemotherapy for non-metastatic breast cancer: a retrospective analysis.

PURPOSE: To examine the impact of diabetes (type 2) and glycemic control on healthcare-related outcomes (healthcare utilization, adverse effects, and treatment modifications) in non-metastatic breast cancer (NMBC) patients during chemotherapy treatment. METHODS: This was a retrospective study of 243 NMBC patients (stages 1-3) with/without diabetes receiving neoadjuvant or adjuvant cytotoxic chemotherapy. The primary study endpoint was to compare healthcare utilization between NMBC patients with and without diabetes. Secondary study endpoints included adverse events and chemotherapy treatment modifications. Additional analyses were conducted to compare these health-related outcomes by glycemic control status. RESULTS: NMBC patients with diabetes had higher utilization of emergency department (ED) services (52% vs. 33%, p = 0.013) and a higher frequency of unplanned inpatient admissions (35% vs. 19%, p = 0.014). Additionally, NMBC patients with diabetes had a higher incidence of infection and treatment modifications. NMBC patients, regardless of diabetes diagnosis, who had poor glycemic control, specifically hyperglycemia (per random blood glucose), during the study period also had increased healthcare utilization, adverse effects, and treatment modifications. Patients with a baseline HbA1c ≥ 7 had a greater number of ED visits and a higher incidence of infection than those without diabetes. CONCLUSION: Diabetes and glycemic control may impact the health-related outcomes of NMBC patients. Additional studies are needed to confirm these findings and determine optimal monitoring and management strategies for NMBC patients with diabetes and/or poor glycemic control during cytotoxic chemotherapy.

Nivolumab/Relatlimab: A Novel Addition to Immune Checkpoint Inhibitor Therapy in Unresectable or Metastatic Melanoma.

OBJECTIVE: The aim of this article is to assess available data regarding use of nivolumab/relatlimab for adult and pediatric patients 12 years of age and older with unresectable or metastatic melanoma. DATA SOURCES: A search of PubMed conducted from August 2019 to August 2022 with the search terms Opdualag, nivolumab AND relatlimab, and BMS-986016 resulted in 14 publications. STUDY SELECTION AND DATA EXTRACTION: Relevant clinical trials written in English language were analyzed. DATA SYNTHESIS: Nivolumab/relatlimab was approved by the Food and Drug Administration following results of a phase 1/2 trial and phase 2/3 RELATIVITY-047 trial. Nivolumab/relatlimab demonstrated a median progression free survival (PFS) of 10.1 months in the first-line setting without new safety signals. The PFS benefits appear greatest in those with programmed cell death-ligand 1 (PD-L1) <1% and lymphocyte activation gene-3 (LAG-3) ≥1%. Adverse effects commonly experienced were immune related in nature and require early identification and prompt management. Grade 3 or 4 adverse effects occurred in 18.9% of patients. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: For patients 12 years of age and older with unresectable or metastatic melanoma, nivolumab/relatlimab offers a new first-line treatment option. Evaluation of PD-L1 expression along with concomitant use of medications with potential interactions should be evaluated when deciding if nivolumab/relatlimab is the most appropriate treatment option. CONCLUSIONS: Nivolumab/relatlimab adds an additional first-line treatment option demonstrating promising improved PFS for patients with unresectable or metastatic melanoma, particularly those with PD-L1 <1% and/or LAG 3 ≥1%. Additional uses of nivolumab/relatlimab may be on the horizon as further clinical trials are ongoing.

Outcomes and Management of Immune Checkpoint Inhibitor-Induced Hypothyroidism: A Retrospective Analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) used in cancer treatment cause immune-related adverse effects (irAEs), including thyroiditis leading to hypothyroidism. The management and outcomes of this irAE are not well established. OBJECTIVE: The purpose of this analysis is to describe the onset, management, and outcomes of patients experiencing hypothyroidism from ICI. METHODS: A retrospective study was conducted of adults receiving ICI therapy at a community cancer center between January 1, 2017, and February 1, 2020. The primary endpoint was to describe onset (timing) of hypothyroidism (thyroid-stimulating hormone [TSH] > 10 µIU/mL). Secondary outcomes included describing hypothyroidism symptoms and levothyroxine use, time to documented disease progression, and occurrence of additional adverse effects (AEs). RESULTS: Of the 200 patients included in the study, 19% developed clinical hypothyroidism (TSH > 10 µIU/mL, or required initiation of or dose increase in levothyroxine). Median time to TSH higher than 10 µIU/mL was 13.3 weeks and symptoms of hypothyroidism occurred in 34% of patients developing clinical hypothyroidism. The median final daily levothyroxine dose was 88 mcg (0.88 mcg/kg). Time to disease progression was longer in those with clinical hypothyroidism (27.4 months vs. 6.8 months, respectively, P = .015). Additional AEs occurred in 68% of those developing hypothyroidism versus 49% without hypothyroidism (P = .029). CONCLUSION AND RELEVANCE: Patients with clinical hypothyroidism during ICI treatment may have improved cancer outcomes, but they also are more likely to develop other AEs. Patients requiring thyroid replacement therapy with levothyroxine may benefit from a starting dose between 50 and 100 mcg/day, approximately 0.88 mcg/kg/day.

Persistent autism-relevant behavioral phenotype and social neuropeptide alterations in female mice offspring induced by maternal transfer of PBDE congeners in the commercial mixture DE-71.

Polybrominated diphenyl ethers (PBDEs) are ubiquitous persistent organic pollutants (POPs) that are known neuroendocrine disrupting chemicals with adverse neurodevelopmental effects. PBDEs may act as risk factors for autism spectrum disorders (ASD), characterized by abnormal psychosocial functioning, although direct evidence is currently lacking. Using a translational exposure model, we tested the hypothesis that maternal transfer of a commercial mixture of PBDEs, DE-71, produces ASD-relevant behavioral and neurochemical deficits in female offspring. C57Bl6/N mouse dams (F0) were exposed to DE-71 via oral administration of 0 (VEH/CON), 0.1 (L-DE-71) or 0.4 (H-DE-71) mg/kg bw/d from 3 wk prior to gestation through end of lactation. Mass spectrometry analysis indicated in utero and lactational transfer of PBDEs (in ppb) to F1 female offspring brain tissue at postnatal day (PND) 15 which was reduced by PND 110. Neurobehavioral testing of social novelty preference (SNP) and social recognition memory (SRM) revealed that adult L-DE-71 F1 offspring display deficient short- and long-term SRM, in the absence of reduced sociability, and increased repetitive behavior. These effects were concomitant with reduced olfactory discrimination of social odors. Additionally, L-DE-71 exposure also altered short-term novel object recognition memory but not anxiety or depressive-like behavior. Moreover, F1 L-DE-71 displayed downregulated mRNA transcripts for oxytocin (Oxt) in the bed nucleus of the stria terminalis (BNST) and supraoptic nucleus, and vasopressin (Avp) in the BNST and upregulated Avp1ar in BNST, and Oxtr in the paraventricular nucleus. Our work demonstrates that developmental PBDE exposure produces ASD-relevant neurochemical, olfactory processing and behavioral phenotypes that may result from early neurodevelopmental reprogramming within central social and memory networks.

A Framework for Utilizing High-Resolution Mass Spectrometry and Nontargeted Analysis in Rapid Response and Emergency Situations.

Unknown chemical releases constitute a large portion of the rapid response situations to which the US Environmental Protection Agency is called on to respond. Workflows used to address unknown chemical releases currently involve screening for a large array of known compounds using many different targeted methods. When matches are not found, expert analytical chemistry knowledge is used to propose possible candidates from the available data, which generally includes low-resolution mass spectra and situational clues such as the location of the release, nearby industrial operations, and other field-reported facts. The past decade has witnessed dramatic improvements in capabilities for identifying unknown compounds using high-resolution mass spectrometry (HRMS) and nontargeted analysis (NTA) approaches. Complementary developments in cheminformatics tools have further enabled an increase in NTA throughput and identification confidence. Together with the expanding availability of HRMS instrumentation in monitoring laboratories, these advancements make NTA highly relevant to rapid response scenarios. In this article, we introduce the concept of NTA as it relates to rapid response needs and describe how it can be applied to address unknown chemical releases. We advocate for the consideration of HRMS-based NTA approaches to support future rapid response scenarios. Environ Toxicol Chem 2022;41:1117-1130. Published 2021. This article is a U.S. Government work and is in the public domain in the USA.

An Introduction to the Benchmarking and Publications for Non-Targeted Analysis Working Group.

Non-targeted analysis (NTA) encompasses a rapidly evolving set of mass spectrometry techniques aimed at characterizing the chemical composition of complex samples, identifying unknown compounds, and/or classifying samples, without prior knowledge regarding the chemical content of the samples. Recent advances in NTA are the result of improved and more accessible instrumentation for data generation and analysis tools for data evaluation and interpretation. As researchers continue to develop NTA approaches in various scientific fields, there is a growing need to identify, disseminate, and adopt community-wide method reporting guidelines. In 2018, NTA researchers formed the Benchmarking and Publications for Non-Targeted Analysis Working Group (BP4NTA) to address this need. Consisting of participants from around the world and representing fields ranging from environmental science and food chemistry to 'omics and toxicology, BP4NTA provides resources addressing a variety of challenges associated with NTA. Thus far, BP4NTA group members have aimed to establish a consensus on NTA-related terms and concepts and to create consistency in reporting practices by providing resources on a public Web site, including consensus definitions, reference content, and lists of available tools. Moving forward, BP4NTA will provide a setting for NTA researchers to continue discussing emerging challenges and contribute to additional harmonization efforts.

Nontargeted Analysis Study Reporting Tool: A Framework to Improve Research Transparency and Reproducibility.

Non-targeted analysis (NTA) workflows using mass spectrometry are gaining popularity in many disciplines, but universally accepted reporting standards are nonexistent. Current guidance addresses limited elements of NTA reporting-most notably, identification confidence-and is insufficient to ensure scientific transparency and reproducibility given the complexity of these methods. This lack of reporting standards hinders researchers' development of thorough study protocols and reviewers' ability to efficiently assess grant and manuscript submissions. To overcome these challenges, we developed the NTA Study Reporting Tool (SRT), an easy-to-use, interdisciplinary framework for comprehensive NTA methods and results reporting. Eleven NTA practitioners reviewed eight published articles covering environmental, food, and health-based exposomic applications with the SRT. Overall, our analysis demonstrated that the SRT provides a valid structure to guide study design and manuscript writing, as well as to evaluate NTA reporting quality. Scores self-assigned by authors fell within the range of peer-reviewer scores, indicating that SRT use for self-evaluation will strengthen reporting practices. The results also highlighted NTA reporting areas that need immediate improvement, such as analytical sequence and quality assurance/quality control information. Although scores intentionally do not correspond to data/results quality, widespread implementation of the SRT could improve study design and standardize reporting practices, ultimately leading to broader use and acceptance of NTA data.

Young children's exposure to phenols in the home: Associations between house dust, hand wipes, silicone wristbands, and urinary biomarkers.

BACKGROUND: Environmental phenols, such as parabens, bisphenol A, and triclosan, are ubiquitous in indoor environments because of their use in packaging, plastics, personal care products, and as anti-microbials. The primary pathways of exposure, as well as habits and behaviors that may lead to greater exposure, are still unclear. OBJECTIVES: Herein, we investigate the relationships between phenols found in residential environments by comparing levels in paired samples of house dust and hand wipes with children's urine. In addition, phenols were analyzed in a novel exposure tool, the silicone wristbands, to investigate which external matrix best correlates with individual exposure based on urinary phenol biomarkers. METHODS: Children aged 3-6 years in central North Carolina, United States, provided paired hand wipe (n = 202), wristband (n = 76), and spot urine samples (n = 180), while legal guardians completed questionnaires on habits and behaviors. House dust samples (n = 186) were collected from the main living area during home visits completed between 2014 and 2016. RESULTS: Environmental phenols were detected frequently in all matrices investigated. Ethyl, methyl, and propylparaben levels observed in hand wipes, dust, and on wristbands were significantly correlated to their associated urinary biomarkers. In addition, intra-paraben correlations were noted, with biomarkers of ethyl, methyl, and propylparabens generally positively and significantly correlated, which suggests co-application of parabens in products. Triclosan levels in dust were positive and significantly correlated with levels in hand wipes and wristbands and with urinary concentrations, suggesting non-personal care product sources may be important in children's overall triclosan exposure. Generally, chemicals on wristbands were more highly correlated with urinary biomarkers than with chemicals in hand wipes or house dust. In addition, more frequent lotion use was positively associated with urinary concentrations of paraben biomarkers. CONCLUSIONS: Our results suggest that the home environment is an important source of exposure which has been under-investigated for some environmental phenols (e.g., triclosan in house dust). Associations between wristbands and biomarkers of exposure, which were stronger than for hand wipes and house dust, suggest that silicone wristbands may provide a suitable exposure assessment tool for some phenols.

Characterization of adipogenic, PPARγ, and TRß activities in house dust extracts and their associations with organic contaminants.

In this study, we sought to expand our previous research on associations between bioactivities in dust and associated organic contaminants. Dust samples were collected from central NC homes (n = 188), solvent extracted, and split into two fractions, one for analysis using three different bioassays (nuclear receptor activation/inhibition and adipocyte development) and one for mass spectrometry (targeted measurement of 124 organic contaminants, including flame retardants, polychlorinated biphenyls, perfluoroalkyl substances, pesticides, phthalates, and polycyclic aromatic hydrocarbons). Approximately 80% of dust extracts exhibited significant adipogenic activity at concentrations that are comparable to estimated exposure for children and adults (e.g. ~20 µg/well dust) via either triglyceride accumulation (65%) and/or pre-adipocyte proliferation (50%). Approximately 76% of samples antagonized thyroid receptor beta (TRß), and 21% activated peroxisome proliferator activated receptor gamma (PPARγ). Triglyceride accumulation was significantly correlated with TRß antagonism. Sixty-five contaminants were detected in at least 75% of samples; of these, 26 were correlated with adipogenic activity and ten with TRß antagonism. Regression models were used to evaluate associations of individual contaminants with adipogenic and TRß bioactivities, and many individual contaminants were significantly associated. An exploratory g-computation model was used to evaluate the effect of mixtures. Contaminant mixtures were positively associated with triglyceride accumulation, and the magnitude of effect was larger than for any individually measured chemical. For each quartile increase in mixture exposure, triglyceride accumulation increased by 212% (RR = 3.12 and 95% confidence interval: 1.58, 6.17). These results suggest that complex mixtures of chemicals present in house dust may induce adipogenic activity in vitro at environmental concentrations and warrants further research.

Per- and Polyfluoroalkyl Substances in Dust Collected from Residential Homes and Fire Stations in North America.

Over the past few years, human exposure to per- and polyfluoroalkyl substances (PFAS) has garnered increased attention. Research has focused on PFAS exposure via drinking water and diet, and fewer studies have focused on exposure in the indoor environment. To support more research on the latter exposure pathway, we conducted a study to evaluate PFAS in indoor dust. Dust samples from 184 homes in North Carolina and 49 fire stations across the United States and Canada were collected and analyzed for a suite of PFAS using liquid and gas chromatography-mass spectrometry. Fluorotelomer alcohols (FTOHs) and di-polyfluoroalkyl phosphoric acid esters (diPAPs) were the most prevalent PFAS in both fire station and house dust samples, with medians of approximately 100 ng/g dust or greater. Notably, perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonate, perfluorononanoic acid, and 6:2 diPAP were significantly higher in dust from fire stations than from homes, and 8:2 FTOH was significantly higher in homes than in fire stations. Additionally, when comparing our results to earlier published values, we see that perfluoroalkyl acid levels in residential dust appear to decrease over time, particularly for PFOA and PFOS. These results highlight a need to better understand what factors contribute to PFAS levels in dust and to understand how much dust contributes to overall human PFAS exposure.

Maternal transfer of environmentally relevant polybrominated diphenyl ethers (PBDEs) produces a diabetic phenotype and disrupts glucoregulatory hormones and hepatic endocannabinoids in adult mouse female offspring.

Polybrominated diphenyl ethers (PBDEs) are brominated flame retardant chemicals and environmental contaminants with endocrine-disrupting properties that are associated with diabetes and metabolic syndrome in humans. However, their diabetogenic actions are not completely characterized or understood. In this study, we investigated the effects of DE-71, a commercial penta-mixture of PBDEs, on glucoregulatory parameters in a perinatal exposure model using female C57Bl/6 mice. Results from in vivo glucose and insulin tolerance tests and ex vivo analyses revealed fasting hyperglycemia, glucose intolerance, reduced sensitivity and delayed glucose clearance after insulin challenge, decreased thermogenic brown adipose tissue mass, and exaggerated hepatic endocannabinoid tone in F1 offspring exposed to 0.1 mg/kg DE-71 relative to control. DE-71 effects on F0 dams were more limited indicating that indirect exposure to developing offspring is more detrimental. Other ex vivo glycemic correlates occurred more generally in exposed F0 and F1, i.e., reduced plasma insulin and altered glucoregulatory endocrines, exaggerated sympathoadrenal activity and reduced hepatic glutamate dehydrogenase enzymatic activity. Hepatic PBDE congener analysis indicated maternal transfer of BDE-28 and -153 to F1 at a collective level of 200 ng/g lipid, in range with maximum values detected in serum of human females. Given the persistent diabetogenic phenotype, especially pronounced in female offspring after developmental exposure to environmentally relevant levels of DE-71, additional animal studies should be conducted that further characterize PBDE-induced diabetic pathophysiology and identify critical developmental time windows of susceptibility. Longitudinal human studies should also be conducted to determine the risk of long-lasting metabolic consequences after maternal transfer of PBDEs during early-life development.

In Vitro Metabolism of Isopropylated and tert-Butylated Triarylphosphate Esters Using Human Liver Subcellular Fractions.

Isopropylated and tert-butylated triarylphosphate esters (ITPs and TBPPs, respectively) are plasticizers and flame retardants that are ubiquitous in indoor environments; however, no studies to date have characterized their metabolism. Using human liver subcellular S9 fractions, phase I and II in vitro metabolism of triphenyl phosphate (TPHP), 4-tert-butylphenyl diphenyl phosphate (4tBPDPP), 2-isopropylphenyl diphenyl phosphate (2IPPDPP), and 4-isopropylphenyl diphenyl phosphate (4IPPDPP) was investigated at 1 and 10 µM doses. Parent depletion and the formation of known or suspected metabolites (e.g., likely hydrolysis or hydroxylated products), including diphenyl phosphate (DPHP), hydroxyl-triphenyl phosphate (OH-TPHP), isopropylphenyl phenyl phosphate (ip-PPP), and tert-butylphenyl phenyl phosphate (tb-PPP), were monitored and quantified via GC/MS or LC-MS/MS. tb-PPP and its conjugates were identified as the major in vitro metabolites of 4tBPDPP and accounted for 71% and 49%, respectively, of the parent molecule that was metabolized during the incubation. While the mass balance between parents and metabolites was conserved for TPHP and 4tBPDPP, approximately 20% of the initial parent mass was unaccounted for after quantifying suspected metabolites of 2IPPDPP and 4IPPDPP that had authentic standards available. Two novel ITP metabolites, mono-isopropenylphenyl diphenyl phosphate and hydroxy-isopropylphenyl diphenyl phosphate, were tentatively identified by high-resolution mass spectrometry and screened for in recently collected human urine where mono-isopropenylphenyl diphenyl phosphate was detected in one of nine samples analyzed. This study provides insight into the biological fate of ITP and TBPP isomers in human tissues and is useful in identifying appropriate biomarkers of exposure to monitor, particularly in support of epidemiological studies.

Comparing the Use of Silicone Wristbands, Hand Wipes, And Dust to Evaluate Children's Exposure to Flame Retardants and Plasticizers.

Organophosphate esters (OPEs) are applied as additive flame retardants, and along with phthalates, are also used as plasticizers in consumer products. As such, human exposure is common and chronic. Deployed as personal passive samplers, silicone wristbands have been shown to detect over a thousand industrial and consumer product chemicals; however, few studies have evaluated chemical concentrations with their corresponding biomarkers of exposure, especially in children. Further, little is known about how well the wristbands predict individual exposure compared to existing validated external exposure tools such as indoor air, dust, and hand wipes. Here, we analyzed wristbands worn by children (ages 3-6) for 18 OPEs and 10 phthalates and compared them to corresponding urinary biomarkers. In wristbands, 13 of 18 OPEs and all phthalates were detected in >80% of wristbands, and 6 OPEs and 4 phthalates were significantly associated with corresponding urinary metabolites (rs = 0.2-0.6, p < 0.05). When compared to paired hand wipes and house dust, wristbands were found to have similar or greater correlation coefficients with respective urinary biomarkers. These results suggest that wristbands can serve as effective and quantitative assessment tools for evaluating personal exposure to some OPEs and phthalates, and for certain chemicals, may provide a better exposure estimate than indoor dust.

Strobilurin fungicides in house dust: is wallboard a source?

Strobilurin fungicides are used primarily in fruits and vegetables, but recently, a patent was issued for one strobilurin fungicide, azoxystrobin, in mold-resistant wallboard. This raises concerns about the potential presence of these chemicals in house dust and potential exposure indoors, particularly in young children. Furthermore, recent toxicological studies have suggested that strobilurins may cause neurotoxicity. Currently, it is not clear whether or not azoxystrobin applications in wallboard lead to exposures in the indoor environments. The purpose of this study was to determine if azoxystrobin, and related strobilurins, could be detected in house dust. We also sought to characterize the concentrations of azoxystrobin in new wallboard samples. To support this study, we collected and analyzed 16 new dry wall samples intentionally marketed for use in bathrooms to inhibit mold. We then analyzed 188 house dust samples collected from North Carolina homes in 2014-2016 for azoxystrobin and related strobilurins, including pyraclostrobin, trifloxystrobin, and fluoxastrobin using liquid chromatography tandem mass spectrometry. Detection frequencies for azoxystrobin, pyraclostrobin, trifloxystrobin, and fluoxastrobin ranged from 34-87%, with azoxystrobin being detected most frequently and at the highest concentrations (geometric mean = 3.5 ng/g; maximum = 10,590 ng/g). Azoxystrobin was also detected in mold-resistant wallboard samples, primarily in the paper covering where it was found at concentrations up to 88.5 µg/g. Cumulatively, these results suggest that fungicides present in wallboard may be migrating to the indoor environment, leading to exposure in the residences that would constitute a separate exposure pathway independent of dietary exposures.