Systematic evidence on migrating and extractable food contact chemicals: Most chemicals detected in food contact materials are not listed for use.

Food packaging is important for today's globalized food system, but food contact materials (FCMs) can also be a source of hazardous chemicals migrating into foodstuffs. Assessing the impacts of FCMs on human health requires a comprehensive identification of the chemicals they contain, the food contact chemicals (FCCs). We systematically compiled the "database on migrating and extractable food contact chemicals" (FCCmigex) using information from 1210 studies. We found that to date 2881 FCCs have been detected, in a total of six FCM groups (Plastics, Paper & Board, Metal, Multi-materials, Glass & Ceramic, and Other FCMs). 65% of these detected FCCs were previously not known to be used in FCMs. Conversely, of the more than 12'000 FCCs known to be used, only 1013 are included in the FCCmigex database. Plastic is the most studied FCM with 1975 FCCs detected. Our findings expand the universe of known FCCs to 14,153 chemicals. This knowledge contributes to developing non-hazardous FCMs that lead to safer food and support a circular economy.

Exposure to a mixture of per-and polyfluoroalkyl substances modulates pulmonary expression of ACE2 and circulating hormones and cytokines.

Genetic and environmental factors impact on the interindividual variability of susceptibility to communicable and non-communicable diseases. A class of ubiquitous chemicals, Per- and polyfluoroalkyl substances (PFAS) have been linked in epidemiological studies to immunosuppression and increased susceptibility to viral infections, but possible mechanisms are not well elucidated. To begin to gain insight into the role of PFAS in susceptibility to one such viral infection, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), male and female C57BL/6 J mice were exposed to control water or a mixture of 5 PFAS (PFOS, PFOA, PFNA, PFHxS, Genx) for 12 weeks and lungs were isolated for examination of expression of SARS-CoV-2-related receptors Angiotensin-Converting Enzyme 2 (ACE2) and others. Secondary analyses included circulating hormones and cytokines which have been shown to directly or indirectly impact on ACE2 expression and severity of viral infections. Changes in mRNA and protein expression were analyzed by RT-qPCR and western blotting and circulating hormones and cytokines were determined by ELISA and MESO QuickPlex. The PFAS mixture decreased Ace2 mRNA 2.5-fold in male mice (p < 0.0001), with no significant change observed in females. In addition, TMPRSS2, ANPEP, ENPEP and DPP4 (other genes implicated in COVID-19 infection) were modulated due to PFAS. Plasma testosterone, but not estrogen were strikingly decreased due to PFAS which corresponded to PFAS-mediated repression of 4 representative pulmonary AR target genes; hemoglobin, beta adult major chain (Hbb-b1), Ferrochelatase (Fech), Collagen Type XIV Alpha 1 Chain (Col14a1), 5'-Aminolevulinate Synthase 2 (Alas2). Finally, PFAS modulated circulating pro and anti-inflammatory mediators including IFN-γ (downregulated 3.0-fold in females; p = 0.0301, 2.1-fold in males; p = 0.0418) and IL-6 (upregulated 5.6-fold in males; p = 0.030, no change in females). In conclusion, our data indicate long term exposure to a PFAS mixture impacts mechanisms related to expression of ACE2 in the lung. This work provides a mechanistic rationale for important future studies of PFAS exposure and subsequent viral infection.

Characterization of Per- and Polyfluorinated Alkyl Substances Present in Commercial Anti-fog Products and Their In Vitro Adipogenic Activity.

Anti-fog sprays and solutions are used on eyeglasses to minimize the condensation of water vapor, particularly while wearing a mask. Given their water-repellent properties, we sought to characterize per- and polyfluorinated alkyl substance (PFAS) compounds in four anti-fog spray products, five anti-fog cloth products, and two commercial fluorosurfactant formulations suspected to be used in preparing anti-fog products. Fluorotelomer alcohols (FTOHs) and fluorotelomer ethoxylates (FTEOs) were detected in all products and formulations. While 6:2 FTOH and the 6:2 FTEO polymeric series were predominant, one anti-fog cloth and one formulation contained 8:2, 10:2, 12:2, 14:2, and 16:2 FTOH and FTEO polymeric series. PFAS concentrations varied in samples and were detected at levels up to 25,000 µg/mL in anti-fog sprays and 185,000 µg (g cloth)-1 in anti-fog cloth products. The total organic fluorine (TOF) measurements of anti-fog products ranged from 190 to 20,700 µg/mL in sprays and 44,200 to 131,500 µg (g cloth)-1 in cloths. Quantified FTOHs and FTEOs accounted for 1-99% of TOF mass. In addition, all four anti-fog sprays and both commercial formulations exhibited significant cytotoxicity and adipogenic activity (either triglyceride accumulation and/or pre-adipocyte proliferation) in murine 3T3-L1 cells. Results suggest that FTEOs are a significant contributor to the adipogenic activity exhibited by the anti-fog sprays. Altogether, these results suggest that FTEOs are present in commercial products at toxicologically relevant levels, and more research is needed to fully understand the health risks from using these PFAS-containing products.

Thyroid Receptor Antagonism of Chemicals Extracted from Personal Silicone Wristbands within a Papillary Thyroid Cancer Pilot Study.

Research suggests that thyroid cancer incidence rates are increasing, and environmental exposures have been postulated to be playing a role. To explore this possibility, we conducted a pilot study to investigate the thyroid disrupting bioactivity of chemical mixtures isolated from personal silicone wristband samplers within a thyroid cancer cohort. Specifically, we evaluated TRß antagonism of chemical mixtures extracted from wristbands (n = 72) worn by adults in central North Carolina participating in a case-control study on papillary thyroid cancer. Sections of wristbands were solvent-extracted and analyzed via mass spectrometry to quantify a suite of semivolatile chemicals. A second extract from each wristband was used in a bioassay to quantify TRß antagonism in human embryonic kidney cells (HEK293/17) at concentrations ranging from 0.1 to 10% of the original extract (by volume). Approximately 70% of the sample extracts tested at a 1% extract concentration exhibited significant TRß antagonism, with a mean of 30% and a range of 0-100%. Inhibited cell viability was noted in >20% of samples that were tested at 5 and 10% concentrations. Antagonism was positively associated with wristband concentrations of several phthalates, organophosphate esters, and brominated flame retardants. These results suggest that personal passive samplers may be useful in evaluating the bioactivities of mixtures that people contact on a daily basis. We also report tentative associations between thyroid receptor antagonism, chemical concentrations, and papillary thyroid cancer case status. Future research utilizing larger sample sizes, prospective data collection, and measurement of serum thyroid hormone levels (which were not possible in this study) should be utilized to more comprehensively evaluate these associations.

Impacts of food contact chemicals on human health: a consensus statement.

Food packaging is of high societal value because it conserves and protects food, makes food transportable and conveys information to consumers. It is also relevant for marketing, which is of economic significance. Other types of food contact articles, such as storage containers, processing equipment and filling lines, are also important for food production and food supply. Food contact articles are made up of one or multiple different food contact materials and consist of food contact chemicals. However, food contact chemicals transfer from all types of food contact materials and articles into food and, consequently, are taken up by humans. Here we highlight topics of concern based on scientific findings showing that food contact materials and articles are a relevant exposure pathway for known hazardous substances as well as for a plethora of toxicologically uncharacterized chemicals, both intentionally and non-intentionally added. We describe areas of certainty, like the fact that chemicals migrate from food contact articles into food, and uncertainty, for example unidentified chemicals migrating into food. Current safety assessment of food contact chemicals is ineffective at protecting human health. In addition, society is striving for waste reduction with a focus on food packaging. As a result, solutions are being developed toward reuse, recycling or alternative (non-plastic) materials. However, the critical aspect of chemical safety is often ignored. Developing solutions for improving the safety of food contact chemicals and for tackling the circular economy must include current scientific knowledge. This cannot be done in isolation but must include all relevant experts and stakeholders. Therefore, we provide an overview of areas of concern and related activities that will improve the safety of food contact articles and support a circular economy. Our aim is to initiate a broader discussion involving scientists with relevant expertise but not currently working on food contact materials, and decision makers and influencers addressing single-use food packaging due to environmental concerns. Ultimately, we aim to support science-based decision making in the interest of improving public health. Notably, reducing exposure to hazardous food contact chemicals contributes to the prevention of associated chronic diseases in the human population.

Chemical Mixtures Isolated from House Dust Disrupt Thyroid Receptor ß Signaling.

House dust is a source of exposure to chemicals that can impact hormone regulation. This study was designed to evaluate the potential of house dust mixtures ( n = 137) to disrupt thyroid hormone nuclear receptor signaling in a cell-based reporter assay and to examine associations with thyroid hormones (TH) measured in residents of the homes. Approximately 41% of the extracts (ranging from 10.5 to 4.097 µg of dust/mL) significantly antagonized thyroid receptor ß (TRß) signaling by 20-67% relative to the hormone control. The concentrations of 12 flame retardants (FRs) quantified in the mixtures were significantly correlated with TRß antagonism; however, they were inactive when tested individually. We hypothesize that the observed antagonism is due to mixture effects or unidentified compounds that co-occur with FRs. Dust extract potency was significantly associated with free thyroxine (FT4, rs = -0.64, p < 0.001), suggesting that more potent dust samples are associated with higher FT4 levels in residents. Overall, these results suggest that house dust is a significant source of exposure to TH-disrupting chemicals, and TRß may have a role in mediating effects of exposure on TH levels. Additional studies are needed to identify the chemical(s) driving the observed effects on TRß and to determine if these changes lead to any adverse outcomes.

Endocrine-Disrupting Activities and Organic Contaminants Associated with Oil and Gas Operations in Wyoming Groundwater.

Unconventional oil and natural gas (UOG) operations couple horizontal drilling with hydraulic fracturing to access previously inaccessible fossil fuel deposits. Hydraulic fracturing, a common form of stimulation, involves the high-pressure injection of water, chemicals, and sand to fracture the target layer and release trapped natural gas and/or oil. Spills and/or discharges of wastewater have been shown to impact surface, ground, and drinking water. The goals of this study were to characterize the endocrine activities and measure select organic contaminants in groundwater from conventional oil and gas (COG) and UOG production regions of Wyoming. Groundwater samples were collected from each region, solid-phase extracted, and assessed for endocrine activities (estrogen, androgen, progesterone, glucocorticoid, and thyroid receptor agonism and antagonism), using reporter gene assays in human endometrial cells. Water samples from UOG and conventional oil areas exhibited greater ER antagonist activities than water samples from conventional gas areas. Samples from UOG areas tended to exhibit progesterone receptor antagonism more often, suggesting there may be a UOG-related impact on these endocrine activities. We also report UOG-specific contaminants in Pavillion groundwater extracts, and these same chemicals at high concentrations in a local UOG wastewater sample. A unique suite of contaminants was observed in groundwater from a permitted drinking water well at a COG well pad and not at any UOG sites; high levels of endocrine activities (most notably, maximal estrogenic activity) were noted there, suggesting putative impacts on endocrine bioactivities by COG. As such, we report two levels of evidence for groundwater contamination by both UOG and COG operations in Wyoming.

Characterization of Adipogenic Activity of House Dust Extracts and Semi-Volatile Indoor Contaminants in 3T3-L1 Cells.

Obesity and metabolic disorders are of great societal concern and generate significant human health care costs. Recently, attention has focused on the potential for environmental contaminants to act as metabolic disruptors. This study sought to evaluate the adipogenic activity of indoor house dust extracts and a suite of semivolatile organic chemicals (SVOCs) that are often ubiquitously detected in indoor environments. 3T3-L1 cells were exposed to extracts of indoor dust or individual SVOCs and assessed for triglyceride accumulation and preadipocyte proliferation. Ten of 11 house dust extracts exhibited significant triglyceride accumulation and/or proliferation at environmentally relevant levels (<20 µg of dust/well), and significant adipogenic activity was also exhibited by 28 of the SVOCs. Notably, pyraclostrobin, dibutyl phthalate, tert-butyl-phenyl diphenyl phosphate, and the isopropylated triaryl phosphates (ITPs) exhibited near maximal or supra-maximal triglyceride accumulation relative to the rosiglitazone-induced maximum. The adipogenic activity in house dust occurred at concentrations below EPA estimated child exposure levels, and raises concerns for human health impacts, particularly in children. Our results delineate a novel potential health threat and identify putative causative SVOCs that are likely contributing to this activity.

Effects of the environmental estrogenic contaminants bisphenol A and 17α-ethinyl estradiol on sexual development and adult behaviors in aquatic wildlife species.

Endocrine disrupting chemicals (EDCs), including the mass-produced component of plastics, bisphenol A (BPA) are widely prevalent in aquatic and terrestrial habitats. Many aquatic species, such as fish, amphibians, aquatic reptiles and mammals, are exposed daily to high concentrations of BPA and ethinyl estradiol (EE2), estrogen in birth control pills. In this review, we will predominantly focus on BPA and EE2, well-described estrogenic EDCs. First, the evidence that BPA and EE2 are detectable in almost all bodies of water will be discussed. We will consider how BPA affects sexual and neural development in these species, as these effects have been the best characterized across taxa. For instance, such chemicals have been in many cases reported to cause sex-reversal of males to females. Even if these chemicals do not overtly alter the gonadal sex, there are indications that several EDCs might demasculinize male-specific behaviors that are essential for attracting a mate. In so doing, these chemicals may reduce the likelihood that these males reproduce. If exposed males do reproduce, the concern is that they will then be passing on compromised genetic fitness to their offspring and transmitting potential transgenerational effects through their sperm epigenome. We will thus consider how diverse epigenetic changes might be a unifying mechanism of how BPA and EE2 disrupt several processes across species. Such changes might also serve as universal species diagnostic biomarkers of BPA and other EDCs exposure. Lastly, the evidence that estrogenic EDCs-induced effects in aquatic species might translate to humans will be considered.

Developmental and reproductive effects of chemicals associated with unconventional oil and natural gas operations.

Unconventional oil and gas (UOG) operations have the potential to increase air and water pollution in communities located near UOG operations. Every stage of UOG operation from well construction to extraction, operations, transportation, and distribution can lead to air and water contamination. Hundreds of chemicals are associated with the process of unconventional oil and natural gas production. In this work, we review the scientific literature providing evidence that adult and early life exposure to chemicals associated with UOG operations can result in adverse reproductive health and developmental effects in humans. Volatile organic compounds (VOCs) [including benzene, toluene, ethyl benzene, and xylene (BTEX) and formaldehyde] and heavy metals (including arsenic, cadmium and lead) are just a few of the known contributors to reduced air and water quality that pose a threat to human developmental and reproductive health. The developing fetus is particularly sensitive to environmental factors, which include air and water pollution. Research shows that there are critical windows of vulnerability during prenatal and early postnatal development, during which chemical exposures can cause potentially permanent damage to the growing embryo and fetus. Many of the air and water pollutants found near UOG operation sites are recognized as being developmental and reproductive toxicants; therefore there is a compelling need to increase our knowledge of the potential health consequences for adults, infants, and children from these chemicals through rapid and thorough health research investigation.

Molecular Assessment of Proadipogenic Effects for Common-Use Contraceptives and Their Mixtures.

Hormonal contraceptives are widely prescribed due to their effectiveness and convenience and have become an integral part of family planning strategies worldwide. In the United States, approximately 65% of reproductive-aged women are estimated to be using contraceptive options, with approximately 33% using one or a combination of hormonal contraceptives. While these methods have undeniably contributed to improved reproductive health, recent studies have raised concerns regarding their potential effect on metabolic health. Despite widespread anecdotal reports, epidemiological research has been mixed as to whether hormonal contraceptives contribute to metabolic health effects. As such, the goals of this study were to assess the adipogenic activity of common hormonal contraceptive chemicals and their mixtures. Five different models of adipogenesis were used to provide a rigorous assessment of metabolism-disrupting effects. Interestingly, every individual contraceptive (both estrogens and progestins) and each mixture promoted significant adipogenesis (eg, triglyceride accumulation and/or preadipocyte proliferation). These effects appeared to be mediated in part through estrogen receptor signaling, particularly for the contraceptive mixtures, as cotreatment with fulvestrant acted to inhibit contraceptive-mediated proadipogenic effects on triglyceride accumulation. In conclusion, this research provides valuable insights into the complex interactions between hormonal contraceptives and adipocyte development. The results suggest that both progestins and estrogens within these contraceptives can influence adipogenesis, and the specific effects may vary based on the receptor disruption profiles. Further research is warranted to establish translation of these findings to in vivo models and to further assess causal mechanisms underlying these effects.

The Conflict between Regulatory Agencies over the 20,000-Fold Lowering of the Tolerable Daily Intake (TDI) for Bisphenol A (BPA) by the European Food Safety Authority (EFSA).

BACKGROUND: The European Food Safety Authority (EFSA) recommended lowering their estimated tolerable daily intake (TDI) for bisphenol A (BPA) 20,000-fold to 0.2 ng/kg body weight (BW)/day. BPA is an extensively studied high production volume endocrine disrupting chemical (EDC) associated with a vast array of diseases. Prior risk assessments of BPA by EFSA as well as the US Food and Drug Administration (FDA) have relied on industry-funded studies conducted under good laboratory practice protocols (GLP) requiring guideline end points and detailed record keeping, while also claiming to examine (but rejecting) thousands of published findings by academic scientists. Guideline protocols initially formalized in the mid-twentieth century are still used by many regulatory agencies. EFSA used a 21st century approach in its reassessment of BPA and conducted a transparent, but time-limited, systematic review that included both guideline and academic research. The German Federal Institute for Risk Assessment (BfR) opposed EFSA's revision of the TDI for BPA. OBJECTIVES: We identify the flaws in the assumptions that the German BfR, as well as the FDA, have used to justify maintaining the TDI for BPA at levels above what a vast amount of academic research shows to cause harm. We argue that regulatory agencies need to incorporate 21st century science into chemical hazard identifications using the CLARITY-BPA (Consortium Linking Academic and Regulatory Insights on BPA Toxicity) nonguideline academic studies in a collaborative government-academic program model. DISCUSSION: We strongly endorse EFSA's revised TDI for BPA and support the European Commission's (EC) apparent acceptance of this updated BPA risk assessment. We discuss challenges to current chemical risk assessment assumptions about EDCs that need to be addressed by regulatory agencies to, in our opinion, become truly protective of public health. Addressing these challenges will hopefully result in BPA, and eventually other structurally similar bisphenols (called regrettable substitutions) for which there are known adverse effects, being eliminated from all food-related and many other uses in the EU and elsewhere. https://doi.org/10.1289/EHP13812.

The Pediatrician's Role in Protecting Children from Environmental Hazards.

Children suffer disproportionately from disease and disability due to environmental hazards, for reasons rooted in their biology. The contribution is substantial and increasingly recognized, particularly due to ever-increasing awareness of endocrine disruption. Regulatory actions can be traced directly to reductions in toxic exposures, with tangible benefits to society. Deep flaws remain in the policy framework in industrialized countries, failing to offer sufficient protection, but are even more limited in industrializing nations where the majority of chemical production and use will occur by 2030. Evidence-based steps for reducing chemical exposures associated with adverse health outcomes exist and should be incorporated into anticipatory guidance.

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 [...].

The regulation of endocrine-disrupting chemicals to minimize their impact on health.

Endocrine-disrupting chemicals (EDCs) are substances generated by human industrial activities that are detrimental to human health through their effects on the endocrine system. The global societal and economic burden posed by EDCs is substantial. Poorly defined or unenforced policies can increase human exposure to EDCs, thereby contributing to human disease, disability and economic damage. Researchers have shown that policies and interventions implemented at both individual and government levels have the potential to reduce exposure to EDCs. This Review describes a set of evidence-based policy actions to manage, minimize or even eliminate the widespread use of these chemicals and better protect human health and society. A number of specific challenges exist: defining, identifying and prioritizing EDCs; considering the non-linear or non-monotonic properties of EDCs; accounting for EDC exposure effects that are latent and do not appear until later in life; and updating testing paradigms to reflect 'real-world' mixtures of chemicals and cumulative exposure. A sound strategy also requires partnering with health-care providers to integrate strategies to prevent EDC exposure in clinical care. Critical next steps include addressing EDCs within global policy frameworks by integrating EDC exposure prevention into emerging climate policy.

Cetyl Alcohol Polyethoxylates Disrupt Metabolic Health in Developmentally Exposed Zebrafish.

Alcohol polyethoxylates (AEOs), such as cetyl alcohol ethoxylates (CetAEOs), are high-production-volume surfactants used in laundry detergents, hard-surface cleaners, pesticide formulations, textile production, oils, paints, and other products. AEOs have been suggested as lower toxicity replacements for alkylphenol polyethoxylates (APEOs), such as the nonylphenol and octylphenol polyethoxylates. We previously demonstrated that nonylphenol polyethoxylates induced triglyceride accumulation in several in vitro adipogenesis models and promoted adiposity and increased body weights in developmentally exposed zebrafish. We also demonstrated that diverse APEOs and AEOs were able to increase triglyceride accumulation and/or pre-adipocyte proliferation in a murine pre-adipocyte model. As such, the goals of this study were to assess the potential of CetAEOs to promote adiposity and alter growth and/or development (toxicity, length, weight, behavior, energy expenditure) of developmentally exposed zebrafish (Danio rerio). We also sought to expand our understanding of ethoxylate chain-length dependent effects through interrogation of varying chain-length CetAEOs. We demonstrated consistent adipogenic effects in two separate human bone-marrow-derived mesenchymal stem cell models as well as murine pre-adipocytes. Immediately following chemical exposures in zebrafish, we reported disrupted neurodevelopment and aberrant behavior in light/dark activity testing, with medium chain-length CetAEO-exposed fish exhibiting hyperactivity across both light and dark phases. By day 30, we demonstrated that cetyl alcohol and CetAEOs disrupted adipose deposition in developmentally exposed zebrafish, despite no apparent impacts on standard length or gross body weight. This research suggests metabolic health concerns for these common environmental contaminants, suggesting further need to assess molecular mechanisms and better characterize environmental concentrations for human health risk assessments.

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.

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.

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.

Correction: Kassotis et al. Nonylphenol Polyethoxylates Enhance Adipose Deposition in Developmentally Exposed Zebrafish. Toxics 2022, 10, 99.

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