Identifying Toxic Consumer Products: A Novel Data Set Reveals Air Emissions of Potent Carcinogens, Reproductive Toxicants, and Developmental Toxicants.

Consumer products are important sources of exposure to harmful chemicals. Product composition is often a mystery to users, however, due to gaps in the laws governing ingredient disclosure. A unique data set that the California Air Resources Board (CARB) uses to determine how volatile organic chemicals (VOCs) from consumer products affect smog formation holds a partial solution. By analyzing CARB data on VOCs in consumer products, we identified and quantified emissions of volatile chemicals regulated under the California Safe Drinking Water and Toxic Enforcement Act ("Prop 65"). We here highlight individual chemicals as well as consumer product categories that people are likely to be exposed to as individual consumers, in the workplace, and at the population level. Of the 33 Prop 65-listed chemicals that appear in the CARB emissions inventory, we classified 18 as "top tier priorities for elimination". Among these, methylene chloride and N-methyl-2-pyrrolidone were most prevalent in products across all three population groups. Of 172 consumer product categories, 105 contained Prop 65-listed chemicals. Although these chemicals are known carcinogens and reproductive/developmental toxicants, they remain in widespread use. Manufacturers and regulators should prioritize product categories containing Prop 65-listed chemicals for reformulation or redesign to reduce human exposures and associated health risks.

Translating community-based participatory research into broadscale sociopolitical change: insights from a coalition of women firefighters, scientists, and environmental health advocates.

BACKGROUND: We report on community-based participatory research (CBPR) initiated by women firefighters in order to share successful elements that can be instructive for other community-engaged research. This CBPR initiative, known as the Women Worker Biomonitoring Collaborative (WWBC) is the first we are aware of to investigate links between occupational exposures and health outcomes, including breast cancer, for a cohort of exclusively women firefighters. METHODS: In order to be reflective of the experiences and knowledge of those most intimately involved, this article is co-authored by leaders of the research initiative. We collected leaders' input via recorded meeting sessions, emails, and a shared online document. We also conducted interviews (N = 10) with key research participants and community leaders to include additional perspectives. RESULTS: Factors contributing to the initiative's success in enacting broadscale social change and advancing scientific knowledge include (1) forming a diverse coalition of impacted community leaders, labor unions, scientists, and advocacy organizations, (2) focusing on impacts at multiple scales of action and nurturing different, yet mutually supportive, goals among partners, (3) adopting innovative communication strategies for study participants, research partners, and the broader community, (4) cultivating a prevention-based ethos in the scientific research, including taking early action to reduce community exposures based on existing evidence of harm, and (5) emphasizing co-learning through all the study stages. Furthermore, we discuss external factors that contribute to success, including funding programs that elevate scientist-community-advocacy partnerships and allow flexibility to respond to emerging science-policy opportunities, as well as institutional structures responsive to worker concerns. CONCLUSIONS: While WWBC shares characteristics with other successful CBPR partnerships, it also advances approaches that increase the ability for CBPR to translate into change at multiple levels. This includes incorporating partners with particular skills and resources beyond the traditional researcher-community partnerships that are the focus of much CBPR practice and scholarly attention, and designing studies so they support community action in the initial stages of research. Moreover, we emphasize external structural factors that can be critical for CBPR success. This demonstrates the importance of critically examining and advocating for institutional factors that better support this research.

A science-based agenda for health-protective chemical assessments and decisions: overview and consensus statement.

The manufacture and production of industrial chemicals continues to increase, with hundreds of thousands of chemicals and chemical mixtures used worldwide, leading to widespread population exposures and resultant health impacts. Low-wealth communities and communities of color often bear disproportionate burdens of exposure and impact; all compounded by regulatory delays to the detriment of public health. Multiple authoritative bodies and scientific consensus groups have called for actions to prevent harmful exposures via improved policy approaches. We worked across multiple disciplines to develop consensus recommendations for health-protective, scientific approaches to reduce harmful chemical exposures, which can be applied to current US policies governing industrial chemicals and environmental pollutants. This consensus identifies five principles and scientific recommendations for improving how agencies like the US Environmental Protection Agency (EPA) approach and conduct hazard and risk assessment and risk management analyses: (1) the financial burden of data generation for any given chemical on (or to be introduced to) the market should be on the chemical producers that benefit from their production and use; (2) lack of data does not equate to lack of hazard, exposure, or risk; (3) populations at greater risk, including those that are more susceptible or more highly exposed, must be better identified and protected to account for their real-world risks; (4) hazard and risk assessments should not assume existence of a "safe" or "no-risk" level of chemical exposure in the diverse general population; and (5) hazard and risk assessments must evaluate and account for financial conflicts of interest in the body of evidence. While many of these recommendations focus specifically on the EPA, they are general principles for environmental health that could be adopted by any agency or entity engaged in exposure, hazard, and risk assessment. We also detail recommendations for four priority areas in companion papers (exposure assessment methods, human variability assessment, methods for quantifying non-cancer health outcomes, and a framework for defining chemical classes). These recommendations constitute key steps for improved evidence-based environmental health decision-making and public health protection.

Exposure to Perfluoroalkyl Substances in a Cohort of Women Firefighters and Office Workers in San Francisco.

Studies of firefighters have shown increased exposures to carcinogenic compounds and elevated rates of certain cancers compared to the general population, yet this research has focused almost exclusively on men. To address this gap, the Women Firefighters Biomonitoring Collaborative created a biological sample archive and analyzed levels of perfluoroalkyl substances (PFAS) among women firefighters (N = 86) and office workers (N = 84) in San Francisco. Serum samples were collected and analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to measure and compare PFAS levels between firefighters and office workers. 7 of 12 PFAS congeners were detected in the least 70% of the study population, and 4 congeners were detected in 100% of participants. In regression models comparing PFAS levels by occupation and adjusting for potential confounders, firefighters had higher geometric mean concentrations of PFAS compared to office workers PFHxS (2.22 (95% CI = 1.55, 3.18)), PFUnDA (1.83 (95% CI = 0.97, 3.45)), and PFNA (1.26 (95% CI = 1.01, 1.58)). Among firefighters, occupational position predicted exposure-firefighters and officers had higher PFNA, PFOA, PFDA, and PFUnDA levels compared to drivers. Women firefighters are exposed to higher levels of some PFAS compared to office workers, suggesting that some of these exposures may be occupationally related.

Integrating Exposure Knowledge and Serum Suspect Screening as a New Approach to Biomonitoring: An Application in Firefighters and Office Workers.

Firefighters (FF) are exposed to recognized and probable carcinogens, yet there are few studies of chemical exposures and associated health concerns in women FFs, such as breast cancer. Biomonitoring often requires a priori selection of compounds to be measured, and so, it may not detect relevant, lesser known, exposures. The Women FFs Biomonitoring Collaborative (WFBC) created a biological sample archive and conducted a general suspect screen (GSS) to address this data gap. Using liquid chromatography-quadrupole time-of-flight tandem mass spectrometry, we sought to identify candidate chemicals of interest in serum samples from 83 women FFs and 79 women office workers (OW) in San Francisco. We identified chemical peaks by matching accurate mass from serum samples against a custom chemical database of 722 slightly polar phenolic and acidic compounds, including many of relevance to firefighting or breast cancer etiology. We then selected tentatively identified chemicals for confirmation based on the following criteria: (1) detection frequency or peak area differences between OW and FF; (2) evidence of mammary carcinogenicity, estrogenicity, or genotoxicity; and (3) not currently measured in large biomonitoring studies. We detected 620 chemicals that matched 300 molecular formulas in the WFBC database, including phthalate metabolites, phosphate flame-retardant metabolites, phenols, pesticides, nitro and nitroso compounds, and per- and polyfluoroalkyl substances. Of the 20 suspect chemicals selected for validation, 8 were confirmed-including two alkylphenols, ethyl paraben, BPF, PFOSAA, benzophenone-3, benzyl p-hydroxybenzoate, and triphenyl phosphate-by running a matrix spike of the reference standards and using m/z, retention time, and the confirmation of at least two fragment ions as criteria for matching. GSS provides a powerful high-throughput approach to identify and prioritize novel chemicals for biomonitoring and health studies.

Adverse outcome pathways for ionizing radiation and breast cancer involve direct and indirect DNA damage, oxidative stress, inflammation, genomic instability, and interaction with hormonal regulation of the breast.

Knowledge about established breast carcinogens can support improved and modernized toxicological testing methods by identifying key mechanistic events. Ionizing radiation (IR) increases the risk of breast cancer, especially for women and for exposure at younger ages, and evidence overall supports a linear dose-response relationship. We used the Adverse Outcome Pathway (AOP) framework to outline and evaluate the evidence linking ionizing radiation with breast cancer from molecular initiating events to the adverse outcome through intermediate key events, creating a qualitative AOP. We identified key events based on review articles, searched PubMed for recent literature on key events and IR, and identified additional papers using references. We manually curated publications and evaluated data quality. Ionizing radiation directly and indirectly causes DNA damage and increases production of reactive oxygen and nitrogen species (RONS). RONS lead to DNA damage and epigenetic changes leading to mutations and genomic instability (GI). Proliferation amplifies the effects of DNA damage and mutations leading to the AO of breast cancer. Separately, RONS and DNA damage also increase inflammation. Inflammation contributes to direct and indirect effects (effects in cells not directly reached by IR) via positive feedback to RONS and DNA damage, and separately increases proliferation and breast cancer through pro-carcinogenic effects on cells and tissue. For example, gene expression changes alter inflammatory mediators, resulting in improved survival and growth of cancer cells and a more hospitable tissue environment. All of these events overlap at multiple points with events characteristic of "background" induction of breast carcinogenesis, including hormone-responsive proliferation, oxidative activity, and DNA damage. These overlaps make the breast particularly susceptible to ionizing radiation and reinforce that these biological activities are important characteristics of carcinogens. Agents that increase these biological processes should be considered potential breast carcinogens, and predictive methods are needed to identify chemicals that increase these processes. Techniques are available to measure RONS, DNA damage and mutation, cell proliferation, and some inflammatory proteins or processes. Improved assays are needed to measure GI and chronic inflammation, as well as the interaction with hormonally driven development and proliferation. Several methods measure diverse epigenetic changes, but it is not clear which changes are relevant to breast cancer. In addition, most toxicological assays are not conducted in mammary tissue, and so it is a priority to evaluate if results from other tissues are generalizable to breast, or to conduct assays in breast tissue. Developing and applying these assays to identify exposures of concern will facilitate efforts to reduce subsequent breast cancer risk.

Health Toll From Open Flame and Cigarette-Started Fires on Flame-Retardant Furniture in Massachusetts, 2003-2016.

Objectives. To evaluate the risk of death and injury in residential fires started on upholstered furniture, with a focus on open flame and cigarette-related heat sources.Methods. We used civilian death and injury data from 34 081 residential fires in the Massachusetts Fire Incident Reporting System from 2003 to 2016. We compared outcomes associated with fires that started on upholstered furniture ignited by smoking materials versus open flames.Results. Although fires starting on upholstered furniture were not common (2.2% of total fires), odds of death and injury were significantly higher in these fires than in fires started on other substrates. Among furniture fires, odds of death were 3 times greater when those fires were ignited by smoking materials than when ignited by open flames (odds ratio = 3.4; 95% confidence interval = 1.3, 10.9).Conclusions. Furniture fires started by smoking materials were associated with more deaths than were furniture fires started by open flames.Public Health Implications. Historically, furniture flammability regulations have focused on open flame heat sources, resulting in the addition of toxic flame retardants to furniture. Interventions to reduce deaths should instead focus on smoking materials.

Environmental justice and drinking water quality: are there socioeconomic disparities in nitrate levels in U.S. drinking water?

BACKGROUND: Low-income and minority communities often face disproportionately high pollutant exposures. The lead crisis in Flint, Michigan, has sparked concern about broader socioeconomic disparities in exposures to drinking water contaminants. Nitrate is commonly found in drinking water, especially in agricultural regions, and epidemiological evidence suggests elevated risk of cancer and birth defects at levels below U.S. EPA's drinking water standard (10 mg/L NO3-N). However, there have been no nationwide assessments of socioeconomic disparities in exposures to nitrate or other contaminants in U.S. drinking water. The goals of this study are to identify determinants of nitrate concentrations in U.S. community water systems (CWSs) and to evaluate disparities related to wealth or race/ethnicity. METHODS: We compiled nitrate data from 39,466 U.S. CWSs for 2010-2014. We used EPA's Safe Drinking Water Information System (SDWIS) to compile CWS characteristics and linked this information with both city- and county-level demographic data gathered from the U.S. Census Bureau. After applying multiple imputation methods to address censored nitrate concentration data, we conducted mixed-effects multivariable regression analyses at national and regional scales. RESULTS: 5.6 million Americans are served by a CWS that had an average nitrate concentration ≥ 5 mg/L NO3-N between 2010 and 2014. Extent of agricultural land use and reliance on groundwater sources were significantly associated with nitrate. The percent of Hispanic residents served by each system was significantly associated with nitrate even after accounting for county-level cropland and livestock production, and CWSs in the top quartile of percent Hispanic residents exceeded 5 mg/L nearly three times as often as CWSs serving the lowest quartile. By contrast, the percent of residents living in poverty and percent African American residents were both inversely associated with nitrate. CONCLUSIONS: Epidemiological evidence for health effects associated with drinking water above 5 mg/L NO3-N raises concerns about increased risk for the 5.6 million Americans served by public water supplies with average nitrate concentrations above this level. The associations we observed between nitrate concentrations and proportions of Hispanic residents support the need for improved efforts to assist vulnerable communities in addressing contamination and protecting source waters. Future studies can extend our methods to evaluate disparities in exposures to other contaminants and links to health effects.

Wrangling environmental exposure data: guidance for getting the best information from your laboratory measurements.

BACKGROUND: Environmental health and exposure researchers can improve the quality and interpretation of their chemical measurement data, avoid spurious results, and improve analytical protocols for new chemicals by closely examining lab and field quality control (QC) data. Reporting QC data along with chemical measurements in biological and environmental samples allows readers to evaluate data quality and appropriate uses of the data (e.g., for comparison to other exposure studies, association with health outcomes, use in regulatory decision-making). However many studies do not adequately describe or interpret QC assessments in publications, leaving readers uncertain about the level of confidence in the reported data. One potential barrier to both QC implementation and reporting is that guidance on how to integrate and interpret QC assessments is often fragmented and difficult to find, with no centralized repository or summary. In addition, existing documents are typically written for regulatory scientists rather than environmental health researchers, who may have little or no experience in analytical chemistry. OBJECTIVES: We discuss approaches for implementing quality assurance/quality control (QA/QC) in environmental exposure measurement projects and describe our process for interpreting QC results and drawing conclusions about data validity. DISCUSSION: Our methods build upon existing guidance and years of practical experience collecting exposure data and analyzing it in collaboration with contract and university laboratories, as well as the Centers for Disease Control and Prevention. With real examples from our data, we demonstrate problems that would not have come to light had we not engaged with our QC data and incorporated field QC samples in our study design. Our approach focuses on descriptive analyses and data visualizations that have been compatible with diverse exposure studies with sample sizes ranging from tens to hundreds of samples. Future work could incorporate additional statistically grounded methods for larger datasets with more QC samples. CONCLUSIONS: This guidance, along with example table shells, graphics, and some sample R code, provides a useful set of tools for getting the best information from valuable environmental exposure datasets and enabling valid comparison and synthesis of exposure data across studies.

Environmental chemicals and breast cancer: An updated review of epidemiological literature informed by biological mechanisms.

BACKGROUND: Many common environmental chemicals are mammary gland carcinogens in animal studies, activate relevant hormonal pathways, or enhance mammary gland susceptibility to carcinogenesis. Breast cancer's long latency and multifactorial etiology make evaluation of these chemicals in humans challenging. OBJECTIVE: For chemicals previously identified as mammary gland toxicants, we evaluated epidemiologic studies published since our 2007 review. We assessed whether study designs captured relevant exposures and disease features suggested by toxicological and biological evidence of genotoxicity, endocrine disruption, tumor promotion, or disruption of mammary gland development. METHODS: We systematically searched the PubMed database for articles with breast cancer outcomes published in 2006-2016 using terms for 134 environmental chemicals, sources, or biomarkers of exposure. We critically reviewed the articles. RESULTS: We identified 158 articles. Consistent with experimental evidence, a few key studies suggested higher risk for exposures during breast development to dichlorodiphenyltrichloroethane (DDT), dioxins, perfluorooctane-sulfonamide (PFOSA), and air pollution (risk estimates ranged from 2.14 to 5.0), and for occupational exposure to solvents and other mammary carcinogens, such as gasoline components (risk estimates ranged from 1.42 to 3.31). Notably, one 50-year cohort study captured exposure to DDT during several critical windows for breast development (in utero, adolescence, pregnancy) and when this chemical was still in use. Most other studies did not assess exposure during a biologically relevant window or specify the timing of exposure. Few studies considered genetic variation, but the Long Island Breast Cancer Study Project reported higher breast cancer risk for polycyclic aromatic hydrocarbons (PAHs) in women with certain genetic variations, especially in DNA repair genes. CONCLUSIONS: New studies that targeted toxicologically relevant chemicals and captured biological hypotheses about genetic variants or windows of breast susceptibility added to evidence of links between environmental chemicals and breast cancer. However, many biologically relevant chemicals, including current-use consumer product chemicals, have not been adequately studied in humans. Studies are challenged to reconstruct exposures that occurred decades before diagnosis or access biological samples stored that long. Other problems include measuring rapidly metabolized chemicals and evaluating exposure to mixtures.

Measurement of endocrine disrupting and asthma-associated chemicals in hair products used by Black women.

BACKGROUND: Personal care products are a source of exposure to endocrine disrupting and asthma-associated chemicals. Because use of hair products differs by race/ethnicity, these products may contribute to exposure and disease disparities. OBJECTIVE: This preliminary study investigates the endocrine disrupting and asthma-associated chemical content of hair products used by U.S. Black women. METHODS: We used gas chromatography/mass spectrometry (GC/MS) to test 18 hair products in 6 categories used by Black women: hot oil treatment, anti-frizz/polish, leave-in conditioner, root stimulator, hair lotion, and relaxer. We tested for 66 chemicals belonging to 10 chemical classes: ultraviolet (UV) filters, cyclosiloxanes, glycol ethers, fragrances, alkylphenols, ethanolamines, antimicrobials, bisphenol A, phthalates, and parabens. RESULTS: The hair products tested contained 45 endocrine disrupting or asthma-associated chemicals, including every targeted chemical class. We found cyclosiloxanes, parabens, and the fragrance marker diethyl phthalate (DEP) at the highest levels, and DEP most frequently. Root stimulators, hair lotions, and relaxers frequently contained nonylphenols, parabens, and fragrances; anti-frizz products contained cyclosiloxanes. Hair relaxers for children contained five chemicals regulated by California's Proposition 65 or prohibited by EU cosmetics regulation. Targeted chemicals were generally not listed on the product label. CONCLUSIONS: Hair products used by Black women and children contained multiple chemicals associated with endocrine disruption and asthma. The prevalence of parabens and DEP is consistent with higher levels of these compounds in biomonitoring samples from Black women compared with White women. These results indicate the need for more information about the contribution of consumer products to exposure disparities. A precautionary approach would reduce the use of endocrine disrupting chemicals in personal care products and improve labeling so women can select products consistent with their values.

Review of Organic Wastewater Compound Concentrations and Removal in Onsite Wastewater Treatment Systems.

Onsite wastewater treatment systems, such as septic systems, serve 20% of U.S. households and are common in areas not served by wastewater treatment plants (WWTPs) globally. They can be sources of nutrients and pathogen pollution and have been linked to health effects in communities where they contaminate drinking water. However, few studies have evaluated their ability to remove organic wastewater compounds (OWCs) such as pharmaceuticals, hormones, and detergents. We synthesized results from 20 studies of 45 OWCs in conventional drainfield-based and alternative onsite wastewater treatment systems to characterize concentrations and removal. For comparison, we synthesized 31 studies of these same OWCs in activated sludge WWTPs. OWC concentrations and removal in drainfields varied widely and depended on wastewater sources and compound-specific removal processes, primarily sorption and biotransformation. Compared to drainfields, alternative systems had similar median and higher maximum concentrations, reflecting a wider range of system designs and redox conditions. OWC concentrations and removal in drainfields were generally similar to those in conventional WWTPs. Persistent OWCs in groundwater and surface water can indicate the overall extent of septic system impact, while the presence of well-removed OWCs, such as caffeine and acetaminophen, may indicate discharges of poorly treated wastewater from failing or outdated septic systems.

Flame Retardant Chemicals in College Dormitories: Flammability Standards Influence Dust Concentrations.

Furniture flammability standards are typically met with chemical flame retardants (FRs). FRs can migrate out of products into dust and are linked to cancer, neurological impairment, and endocrine disruption. We collected 95 dust samples from dormitory common areas and student rooms on two U.S. college campuses adhering to two different furniture flammability standards: Technical Bulletin 117 (TB117) and Technical Bulletin 133 (TB133). Because TB133 requires furniture to withstand a much-more-demanding test flame than TB117, we hypothesized that spaces with TB133 furniture would have higher levels of FRs in dust. We found all 47 targeted FRs, including 12 polybrominated diphenyl ether (PBDE) congeners, 19 other brominated FRs, 11 phosphorus FRs (PFRs), 2 Dechlorane-Plus (DP) isomers, and 3 hexabromocyclododecane (HBCDD) isomers in the 95 dust samples. We measured the highest reported U.S. concentrations for a number of FRs, including BDE 209 (up to 990 000 ng/g), which may be used to meet the TB133 standard. We prioritized 16 FRs and analyzed levels in relation to flammability standard as well as presence and age of furniture and electronics. Adherence to TB133 was associated with higher concentrations of BDE 209, decabromodiphenylethane (DBDPE), DPs, and HBCDD compared to adherence to TB117 in univariate models (p < 0.05). Student dormitory rooms tended to have higher levels of some FRs compared to common rooms, likely a result of the density of furniture and electronics. As flammability standards are updated, it is critical to understand their impact on exposure and health risks.

Semivolatile organic compounds in homes: strategies for efficient and systematic exposure measurement based on empirical and theoretical factors.

Residential exposure can dominate total exposure for commercial chemicals of health concern; however, despite the importance of consumer exposures, methods for estimating household exposures remain limited. We collected house dust and indoor air samples in 49 California homes and analyzed for 76 semivolatile organic compounds (SVOCs)--phthalates, polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), and pesticides. Sixty chemicals were detected in either dust or air and here we report 58 SVOCs detected in dust for the first time. In dust, phthalates (bis(2-ethylhexyl) phthalate, benzyl butyl phthalate, di-n-butyl phthalate) and flame retardants (PBDE 99, PBDE 47) were detected at the highest concentrations relative to other chemicals at the 95th percentile, while phthalates were highest at the median. Because SVOCs are found in both gas and condensed phases and redistribute from their original source over time, partitioning models can clarify their fate indoors. We use empirical data to validate air-dust partitioning models and use these results, combined with experience in SVOC exposure assessment, to recommend residential exposure measurement strategies. We can predict dust concentrations reasonably well from measured air concentrations (R(2) = 0.80). Partitioning models and knowledge of chemical Koa elucidate exposure pathways and suggest priorities for chemical regulation. These findings also inform study design by allowing researchers to select sampling approaches optimized for their chemicals of interest and study goals. While surface wipes are commonly used in epidemiology studies because of ease of implementation, passive air sampling may be more standardized between homes and also relatively simple to deploy. Validation of passive air sampling methods for SVOCs is a priority.

Urinary biomonitoring of phosphate flame retardants: levels in California adults and recommendations for future studies.

Phosphate flame retardants (PFRs) are abundant and found at the highest concentrations relative to other flame retardant chemicals in house dust; however, little is known about the biological levels of PFRs and their relationship with house dust concentrations. These relationships provide insight into major exposure pathways and potential health risks. We analyzed urine samples from 16 California residents in 2011 for 6 chlorinated and nonchlorinated dialkyl or diaryl phosphates (DAPs), the expected major metabolites of the most prominent PFRs, and qualitatively screened for 18 other metabolites predicted from in vitro studies. We detected all 6 DAPs within the range of previously reported levels, although very few comparisons are available. We found weakly positive nonsignificant correlations between urine and dust concentrations and maxima urine corresponding to maxima dust for the pairs bis(1,3-dichloro-2-propyl) phosphate (BDCIPP)-tris(1,3-dichloro-isopropyl) phosphate (TDCIPP) and bis(2-chloroethyl) phosphate (BCEP)-tris(2-chloroethyl) phosphate (TCEP). Metabolite levels of PFRs were correlated for many PFR combinations, suggesting they commonly co-occur. As far as we know, this is the first study to measure these 6 DAP metabolites simultaneously and to detect other PFR metabolites in US urine samples. We recommend biomonitoring studies include these 6 DAPs as well as several additional compounds detected through qualitative screening and previous ADME studies. PFRs represent a class of poorly studied commercial chemicals with widespread exposure and raise concerns for health effects including carcinogenicity and neurotoxicity.

Reporting individual results for biomonitoring and environmental exposures: lessons learned from environmental communication case studies.

Measurement methods for chemicals in biological and personal environmental samples have expanded rapidly and become a cornerstone of health studies and public health surveillance. These measurements raise questions about whether and how to report individual results to study participants, particularly when health effects and exposure reduction strategies are uncertain. In an era of greater public participation and open disclosure in science, researchers and institutional review boards (IRBs) need new guidance on changing norms and best practices. Drawing on the experiences of researchers, IRBs, and study participants, we discuss ethical frameworks, effective methods, and outcomes in studies that have reported personal results for a wide range of environmental chemicals. Belmont Report principles and community-based participatory research ethics imply responsibilities to report individual results, and several recent biomonitoring guidance documents call for individual reports. Meaningful report-back includes contextual information about health implications and exposure reduction strategies. Both narrative and graphs are helpful. Graphs comparing an individual's results with other participants in the study and benchmarks, such as the National Exposure Report, are helpful, but must be used carefully to avoid incorrect inferences that higher results are necessarily harmful or lower results are safe. Methods can be tailored for specific settings by involving participants and community members in planning. Participants and researchers who have participated in report-back identified benefits: increasing trust in science, retention in cohort studies, environmental health literacy, individual and community empowerment, and motivation to reduce exposures. Researchers as well as participants gained unexpected insights into the characteristics and sources of environmental contamination. Participants are almost universally eager to receive their results and do not regret getting them. Ethical considerations and empirical experience both support study participants' right to know their own results if they choose, so report-back should become the norm in studies that measure personal exposures. Recent studies provide models that are compiled in a handbook to help research partnerships that are planning report-back. Thoughtful report-back can strengthen research experiences for investigators and participants and expand the translation of environmental health research in communities.

Application of the Key Characteristics Framework to Identify Potential Breast Carcinogens Using Publicly Available in Vivo, in Vitro, and in Silico Data.

BACKGROUND: Chemicals that induce mammary tumors in rodents or activate estrogen or progesterone signaling are likely to increase breast cancer (BC) risk. Identifying chemicals with these activities can prompt steps to protect human health. OBJECTIVES: We compiled data on rodent tumors, endocrine activity, and genotoxicity to assess the key characteristics (KCs) of rodent mammary carcinogens (MCs), and to identify other chemicals that exhibit these effects and may therefore increase BC risk. METHODS: Using authoritative databases, including International Agency for Research on Cancer (IARC) Monographs and the US Environmental Protection's (EPA) ToxCast, we selected chemicals that induce mammary tumors in rodents, stimulate estradiol or progesterone synthesis, or activate the estrogen receptor (ER) in vitro. We classified these chemicals by their genotoxicity and strength of endocrine activity and calculated the overrepresentation (enrichment) of these KCs among MCs. Finally, we evaluated whether these KCs predict whether a chemical is likely to induce mammary tumors. RESULTS: We identified 279 MCs and an additional 642 chemicals that stimulate estrogen or progesterone signaling. MCs were significantly enriched for steroidogenicity, ER agonism, and genotoxicity, supporting the use of these KCs to predict whether a chemical is likely to induce rodent mammary tumors and, by inference, increase BC risk. More MCs were steroidogens than ER agonists, and many increased both estradiol and progesterone. Enrichment among MCs was greater for strong endocrine activity vs. weak or inactive, with a significant trend. DISCUSSION: We identified hundreds of compounds that have biological activities that could increase BC risk and demonstrated that these activities are enriched among MCs. We argue that many of these should not be considered low hazard without investigating their ability to affect the breast, and chemicals with the strongest evidence can be targeted for exposure reduction. We describe ways to strengthen hazard identification, including improved assessments for mammary effects, developing assays for more KCs, and more comprehensive chemical testing. https://doi.org/10.1289/EHP13233.

After the PBDE phase-out: a broad suite of flame retardants in repeat house dust samples from California.

Higher house dust levels of PBDE flame retardants (FRs) have been reported in California than other parts of the world, due to the state's furniture flammability standard. However, changing levels of these and other FRs have not been evaluated following the 2004 U.S. phase-out of PentaBDE and OctaBDE. We analyzed dust collected in 16 California homes in 2006 and again in 2011 for 62 FRs and organohalogens, which represents the broadest investigation of FRs in homes. Fifty-five compounds were detected in at least one sample; 41 in at least 50% of samples. Concentrations of chlorinated OPFRs, including two (TCEP and TDCIPP) listed as carcinogens under California's Proposition 65, were found up to 0.01% in dust, higher than previously reported in the U.S. In 75% of the homes, we detected TDBPP, or brominated "Tris," which was banned in children's sleepwear because of carcinogenicity. To our knowledge, this is the first report on TDBPP in house dust. Concentrations of Firemaster 550 components (EH-TBB, BEH-TEBP, and TPHP) were higher in 2011 than 2006, consistent with its use as a PentaBDE replacement. Results highlight the evolving nature of FR exposures and suggest that manufacturers continue to use hazardous chemicals and replace chemicals of concern with chemicals with uncharacterized toxicity.

Cheminformatics analysis of chemicals that increase estrogen and progesterone synthesis for a breast cancer hazard assessment.

Factors that increase estrogen or progesterone (P4) action are well-established as increasing breast cancer risk, and many first-line treatments to prevent breast cancer recurrence work by blocking estrogen synthesis or action. In previous work, using data from an in vitro steroidogenesis assay developed for the U.S. Environmental Protection Agency (EPA) ToxCast program, we identified 182 chemicals that increased estradiol (E2up) and 185 that increased progesterone (P4up) in human H295R adrenocortical carcinoma cells, an OECD validated assay for steroidogenesis. Chemicals known to induce mammary effects in vivo were very likely to increase E2 or P4 synthesis, further supporting the importance of these pathways for breast cancer. To identify additional chemical exposures that may increase breast cancer risk through E2 or P4 steroidogenesis, we developed a cheminformatics approach to identify structural features associated with these activities and to predict other E2 or P4 steroidogens from their chemical structures. First, we used molecular descriptors and physicochemical properties to cluster the 2,012 chemicals screened in the steroidogenesis assay using a self-organizing map (SOM). Structural features such as triazine, phenol, or more broadly benzene ramified with halide, amine or alcohol, are enriched for E2 or P4up chemicals. Among E2up chemicals, phenol and benzenone are found as significant substructures, along with nitrogen-containing biphenyls. For P4up chemicals, phenol and complex aromatic systems ramified with oxygen-based groups such as flavone or phenolphthalein are significant substructures. Chemicals that are active for both E2up and P4up are enriched with substructures such as dihydroxy phosphanedithione or are small chemicals that contain one benzene ramified with chlorine, alcohol, methyl or primary amine. These results are confirmed with a chemotype ToxPrint analysis. Then, we used machine learning and artificial intelligence algorithms to develop and validate predictive classification QSAR models for E2up and P4up chemicals. These models gave reasonable external prediction performances (balanced accuracy ~ 0.8 and Matthews Coefficient Correlation ~ 0.5) on an external validation. The QSAR models were enriched by adding a confidence score that considers the chemical applicability domain and a ToxPrint assessment of the chemical. This profiling and these models may be useful to direct future testing and risk assessments for chemicals related to breast cancer and other hormonally-mediated outcomes.