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.

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.

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.

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.

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.

Chemical Effects on Breast Development, Function, and Cancer Risk: Existing Knowledge and New Opportunities.

Population studies show worrisome trends towards earlier breast development, difficulty in breastfeeding, and increasing rates of breast cancer in young women. Multiple epidemiological studies have linked these outcomes with chemical exposures, and experimental studies have shown that many of these chemicals generate similar effects in rodents, often by disrupting hormonal regulation. These endocrine-disrupting chemicals (EDCs) can alter the progression of mammary gland (MG) development, impair the ability to nourish offspring via lactation, increase mammary tissue density, and increase the propensity to develop cancer. However, current toxicological approaches to measuring the effects of chemical exposures on the MG are often inadequate to detect these effects, impairing our ability to identify exposures harmful to the breast and limiting opportunities for prevention. This paper describes key adverse outcomes for the MG, including impaired lactation, altered pubertal development, altered morphology (such as increased mammographic density), and cancer. It also summarizes evidence from humans and rodent models for exposures associated with these effects. We also review current toxicological practices for evaluating MG effects, highlight limitations of current methods, summarize debates related to how effects are interpreted in risk assessment, and make recommendations to strengthen assessment approaches. Increasing the rigor of MG assessment would improve our ability to identify chemicals of concern, regulate those chemicals based on their effects, and prevent exposures and associated adverse health effects.

Reactive Oxygen Species in the Adverse Outcome Pathway Framework: Toward Creation of Harmonized Consensus Key Events.

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are formed as a result of natural cellular processes, intracellular signaling, or as adverse responses associated with diseases or exposure to oxidizing chemical and non-chemical stressors. The action of ROS and RNS, collectively referred to as reactive oxygen and nitrogen species (RONS), has recently become highly relevant in a number of adverse outcome pathways (AOPs) that capture, organize, evaluate and portray causal relationships pertinent to adversity or disease progression. RONS can potentially act as a key event (KE) in the cascade of responses leading to an adverse outcome (AO) within such AOPs, but are also known to modulate responses of events along the AOP continuum without being an AOP event itself. A substantial discussion has therefore been undertaken in a series of workshops named "Mystery or ROS" to elucidate the role of RONS in disease and adverse effects associated with exposure to stressors such as nanoparticles, chemical, and ionizing and non-ionizing radiation. This review introduces the background for RONS production, reflects on the direct and indirect effects of RONS, addresses the diversity of terminology used in different fields of research, and provides guidance for developing a harmonized approach for defining a common event terminology within the AOP developer community.

Influence of living in the same home on biomonitored levels of consumer product chemicals.

BACKGROUND: Individuals living in the same home may share exposures from direct contact with sources or indirectly through contamination of the home environment. OBJECTIVE: We investigated the influence of sharing a home on urine levels of ten phenolic chemicals present in some consumer products. METHODS: We used data from Silent Spring Institute's Detox Me Action Kit (DMAK), a crowdsourced biomonitoring program in the US. Of the 726 DMAK participants, 185 lived in the same home with one or more other DMAK participants (n = 137 pairs, up to six participants in a home). The concentration distributions included values below the detection limit so we used statistical methods that account for left-censored data, including non-parametric correlation estimation and hierarchical Bayesian regression models. RESULTS: Concentrations were significantly positively correlated between pair-members sharing a home for nine of the ten chemicals. Concentrations of 2,5-dichlorophenol were the most strongly correlated between pair-members (tau = 0.46), followed by benzophenone-3 (tau = 0.31) and bisphenol A (tau = 0.21). The relative contribution of personal product use reported product use of other household members (up to 5 others), and the residual contribution from a shared household, including exposures not asked about, varied by chemical. Paraben concentrations were largely influenced by personal behaviors whereas dichlorophenol and bisphenol concentrations were largely influenced by shared home exposures not related to reported behaviors. SIGNIFICANCE: Measuring the influence of personal and household practices on biomonitoring exposures helps pinpoint major sources of exposure and highlights chemical-specific intervention strategies to reduce them.

Application of an in Vitro Assay to Identify Chemicals That Increase Estradiol and Progesterone Synthesis and Are Potential Breast Cancer Risk Factors.

BACKGROUND: Established breast cancer risk factors, such as hormone replacement therapy and reproductive history, are thought to act by increasing estrogen and progesterone (P4) activity. OBJECTIVE: We aimed to use in vitro screening data to identify chemicals that increase the synthesis of estradiol (E2) or P4 and evaluate potential risks. METHOD: Using data from a high-throughput (HT) in vitro steroidogenesis assay developed for the U.S. Environmental Protection Agency (EPA) ToxCast program, we identified chemicals that increased estradiol (E2-up) or progesterone (P4-up) in human H295R adrenocortical carcinoma cells. We prioritized chemicals by their activity. We compiled in vivo studies and assessments about carcinogenicity and reproductive/developmental (repro/dev) toxicity. We identified exposure sources and predicted intakes from the U.S. EPA's ExpoCast. RESULTS: We found 296 chemicals increased E2 (182) or P4 (185), with 71 chemicals increasing both. In vivo data often showed effects consistent with this mechanism. Of the E2- and P4-up chemicals, about 30% were likely repro/dev toxicants or carcinogens, whereas only 5-13% were classified as unlikely. However, most of the chemicals had insufficient in vivo data to evaluate their effects. Of 45 chemicals associated with mammary gland effects, and also tested in the H294R assay, 29 increased E2 or P4, including the well-known mammary carcinogen 7,12-dimethylbenz(a)anthracene. E2- and P4-up chemicals include pesticides, consumer product ingredients, food additives, and drinking water contaminants. DISCUSSION: The U.S. EPA's in vitro screening data identified several hundred chemicals that should be considered as potential risk factors for breast cancer because they increased E2 or P4 synthesis. In vitro data is a helpful addition to current toxicity assessments, which are not sensitive to mammary gland effects. Relevant effects on the mammary gland are often not noticed or are dismissed, including for 2,4-dichlorophenol and cyfluthrin. Fifty-three active E2-up and 59 active P4-up chemicals that are in consumer products, food, pesticides, or drugs have not been evaluated for carcinogenic potential and are priorities for study and exposure reduction. https://doi.org/10.1289/EHP8608.

Gaussian graphical modeling of the serum exposome and metabolome reveals interactions between environmental chemicals and endogenous metabolites.

Given the complex exposures from both exogenous and endogenous sources that an individual experiences during life, exposome-wide association studies that interrogate levels of small molecules in biospecimens have been proposed for discovering causes of chronic diseases. We conducted a study to explore associations between environmental chemicals and endogenous molecules using Gaussian graphical models (GGMs) of non-targeted metabolomics data measured in a cohort of California women firefighters and office workers. GGMs revealed many exposure-metabolite associations, including that exposures to mono-hydroxyisononyl phthalate, ethyl paraben and 4-ethylbenzoic acid were associated with metabolites involved in steroid hormone biosynthesis, and perfluoroalkyl substances were linked to bile acids-hormones that regulate cholesterol and glucose metabolism-and inflammatory signaling molecules. Some hypotheses generated from these findings were confirmed by analysis of data from the National Health and Nutrition Examination Survey. Taken together, our findings demonstrate a novel approach to discovering associations between chemical exposures and biological processes of potential relevance for disease causation.

Rethinking Environmental Carcinogenesis.

The 2010 report of the President's Cancer Panel concluded that the burden of cancer from chemical exposures is substantial, while the programs for testing and regulation of carcinogens remain inadequate. New research on the role of early life exposures and the ability of chemicals to act via multiple biological pathways, including immunosuppression, inflammation, and endocrine disruption as well as mutagenesis, further supports the potential for chemicals and chemical mixtures to influence disease. Epidemiologic observations, such as higher leukemia incidence in children living near roadways and industrial sources of air pollution, and new in vitro technologies that decode carcinogenesis at the molecular level, illustrate the diverse evidence that primary prevention of some cancers may be achieved by reducing harmful chemical exposures. The path forward requires cross-disciplinary approaches, increased environmental research investment, system-wide collaboration to develop safer economic alternatives, and community engagement to support evidence-informed action. Engagement by cancer researchers to integrate environmental risk factors into prevention initiatives holds tremendous promise for reducing the rates of disease.See all articles in this CEBP Focus section, "Environmental Carcinogenesis: Pathways to Prevention."

Consumer behavior and exposure to parabens, bisphenols, triclosan, dichlorophenols, and benzophenone-3: Results from a crowdsourced biomonitoring study.

Nearly all Americans have detectable concentrations of endocrine disrupting chemicals from consumer products in their bodies, and expert panels recommend reducing exposures. To inform exposure reduction, we investigated whether consumers who are trying to avoid certain chemicals in consumer products have lower exposures than those who are not. We also aimed to make exposure biomonitoring more widely available. We enrolled 726 participants in a crowdsourced biomonitoring study. We targeted phenolic compounds-specifically parabens, bisphenol A (BPA) and analogs bisphenol F (BPF) and bisphenol S (BPS), the UV filter benzophenone-3, the anti-microbial triclosan, 2,4-dichlorophenol, and 2,5-dichlorophenol-and collected survey data on consumer products, cleaning habits, and efforts to avoid related chemicals. We investigated associations between 68 self-reported exposure behaviors and urine concentrations of ten chemicals, and evaluated whether associations were modified by intention to avoid exposures. A large majority (87%) of participants reported taking steps to limit exposure to specific chemicals, and, overall, participants achieved lower concentrations than the general U.S. population for parabens, BPA, triclosan, and benzophenone-3 but not BPF and BPS. Participants who reported avoiding all four ingredient groups-parabens, triclosan, bisphenols, and fragrances-were twice as likely as others to be in the lowest quartile of cumulative exposure. Avoiding certain products and reading ingredient labels to avoid chemicals was most effective for parabens, triclosan, and benzophenone-3. Avoiding BPA was not effective for reducing bisphenol exposures. Avoiding certain chemicals in products was generally associated with reduced exposure for chemicals listed on labels. Greater ingredient transparency will help consumers who read labels to reduce their exposure to a wider range of potentially harmful chemicals. In order to more equitably address public health, labeling policies should be complemented by regulations that exclude harmful chemicals from consumer products.

US EPA's regulatory pesticide evaluations need clearer guidelines for considering mammary gland tumors and other mammary gland effects.

Breast cancer risk from pesticides may be missed if effects on mammary gland are not assessed in toxicology studies required for registration. Using US EPA's registration documents, we identified pesticides that cause mammary tumors or alter development, and evaluated how those findings were considered in risk assessment. Of 28 pesticides that produced mammary tumors, EPA's risk assessment acknowledges those tumors for nine and dismisses the remaining cases. For five pesticides that alter mammary gland development, the implications for lactation and cancer risk are not assessed. Many of the mammary-active pesticides activate pathways related to endocrine disruption: altering steroid synthesis in H295R cells, activating nuclear receptors, or affecting xenobiotic metabolizing enzymes. Clearer guidelines based on breast cancer biology would strengthen assessment of mammary gland effects, including sensitive histology and hormone measures. Potential cancer risks from several common pesticides should be re-evaluated, including: malathion, triclopyr, atrazine, propylene oxide, and 3-iodo-2-propynyl butylcarbamate (IPBC).

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.

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.

Correction: Guideline levels for PFOA and PFOS in drinking water: the role of scientific uncertainty, risk assessment decisions, and social factors.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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.

Privacy Risks of Sharing Data from Environmental Health Studies.

BACKGROUND: Sharing research data uses resources effectively; enables large, diverse data sets; and supports rigor and reproducibility. However, sharing such data increases privacy risks for participants who may be re-identified by linking study data to outside data sets. These risks have been investigated for genetic and medical records but rarely for environmental data. OBJECTIVES: We evaluated how data in environmental health (EH) studies may be vulnerable to linkage and we investigated, in a case study, whether environmental measurements could contribute to inferring latent categories (e.g., geographic location), which increases privacy risks. METHODS: We identified 12 prominent EH studies, reviewed the data types collected, and evaluated the availability of outside data sets that overlap with study data. With data from the Household Exposure Study in California and Massachusetts and the Green Housing Study in Boston, Massachusetts, and Cincinnati, Ohio, we used k-means clustering and principal component analysis to investigate whether participants' region of residence could be inferred from measurements of chemicals in household air and dust. RESULTS: All 12 studies included at least two of five data types that overlap with outside data sets: geographic location (9 studies), medical data (9 studies), occupation (10 studies), housing characteristics (10 studies), and genetic data (7 studies). In our cluster analysis, participants' region of residence could be inferred with 80%-98% accuracy using environmental measurements with original laboratory reporting limits. DISCUSSION: EH studies frequently include data that are vulnerable to linkage with voter lists, tax and real estate data, professional licensing lists, and ancestry websites, and exposure measurements may be used to identify subgroup membership, increasing likelihood of linkage. Thus, unsupervised sharing of EH research data potentially raises substantial privacy risks. Empirical research can help characterize risks and evaluate technical solutions. Our findings reinforce the need for legal and policy protections to shield participants from potential harms of re-identification from data sharing. https://doi.org/10.1289/EHP4817.