Advancing the science on chemical classes.

BACKGROUND: Hazard identification, risk assessment, regulatory, and policy activity are usually conducted on a chemical-by-chemical basis. Grouping chemicals into categories or classes is an underutilized approach that could make risk assessment and management of chemicals more efficient for regulators. OBJECTIVE AND METHODS: While there are some available methods and regulatory frameworks that include the grouping of chemicals (e.g.,same molecular mechanism or similar chemical structure) there has not been a comprehensive evaluation of these different approaches nor a recommended course of action to better consider chemical classes in decision-making. This manuscript: 1) reviews current national and international approaches to grouping; 2) describes how groups could be defined based on the decision context (e.g., hazard/risk assessment, restrictions, prioritization, product development) and scientific considerations (e.g., intrinsic physical-chemical properties); 3) discusses advantages of developing a decision tree approach for grouping; 4) uses ortho-phthalates as a case study to identify and organize frameworks that could be used across agencies; and 5) discusses opportunities to advance the class concept within various regulatory decision-making scenarios. RESULTS: Structural similarity was the most common grouping approach for risk assessment among regulatory agencies (national and state level) and non-regulatory organizations, albeit with some variations in its definition. Toxicity to the same target organ or to the same biological function was also used in a few cases. The phthalates case study showed that a decision tree approach for grouping should include questions about uses regulated by other agencies to encourage more efficient, coherent, and protective chemical risk management. DISCUSSION AND CONCLUSION: Our evaluation of how classes of chemicals are defined and used identified commonalities and differences based on regulatory frameworks, risk assessments, and business strategies. We also identified that using a class-based approach could result in a more efficient process to reduce exposures to multiple hazardous chemicals and, ultimately, reduce health risks. We concluded that, in the absence of a prescribed method, a decision tree approach could facilitate the selection of chemicals belonging to a pre-defined class (e.g., chemicals with endocrine-disrupting activity; organohalogen flame retardants [OFR]) based on the decision-making context (e.g., regulatory risk management).

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.

Cumulative Environmental Impacts: Science and Policy to Protect Communities.

Many communities are located near multiple sources of pollution, including current and former industrial sites, major roadways, and agricultural operations. Populations in such locations are predominantly low-income, with a large percentage of minorities and non-English speakers. These communities face challenges that can affect the health of their residents, including limited access to health care, a shortage of grocery stores, poor housing quality, and a lack of parks and open spaces. Environmental exposures may interact with social stressors, thereby worsening health outcomes. Age, genetic characteristics, and preexisting health conditions increase the risk of adverse health effects from exposure to pollutants. There are existing approaches for characterizing cumulative exposures, cumulative risks, and cumulative health impacts. Although such approaches have merit, they also have significant constraints. New developments in exposure monitoring, mapping, toxicology, and epidemiology, especially when informed by community participation, have the potential to advance the science on cumulative impacts and to improve decision making.

Tracking Environmental and Health Disparities to Strengthen Resilience Before the Next Crisis.

The COVID-19 pandemic has underscored how underlying disparities in environmental and health conditions exacerbate vulnerability during public health emergencies in low-income and communities of color. Neglected epidemics-high rates of pollution, chronic disease, and racial and socioeconomic health disparities-have continued amid persistent systemic racism and declining investment in public health. Recognized too late due to shortcomings in public health data tracking, COVID-19 has surged through vulnerable communities. Improved public health tracking is critical for informing the country's recovery from COVID-19, and it can be leveraged to measure and reduce health disparities and strengthen community resilience to respond more effectively to the next public health crisis. We emphasize how public health tracking agencies can engage communities in data collection and reporting; we also discuss the complementary role that communities can take to mobilize data to change policies and institutions, strengthening resilience through increased information and capacity driven by community priorities. Success requires the continuous collection of timely data at a community scale, and public health agencies partnering with communities to use the information in decision making and evaluation to ensure progress over time. We highlight community-engaged data collection and reporting-community air monitoring in Imperial County, CA-as an example of working with communities to improve public health data collection and reporting, increase community dialogue and engagement in governmental decision making, and inform public health tracking to reduce health disparities and strengthen community resilience.

Organic Chemical Contaminants in Water System Infrastructure Following Wildfire.

Wildfires have destroyed multiple residential communities in California in recent years. After fires in 2017 and 2018, high concentrations of benzene and other volatile organic compounds (VOCs) were found in public drinking water systems in fire-affected areas. The sources of the contamination and appropriate remediation have been urgent matters for investigation. This study characterizes target and non-target VOCs and semi volatile organic compounds (SVOCs) in water from a highly contaminated service line after the 2018 Camp Fire (Paradise, CA). Ninety-five organic compounds were identified or tentatively identified in the service line. Laboratory combustion experiments with drinking water pipes made of polyvinyl chloride (PVC), cross-linked polyethylene (PEX) and high-density polyethylene (HDPE) and a review of the literature were used to evaluate potential sources of the detected chemicals. Among the service line contaminants were thirty-two compounds associated with PVC pyrolysis and twenty-eight organic compounds also associated with the pyrolysis of polyethylene. The service line sample also contained fifty-five compounds associated with uncontrolled burning of biomass and waste materials. The findings support hypotheses that wildfires can contaminate drinking water systems both by thermal damage to plastic pipes and intrusion of smoke. Residual chlorine disinfectant in the water system modifies the contaminant distribution observed.

The Interplay of Environmental Exposures and Mental Health: Setting an Agenda.

BACKGROUND: To date, health-effects research on environmental stressors has rarely focused on behavioral and mental health outcomes. That lack of research is beginning to change. Science and policy experts in the environmental and behavioral health sciences are coming together to explore converging evidence on the relationship-harmful or beneficial-between environmental factors and mental health. OBJECTIVES: To organize evidence and catalyze new findings, the National Academy of Sciences, Engineering, and Medicine (NASEM) hosted a workshop 2-3 February 2021 on the interplay of environmental exposures and mental health outcomes. METHODS: This commentary provides a nonsystematic, expert-guided conceptual review and interdisciplinary perspective on the convergence of environmental and mental health, drawing from hypotheses, findings, and research gaps presented and discussed at the workshop. Featured is an overview of what is known about the intersection of the environment and mental health, focusing on the effects of neurotoxic pollutants, threats related to climate change, and the importance of health promoting environments, such as urban green spaces. DISCUSSION: We describe what can be gained by bridging environmental and psychological research disciplines and present a synthesis of what is needed to advance interdisciplinary investigations. We also consider the implications of the current evidence for a) foundational knowledge of the etiology of mental health and illness, b) toxicant policy and regulation, c) definitions of climate adaptation and community resilience, d) interventions targeting marginalized communities, and e) the future of research training and funding. We include a call to action for environmental and mental health researchers, focusing on the environmental contributions to mental health to unlock primary prevention strategies at the population level and open equitable paths for preventing mental disorders and achieving optimal mental health for all. https://doi.org/10.1289/EHP9889.

Fire and Water: Assessing Drinking Water Contamination After a Major Wildfire.

We investigated patterns of volatile organic compound (VOC) contamination in drinking water systems affected by the California 2018 Camp Fire. We performed spatial analysis of over 5000 water samples collected over a 17 month period by a local water utility, sampled tap water for VOCs in approximately 10% (N = 136) of standing homes, and conducted additional nontargeted chemical analysis of 10 samples. Benzene contamination was present in 29% of service connections to destroyed structures and 2% of service connections to standing homes. A spatial pattern was apparent. Tap water in standing homes 11 months after the fire contained low concentrations of benzene in 1% of samples, but methylene chloride was present in 19% of samples, including several above regulatory limits. Elevated methylene chloride was associated with greater distance from the water meter to the tap, longer stagnation time, and the presence of a destroyed structure on the service connection; it was inversely associated with certain trihalomethanes. Nontargeted analysis identified multiple combustion byproducts in the water at 2/10 homes. Our findings support the hypothesis that pyrolysis and smoke intrusion from depressurization contributed to the benzene contamination. Further research is needed to test the hypothesis that methylene chloride may be generated from the dehalogenation of disinfection byproducts stagnating in galvanized iron pipes.

Toxicity testing in the 21st century: a vision and a strategy.

With the release of the landmark report Toxicity Testing in the 21st Century: A Vision and a Strategy, the U.S. National Academy of Sciences, in 2007, precipitated a major change in the way toxicity testing is conducted. It envisions increased efficiency in toxicity testing and decreased animal usage by transitioning from current expensive and lengthy in vivo testing with qualitative endpoints to in vitro toxicity pathway assays on human cells or cell lines using robotic high-throughput screening with mechanistic quantitative parameters. Risk assessment in the exposed human population would focus on avoiding significant perturbations in these toxicity pathways. Computational systems biology models would be implemented to determine the dose-response models of perturbations of pathway function. Extrapolation of in vitro results to in vivo human blood and tissue concentrations would be based on pharmacokinetic models for the given exposure condition. This practice would enhance human relevance of test results, and would cover several test agents, compared to traditional toxicological testing strategies. As all the tools that are necessary to implement the vision are currently available or in an advanced stage of development, the key prerequisites to achieving this paradigm shift are a commitment to change in the scientific community, which could be facilitated by a broad discussion of the vision, and obtaining necessary resources to enhance current knowledge of pathway perturbations and pathway assays in humans and to implement computational systems biology models. Implementation of these strategies would result in a new toxicity testing paradigm firmly based on human biology.

New Toxicology Tools and the Emerging Paradigm Shift in Environmental Health Decision-Making.

BACKGROUND: Numerous types of rapid toxicity or exposure assays and platforms are providing information relevant to human hazard and exposure identification. They offer the promise of aiding decision-making in a variety of contexts including the regulatory management of chemicals, evaluation of products and environmental media, and emergency response. There is a need to consider both the scientific validity of the new methods and the values applied to a given decision using this new information to ensure that the new methods are employed in ways that enhance public health and environmental protection. In 2018, a National Academies of Sciences, Engineering, and Medicine (NASEM) workshop examined both the toxicological and societal aspects of this challenge. OBJECTIVES: Our objectives were to explore the challenges of adopting new data streams into regulatory decision-making and highlight the need to align new methods with the information and confidence needs of the decision contexts in which the data may be applied. METHODS: We go beyond the NASEM workshop to further explore the requirements of different decision contexts. We also call for the new methods to be applied in a manner consistent with the core values of public health and environmental protection. We use the case examples presented in the NASEM workshop to illustrate a range of decision contexts that have applied or could benefit from these new data streams. Organizers of the NASEM workshop came together to further evaluate the main themes from the workshop and develop a joint assessment of the critical needs for improved use of emerging toxicology tools in decision-making. We have drawn from our own experience and individual decision or research contexts as well as from the case studies and panel discussions from the workshop to inform our assessment. DISCUSSION: Many of the statutes that regulate chemicals in the environment place a high priority on the protection of public health and the environment. Moving away from the sole reliance on traditional approaches and information sources used in hazard, exposure, and risk assessment, toward the more expansive use of rapidly acquired chemical information via in vitro, in silico, and targeted testing strategies will require careful consideration of the information needed and values considerations associated with a particular decision. In this commentary, we explore the ability and feasibility of using emerging data streams, particularly those that allow for the rapid testing of a large number of chemicals across numerous biological targets, to shift the chemical testing paradigm to one in which potentially harmful chemicals are more rapidly identified, prioritized, and addressed. Such a paradigm shift could ultimately save financial and natural resources while ensuring and preserving the protection of public health. https://doi.org/10.1289/EHP4745.

Transgenerational exposures: persistent chemical pollutants in the environment and breast milk.

Persistent organic pollutants (POPs) are anthropogenic chemicals that are poorly biodegradable and have the potential for adverse human health effects. Although national regulations and an international treaty have resulted in the gradual decline of many POPs in human blood and breast milk, the levels of other POPs continue to rise. Children and developing fetuses are sensitive to health effects from these substances. This article reviews the health risks posed by the POPs that have been largely banned or regulated and the potential for health effects from a variety of other chemicals in widespread use today.

Health effects of common home, lawn, and garden pesticides.

Children encounter pesticide products and their residues where they live and play and in the food supply. Pesticide exposure affects pediatric health both acutely and chronically; effects range from mild and subtle to severe. Pediatricians play an important role in identifying and reducing significant pesticide exposure in their patients by taking an exposure history to clarify the extent and types of exposures that may have occurred during acute care and preventive care visits. Developing knowledge about the toxicity of various chemicals, identifying reliable resources for pesticide information, and providing a common-sense approach toward recommending the safest practical alternatives is necessary.

Airborne mold and endotoxin concentrations in New Orleans, Louisiana, after flooding, October through November 2005.

BACKGROUND: The hurricanes and flooding in New Orleans, Louisiana, in October and November 2005 resulted in damp conditions favorable to the dispersion of bioaerosols such as mold spores and endotoxin. OBJECTIVE: Our objective in this study was to assess potential human exposure to bioaerosols in New Orleans after the flooding of the city. METHODS: A team of investigators performed continuous airborne sampling for mold spores and endotoxin outdoors in flooded and nonflooded areas, and inside homes that had undergone various levels of remediation, for periods of 5-24 hr during the 2 months after the flooding. RESULTS: The estimated 24-hr mold concentrations ranged from 21,000 to 102,000 spores/m3 in outdoor air and from 11,000 to 645,000 spores/m3 in indoor air. The mean outdoor spore concentration in flooded areas was roughly double the concentration in nonflooded areas (66,167 vs. 33,179 spores/m3 ; p < 0.05) . The highest concentrations were inside homes. The most common mold species were from the genera of Cladosporium and Aspergillus/Penicillium ; Stachybotrys was detected in some indoor samples. The airborne endotoxin concentrations ranged from 0.6 to 8.3 EU (endotoxin units) /m3 but did not vary with flooded status or between indoor and outdoor environments. CONCLUSIONS: The high concentration of mold measured indoors and outdoors in the New Orleans area is likely to be a significant respiratory hazard that should be monitored over time. Workers and returning residents should use appropriate personal protective equipment and exposure mitigation techniques to prevent respiratory morbidity and long-term health effects.

Screening for Chemical Contributions to Breast Cancer Risk: A Case Study for Chemical Safety Evaluation.

BACKGROUND: Current approaches to chemical screening, prioritization, and assessment are being reenvisioned, driven by innovations in chemical safety testing, new chemical regulations, and demand for information on human and environmental impacts of chemicals. To conceptualize these changes through the lens of a prevalent disease, the Breast Cancer and Chemicals Policy project convened an interdisciplinary expert panel to investigate methods for identifying chemicals that may increase breast cancer risk. METHODS: Based on a review of current evidence, the panel identified key biological processes whose perturbation may alter breast cancer risk. We identified corresponding assays to develop the Hazard Identification Approach for Breast Carcinogens (HIA-BC), a method for detecting chemicals that may raise breast cancer risk. Finally, we conducted a literature-based pilot test of the HIA-BC. RESULTS: The HIA-BC identifies assays capable of detecting alterations to biological processes relevant to breast cancer, including cellular and molecular events, tissue changes, and factors that alter susceptibility. In the pilot test of the HIA-BC, chemicals associated with breast cancer all demonstrated genotoxic or endocrine activity, but not necessarily both. Significant data gaps persist. CONCLUSIONS: This approach could inform the development of toxicity testing that targets mechanisms relevant to breast cancer, providing a basis for identifying safer chemicals. The study identified important end points not currently evaluated by federal testing programs, including altered mammary gland development, Her2 activation, progesterone receptor activity, prolactin effects, and aspects of estrogen receptor ß activity. This approach could be extended to identify the biological processes and screening methods relevant for other common diseases.

Chemical contaminants in breast milk: time trends and regional variability.

Research on environmentally related chemical contaminants in breast milk spans several decades and dozens of countries. The ability to use this research as an environmental indicator is limited because of a lack of consistent protocols. Data on xenobiotics in breast milk are influenced by choices in sample selection, sample pooling, analysis, and reporting. In addition, most studies have focused only on a small panel of persistent organic pollutants, despite indications that a wide range of additional chemical contaminants may also enter breast milk. Despite these limitations, however, it is possible to draw some generalizations. In this paper we review available data on levels of organochlorine pesticides, polychlorinated biphenyls (PCBs), polychlorinated dibenzodioxins (PCDDs), polybrominated diphenyl ethers (PBDEs), metals, and solvents in breast milk. Examples drawn from around the world illustrate the available data and the patterns that have appeared in various areas over time. Over the past few decades, levels of the organochlorine pesticides, PCBs, and dioxins have declined in breast milk in countries where these chemicals have been banned or otherwise regulated. In contrast, the levels of PBDEs are rising. Regional differences in levels of xenobiotics in breast milk are related to historical and current local use patterns. Diet is a major factor that influences breast milk levels of persistent organic pollutants, with patterns in fish consumption playing a particularly significant role. Improved global breast milk monitoring programs would allow for more consistent data on trends over time, detection of new xenobiotics in breast milk, and identification of disproportionately exposed populations.

Seafood contamination after the BP Gulf oil spill and risks to vulnerable populations: a critique of the FDA risk assessment.

BACKGROUND: The BP oil spill of 2010 resulted in contamination of one of the most productive fisheries in the United States by polycyclic aromatic hydrocarbons (PAHs). PAHs, which can accumulate in seafood, are known carcinogens and developmental toxicants. In response to the oil spill, the U.S. Food and Drug Administration (FDA) developed risk criteria and established thresholds for allowable levels [levels of concern (LOCs)] of PAH contaminants in Gulf Coast seafood. OBJECTIVES: We evaluated the degree to which the FDA's risk criteria adequately protect vulnerable Gulf Coast populations from cancer risk associated with PAHs in seafood. DISCUSSION: The FDA LOCs significantly underestimate risk from seafood contaminants among sensitive Gulf Coast populations by failing to a) account for the increased vulnerability of the developing fetus and child; b) use appropriate seafood consumption rates; c) include all relevant health end points; and d) incorporate health-protective estimates of exposure duration and acceptable risk. For benzo[a]pyrene and naphthalene, revised LOCs are between two and four orders of magnitude below the level set by the FDA. Comparison of measured levels of PAHs in Gulf seafood with the revised LOCs revealed that up to 53% of Gulf shrimp samples were above LOCs for pregnant women who are high-end seafood consumers. CONCLUSIONS: FDA risk assessment methods should be updated to better reflect current risk assessment practices and to protect vulnerable populations such as pregnant women and children.

Six climate change-related events in the United States accounted for about $14 billion in lost lives and health costs.

The future health costs associated with predicted climate change-related events such as hurricanes, heat waves, and floods are projected to be enormous. This article estimates the health costs associated with six climate change-related events that struck the United States between 2000 and 2009. The six case studies came from categories of climate change-related events projected to worsen with continued global warming-ozone pollution, heat waves, hurricanes, infectious disease outbreaks, river flooding, and wildfires. We estimate that the health costs exceeded $14 billion, with 95 percent due to the value of lives lost prematurely. Actual health care costs were an estimated $740 million. This reflects more than 760,000 encounters with the health care system. Our analysis provides scientists and policy makers with a methodology to use in estimating future health costs related to climate change and highlights the growing need for public health preparedness.