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.

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.

Proposed Key Characteristics of Female Reproductive Toxicants as an Approach for Organizing and Evaluating Mechanistic Data in Hazard Assessment.

BACKGROUND: Identification of female reproductive toxicants is currently based largely on integrated epidemiological and in vivo toxicology data and, to a lesser degree, on mechanistic data. A uniform approach to systematically search, organize, integrate, and evaluate mechanistic evidence of female reproductive toxicity from various data types is lacking. OBJECTIVE: We sought to apply a key characteristics approach similar to that pioneered for carcinogen hazard identification to female reproductive toxicant hazard identification. METHODS: A working group of international experts was convened to discuss mechanisms associated with chemical-induced female reproductive toxicity and identified 10 key characteristics of chemicals that cause female reproductive toxicity: 1) alters hormone receptor signaling; alters reproductive hormone production, secretion, or metabolism; 2) chemical or metabolite is genotoxic; 3) induces epigenetic alterations; 4) causes mitochondrial dysfunction; 5) induces oxidative stress; 6) alters immune function; 7) alters cell signal transduction; 8) alters direct cell­cell interactions; 9) alters survival, proliferation, cell death, or metabolic pathways; and 10) alters microtubules and associated structures. As proof of principle, cyclophosphamide and diethylstilbestrol (DES), for which both human and animal studies have demonstrated female reproductive toxicity, display at least 5 and 3 key characteristics, respectively. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), for which the epidemiological evidence is mixed, exhibits 5 key characteristics. DISCUSSION: Future efforts should focus on evaluating the proposed key characteristics against additional known and suspected female reproductive toxicants. Chemicals that exhibit one or more of the key characteristics could be prioritized for additional evaluation and testing. A key characteristics approach has the potential to integrate with pathway-based toxicity testing to improve prediction of female reproductive toxicity in chemicals and potentially prevent some toxicants from entering common use. https://doi.org/10.1289/EHP4971.

How much green does it take to be orange? Determining the cost associated with trauma center readiness.

BACKGROUND: Readiness costs are real expenses incurred by trauma centers to maintain essential infrastructure to provide emergent services on a 24/7 basis. Although the components for readiness are well described in the American College of Surgeons' Resources for Optimal Care of the Injured Patient, the cost associated with each component is not well defined. We hypothesized that meeting the requirements of the 2014 Resources for Optimal Care of the Injured Patient would result in significant costs for trauma centers. METHODS: The state trauma commission in conjunction with trauma medical directors, program managers, and financial officers of each trauma center standardized definitions for each component of trauma center readiness cost and developed a survey tool for reporting. Readiness costs were grouped into four categories: administrative/program support staff, clinical medical staff, in-house operating room, and education/outreach. To verify consistent cost reporting, a financial auditor analyzed all data. Trauma center outliers were further evaluated to validate variances. All level I/level II trauma centers (n = 16) completed the survey on 2016 data. RESULTS: Average annual readiness cost is US $10,078,506 for a level I trauma center and US $4,925,103 for level IIs. Clinical medical staff was the costliest component representing 55% of costs for level Is and 64% for level IIs. Although education/outreach is mandated, levels I and II trauma centers only spend approximately US $100,000 annually on this category (1%-2%), demonstrating a lack of resources. CONCLUSION: This study defines the cost associated with each component of readiness as defined in the Resources for Optimal Care of the Injured Patient manual. Average readiness cost for a level I trauma center is US $10,078,506 and US $4,925,103 for a level II. The significant cost of trauma center readiness highlights the need for additional trauma center funding to meet the requirements set forth by the American College of Surgeons. LEVEL OF EVIDENCE: Economic and value-based evaluations, level III.

Successful Incorporation of Performance Based Payments for Trauma Center Readiness Costs into the Georgia Trauma System.

As quality and outcomes have moved to the fore front of medicine in this era of healthcare reform, a state trauma system Performance Based Payments (PBP) program has been incorporated into trauma center readiness funding. The purpose of this study was to evaluate the impact of a PBP on trauma center revenue. From 2010 to 2016, a percentage of readiness costs funding to trauma centers was placed in a PBP and withheld until the PBP criteria were completed. To introduce the concept, only three performance criteria and 10 per cent of readiness costs funding were tied to PBP in 2010. The PBP has evolved over the last several years to now include specific criteria by level of designation with an increase to 50 per cent of readiness costs funding being tied to PBP criteria. Final PBP distribution to trauma centers was based on the number of performance criteria completed. During 2016, the PBP criteria for Level I and II trauma centers included participation in official state meetings/conference calls, required attendance to American College of Surgeons state chapter meetings, Trauma Quality Improvement Program, registry reports, and surgeon participation in Peer Review Committee and trauma alert response times. Over the seven-year study period, $36,261,469 was available for readiness funds with $11,534,512 eligible for the PBP. Only $636,383 (6%) was withheld from trauma centers. A performance-based program was successfully incorporated into trauma center readiness funding, supporting state performance measures without adversely affecting the trauma center revenue. Future PBP criteria may be aligned to designation standards and clinical quality performance metrics.

What Are the Costs of Trauma Center Readiness? Defining and Standardizing Readiness Costs for Trauma Centers Statewide.

Trauma center readiness costs are incurred to maintain essential infrastructure and capacity to provide emergent services on a 24/7 basis. These costs are not captured by traditional hospital cost accounting, and no national consensus exists on appropriate definitions for each cost. Therefore, in 2010, stakeholders from all Level I and II trauma centers developed a survey tool standardizing and defining trauma center readiness costs. The survey tool underwent minor revisions to provide further clarity, and the survey was repeated in 2013. The purpose of this study was to provide a follow-up analysis of readiness costs for Georgia's Level I and Level II trauma centers. Using the American College of Surgeons Resources for Optimal Care of the Injured Patient guidelines, four readiness cost categories were identified: Administrative, Clinical Medical Staff, Operating Room, and Education/Outreach. Through conference calls, webinars and face-to-face meetings with financial officers, trauma medical directors, and program managers from all trauma centers, standardized definitions for reporting readiness costs within each category were developed. This resulted in a survey tool for centers to report their individual readiness costs for one year. The total readiness cost for all Level I trauma centers was $34,105,318 (avg $6,821,064) and all Level II trauma centers was $20,998,019 (avg $2,333,113). Methodology to standardize and define readiness costs for all trauma centers within the state was developed. Average costs for Level I and Level II trauma centers were identified. This model may be used to help other states define and standardize their trauma readiness costs.

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.

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.

Meeting report: moving upstream-evaluating adverse upstream end points for improved risk assessment and decision-making.

BACKGROUND: Assessing adverse effects from environmental chemical exposure is integral to public health policies. Toxicology assays identifying early biological changes from chemical exposure are increasing our ability to evaluate links between early biological disturbances and subsequent overt downstream effects. A workshop was held to consider how the resulting data inform consideration of an "adverse effect" in the context of hazard identification and risk assessment. OBJECTIVES: Our objective here is to review what is known about the relationships between chemical exposure, early biological effects (upstream events), and later overt effects (downstream events) through three case studies (thyroid hormone disruption, antiandrogen effects, immune system disruption) and to consider how to evaluate hazard and risk when early biological effect data are available. DISCUSSION: Each case study presents data on the toxicity pathways linking early biological perturbations with downstream overt effects. Case studies also emphasize several factors that can influence risk of overt disease as a result from early biological perturbations, including background chemical exposures, underlying individual biological processes, and disease susceptibility. Certain effects resulting from exposure during periods of sensitivity may be irreversible. A chemical can act through multiple modes of action, resulting in similar or different overt effects. CONCLUSIONS: For certain classes of early perturbations, sufficient information on the disease process is known, so hazard and quantitative risk assessment can proceed using information on upstream biological perturbations. Upstream data will support improved approaches for considering developmental stage, background exposures, disease status, and other factors important to assessing hazard and risk for the whole population.