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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., (© 2022. The Author(s).)

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.

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.

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.