Building Confidence In New Evidence Streams For Human Health Risk Assessment

As part of its core mission, the U.S. Environmental Protection Agency (EPA) is tasked with assessing the hazards and risks to human health from exposure to pollutants. While some pollutants are well studied, there are little or no data on the potential health effects for many thousands of chemicals that can make their way into the environment, such as PFAS. EPA still relies on laboratory mammalian studies as the foundation of most human health risk assessments, which are limited by high costs, long timelines, and other concerns. New approach methods (NAMs) in toxicology, for example new in vivo and in vitro strategies and computational systems biology, offer opportunities to inform timely decision-making when no data are available from laboratory mammalian toxicity tests or epidemiological studies. NAMs may also help inform efforts to protect susceptible and vulnerable populations by characterizing subtle health perturbations, better encompassing genetic diversity, and accounting for nonchemical stressors. While the promise and need for NAMs is clear, many barriers to their use remain. This report aims to bridge the gap between the potential of NAMs and their practical application in human health risk assessment. Building Confidence in New Evidence Streams for Human Health Risk Assessment draws lessons learned from laboratory mammalian toxicity tests to help inform approaches for building scientific confidence in NAMs and for incorporating such data into risk assessment and decision-making. Overall, the report recommendations aim to ensure a seamless handoff from the evaluation of NAM-based testing strategies in the laboratory to the incorporation of NAM data into modern, systematic-review-based risk assessments.

Advances in molecular biology and toxicology are paving the way for major improvements in the evaluation of the hazards posed by the large number of chemicals found at low levels in the environment. The National Research Council was asked by the U.S. Environmental Protection Agency to review the state of the science and create a far-reaching vision for the future of toxicity testing. The book finds that developing, improving, and validating new laboratory tools based on recent scientific advances could significantly improve our ability to understand the hazards and risks posed by chemicals. This new knowledge would lead to much more informed environmental regulations and dramatically reduce the need for animal testing because the new tests would be based on human cells and cell components. Substantial scientific efforts and resources will be required to leverage these new technologies to realize the vision, but the result will be a more efficient, informative and less costly system for assessing the hazards posed by industrial chemicals and pesticides.

Trichloroethylene (TCE) is a solvent that is used as a degreasing agent, a chemical intermediate in refrigerant manufacture, and a component of spot removers and adhesives. It is produced in mass quantities but creates dangerous vapors and is an environmental contaminant at many industrial and government facilities, including facilities run by the U.S. Department of Defense (DoD). It is important to determine the safe occupational exposure level (OEL) for the solvent in order to protect the health of workers who are exposed to its vapors. However, there are concerns that the current occupational standards insufficiently protect workers from these health threats. Review of DOD's Approach to Deriving an Occupational Exposure Level for Trichloroethylene makes recommendations to improve the DoD's approach to developing an OEL for TCE, strengthen transparency of the process, and improve confidence in the final OEL value. This report reviews the DoD's approach using a literature review, evidence synthesis based on weight of evidence [WOE], point-of-departure derivation, physiologically based pharmacokinetic modeling, extrapolation tools, and explores other elements of the process of deriving an OEL for TCE. It examines scientific approaches to developing exposure values and cancer risk levels, defining the scope of the problem, and improving hazard identification.

Much has been written about the care of research animals. Yet little guidance has appeared on protecting the health and safety of the people who care for or use these animals. This book, an implementation handbook and companion to Guide For the Care and Use of Laboratory Animals, identifies principles for building a program and discusses the accountability of institutional leaders, managers, and employees for a program's success. It provides a detailed description of risks-- physical and chemical hazards, allergens and zoonoses, and hazards from experiments--which will serve as a continuing reference for the laboratory. The book offers specific recommendations for controlling risk through administrative procedures, facility design, engineering controls, and periodic evaluations. The volume focuses on the worker, with detailed discussions of work practices, the use of personal protective gear, and the development of an emergency response plan. This handbook will be invaluable to administrators, researchers, and employees in any animal research facility. It will also be of interest to personnel in zoos, animal shelters, and veterinary facilities.

Neurotoxicity of Halogenated Organic Compounds, Volume 10 covers three groups of Halogenated Organic Compounds (Chlorinated, Brominated, and Fluorinated Compounds) that are legacy and emerging contaminants, providing background information, characteristics, physicochemical properties, environmental contamination, and human exposure. Specific chapters covered in this release include Perspective on Halogenated Organic Compounds, The Neurotoxicity of Polychlorinated Biphenyls (PCBs), Neuroendocrine Effects of Polychlorinated Biphenyls (PCBs), Mechanisms of PCB Neurotoxicity: AHR and THR Dogma meet RYR reality, Microbiome and the Neurotoxicity of Brominated Flame Retardants (BFRs), and much more. Other chapters cover Neuroendocrine Effects of Brominated Flame Retardants (BFRs), Focused on Polybrominated Diphenyl Ethers (PBDEs), Neurochemical Effects of Halogenated Organic Compounds: Possible Mode(s) of action and Structure-Activity Relationships, The Neurotoxic Effects of Perfluoroalkyl Substances (PFAS) in Animal Models and Human Cohorts, Neurochemical Mechanisms of Perfluoroalkyl Substances (PFAS) Neurotoxic Action, and Future Directions and Regulatory aspects of Halogenated Organic Compounds. Presents the latest on the Neurotoxicity of Halogenated Organic Compounds: Epidemiological, Behavioral and other effects Covers Neurochemical and Neuroendocrine effects of Halogenated Organic Compounds Provides Regulatory aspects of Halogenated Organic Compounds

In 2007, the National Research Council envisioned a new paradigm in which biologically important perturbations in key toxicity pathways would be evaluated with new methods in molecular biology, bioinformatics, computational toxicology, and a comprehensive array of in vitro tests based primarily on human biology. Although some considered the vision too optimistic with respect to the promise of the new science, no one can deny that a revolution in toxicity testing is under way. New approaches are being developed, and data are being generated. As a result, the U.S. Environmental Protection Agency (EPA) expects a large influx of data that will need to be evaluated. EPA also is faced with tens of thousands of chemicals on which toxicity information is incomplete and emerging chemicals and substances that will need risk assessment and possible regulation. Therefore, the agency asked the National Research Council to convene a symposium to stimulate discussion on the application of the new approaches and data in risk assessment. The symposium was held on May 11-13, 2009, in Washington, DC, and included presentations and discussion sessions on pathway-based approaches for hazard identification, applications of new approaches to mode-of-action analyses, the challenges to and opportunities for risk assessment in the changing paradigm, and future directions.

Risk assessment has become a dominant public policy tool for making choices, based on limited resources, to protect public health and the environment. It has been instrumental to the mission of the U.S. Environmental Protection Agency (EPA) as well as other federal agencies in evaluating public health concerns, informing regulatory and technological decisions, prioritizing research needs and funding, and in developing approaches for cost-benefit analysis. However, risk assessment is at a crossroads. Despite advances in the field, risk assessment faces a number of significant challenges including lengthy delays in making complex decisions; lack of data leading to significant uncertainty in risk assessments; and many chemicals in the marketplace that have not been evaluated and emerging agents requiring assessment. Science and Decisions makes practical scientific and technical recommendations to address these challenges. This book is a complement to the widely used 1983 National Academies book, Risk Assessment in the Federal Government (also known as the Red Book). The earlier book established a framework for the concepts and conduct of risk assessment that has been adopted by numerous expert committees, regulatory agencies, and public health institutions. The new book embeds these concepts within a broader framework for risk-based decision-making. Together, these are essential references for those working in the regulatory and public health fields.

Arranging the transportation of animals at research facilities is often an ordeal. There is a confusing patchwork of local, national, and international regulations; a perceived lack of high-quality shipping services; a dearth of science-based good practices; and a lack of biosafety standards. It's a challenge â€"and an impediment to biomedical research. Guidelines for the Humane Transportation of Research Animals identifies the current problems encountered in the transportation of research animals and offers recommendations aimed at local and federal officials to rectify these problems. This book also includes a set of good practices based on the extensive body of literature on transportation of agricultural animals, universal concepts of physiology, and a scientific understanding of species-specific needs and differences. Good practices were developed by the committee to address thermal environment, space requirements, food and water requirements, social interaction, monitoring of transportation, emergency procedures, personnel training, and biosecurity. Guidelines for the Humane Transportation of Research Animals is an essential guide for all researchers, animal care technicians, facilities managers, administrators, and animal care and use committees at research institutions.