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1 Introduction and Background1 Humans are potentially exposed to more than 80,000 toxic chemicals in the environment,2 yet their impacts on brain health and disease are not well understood (Hamblin, 2014). The sheer number of these chemicals has overwhelmed the ability to determine their individual toxicity, much less potential interactive effects. Early life exposures to chemicals can have permanent consequences for neurodevelopment and for neurodegeneration in later life (Bellinger, 2013). Toxic effects resulting from chemical exposure can interact with other risk factors such as prenatal stress, and persistence of some chemicals in the brain over time may result in cumulative toxic- ity. Because neurodevelopmental and neurodegenerative disordersâsuch as attention-deficit hyperactivity disorder and Parkinsonâs diseaseâcannot be fully explained by genetic risk factors alone, understanding the role of individual environmental chemical exposures is critical (Berkowitz, 2020; Ellis et al., 2011). Workshop co-chair Deborah Cory-Slechta, professor of environmental medicine at the University of Rochester Medical Center, referred to environ- mental chemical exposures as âthe ignored environmental risk factors for 1 The planning committeeâs role was limited to planning the workshop, and the Proceedings of a Workshop was prepared by the workshop rapporteurs as a factual summary of what oc- curred at the workshop. Statements, recommendations, and opinions expressed are those of individual presenters and participants, and have not been endorsed or verified by the National Academies of Sciences, Engineering, and Medicine. They should not be construed as reflecting any group consensus. 2 For more information, see https://www.epa.gov/laws-regulations/summary-toxic- substances-control-act (accessed August 12, 2020). 1 PREPUBLICATION COPYâUncorrected Proofs
2 ENVIRONMENTAL NEUROSCIENCE neurodevelopmental disease and disorders.â However, as recognition has grown about the substantial vulnerability of the nervous system to envi- ronmental effects, environmental neuroscience is emerging as an important topic in neuroscience, said Frances Jensen, professor and chair of neurology at the University of Pennsylvania Perelman School of Medicine. This has fueled a proliferation of clinical neuroscience research around the role of chemical pollutants and other kinds of environmental threats to the nervous system. The purpose of this workshop, hosted by the National Academies of Sciences, Engineering, and Medicineâs Forum on Neuroscience and Ner- vous System Disorders on June 25, 2020, was to lay the foundation for future advances in environmental neuroscience, said Jensen (see Box 1-1). Workshop co-chair Walter Koroshetz, director of the National Insti- tute of Neurological Disorders and Stroke, added that the workshop was designed to explore new opportunities to bridge the gap between what is known about the genetic contribution to brain disorders and what is known, and not known, about the contribution of environmental influ- BOX 1-1 Statement of Task A planning committee of the National Academies of Sciences, Engineering, and Medicine will organize and conduct a 1-day public workshop that brings to- gether experts and key stakeholders from academia, government, industry, and nonprofit organizations to explore the current knowledge landscape and future opportunities in neurotoxicology. Invited presentations will be designed to: â¢ Provide an overview of what is known about neurotoxic exposures and how they lead to neurodevelopmental and neurodegenerative disorders; â¢ Explore how new technologies can be harnessed to identify previously unknown neurotoxic chemicals; â¢ Consider whether algorithms can be developed to better predict the ef- fects of cumulative exposures and interactions across the life span on brain health; and â¢ Discuss research gaps and collaborative opportunities between neuro- scientists and environmental health scientists. The committee will develop the agenda for the workshop, select and invite speakers and discussants, and moderate the discussions. A proceedings of the presentations and discussions at the workshop will be prepared by a designated rapporteur in accordance with institutional guidelines. PREPUBLICATION COPYâUncorrected Proofs
INTRODUCTION AND BACKGROUND 3 ences, as well as to discuss what is known about how genetic and envi- ronmental factors interact. Noting that the problem spans variable types of environmental influences as well as multiple types of brain conditions, Koroshetz added that the workshop would focus on new technologies that allow previously unapproachable questions to be answered regarding chemicals and particular toxicants and their effects on neurodevelopmental and neurodegenerative conditions. Held virtually in the shadow of the coronavirus disease 2019 (COVID- 19) pandemic, the workshop also provided a unique and timely opportunity to discuss how pathogen-driven infections may interact with environmental toxicants. Moreover, behavioral changes in response to COVID-19 that have altered some environmental exposures, such as reducing air pol- lution in various cities, have provided new research opportunities, said Tracey Woodruff, the Alison S. Carlson Endowed Professor of Obstetrics, Gynecology, and Reproductive Sciences at the University of California, San Francisco. Cory-Slechta added that because both COVID-19 and toxic environmental exposures preferentially affect communities of color and low socioeconomic status, issues related to environmental justice must also be considered in discussions of environmental neuroscience. WORKSHOP OBJECTIVES A goal of the workshop, said Koroshetz, was to bring the fields of mechanistic and clinical neuroscience closer together with the fields of neu- rotoxicology and environmental health sciences. By building evidence from observational, population-based, and epidemiological studies and combin- ing that evidence with neurobiological mechanistic studies, scientists from these two fields, working together, may find the central issue of causation. Thus, an aim of the workshop was to discuss a pathway to achieving that goal, said Koroshetz. The discussions focused on four major themes: (1) What toxicants are of most concern? (2) What is the biology of toxicant interaction with the nervous system? (3) What is known about particular toxicants as drivers of abnormal development or neurodegeneration? and (4) What are the implications of this knowledge for policy and future research, including identifying gaps and opportunities to bridge those gaps? While the impact of neurotoxicants on neuropsychiatric and other neurological disorders is also a critical issue, it was not included in this 1-day workshop in the interests of time. PREPUBLICATION COPYâUncorrected Proofs
4 ENVIRONMENTAL NEUROSCIENCE ORGANIZATION OF THE PROCEEDINGS The organization of these proceedings reflects the fact that the topics discussed are intimately linked and cannot be discussed in isolation. Thus, Chapter 2 focuses on the neurotoxicants themselves; Chapter 3 considers what is known about how neurotoxicants impact neurological disorders; and Chapter 4 focuses through the lens of these disorders. Research gaps and opportunities are summarized in Chapter 5; and frameworks for mov- ing forward as well as opportunities for multidisciplinary collaboration are discussed in Chapter 6. PREPUBLICATION COPYâUncorrected Proofs