Perspectives | Brief Communications July 2016 | Volume 124 | Issue 7
Project TENDR: Targeting Environmental Neuro-Developmental Risks. The TENDR Consensus Statement
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- SUMMARY: Children in America today are at an unacceptably high risk of developing neurodevelopmental disorders that affect the brain and nervous system including autism, attention deficit hyperactivity disorder, intellectual disabilities, and other learning and behavioral disabilities. These are complex disorders with multiple causes—genetic, social, and environmental. The contribution of toxic chemicals to these disorders can be prevented. APPROACH: Leading scientific and medical experts, along with children’s health advocates, came together in 2015 under the auspices of Project TENDR: Targeting Environmental Neuro-Developmental Risks to issue a call to action to reduce widespread exposures to chemicals that interfere with fetal and children’s brain development. Based on the available scientific evidence, the TENDR authors have identified prime examples of toxic chemicals and pollutants that increase children’s risks for neurodevelopmental disorders. These include chemicals that are used extensively in consumer products and that have become widespread in the environment. Some are chemicals to which children and pregnant women are regularly exposed, and they are detected in the bodies of virtually all Americans in national surveys conducted by the U.S. Centers for Disease Control and Prevention. The vast majority of chemicals in industrial and consumer products undergo almost no testing for developmental neurotoxicity or other health effects. CONCLUSION: Based on these findings, we assert that the current system in the United States for evaluating scientific evidence and making health-based decisions about environmental chemicals is fundamentally broken. To help reduce the unacceptably high prevalence of neurodevelopmental disorders in our children, we must eliminate or significantly reduce exposures to chemicals that contribute to these conditions. We must adopt a new framework for assessing chemicals that have the potential to disrupt brain development and prevent the use of those that may pose a risk. This consensus statement lays the foundation for developing recommendations to monitor, assess, and reduce exposures to neurotoxic chemicals. These measures are urgently needed if we are to protect healthy brain development so that current and future generations can reach their fullest potential.
Citation: Bennett D, Bellinger DC, Birnbaum LS, Bradman A, Chen A, Cory-Slechta DA, Engel SM, Fallin MD, Halladay A, Hauser R, Hertz-Picciotto I, Kwiatkowski CF, Lanphear BP, Marquez E, Marty M, McPartland J, Newschaffer CJ, Payne-Sturges D, Patisaul HB, Perera FP, Ritz B, Sass J, Schantz SL, Webster TF, Whyatt RM, Woodruff TJ, Zoeller RT, Anderko L, Campbell C, Conry JA, DeNicola N, Gould RM, Hirtz D, Huffling K, Landrigan PJ, Lavin A, Miller M, Mitchell MA, Rubin L, Schettler T, Tran HL, Acosta A, Brody C, Miller E, Miller P, Swanson M, Witherspoon NO. 2016. Project TENDR: Targeting Environmental Neuro-Developmental Risks. The TENDR Consensus Statement. Environ Health Perspect 124:A118–A122; http://dx.doi.org/10.1289/EHP358.
Address correspondence to I. Hertz-Picciotto, University of California, Davis, Department of Public Health Sciences, MS1C, One Shields Ave., Davis, California USA 95616-8500. Telephone: 530-752-3025. E-mail: email@example.com; firstname.lastname@example.org
The views expressed in this statement are solely those of the authors and signatories.
Project TENDR has been supported by grants from the John Merck Fund, Ceres Trust, Passport Foundation, and the National Institute of Environmental Health Sciences (R13ES026504).
D.B. has served as an expert witness in civil litigation cases and criminal cases involving exposures to environmental chemicals. He has been paid for these activities. He has provided opinions for plaintiffs and for defendants, depending on the facts of the case. He also served as a paid expert witness to a Commission of Inquiry into lead contamination in Hong Kong’s drinking water. A.B. has served as a consultant to nonprofit organizations developing environmental health educational curricula for child care programs and has participated as a volunteer member on the Board of the Organic Center, a nonprofit organization that provides information for scientific research about organic food and farming. C.K. is employed by The Endocrine Disruption Exchange (TEDX), a U.S. 501(c)3 organization that occasionally provides consultation, legal assistance, or expert testimony on the topic of endocrine-disrupting chemicals. Neither C.K. nor TEDX stands to gain or lose financially through the publication of this article. This work was supported by private foundations that did not have scientific or editorial input or control. J.S. is employed by the Natural Resources Defense Council, an environmental non-governmental organization (NGO) that routinely engages in public advocacy, lobbying, and litigation to expand protections for the environment and public health and to enforce existing environmental laws regulating toxic chemicals, including some of the chemicals identified in this manuscript. I.H-P. has received travel reimbursements for her service on the Scientific Advisory Committee of Autism Speaks, in which she provided comments on broad directions for the organization’s research programs. She also received payment for reviewing grant proposals for the Research Screening Committee of the California Air Resources Board, which is a branch of the California state government involved in air quality regulation. E.M. works at Pesticide Action Network, an NGO advocating for a farming system that is not reliant on pesticides. M.S. is the Director of the Healthy Children Project for the Learning Disabilities Association of America. Her position is funded by the John Merck Fund, which also contributed some of the funding for Project TENDR.
The authors certify that all actual or potential competing financial interests have been declared, and the authors’ freedom to design, conduct, interpret, and publish research is not compromised by any controlling sponsor as a condition of review and publication.
Final Publication: 1 July 2016
A Call to Action
The TENDR Consensus Statement is a call to action to reduce exposures to toxic chemicals that can contribute to the prevalence of neurodevelopmental disabilities in America’s children. The TENDR authors agree that widespread exposures to toxic chemicals in our air, water, food, soil, and consumer products can increase the risks for cognitive, behavioral, or social impairment, as well as specific neurodevelopmental disorders such as autism and attention deficit hyperactivity disorder (ADHD) (Di Renzo et al. 2015; Gore et al. 2015; Lanphear 2015; Council on Environmental Health 2011). This preventable threat results from a failure of our industrial and consumer markets and regulatory systems to protect the developing brain from toxic chemicals. To lower children’s risks for developing neurodevelopmental disorders, policies and actions are urgently needed to eliminate or significantly reduce exposures to these chemicals. Further, if we are to protect children, we must overhaul how government agencies and business assess risks to human health from chemical exposures, how chemicals in commerce are regulated, and how scientific evidence informs decision making by government and the private sector.
Trends in Neurodevelopmental Disorders
We are witnessing an alarming increase in learning and behavioral problems in children. Parents report that 1 in 6 children in the United States, 17% more than a decade ago, have a developmental disability, including learning disabilities, ADHD, autism, and other developmental delays (Boyle et al. 2011). As of 2012, 1 in 10 (> 5.9 million) children in the United States are estimated to have ADHD (Bloom et al. 2013). As of 2014, 1 in 68 children in the United States has an autism spectrum disorder (based on 2010 reporting data) (CDC 2014).
The economic costs associated with neurodevelopmental disorders are staggering. On average, it costs twice as much in the United States to educate a child who has a learning or developmental disability as it costs for a child who does not (Chambers et al. 2004). A recent study in the European Union found that costs associated with lost IQ points and intellectual disability arising from two categories of chemicals—polybrominated diphenyl ether flame retardants (PBDEs) and organophosphate (OP) pesticides—are estimated at 155.44 billion euros ($169.43 billion dollars) annually (Bellanger et al. 2015). A 2009 analysis in the United States found that for every $1 spent to reduce exposures to lead, a potent neurotoxicant, society would benefit by $17–$221 (Gould 2009).
Vulnerability of the Developing Brain to Chemicals
Many toxic chemicals can interfere with healthy brain development, some at extremely low levels of exposure (Adamkiewicz et al. 2011; Bellinger 2008; Committee on Improving Analysis Approaches Used by the U.S. EPA 2009; Zoeller et al. 2012). Research in the neurosciences has identified “critical windows of vulnerability” during embryonic and fetal development, infancy, early childhood and adolescence (Lanphear 2015; Lyall et al. 2014; Rice and Barone 2000). During these windows of development, toxic chemical exposures may cause lasting harm to the brain that interferes with a child’s ability to reach his or her full potential.
The developing fetus is continuously exposed to a mixture of environmental chemicals (Mitro et al. 2015). A 2011 analysis of the U.S. Centers for Disease Control and Prevention’s (CDC) biomonitoring data found that 90% of pregnant women in the United States have detectable levels of 62 chemicals in their bodies, out of 163 chemicals for which the women were screened (Woodruff et al. 2011). Among the chemicals found in the vast majority of pregnant women are PBDEs, polycyclic aromatic hydrocarbons (PAHS), phthalates, perfluorinated compounds, polychlorinated biphenyls (PCBs), perchlorate, lead and mercury (Woodruff et al. 2011). Many of these chemicals can cross the placenta during pregnancy and are routinely detected in cord blood or other fetal tissues (ATSDR 2011; Brent 2010; Chen et al. 2013; Lien et al. 2011).
Prime Examples of Neurodevelopmentally Toxic Chemicals
The following list provides prime examples of toxic chemicals that can contribute to learning, behavioral, or intellectual impairment, as well as specific neurodevelopmental disorders such as ADHD or autism spectrum disorder:
- Organophosphate (OP) pesticides (Eskenazi et al. 2007; Fortenberry et al. 2014; Furlong et al. 2014; Marks et al. 2010; Rauh et al. 2006; Shelton et al. 2014).
- PBDE flame retardants (Chen et al. 2014; Cowell et al. 2015; Eskenazi et al. 2013; Herbstman et al. 2010).
- Combustion-related air pollutants, which generally include PAHs, nitrogen dioxide and particulate matter, and other air pollutants for which nitrogen dioxide and particulate matter are markers (Becerra et al. 2013; Clifford et al. 2016; Jedrychowski et al. 2015; Kalkbrenner et al. 2014; Suades-González et al. 2015; Volk et al. 2013).
- Lead (Eubig et al. 2010; Lanphear et al. 2005; Needleman et al. 1979).
- Mercury (Grandjean et al. 1997; Karagas et al. 2012; Sagiv et al. 2012).
- PCBs (Eubig et al. 2010; Jacobson and Jacobson 1996; Schantz et al. 2003).
The United States has restricted some of the production, use and environmental releases of these particular chemicals, but those measures have tended to be too little and too late. We face a crisis from both legacy and ongoing exposures to toxic chemicals. For lead, OP pesticides, PBDEs and air pollution, communities of color and socioeconomically stressed communities face disproportionately high exposures and health impacts (Adamkiewicz et al. 2011; Engel et al. 2015; Zota et al. 2010).
Policies to ban lead from gasoline, paints and other products have been successful in lowering blood lead levels in the American population (Jones et al. 2009), yet lead exposure continues to be a preventable cause of intellectual impairment, ADHD and maladaptive behaviors for millions of children (CDC 2015). Scientists agree that there is no safe level of lead exposure for fetal or early childhood development (Lanphear et al. 2005; Schnur and John 2014), and studies have documented the potential for cumulative and synergistic health effects from combined exposure to lead and social stressors (Bellinger et al. 1988; Cory-Slechta et al. 2004). Thus, taking further preventive actions is imperative.
Epidemiological, toxicological, and mechanistic studies have together provided evidence that clearly demonstrates or strongly suggests neurodevelopmental toxicity for lead, mercury, OP pesticides, air pollution, PBDEs, and PCBs. The level and type of available evidence linking exposures to toxic chemicals with neurodevelopmental disorders, including the examples in this statement, vary both within and among chemical classes. In light of this extensive evidence and continued widespread exposure, the risks for learning and developmental disorders can likely be lowered through targeted exposure reduction, starting with these example chemicals.
Majority of Chemicals Untested for Neurodevelopmental Effects
The examples of developmental neurotoxic chemicals that we list here likely represent the tip of the iceberg. Of the tens of thousands of chemicals on the U.S. Environmental Protection Agency (EPA) chemical inventory, nearly 7,700 are manufactured or imported into the United States at ≥ 25,000 pounds per year (U.S. EPA 2012). The U.S. EPA has identified nearly 3,000 chemicals that are produced or imported at > 1 million pounds per year (U.S. EPA 2006).
Only a minority of chemicals has been evaluated for neurotoxic effects in adults. Even fewer have been evaluated for potential effects on brain development in children (Grandjean and Landrigan 2006, 2014). Further, toxicological studies and regulatory evaluation seldom address combined effects of chemical mixtures, despite evidence that all people are exposed to dozens of chemicals at any given time.
Need for a New Approach to Evaluating Evidence
Our failures to protect children from harm underscore the urgent need for a better approach to developing and assessing scientific evidence and using it to make decisions. We as a society should be able to take protective action when scientific evidence indicates a chemical is of concern, and not wait for unequivocal proof that a chemical is causing harm to our children.
Evidence of neurodevelopmental toxicity of any type—epidemiological or toxicological or mechanistic—by itself should constitute a signal sufficient to trigger prioritization and some level of action. Such an approach would enable policy makers and regulators to proactively test and identify chemicals that are emerging concerns for brain development and prevent widespread human exposures.
Some chemicals, like those that disrupt the endocrine system, present a concern because they interfere with the activity of endogenous hormones that are essential for healthy brain development. Endocrine-disrupting chemicals (EDCs) include many pesticides, flame retardants, fuels, and plasticizers. One class of EDCs that is ubiquitous in consumer products are the phthalates. These are an emerging concern for interference with brain development and therefore demand attention (Boas et al. 2012; Ejaredar et al. 2015; Mathieu-Denoncourt et al. 2015; Miodovnik et al. 2014; U.S. Consumer Product Safety Commission 2014).
Under our current system, when a toxic chemical or category of chemicals is finally removed from the market, chemical manufacturers often substitute similar chemicals that may pose similar concerns or be virtually untested for toxicity. This practice can result in “regrettable substitution” whereby the cycle of exposures and adverse effects starts all over again. The following list provides examples of this cycle:
- When the federal government banned some uses of OP pesticides, manufacturers responded by expanding the use of neonicotinoid and pyrethroid pesticides. Evidence is emerging that these widely used classes of pesticides pose a threat to the developing brain (Kara et al. 2015; Richardson et al. 2015; Shelton et al. 2014).
- When the U.S. Government reached a voluntary agreement with flame retardant manufacturers to stop making PBDEs, the manufacturers substituted other halogenated and organophosphate flame retardant chemicals. Many of these replacement flame retardants are similar in structure to other neurotoxic chemicals but have not undergone adequate assessment of their effects on developing brains.
- When the federal government banned some phthalates in children’s products, the chemical industry responded by replacing the banned chemicals with structurally similar new phthalates. These replacements are now under investigation for disrupting the endocrine system.
Our system for evaluating scientific evidence and making decisions about environmental chemicals is broken. We cannot continue to gamble with our children’s health. We call for action now to prevent exposures to chemicals and pollutants that can contribute to the prevalence of neurodevelopmental disabilities in America’s children.
We need to overhaul our approach to developing and assessing evidence on chemicals of concern for brain development. Toward this end, we call on regulators to follow scientific guidance for assessing how chemicals affect brain development, such as taking into account the special vulnerabilities of the developing fetus and children, cumulative effects resulting from combined exposures to multiple toxic chemicals and stressors, and the lack of a safety threshold for many of these chemicals (Committee on Improving Analysis Approaches Used by the U.S. EPA 2009). We call on businesses to eliminate neurodevelopmental toxicants from their supply chains and products, and on health professionals to integrate knowledge about environmental toxicants into patient care and public health practice.
Finally, we call on policy makers to take seriously the need to reduce exposures of all children to lead—by accelerating the clean up from our past uses of lead such as in paint and water pipes, by halting the current uses of lead, and by better regulating the industrial processes that cause new lead contamination.
We are confident that reducing exposures to chemicals that can interfere with healthy brain development will help to lower the prevalence of neurodevelopmental disabilities, and thus enable many more children to reach their full potential.
TENDR Statement Authors
Deborah Bennett, PhD
Associate Professor, Department of Public Health Sciences, School of Medicine, University of California, Davis
David C. Bellinger, PhD, MSc
Boston Children’s Hospital
Harvard Medical School
Harvard T.H. Chan School of Public Health
Linda S. Birnbaum, PhD, DABT, A.T.S
Director, National Institute of Environmental Health Sciences
Director, National Toxicology Program
Asa Bradman, PhD, MS
Associate Director, Center for Environmental Research and Children’s Health (CERCH)
Associate Adjunct Professor of Environmental Health Sciences, School of Public Health, UC Berkeley
Aimin Chen, MD, PhD
Associate Professor, Division of Epidemiology
Department of Environmental Health
University of Cincinnati College of Medicine
Deborah A. Cory-Slechta, PhD
Professor of Environmental Medicine, Pediatrics and Public Health Sciences; Acting Chair, Department of Environmental Medicine;
Director, University of Rochester Medical School Environmental Health Sciences Center
Stephanie M. Engel, PhD
Associate Professor, Department of Epidemiology, Gillings School of Global Public Health University of North Carolina, Chapel Hill
M. Daniele Fallin, PhD
Sylvia and Harold Halpert Professor and Chair, Dept. of Mental Health; Director, Wendy Klag Center for Autism and Developmental Disabilities, Johns Hopkins Bloomberg School of Public Health
Alycia Halladay, PhD
Chief Science Officer, Autism Science Foundation, Adjunct, Dept. of Pharmacology and Toxicology, Rutgers University
Russ Hauser, MD, ScD, MPH
Frederick Lee Hisaw Professor of Reproductive Physiology; Professor of Environmental and Occupational Epidemiology, Harvard T.H. Chan School of Public Health; Professor of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School
Irva Hertz-Picciotto, PhD
Director, UC Davis Environmental Health Sciences Center; Professor, Department of Public Health Sciences & Medical Investigations of Neurodevelopmental Disorders (MIND) Institute,
University of California, Davis
Carol F. Kwiatkowski, PhD
Executive Director, The Endocrine Disruption Exchange (TEDX)
Assistant Professor Adjunct, Dept. of Integrative Physiology, University of Colorado, Boulder
Bruce P. Lanphear, MD, MPH
Clinician Scientist, Child & Family Research Institute, BC Children’s Hospital Professor, Faculty of Health Sciences, Simon Fraser University, Vancouver, BC
Emily Marquez, PhD
Pesticide Action Network North America
Melanie Marty, PhD
Adjunct Associate Professor
University of California, Davis
Jennifer McPartland, PhD
Environmental Defense Fund
Craig J. Newschaffer, PhD
Director, A.J. Drexel Autism Institute
Professor, Epidemiology and Biostatistics,
Devon Payne-Sturges, DrPH
Assistant Professor, Maryland Institute for Applied Environmental Health, School of Public Health, University of Maryland
Heather B. Patisaul, PhD
Professor, Biological Sciences, Center for Human Health and the Environment, WM Keck Center for Behavioral Biology, NC State University
Frederica P. Perera, DrPH, PhD
Professor of Public Health
Director, Columbia Center for Children’s Environmental Health; Professor, Dept. of Environmental Health Sciences, Mailman School of Public Health, Columbia University
Beate Ritz MD, PhD
Professor of Epidemiology
Center for Occupational and Environmental Health
Fielding School of Public Health, University of California Los Angeles
Jennifer Sass, PhD
Senior Scientist, Natural Resources Defense Council
Professorial Lecturer, George Washington University
Susan L. Schantz, PhD
Professor of Toxicology and Neuroscience, Illinois Children’s Environmental Health Research Center; Director, Beckman Institute for Advanced Science and Technology, University of Illinois, Urbana-Champaign
Thomas F. Webster, DSc
Professor, Department of Environmental Health, Boston University School of Public Health
Robin M. Whyatt, DrPH
Professor Emeritus, Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University
Tracey J. Woodruff, PhD, MPH
Professor and Director, Program on Reproductive Health and the Environment, Dept. of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco
R. Thomas Zoeller, PhD
Professor of Biology
Director, Laboratory of Molecular & Cellular Biology,
University of Massachusetts Amherst
Health Professionals and Providers
Laura Anderko, PhD, RN
Robert and Kathleen Scanlon Endowed Chair in Values Based Health Care & Professor, School of Nursing and Health Studies, Georgetown University
Director, Mid-Atlantic Center for Children’s Health and the Environment
Carla Campbell, MD, MS, FAAP
Visiting Clinical Associate Professor of Public Health University of Texas at El Paso
Jeanne A. Conry, MD, PhD
Past President, American College of Obstetricians and Gynecologists; Assistant Physician in Chief, The Permanente Medical Group
Nathaniel DeNicola, MD, MSHP, FACOG
American College of Obstetricians & Gynecologists Liaison to American Academy of Pediatrics Executive Council on Environmental Health; Clinical Associate in Obstetrics & Gynecology, U. of Pennsylvania
Robert M. Gould, MD
Associate Adjunct Professor, Program on Reproductive Health and the Environment,
Dept. of Obstetrics, Gynecology and Reproductive Sciences, UCSF School of Medicine; Immediate Past President, Physicians for Social Responsibility
Deborah Hirtz, MD
Professor, Neurological Sciences and Pediatrics
University of Vermont School of Medicine
Katie Huffling, RN, MS, CNM
Director of Programs
Alliance of Nurses for Healthy Environments
Philip J. Landrigan, MD, MSc, FAAP
Dean for Global Health, Arnhold Institute for Global Health; Professor of Preventive Medicine and Pediatrics, Icahn School of Medicine at Mount Sinai
Arthur Lavin, MD, FAAP
Associate Clinical Professor of Pediatrics
Case Western Reserve University School of Medicine
Mark Miller, MD, MPH
Director, University of California San Francisco Pediatric Environmental Health Specialty Unit
Mark A. Mitchell, MD, MPH
President, Mitchell Environmental Health Associates
Chair, Council on Medical Legislation and
Co-Chair, Commission on Environmental Health
National Medical Association
Leslie Rubin, MD
President, Innovative Solutions for Disadvantage and Disability; Associate Professor, Dept. of Pediatrics, Morehouse School of Medicine; Co-director, Southeast Pediatric Environmental Health Specialty Unit, Emory University; Medical Director, Developmental Pediatric Specialists
Ted Schettler, MD, MPH
Science and Environmental Health Network
Ho Luong Tran, MD, MPH
President and CEO
National Council of Asian Pacific Islander Physicians
Children’s Health and Disabilities Advocates
Director of Fiscal and Family Support Policy
Charlotte Brody, RN
National Coordinator, Healthy Babies Bright Futures Vice President of Health Initiatives, BlueGreen Alliance
Elise Miller, MEd
Director, Collaborative on Health and the Environment (CHE)
Pamela Miller, MS
Alaska Community Action on Toxics
Maureen Swanson, MPA
Healthy Children Project Director
Learning Disabilities Association of America
Nsedu Obot Witherspoon, MPH
Executive Director, Children’s Environmental Health Network
Organizations that Endorse or Support the TENDR Consensus Statement
American College of Obstetricians and Gynecologists (ACOG)
ACOG supports the value of this clinical document as an educational tool (March 2016)
Child Neurology Society
International Neurotoxicology Association
International Society for Children’s Health and the Environment
International Society for Environmental Epidemiology
National Council of Asian Pacific Islander Physicians
National Hispanic Medical Association
National Medical Association
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Among the Resources now available on our Children’s Health page is the text of Executive Order 13045, “Protection of Children from Environmental Health Risks and Safety Risks” (21 April 1997). The Executive Order noted the particular vulnerabilities of children to environmental hazards, codified the need to identify and alleviate such risks, and created the President’s Task Force on Environmental Health Risks and Safety Risks to Children to identify data resources and promote research in these areas. As we mark 20 years since the order was enacted, we can see how these efforts have produced important research and mitigation of hazards—a strong base for continued work on behalf of children’s environmental health.
EHP is excited to announce that, starting later in May 2017, the journal will transition from a traditional, issue-by-issue publishing model, to a new, article-by-article publishing model known as continuous publication. This is a more modern way of publishing an online journal, and one that should help to significantly improve EHP’s time to publication. (more…)