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Approximately 2000 official and potential Superfund sites are located within 25 miles of the East or Gulf coasts, many of which will be at risk of flooding as sea levels rise. More than 60 million people across the United States live within 3 miles of a Superfund site. Disentangling multifaceted environmental health problems compounded by climate change requires a multidisciplinary systems approach to inform better strategies to prevent or reduce exposures and protect human health. The purpose of this minireview is to present the National Institute of Environmental Health Sciences Superfund Research Program (SRP) as a useful model of how this systems approach can help overcome the challenges of climate change while providing flexibility to pivot to additional needs as they arise. It also highlights broad-ranging SRP-funded research and tools that can be used to promote health and resilience to climate change in diverse contexts.

Background An unusual feature of SARS-Cov-2 infection and the COVID-19 pandemic is that children are less severely affected than adults. This is especially paradoxical given the epidemiological links between poor air quality and increased COVID-19 severity in adults and that children are generally more vulnerable than adults to the adverse consequences of air pollution. Objectives To identify gaps in knowledge about the factors that protect children from severe SARS-Cov-2 infection even in the face of air pollution, and to develop a transdisciplinary research strategy to address these gaps. Methods An international group of researchers interested in children’s environmental health was invited to identify knowledge gaps and to develop research questions to close these gaps. Discussion Key research questions identified include: what are the effects of SAR-Cov-2 infection during pregnancy on the developing fetus and child; what is the impact of age at infection and genetic susceptibility on disease severity; why do some children with COVID-19 infection develop toxic shock and Kawasaki-like symptoms; what are the impacts of toxic environmental exposures including poor air quality, chemical and metal exposures on innate immunity, especially in the respiratory epithelium; what is the possible role of a “dirty” environment in conveying protection – an example of the “hygiene hypothesis”; and what are the long term health effects of SARS-Cov-2 infection in early life. Conclusion A concerted research effort by a multidisciplinary team of scientists is needed to understand the links between environmental exposures, especially air pollution and COVID-19. We call for specific research funding to encourage basic and clinical research to understand if/why exposure to environmental factors is associated with more severe disease, why children appear to be protected, and how innate immune responses may be involved. Lessons learned about SARS-Cov-2 infection in our children will help us to understand and reduce disease severity in adults, the opposite of the usual scenario.

Deaths from complex, noncommunicable diseases such as cancer are predicted to continue to increase worldwide, with low- and middle-income countries bearing the brunt of the burden. This problem requires a concentrated global effort to avoid devastating losses of life as well as economic losses. Cholangiocarcinoma (CCA) is a readily studied model of complex, noncommunicable disease, but it receives little attention outside of the scientific community in Southeast Asia. Here, we bring attention to the opportunity to study CCA as a model to understand the role of multiple, complex factors in cancer. These factors include allostatic load, individual genetic susceptibility, and environmental exposures such as chemicals, diet, socioeconomic factors, and psychosocial stress. The study of CCA offers a unique opportunity to make novel observations that could advance progress in prevention and intervention approaches for prevalent diseases that involve complex, multifactorial interactions.

Waste electronic and electrical equipment (e-waste) consists of used and discarded electrical and electronic items ranging from refrigerators to cell phones and printed circuit boards. It is frequently moved from developed countries to developing countries where it is dismantled for valuable metals in informal settings, resulting in significant human exposure to toxic substances. E-waste is a major concern in Africa, with large sites in Ghana and Nigeria where imported e-waste is dismantled under unsafe conditions. However, as in many developing countries, used electronic and electrical devices are imported in large quantities because they are in great demand and are less expensive than new ones. Many of these used products are irreparable and are discarded with other solid waste to local landfills. These items are then often scavenged for the purpose of extracting valuable metals by heating and burning, incubating in acids and other methods. These activities pose significant health risks to workers and residents in communities near recycling sites. E-waste burning and dismantling activities are frequently undertaken at e-waste sites, often in or near homes. As a result, children and people living in the surrounding areas are exposed, even if they are not directly involved in the recycling. While toxic substances are dangerous to individuals at any age, children are more vulnerable as they are going through important developmental processes, and some adverse health impacts may have long-term impacts. We review the e-waste situation in Africa with a focus on threats to children’s health.

The National Institute of Environmental Health Sciences Superfund Research Program (SRP) funds university-based, solution-oriented research to understand how hazardous substances contribute to disease and how to prevent exposures to these hazardous substances. A unique aspect of the SRP is that, beyond the biomedical, environmental sciences, and engineering research projects, SRP-funded centers are required to include community engagement to build partnerships with affected communities and research translation to communicate and facilitate the use of research findings. The SRP views both as effective ways to inform and advance science for protection of public health. The purpose of community engagement within the centers is to ensure bidirectional communication between the researchers and the community, identify best practices and activities in community engagement for prevention and intervention activities, enhance knowledge, and support the needs of the communities impacted by hazardous waste sites. The SRP views research translation as communicating and facilitating the use of research findings emanating from the center in a manner most appropriate for their application and for the advancement of a center’s research objectives. The SRP has a strong history of seeking opportunities to work with communities and stakeholders, by translating and sharing research findings in an impactful and informative manner with long-lasting benefits to improve public health.

Background: Exposure to inorganic and organic arsenic compounds is a major public health problem that affects hundreds of millions of people worldwide. Exposure to arsenic is associated with cancer and noncancer effects in nearly every organ in the body, and evidence is mounting for health effects at lower levels of arsenic exposure than previously thought. Building from a tremendous knowledge base with > 1,000 scientific papers published annually with “arsenic” in the title, the question becomes, what questions would best drive future research directions? Objectives: The objective is to discuss emerging issues in arsenic research and identify data gaps across disciplines. Methods: The National Institutes of Health’s National Institute of Environmental Health Sciences Superfund Research Program convened a workshop to identify emerging issues and research needs to address the multi-faceted challenges related to arsenic and environmental health. This review summarizes information captured during the workshop. Discussion: More information about aggregate exposure to arsenic is needed, including the amount and forms of arsenic found in foods. New strategies for mitigating arsenic exposures and related health effects range from engineered filtering systems to phytogenetics and nutritional interventions. Furthermore, integration of omics data with mechanistic and epidemiological data is a key step toward the goal of linking biomarkers of exposure and susceptibility to disease mechanisms and outcomes. Conclusions: Promising research strategies and technologies for arsenic exposure and adverse health effect mitigation are being pursued, and future research is moving toward deeper collaborations and integration of information across disciplines to address data gaps. Citation: Carlin DJ, Naujokas MF, Bradham KD, Cowden J, Heacock M, Henry HF, Lee JS, Thomas DJ, Thompson C, Tokar EJ, Waalkes MP, Birnbaum LS, Suk WA. 2016. Arsenic and environmental health: state of the science and future research opportunities. Environ Health Perspect 124:890–899; http://dx.doi.org/10.1289/ehp.1510209

Background: The National Institute of Environmental Health Sciences (NIEHS) Superfund Basic Research and Training Program (SRP) funds a wide range of transdisciplinary research projects spanning the biomedical and environmental sciences and engineering, supporting and promoting the application of that research to solving real-world problems. Objectives: We used a case study approach to identify the economic and societal benefits of SRP-funded research, focusing on the use of potentially hazardous substance remediation and site monitoring tools. We also identified successes and challenges involved in translating SRP grantees’ research findings and advances into application. Discussion: We identified remediation and detection research projects supported by the SRP with the most potential for economic and societal benefits and selected 36 for analysis. To examine the benefits of these applied technologies, we interviewed 28 SRP-supported researchers and 41 partners. Five case studies emerged with the most complete information on cost savings—total savings estimated at >$100 million. Our analysis identified added societal benefits such as creation of small businesses, land and water reuse, sustainable technologies, exposure reduction, and university–industry partnerships. Conclusions: Research funded by the SRP has yielded significant cost savings while providing additional societal benefits. https://doi.org/10.1289/EHP3534

Background Chronic diseases are increasing among children in Latin America. Objective and Methods To examine environmental risk factors for chronic disease in Latin American children and to develop a strategic initiative for control of these exposures, the World Health Organization (WHO) including the Pan American Health Organization (PAHO), the Collegium Ramazzini, and Latin American scientists reviewed regional and relevant global data. Results Industrial development and urbanization are proceeding rapidly in Latin America, and environmental pollution has become widespread. Environmental threats to children’s health include traditional hazards such as indoor air pollution and drinking-water contamination; the newer hazards of urban air pollution; toxic chemicals such as lead, asbestos, mercury, arsenic, and pesticides; hazardous and electronic waste; and climate change. The mix of traditional and modern hazards varies greatly across and within countries reflecting industrialization, urbanization, and socioeconomic forces. Conclusions To control environmental threats to children’s health in Latin America, WHO, including PAHO, will focus on the most highly prevalent and serious hazards—indoor and outdoor air pollution, water pollution, and toxic chemicals. Strategies for controlling these hazards include developing tracking data on regional trends in children’s environmental health (CEH), building a network of Collaborating Centres, promoting biomedical research in CEH, building regional capacity, supporting development of evidence-based prevention policies, studying the economic costs of chronic diseases in children, and developing platforms for dialogue with relevant stakeholders. Citation Laborde A, Tomasina F, Bianchi F, Bruné MN, Buka I, Comba P, Corra L, Cori L, Duffert CM, Harari R, Iavarone I, McDiarmid MA, Gray KA, Sly PD, Soares A, Suk WA, Landrigan PJ. 2015. Children’s health in Latin America: the influence of environmental exposures. Environ Health Perspect 123:201–209; http://dx.doi.org/10.1289/ehp.1408292

Summary: Pollution is a major, overlooked, global health threat that was responsible in 2015 for an estimated 9 million deaths and great economic losses. To end neglect of pollution and advance prevention of pollution-related disease, we formed the Lancet Commission on Pollution and Health. Despite recent gains in understanding of pollution and its health effects, this Commission noted that large gaps in knowledge remain. To close these gaps and guide prevention, the Commission made research recommendations and proposed creation of a Global Observatory on Pollution and Health. We posit that successful pollution research will be translational and based on transdisciplinary collaborations among exposure science, epidemiology, data science, engineering, health policy, and economics. We envision that the Global Observatory on Pollution and Health will be a multinational consortium based at Boston College and the Harvard T.H. Chan School of Public Health that will aggregate, geocode, and archive data on pollution and pollution-related disease; analyze these data to discern trends, geographic patterns, and opportunities for intervention; and make its findings available to policymakers, the media, and the global public to catalyze research, inform policy, and assist cities and countries to target pollution, track progress, and save lives. https://doi.org/10.1289/EHP3141

Background: Concerns for arsenic exposure are not limited to toxic waste sites and massive poisoning events. Chronic exposure continues to be a major public health problem worldwide, affecting hundreds of millions of persons. Objectives: We reviewed recent information on worldwide concerns for arsenic exposures and public health to heighten awareness of the current scope of arsenic exposure and health outcomes and the importance of reducing exposure, particularly during pregnancy and early life. Methods: We synthesized the large body of current research pertaining to arsenic exposure and health outcomes with an emphasis on recent publications. Discussion: Locations of high arsenic exposure via drinking water span from Bangladesh, Chile, and Taiwan to the United States. The U.S. Environmental Protection Agency maximum contaminant level (MCL) in drinking water is 10 µg/L; however, concentrations of > 3,000 µg/L have been found in wells in the United States. In addition, exposure through diet is of growing concern. Knowledge of the scope of arsenic-associated health effects has broadened; arsenic leaves essentially no bodily system untouched. Arsenic is a known carcinogen associated with skin, lung, bladder, kidney, and liver cancer. Dermatological, developmental, neurological, respiratory, cardiovascular, immunological, and endocrine effects are also evident. Most remarkably, early-life exposure may be related to increased risks for several types of cancer and other diseases during adulthood. Conclusions: These data call for heightened awareness of arsenic-related pathologies in broader contexts than previously perceived. Testing foods and drinking water for arsenic, including individual private wells, should be a top priority to reduce exposure, particularly for pregnant women and children, given the potential for life-long effects of developmental exposure.

Background Millions of individuals worldwide, particularly those living in rural and developing areas, are exposed to harmful levels of inorganic arsenic (iAs) in their drinking water. Inorganic As exposure during key developmental periods is associated with a variety of adverse health effects, including those that are evident in adulthood. There is considerable interest in identifying the molecular mechanisms that relate early-life iAs exposure to the development of these latent diseases, particularly in relationship to cancer. Objectives This work summarizes research on the molecular mechanisms that underlie the increased risk of cancer development in adulthood that is associated with early-life iAs exposure. Discussion Epigenetic reprogramming that imparts functional changes in gene expression, the development of cancer stem cells, and immunomodulation are plausible underlying mechanisms by which early-life iAs exposure elicits latent carcinogenic effects. Conclusions Evidence is mounting that relates early-life iAs exposure and cancer development later in life. Future research should include animal studies that address mechanistic hypotheses and studies of human populations that integrate early-life exposure, molecular alterations, and latent disease outcomes. Citation Bailey KA, Smith AH, Tokar EJ, Graziano JH, Kim KW, Navasumrit P, Ruchirawat M, Thiantanawat A, Suk WA, Fry RC. 2016. Mechanisms underlying latent disease risk associated with early-life arsenic exposure: current research trends and scientific gaps. Environ Health Perspect 124:170–175; http://dx.doi.org/10.1289/ehp.1409360

Background: The paradigm of human risk assessment includes many variables that must be viewed collectively in order to improve human health and prevent chronic disease. The pathology of chronic diseases is complex, however, and may be influenced by exposure to environmental pollu-tants, a sedentary lifestyle, and poor dietary habits. Much of the emerging evidence suggests that nutrition can modulate the toxicity of environmental pollutants, which may alter human risks associated with toxicant exposures. Objectives: In this commentary, we discuss the basis for recommending that nutrition be considered a critical variable in disease outcomes associated with exposure to environmental pollutants, thus establishing the importance of incorporating nutrition within the context of cumulative risk assessment. Discussion: A convincing body of research indicates that nutrition is a modulator of vulnerability to environmental insults; thus, it is timely to consider nutrition as a vital component of human risk assessment. Nutrition may serve as either an agonist or an antagonist (e.g., high-fat foods or foods rich in antioxidants, respectively) of the health impacts associated with exposure to environmental pollutants. Dietary practices and food choices may help explain the large variability observed in human risk assessment. Conclusion: We recommend that nutrition and dietary practices be incorporated into future environmental research and the development of risk assessment paradigms. Healthful nutrition interventions might be a powerful approach to reduce disease risks associated with many environmental toxic insults and should be considered a variable within the context of cumulative risk assessment and, where appropriate, a potential tool for subsequent risk reduction.

The 2006–2011 National Institute of Environmental Health Sciences’ (NIEHS) Strategic Plan New Frontiers in Environmental Sciences and Human Health (NIEHS 2006c) seeks to “challeng[e] and energiz[e] the scientific community to use environmental health sciences to understand the causes of disease and to improve human health” (National Institutes of Health 2006). The strategic plan emphasizes, among other things, integrative research, community-linked research, and prioritizing environmental factors that are most likely contributing to human disease. Consistent with the goals of the strategic plan, new technologies in information systems, data federation, grid systems, and spatial analytics all hold great promise of enabling integrated science teamwork while helping to disentangle genetic, environmental, and other factors that contribute to the complex etiology of common human diseases. Such systems will provide effective means of knowledge and data sharing among scientists, as well as rapid and efficient approaches for sorting through and analyzing large data sets; thus, these systems will support both the scientific and policy processes while accelerating the rate of knowledge production and discovery. The need for such systems to address environmental health concerns was made especially apparent when a series of devastating hurricanes ripped across the Gulf Coast of the United States during 2005 (Schwartz 2005). The effects of Hurricane Katrina were especially severe: The human and environmental health impacts on New Orleans, Louisiana, and other Gulf Coast communities will be felt for many decades to come [Daniels et al. 2006; Nates and Moyer 2005; Pastor et al. 2006; Pezzoli et al. 2006; U.S. Environmental Protection Agency (EPA) 2006]. The Federal Emergency Management Agency (FEMA) estimates that Katrina’s destruction (exacerbated by the chronic loss of wetlands, land subsidence, and inadequate infrastructure) disrupted the lives of roughly 650,000 Americans (U.S. Department of Commerce 2006). Over 1,300 people died. The projected economic costs for recovery and reconstruction are unprecedented—likely to exceed $125 billion (Pastor et al. 2006). The density of industrial operations in New Orleans and the Mississippi Delta before the Katrina disaster combined with the release of contaminants into floodwaters and their transport throughout urbanized areas to give rise to many significant environmental health concerns. At the same time, the flooding of thousands of homes and > 100 schools may have created indoor environments that threaten human respiratory and neurologic health through the growth of mold and other bioaeroallergens. All of these potential exposures took place within the context of high psychosocial stress and, for many, low socioeconomic status—conditions that often exacerbate the effects of adverse environmental exposures (Berube and Katz 2005). Health disparities that result from poverty and inadequate infrastructure raise serious concerns about environmental justice (Pellow and Brulle 2005; Thomson et al. 2006). The scale and complexity of the ensuing environmental health issues made tracking environmental hazards and focusing medical and environmental response and recovery resources in areas of greatest need an obvious priority. A unique opportunity arose to deploy a system to meet these needs, while also creating a test bed for technologies that will help advance environmental health sciences research into the modern scientific and computing era.

More than 150 scientists from the Americas, Europe, and Asia met in Brno, Czech Republic, in May 2002 at the Second PCB Workshop, entitled “Recent Advances in the Environmental Toxicology and Health Effects of PCBs”. NIEHS/EPA-Superfund Basic Research Program, the Graduate Center for Toxicology at the University of Kentucky, and the Research Centre for Atmospheric and Environmental Chemistry and Ecotoxicology of Masaryk University, Brno, sponsored the Workshop. At six separate sessions (including posters) the origins, human residues and exposures, actions, biomarkers, risk and remediation issues relating to PCBs were discussed.

The Precautionary Principle is founded on the use of comprehensive, coordinated research to protect human health in the face of uncertain risks. Research directed at key data gaps may significantly reduce the uncertainty underlying the complexities of assessing risk to mixtures. The National Institute of Environmental Health Sciences (NIEHS) has taken a leadership role in building the scientific infrastructure to address these uncertainties. The challenge is to incorporate the objectives as defined by the Precautionary Principle with the knowledge gained in understanding the multifactorial nature of gene-environment interactions. Through efforts such as the National Center for Toxicogenomics, the National Toxicology Program, and the Superfund Basic Research Program, NIEHS is translating research findings into public health prevention strategies using a 3-pronged approach: (1) identify/evaluate key deviations from additivity for mixtures; (2) develop/apply/link advanced technologies and bioinforma...

Arctic indigenous peoples face significant challenges resulting from the contamination of Arctic air, water, and soil by persistent organic pollutants, heavy metals, and radionuclides. International cooperative efforts among governments and research institutions are under way to collect the information needed by environmental health scientists and public health officials to address environmental contamination in the Arctic. However, the climatic, political, and cultural conditions of the land and its native populations combine to present a unique set of scientific and logistic challenges to addressing this important public health issue. Public health officials have the responsibility to respect the cultural traditions of indigenous communities, while simultaneously designing strategies that will reduce their exposure to environmental contaminants and rates of disease and dysfunction. Researchers can better understand the link between environmental exposures and disease through monitoring programs for both the subsistence diets and health status of the indigenous populations. We suggest that the incorporation of community-based participatory research methods into programs designed to assess biomarkers of contaminant exposure in children and adults may be a valuable addition to ongoing and newly developed research programs. This approach could serve as a model for international environmental health initiatives, because it involves the participation of the local communities and seeks to builds trust between all stakeholders.

Patterns of illness in children have changed dramatically in the last century, and will continue to change in this century. The major diseases confronting children are now chronic and disabling conditions termed the "new pediatric morbidity"-asthma, leukemia and brain cancer, neurodevelopmental dysfunction and neurobehavioral abnormality, reproductive and systemic developmental problems. Chemical toxicants in the environment, poverty, and little or no access to health care are all factors contributing to life-threatening pediatric diseases; children are uniquely vulnerable to chemical toxicants because of their disproportionately heavy exposures and their inherent biological growth and development. Genetic susceptibility and environmental exposures during vulnerable periods of development are also important contributors to the etiologies of many diseases of childhood. It is vital that we develop a better understanding of the mechanisms and interactions between nutrition, infectious disease, environmental exposures, and genetic predisposition in order to develop better prevention methods. This paper briefly examines modern contributors to children's environmental health problems, efforts to date on both the regional and international level to address these challenges, and reflects upon major research needs that must be addressed in order to close the gaps that exist in our understanding of the relationship between environmental exposures and children's health.

We need to critically assess the present quality of the marine ecosystem, especially the connection between ecosystem change and threats to human health. In this article we review the current state of indicators to link changes in marine organisms with eventual effects to human health, identify research opportunities in the use of indicators of ocean and human health, and discuss how to establish collaborations between national and international governmental and private sector groups. We present a synthesis of the present state of understanding of the connection between ocean health and human health, a discussion of areas where resources are required, and a discussion of critical research needs and a template for future work in this field. To understand fully the interactions between ocean health and human health, programs should be organized around a "models-based" approach focusing on critical themes and attributes of marine environmental and public health risks. Given the extent and complex nature of ocean and human health issues, a program networking across geographic and disciplinary boundaries is essential. The overall goal of this approach would be the early detection of potential marine-based contaminants, the protection of marine ecosystems, the prevention of associated human illness, and by implication, the development of products to enhance human well-being. The tight connection between research and monitoring is essential to develop such an indicator-based effort.

Background Complex problems do not respect academic disciplinary boundaries. Environmental health research is complex and often moves beyond these boundaries, integrating diverse knowledge resources to solve such challenges. Here we describe an evolving paradigm for interweaving approaches that integrates widely diverse resources outside of traditional academic environments in full partnerships of mutual respect and understanding. We demonstrate that scientists, social scientists, and engineers can work with government agencies, industry, and communities to interweave their expertise into metaphorical knowledge fabrics to share understanding, resources, and enthusiasm. Objective Our goal is to acknowledge and validate how interweaving research approaches can contribute to research-driven, solution-oriented problem solving in environmental health, and to inspire more members of the environmental health community to consider this approach. Discussion The National Institutes of Health’s National Institute of Environmental Health Sciences Superfund Research Program (SRP), as mandated by Congress, has evolved to become a program that reaches across a wide range of knowledge resources. SRP fosters interweaving multiple knowledge resources to develop innovative multidirectional partnerships for research and training. Here we describe examples of how motivation, ideas, knowledge, and expertise from different people, institutions, and agencies can integrate to tackle challenges that can be as complex as the resources they bring to bear on it. Conclusions By providing structure for interweaving science with its stakeholders, we are better able to leverage resources, increase potential for innovation, and proactively ensure a more fully developed spectrum of beneficial outcomes of research investments. Citation Anderson BE, Naujokas MF, Suk WA. 2015. Interweaving knowledge resources to address complex environmental health challenges. Environ Health Perspect 123:1095–1099; http://dx.doi.org/10.1289/ehp.1409525

989 Environmental Threats to the Health of Children: The Asian Perspective David O. Carpenter,1 Fook Tim Chew,2 Terri Damstra,3 Le Hung Lam,4 Philip J. Landrigan,5 Irma Makalinao,6 Genandrialine L. Peralta,7 and William A. Suk 8 1School of Public Health, University at Albany, Rensselaer, New York, USA; 2Faculty of Medicine, Department of Pediatrics, National University of Singapore, Singapore, Republic of Singapore; 3WHO-IPCS/IRRU, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA; 4Hanoi School of Public Health, Hanoi, Vietnam; 5Center for Childrens’ Health and the Environment, Department of Community and Preventive Medicine, Mt. Sinai School of Medicine, New York, New York, USA; 6National Poison Controls and Information Service, Philippine General Hospital, University of the Philippines College of Medicine, Manila, Republic of the Philippines; 7 Environmental Engineering, National Engineering Center, University of the Philippines, Quezon City, Republic of the Philippines; 8Division of Extramural Research and Training, Office of Program Development, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA

The discovery in the mid-1970s that occupational exposures to pesticides could diminish or destroy the fertility of workers sparked concern about the effects of hazardous substances on male reproductive health. More recently, there is evidence that sperm quantity and quality may have declined worldwide, that the incidence of testicular cancer has progressively increased in many countries, and that other disorders of the male reproductive tract such as hypospadias and cryptorchidism may have also increased. There is growing concern that occupational factors and environmental chemical exposures, including in utero and childhood exposures to compounds with estrogenic activity, may be correlated with these observed changes in male reproductive health and fertility. We review the evidence and methodologies that have contributed to our current understanding of environmental effects on male reproductive health and fertility and discuss the methodologic issues which confront investigators in this area. One of the greatest challenges confronting researchers in this area is assessing and comparing results from existing studies. We elaborate recommendations for future research. Researchers in the field of male reproductive health should continue working to prioritize hazardous substances; elucidate the magnitude of male reproductive health effects, particularly in the areas of testicular cancer, hypospadias, and cryptorchidism; develop biomarkers of exposure to reproductive toxins and of reproductive health effects for research and clinical use; foster collaborative interdisciplinary research; and recognize the importance of standardized laboratory methods and sample archiving.

Three to 4 million children and adolescents in the United States live within 1 mile of a federally designated Superfund hazardous waste disposal site and are at risk of exposure to chemical toxicants released from these sites into air, groundwater, surface water, and surrounding communities. Because of their patterns of exposure and their biological vulnerability, children are uniquely susceptible to health injury resulting from exposures to chemical toxicants in the environment. The Superfund Basic Research Program, funded by the U.S. Environmental Protection Agency and directed by the National Institute of Environmental Health Sciences, is extremely well positioned to organize multidisciplinary research that will assess patterns of children's exposures to hazardous chemicals from hazardous waste disposal sites; quantify children's vulnerability to environmental toxicants; assess causal associations between environmental exposures and pediatric disease; and elucidate the mechanisms of environmental disease in children at the cellular and molecular level.

Background Nutrition and lifestyle are well-defined modulators of chronic diseases. Poor dietary habits (such as high intake of processed foods rich in fat and low intake of fruits and vegetables), as well as a sedentary lifestyle clearly contribute to today’s compromised quality of life in the United States. It is becoming increasingly clear that nutrition can modulate the toxicity of environmental pollutants. Objectives Our goal in this commentary is to discuss the recommendation that nutrition should be considered a necessary variable in the study of human disease associated with exposure to environmental pollutants. Discussion Certain diets can contribute to compromised health by being a source of exposure to environmental toxic pollutants. Many of these pollutants are fat soluble, and thus fatty foods often contain higher levels of persistent organics than does vegetable matter. Nutrition can dictate the lipid milieu, oxidative stress, and antioxidant status within cells. The modulation of these parameters by an individual’s nutritional status may have profound affects on biological processes, and in turn influence the effects of environmental pollutants to cause disease or dysfunction. For example, potential adverse health effects associated with exposure to polychlorinated biphenyls may increase as a result of ingestion of certain dietary fats, whereas ingestion of fruits and vegetables, rich in antioxidant and anti-inflammatory nutrients or bioactive compounds, may provide protection. Conclusions We recommend that future directions in environmental health research explore this nutritional paradigm that incorporates a consideration of the relationships between nutrition and lifestyle, exposure to environmental toxicants, and disease. Nutritional interventions may provide the most sensible means to develop primary prevention strategies of diseases associated with many environmental toxic insults.

On 20 September 2010, the children of the world, and all of us who work in children’s environmental health and pediatric toxicology, lost a beloved friend and global champion with the untimely death of Jenny Pronczuk de Garbino at 63 years of age. Pronczuk was a physician and, for many years, a medical officer in the Department of Public Health and Environment of the World Health Organization (WHO). She was the founder and, for more than a decade, the charismatic and inspirational leader of the WHO Initiative in Children’s Environmental Health. Her work improved the lives of children in all regions of the world. Pronczuk was born in Uruguay of Ukrainian parents. She grew up in Montevideo and the wild countryside of rural Uruguay, which she loved deeply. She was trained as a physician at the School of Medicine of the Universidad de la Republica in Uruguay, completing her postgraduate studies in clinical toxicology and occupational health. She undertook further clinical training at the Universite de Paris, Lariboisiere–St Louis, and then at Baylor College of Medicine in Houston, Texas, through a Fulbright Scholarship. On completion of her training, she was appointed Head Professor of Clinical Toxicology and Director of the National Poisons Centre in Montevideo. Pronczuk joined WHO in 1991, working initially in WHO’s International Programme on Chemical Safety. In this position, she facilitated the establishment of poison control centers worldwide, developed training programs in medical toxicology throughout the developing world, and published numerous authoritative articles. In 1999, Pronczuk established the WHO Task Force for the Protection of Children’s Environmental Health, which became the WHO Initiative in Children’s Environmental Health. In 2002, WHO Director-General Gro Harlem Brundtland formally launched the initiative during the World Summit on Sustainable Development. The goal of the initiative was to prevent children’s disease and disability associated with environmental threats to health. It was here that Pronczuk truly found her life’s work. Over the next decade, Pronczuk worked tirelessly to build the WHO Initiative in Children’s Environmental Health. She was an extraordinary leader with a truly amazing ability to bring people together to work joyfully to protect the health of children. She convened a series of landmark conferences and consultations in Bangkok, Thailand (2002); Mar del Plata, Argentina (2005); Buenos Aires, Argentina (2005); and Busan, Republic of Korea (2009). These conferences established priorities for action, built commitments to national and international programs, and energized pediatricians and medical societies. They led to the creation of a global network of Centers for Excellence in Children’s Environmental Health and also built collaborations among prospective birth cohort studies around the world examining environmental influences on children’s health and development. Important proclamations at these conferences provided critical guidance to the global development of children’s environmental health: the Bangkok Statement on Children’s Environmental Health (Suk et al. 2003; World Health Organization 2002); the Declaration of Mar del Plata, in which Ministries of Health and national pediatric societies in seven countries of the Southern Cone of South America pledged to make the protection of children against environmental threats to health a high national priority (Health and Environment Ministers of the Americas 2005); and the Busan Pledge for Action on Children’s Health and the Environment (Third WHO International Conference on Children’s Health and the Environment 2009), which called for a global plan of action to improve children’s environmental health in countries around the world (Gavidia et al. 2010). Pronczuk led the development of an extraordinary body of work that created a firm intellectual foundation for children’s environmental health in countries around the world. She led the development of a training tool—the WHO Training Package for Health Care Providers, specifically for children’s environmental health (WHO 2011)—and implemented training workshops based on this tool. She oversaw construction of the “Green Page” for environmental health history taking (WHO 2012). She spearheaded the incorporation of a children’s environmental health module, based on the Green Page, into WHO’s Integrated Management of Childhood Illnesses (WHO 2015). She led the development of environmental health indicators for use in countries around the world (WHO 2009). Pronczuk promoted cooperative research, for example, in childhood asthma, arsenic exposure in pregnant women and their children in Thailand, and asthma and air pollution in urban areas in India. She also stimulated important contributions to the Global Burden of Disease project, showing, for example, that lead is responsible for approximately 1% of the global burden of disease (Fewtrell et al. 2004) and that toxic chemicals are responsible for 5.7% (Pruss-Ustun et al. 2011). Pronczuk built strong proactive partnerships with nongovernmental organizations such as the International Society of Doctors for the Environment, the International Conference on Children’s Health and the Environment, and the Nurses Network. She worked with the United Nations Environment Programme to remove lead from gasoline worldwide. Pronczuk also worked closely with colleagues at the National Institute of Environmental Health Sciences (NIEHS), especially with Bill Suk. She was for many years the co-principal investigator of a cooperative agreement between NIEHS and WHO. She collaborated with scientists at NIEHS on initiatives to improve children’s health and to build effective partnerships worldwide. Pronczuk was remembered at NIEHS for her contagious laugh and her passion for making a difference in children’s lives all over the world. In 2008, Pronczuk was recognized by the U.S. Environmental Protection Agency as the International Children’s Environmental Health Champion because of her outstanding efforts and commitment to advancing children’s environmental health issues around the world. The memory and life’s work of Pronczuk were honored on 22–24 March 2012 at an International Scientific Conference on Environmental Health in the Political Agenda, held in Montevideo, Uruguay, her birthplace. The conference was convened by the Faculty of Medicine of the University of the Republic of Uruguay, the Pan American Health Organization, WHO, the Collegium Ramazzini, and NIEHS. The goal was to address critical and emerging issues in children’s environmental health, especially focusing on Latin America and the Caribbean. The conference looked to the future while celebrating Pronczuk’s extraordinary achievements. The first Jenny Pronczuk Award for Research and Intervention in Children’s Environmental Health and Toxicology was awarded at the conference to Maria Gabriela Rovedatti and colleagues for their paper, “Impact of Pesticide Environmental Exposure in the Triad Mother–Placenta–Fetus and Preventive Actions,” subsequently published (Cecchi et al. 2012). A report from the conference titled “Children’s Health in Latin America: The Influence of Environmental Exposures” (LaBorde et al. 2015) is published in this issue of Environmental Health Perspectives. Pronczuk’s great legacy lies in the programs she built, the friends and colleagues she brought together, the young physicians and scientists whom she inspired, and the lives of the millions of children in countries around the world whose health she steadfastly protected.

For the last 50 years, the economic and industrial development of the nations of Central and Eastern Europe has been achieved at the cost of environmental degradation. The health risks posed by this pollution to children and the steps necessary to ameliorate such risks are only beginning to be investigated. At a recent conference in Poland, sponsored in part by the National Institute of Environmental Health Sciences, participants from 11 countries in the region, together with scientists from Western Europe and the United States, met to share information regarding pediatric environmental health in Central and Eastern Europe, to consider methodologic issues in the design and conduct of such studies, and to discuss preventive strategies. This report summarizes the deliberations, outlines problem areas such as heavy metals and air pollution, delineates research and training needs to help Central and Eastern Europeans deal more effectively with such problems, and recommends specific future actions and collaborative efforts.

Environmental health and environmental quality issues along the U.S.-Mexico border have been of concern for several years. The enactment of the North American Free Trade Agreement and the presence ...

The countries of Eastern and Central Europe have emerged from a political system which for decades has ignored protection of human health from hazardous wastes. While the economies of the countries...

Background Accumulating evidence indicates that in utero exposure to arsenic is associated with congenital defects and long-term disease consequences including cancers. Recent studies suggest that arsenic carcinogenesis results from epigenetic changes, particularly in DNA methylation. This study aimed to investigate DNA methylation changes as a result of arsenic exposure in utero and in vitro. Methods For the exposure in utero study, a total of seventy-one newborns (fifty-five arsenic-exposed and sixteen unexposed newborns) were recruited. Arsenic concentrations in the drinking water were measured, and exposure in newborns was assessed by measurement of arsenic concentrations in cord blood, nails and hair by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). In the in vitro study, human lymphoblasts were treated with arsenite at 0-100 μM for two, four and eight hours (short-term) and at 0, 0.5 and 1.0 μM for eight-weeks period (long-term). DNA methylation was analyzed in cord blood lymphocytes and lymphoblasts treated with arsenite in vitro. Global DNA methylation was determined as LINE-1 methylation using combined bisulfite restriction analysis ( COBRA) and total 5-methyldeoxycytidine (5MedC) content which was determined by HPLC-MS/MS. Methylation of p53 was determined at the promoter region using methylation-specific restriction endonuclease digestion with MspI and HpaII. Results Results showed that arsenic-exposed newborns had significantly higher levels of arsenic in cord blood, fingernails, toenails and hair than those of the unexposed subjects and a slight increase in promoter methylation of p53 in cord blood lymphocytes which significantly correlated with arsenic accumulation in nails (p < 0.05) was observed, while LINE-1 methylation was unchanged. Short-term in vitro arsenite treatment in lymphoblastoid cells clearly demonstrated a significant global hypomethylation, determined as reduction in LINE-1 methylation and total 5-MedC content, and p53 hypermethylation (p < 0.05). However, a slight LINE-1 hypomethylation and transient p53 promoter hypermethylation were observed following long-term in vitro treatment. Conclusions This study provides an important finding that in utero arsenic exposure affects DNA methylation, particularly at the p53 promoter region, which may be linked to the mechanism of arsenic carcinogenesis and the observed increased incidence of cancer later in life.

Participants at the Napa Conference on Genetic and Molecular Ecotoxicology assessed the status of this field in light of heightened concerns about the genetic effects of exposure to hazardous substances and recent advancements in our capabilities to measure those effects. We present here a synthesis of the ideas discussed throughout the conference, including definitions of important concepts in the field and critical research needs and opportunities. While there were many opinions expressed on these topics, there was general agreement that there are substantive new opportunities to improve the impact of genetic and molecular ecotoxicology on prediction of sublethal effects of exposure to hazardous substances. Future studies should emphasize integration of genetic ecotoxicology, ecological genetics, and molecular biology and should be directed toward improving our understanding of the ecological implications of genotoxic responses. Ecological implications may be assessed at either the population or ecosystem level; however, a population-level focus may be most pragmatic. Recent technical advancements in measuring genetic and molecular responses to toxicant exposure will spur rapid progress. These new techniques have considerable promise for increasing our understanding of both mechanisms of toxicity on genes or gene products and the relevance of detrimental effects to individual fitness. — Environ Health Perspect 102(Suppl 12):3–8 (1994)

The principal conclusions and opportunities that can be drawn from this conference are as follows. The meeting demonstrated the large communication gap that still exists between most epidemiologists and laboratory scientists. This problem could be overcome if epidemiologists worked closely with laboratory scientists at the outset of any project so that a better understanding could be built between them. Epidemiologists need simple, well-characterized, reproducible assays that can be applied to hundreds or thousands of people. Most laboratory scientists have little interest in running large numbers of assays, but wish to continually refine their methods so that they stay on the "cutting edge" of basic research. This problem could be overcome if the new laboratory technology could be transferred to contract laboratories or small companies. Problems of technology transfer therefore need to be addressed. Current and new biomarkers need to be better validated in the field and by studying animal models. More information on the background expression of biomarkers in the general population is needed (i.e. what is the normal range?). Ethical issues, such as the possibility that biomarkers of susceptibility could be used to exclude people from the workplace, need to be addressed.

Assessing human exposure to chemicals from Superfund sites requires knowledge of basic physical, chemical, and biological processes occurring in the environment and specific information about the local environment and population in the vicinity of sites of interest. Although progress is being made in both areas, there is still a tremendous amount to be done. Participants at this meeting have identified several of the areas in need of greater understanding, and they are listed below. Movement of dissolved and volatile organics, especially NAPLs, in the subsurface environment. This includes study of the partitioning of compounds between NAPLs, air, water, and soil. Partitioning of volatilized chemicals between gaseous and aerosol components of the atmosphere. This includes understanding how these components influence both wet and dry deposition. Long-term movement from sediments into biota and how these affect chronic toxicity to sediment biota. Broad validation of PBPK models describing partitioning of compounds from sediment and water into fish. Reactions of chemicals sorbed to atmospheric particles. This includes application of laboratory models to real and varied atmospheric conditions. Interactions between biotic and abiotic transformations in soil and sediment. Applicability of physiological pharmacokinetic models developed in laboratory studies of experimental animals and clinical investigations of humans to environmental chemicals, concentrations, and routes of exposure in humans. Use of human and wildlife behavioral and biomonitoring information to estimate exposure. This includes better understanding of human variability and the applicability of information gathered from particular wildlife species. To successfully address these gaps in our knowledge, much more analytical data must be collected.(ABSTRACT TRUNCATED AT 250 WORDS)

New technologies and methods for assessing human exposure to chemicals, dietary and lifestyle factors, infectious agents, and other stressors provide an opportunity to extend the range of human health investigations and advance our understanding of the relationship between environmental exposure and disease. An ad hoc Committee on Environmental Exposure Technology Development was convened to identify new technologies and methods for deriving personalized exposure measurements for application to environmental health studies. The committee identified a "toolbox" of methods for measuring external (environmental) and internal (biologic) exposure and assessing human behaviors that influence the likelihood of exposure to environmental agents. The methods use environmental sensors, geographic information systems, biologic sensors, toxicogenomics, and body burden (biologic) measurements. We discuss each of the methods in relation to current use in human health research; specific gaps in the development, validation, and application of the methods are highlighted. We also present a conceptual framework for moving these technologies into use and acceptance by the scientific community. The framework focuses on understanding complex human diseases using an integrated approach to exposure assessment to define particular exposure-disease relationships and the interaction of genetic and environmental factors in disease occurrence. Improved methods for exposure assessment will result in better means of monitoring and targeting intervention and prevention programs.

One of the most formidable questions facing the environmental health research community today is how to translate basic fundamental research into a product (e.g., disease outcome) that meets the needs of its stakeholders--the medical community, regulatory agencies, and ultimately, the citizens of our nation. Historically, a successful research program could be defined as one that received continuous funding, produced high-quality publications, and was respected by scientists in related fields. However, it is now apparent that this is not sufficient for attaining improved public health--the ultimate goal of these research efforts. Research results must be transferred in a more active way to the communities and professionals who have need of this information. The link must be recognized, and the roles of the stakeholders in the entire research process must be acknowledged to ensure full impact of the research endeavors. Images pA338-a pA338-b Figure 1

This April marks the celebration of two significant global events relevant to the mission of the National Institute of Environmental Health Sciences (NIEHS). The World Health Organization (WHO) has designated 7 April to be World Health Day, and the theme of this year’s event is protecting health from climate change (WHO 2008). On 22 April an estimated 1 billion people around the world will celebrate Earth Day, which this year focuses on solving issues of climate change (Earth Day Network 2008). It is not by accident that the planners of both of these events chose climate change as the lens through which to focus our attention; many regard climate change as the greatest global challenge we have ever faced. Just as climate change may represent the intersection of human health and the environment in its worst iteration, global environmental health may represent our greatest opportunity to understand and ultimately affect the outcome of this relationship. The NIEHS, with a public health mandate, a strong history of global cooperation on environmental health problems, and a research vision aimed at solving the puzzles of environmental disease, is uniquely poised at the front lines of global environmental health. Although not always defined in a global context, it can be argued—particularly in today’s modern society of fluid borders, global transport and economies, competition for natural resources, and transboundary pollution—that essentially all environmental health is global. Examples such as lead in toys that are made in one country and sold in another, food that is grown or harvested locally and shipped to tables worldwide, and pollution that is generated in one place and migrates through air or water with far-reaching and often unexpected consequences show us that our perspective on environmental health must be broad. For the NIEHS, this is a longstanding and ongoing approach. As a public health institute, the NIEHS has always had a commitment to the goals of protecting and improving global health. Former NIEHS director David Rall served as the U.S. coordinator of cooperative environmental health programs between the United States and the former U.S.S.R. (Union of Soviet Socialist Republics), the United Kingdom, Egypt, Japan, the People’s Republic of China, Taiwan, Italy, Finland, and Spain. In 1975, the NIEHS was named by the WHO as a Collaborating Center for Environmental Health Effects. The NIEHS has also participated for 27 years in a cooperative agreement with the International Programme on Chemical Safety, through which the institute has helped to provide scientific leadership and expertise to efforts to protect public health worldwide from effects of toxic chemicals. Similarly, NIEHS scientists have historically lent their expertise to international organizations formulating scientific consensus such as the International Agency for Research on Cancer, the International Labor Organization, and the United Nations Environment Program. However, the NIEHS investment in global environmental health goes well beyond shared expertise. Over the years the institute has funded and collaborated in wide-ranging scientific endeavors in partnership with scientists and scientific organizations in other countries, and continues to invest significant resources in such projects. A recent analysis of this investment shows that from 2005 to 2007, the NIEHS was engaged in 57 projects in 37 different countries (Drew et al. 2008). These projects range from investigating the effects of heavy metals on children’s development along the U.S.–Mexico border, to elucidating the role of aflatoxin in inducing liver cancer in people in rural China, to following the long-term disease consequences for women exposed to dioxin in Italy. Similarly, NIEHS intramural scientists are also involved in a number of collaborations with researchers in foreign countries, such as investigating possible genetic risks for preeclampsia in Norway and genetic mechanisms of host response to respiratory syncytial virus (RSV) infection in infants in Argentina. The justification for investing in global environmental research is simple: You must go where the exposures are. It is an unfortunate truism that the greatest exposures also hold the greatest opportunity for understanding how factors in our environment interact with the human body to cause and exacerbate disease. The more we understand these most basic interactions, the more hope we can have for finding ways to prevent and treat adverse environmental effects and improve human health. In many cases, the greatest exposures are occurring in countries outside the United States; however, the level of resources and scientific expertise enjoyed by our nation demands that we take a stewardship role in global environmental health research. The NIEHS is committed to this goal in a number of ways: through direct funding of research projects, through scientific collaboration, and through environmental health science training and capacity building. Almost from its inception, the NIEHS began welcoming foreign researchers and students to its North Carolina campus to train with the best scientists our public health system had to offer. To date, thousands of visiting fellows and other foreign trainees have taken advantage of the expertise and facilities of the NIEHS to learn cutting-edge science, improve their knowledge and skills, and bring these abilities to bear on pressing environmental health problems around the world. Currently the NIEHS supports approximately 100 international fellows each year in an effort to build global scientific capacity, as well as to create networks of collaborators who can leverage the power of multiple minds and perspectives on environmental health issues. The NIEHS also supports a number of other activities that either directly or indirectly build environmental health science capacity in other countries such as scientific conferences and meetings, including two in 2006 specifically targeted at identifying global environmental health issues and exploring research partnerships (NIEHS 2007). Perhaps the most visible aspect of this capacity building is the NIEHS’s publication of Environmental Health Perspectives, which through its policy of Open Access and commitment to dissemination of research and information to the developing world, provides a global foundation of knowledge on environmental health science. It is from this fertile background that the vision of the next phase of the NIEHS’s commitment to global environmental health is emerging. The first crystallization of this vision is an NIEHS website that will serve as a portal to information on the institute’s investment in this area (NIEHS 2008). Initially, this new site will catalog and describe ongoing NIEHS activities in the categories of research collaborations, training, outreach and capacity building, and international scientific service. Our goal for this new website is to enable us to leverage the research already being done by connecting interested parties around the world looking at the same or similar problems. The site will also provide more visibility to NIEHS funding mechanisms for international research and training programs, and it will provide a dedicated venue for communicating the outcomes and value of this investment to the public. In the long term, we envision expanding this website into a much broader and more robust networking space that will include online collaboration tools and interactive research technologies with the capacity to connect scientists around the world in real time to enhance real progress. The NIEHS is strongly committed to continuing its tradition of active engagement and leadership in global environmental health. In fact, the NIEHS 2006–2011 Strategic Plan (NIEHS 2006) specifically identifies global environmental health research, capacity building, training, and partnerships as a priority for our institute. As the celebrations of World Health Day and Earth Day this month bring into sharp relief, there has never been a greater need or a better time for the NIEHS to reaffirm our efforts toward these goals.

Because the human population is biologically diverse and genetically heterogeneous, it is not surprising that differences in susceptibility to disease among individuals with or without exposure to environmental agents exist. Individuals vary greatly in their susceptibility to disease. This is true of adults and children. The etiologies of many diseases of childhood are due to a combination of factors, including genetic susceptibility and environmental exposures during vulnerable periods of development. Genes regulate cellular growth and development, DNA replication and repair, the metabolism of endogenous agents in the body, and the metabolism and excretion of exogenous agents that the body comes in contact with in the environment. This regulation varies over the life span, contributing to the cellular consequences of the environmental exposures. This paper summarizes the contributions of genetics in understanding the etiology of environmentally induced diseases in children. The use of biomarkers of genetic susceptibility in the study of these diseases will be discussed. Future research needs for expanding our knowledge of the interactions between genetic and environmental components of childhood diseases will be presented.

Patterns of illness in American children have changed dramatically in this century. The ancient infectious diseases have largely been controlled. The major diseases confronting children now are chronic and disabling conditions termed the "new pediatric morbidity"--asthma mortality has doubled; leukemia and brain cancer have increased in incidence; neurodevelopmental dysfunction is widespread; hypospadias incidence has doubled. Chemical toxicants in the environment as well as poverty, racism, and inequitable access to medical care are factors known and suspected to contribute to causation of these pediatric diseases. Children are at risk of exposure to over 15,000 high-production-volume synthetic chemicals, nearly all of them developed in the past 50 years. These chemicals are used widely in consumer products and are dispersed in the environment. More than half are untested for toxicity. Children appear uniquely vulnerable to chemical toxicants because of their disproportionately heavy exposures and their inherent biological susceptibility. To prevent disease of environmental origin in America's children, the Children's Environmental Health Network (CEHN) calls for a comprehensive, national, child-centered agenda. This agenda must recognize children's vulnerabilities to environmental toxicants. It must encompass a) a new prevention-oriented research focus; b) a new child-centered paradigm for health risk assessment and policy formulation; and c) a campaign to educate the public, health professionals, and policy makers that environmental disease is caused by preventable exposures and is therefore avoidable. To anchor the agenda, CEHN calls for long-term, stable investment and for creation of a national network of pediatric environmental health research and prevention centers.

The National Institute of Environmental Health Sciences' Superfund Basic Research Program is currently funding 142 separate research projects within 18 programs encompassing 29 universities and institutions around the United States. The research under this program covers a wide range of interdisciplinary science from both the biomedical and nonbiomedical perspectives. This is a unique program of technology-driven research. Nonetheless, there are some areas of research that should be investigated or investigated further, should funds become available. Environmental health risk posed by the location of Superfund sites may be distributed inequitably across socioeconomic status and racial groups. Since one in five children now lives below the poverty line, an important aspect of environmental equity must be the investigation of the health effects of environmental factors on children. The multidisciplinary investigation of the effects of hazardous substance exposure on children is an area that needs much research due to the fact that most of the toxicologic data available are based on adults and animals. This program is funding 27 projects on ecologic damage posed by hazardous wastes. Much more research is needed in the investigation of toxic effects on natural succession of ecosystems as well as on their effects on biodiversity to further our understanding of the food web in the role of bioavailability in human health, and to examine the bioaccumulation of these chemicals as it relates to their fate and transport. This program is researching and developing many innovative technologies for detecting, assessing, and reducing toxic materials in the environment.(ABSTRACT TRUNCATED AT 250 WORDS)

The study of chemical mixtures is an important area of research because of its potential impact on how risk is assessed in popuiations exposed to multiple environmental agents. Clearly, individuals are exposed to myriad chemical agents during their lifetime. Low-dose chronic exposure to environmental agents and the additional lifestyle factors that may affect health are extremely difficult to assess by conventional approaches. Classic scientific approaches, while serving the research community well in assessing the impact of single chemicals on the functioning of biological systems, may be inadequate to address aggregate and cumulative exposures of multiple chemicals in lrving systems. Over the past decades, there have been extraordinary scientific and computational technology advances. Through the incorporation of technological advances in microarrays, laser capture microdissection, imaging, and high through-put technologies, we can now study in greater detail the properties of mixtures and begin to define those characteristics that are sufficiendy similar to allow extrapolation of data frorn one mixture to another. Bioinformatics and other computational approaches would also be integrated into this research scheme, not only for data analysis but also to develop predictive models that could be used for risk assessment. Integrated approaches that address these issues will be necessary to advance our understanding of the health relevance of exposure to mixtures.

Issues of hazardous waste management are major concerns in the countries of eastern and central Europe. A National Institute of Environmental Health Sciences-supported conference was held in Prague, Czech Republic, as a part of a continuing effort to provide information and promote discussion among the countries of eastern and central Europe on issues related to hazardous wastes. The focus was on incineration as a means of disposal of hazardous wastes, with discussions on both engineering methods for safe incineration, and possible human health effects from incineration by-products. Representatives from government agencies, academic institutions, and local industries from 14 countries in the region participated along with a few U.S. and western European experts in this field. A series of 12 country reports documented national issues relating to the environment, with a focus on use of incineration for hazardous waste disposal. A particularly valuable contribution was made by junior scientists from the region, who described results of environmental issues in their countries.

Formulating health policy without a thorough understanding of the implications of the environment’s influence on health can be compared to building an airplane without an understanding of basic physics: though it may appear to have all the appropriate parts in the appropriate places, without the underlying engineering required for flight, it will never get off the ground. Or worse, it will manage to take off but be unable to sustain itself in flight, with sometimes devastating consequences. Currently, many health policies, including those in the environmental health arena, are formulated and implemented with only a limited foundation in understanding the role of the environment in causing or modulating the disease process. The responsibility can be shared by those in the scientific community who have focused on the science without adequate consideration of its translation, and by public health officials and medical professionals who, perhaps daunted by the technicality of science, have not wholeheartedly sought a complete understanding of the relevant science, or simply haven’t known the right questions to ask. In either case, the result is the same—health decisions don’t always effectively use sound science to guide policy. The need to fill this gap in improving policy through improved research translation should be a priority for all concerned. The problems of modern society only become more complex over time; similarly, the science required to address these problems, particularly in the area of human health and disease, is increasingly complex. A response to this critical need might be found in a bi-directional approach that trains scientists to effectively translate technical research into understandable components useful to regulators, medical professionals, and public health officials, who, in turn, may use their better understanding of science to direct the scientific community toward the most needed and valuable research. The eventual goal of a program in health policy training is to improve the overall utility of scientific discoveries in environmental health to local, state, national, and international health policies. The scientific community would benefit from a training program to provide those from an applied, basic, or clinical research background with the knowledge and skills to participate effectively in the larger context of environmental health policy. Examples of such knowledge and skills would include the abilities to estimate health risks from environmental exposures; use environmental factors to define and modify clinical management of a disease; use emerging science to identify and quantify uncertainty in avenues for mitigating health risks in both the clinical arena and the population health arena; use risk assessment to set priorities for managing environmental health hazards; evaluate the impact of environmental exposures on disease etiology; enhance capacity to assess new biomedical technologies for their application to environmental health problems; and use knowledge of the internal structure and function of government, academic, corporate, and advocacy institutions to provide scientific guidance in effecting health policy. The scientific community would benefit from a training program to provide those from an applied, basic, or clinical research background with the knowledge and skills to participate effectively in the larger context of environmental health policy. Health policy experts at institutions such as research-intensive universities, hospitals, managed health care systems, health advocacy groups, corporate medical departments, health and environmental consulting firms, state and local health departments, legislative committees, federal regulatory agencies, and international agencies should consider investing time and effort to better understand the scientific community, and to invent new mechanisms to interface science with policy decisions. They should also be prepared to apprise the scientific community of gaps in knowledge that affect the development and delivery of effective policies to help guide the allocation of research resources. Creation of a training program that encourages scientists to actively participate in health policy discussions by enabling them to more effectively bring what they know to the table would yield multiple benefits. It would provide scientists with a means of quantifying the applicability of their research and guide their future efforts. It would greatly enhance the scientific foundation of public health policy. Such a program would create a cadre of scientists who fully comprehend how health policy decision making can be better informed using information from research in basic, applied, and clinical sciences, and who can utilize the tools available in both environmental health science and the science of health policy to further decision making with regard to environmentally related diseases and health practices. By focusing knowledge, efforts, and resources on solving environmental health and human disease problems, environmental health policy training would allow public health to soar.

Epidemiological studies have taken advantage of a number of strategies to monitor human populations for mortality, incidence, and exposure to hazardous environmental agents. These studies have been compromised by the lack of individual exposure assessment data that precisely quantified internal dose. As methods improve in analytical chemistry and molecular biology, direct biological monitoring of exposed populations is possible. Biomarkers have been developed and validated in exposed populations that quantify individual exposure, susceptibility, and early markers of health effects and can be used to study relationships between exposures and environmentally induced diseases. This paper provides background on the state of the art of human populations monitoring and, through a series of case studies, provides examples of novel biomarkers of exposure, susceptibility, and effect that highlight new opportunities for biomonitoring. Prevention of human disease due to environmental contaminants can be accomplished by implementing strategies such as those discussed to monitor exposure and early health effects in human populations.