Primary prevention and precaution in hazard identification in the NIEHS/NTP: body in the morgue approach

In the spirit of stimulating reevaluation of the methods of public health science, this article explores the methods of cancer hazard identification at the National Toxicology Program (NTP) from the perspective of primary prevention and precaution. The NTP is a cooperative effort of three federal agencies: The National Institute of Environmental Health Sciences (NIEHS, the lead government institute); the National Institute for Occupational Health (NIOSH), in the Centers for Disease Control and Prevention; and the National Center for Toxicology Research (NCTR), in the Food and Drug Administration. NTP coordinates toxicological research and testing programs within the Department of Health and Human Services (DHHS), and through its annual Report on Carcinogens (RoC), identifies and characterizes cancer hazards-the first step in quantitative risk assessment-for the federal government. The foundation of NIEHS policies, for environmental health research, is quantitative risk assessment (QRA). The author examines the opportunities for primary prevention and precaution, and the extent to which the policies of NIEHS in general, and the NTP in particular, do and do not realize that potential. Special attention is paid to the issue of cancer hazard identification. Critical comments on the process of classifying carcinogens in the Ninth and Tenth Reports on Carcinogens are presented, based on the minutes of the Board of Scientific Counselors Subcommittee meetings.     

ONE Nano: NIEHS’s Strategic Initiative on the Health and Safety Effects of Engineered Nanomaterials

Background: The past decade has seen tremendous expansion in the production and application of engineered nanomaterials (ENMs). The unique properties that make ENMs useful in the marketplace also make their interactions with biological systems difficult to anticipate and critically important to explore. Currently, little is known about the health effects of human exposure to these materials.Objectives: As part of its role in supporting the National Nanotechnology Initiative, the National Institute of Environmental Health Sciences (NIEHS) has developed an integrated, strategic research program—“ONE Nano”—to increase our fundamental understanding of how ENMs interact with living systems, to develop predictive models for quantifying ENM exposure and assessing ENM health impacts, and to guide the design of second-generation ENMs to minimize adverse health effects.Discussion: The NIEHS’s research investments in ENM health and safety include extramural grants and grantee consortia, intramural research activities, and toxicological studies being conducted by the National Toxicology Program (NTP). These efforts have enhanced collaboration within the nanotechnology research community and produced toxicological profiles for selected ENMs, as well as improved methods and protocols for conducting in vitro and in vivo studies to assess ENM health effects.Conclusion: By drawing upon the strengths of the NIEHS’s intramural, extramural, and NTP programs and establishing productive partnerships with other institutes and agencies across the federal government, the NIEHS’s strategic ONE Nano program is working toward new advances to improve our understanding of the health impacts of engineered nanomaterials and support the goals of the National Nanotechnology Initiative.     

Superfund research program--accomplishments and future opportunities

This special issue of the International Journal of Hygiene and Environmental Health provides extensive background on the Superfund programs, findings of specific research studies and future directions. Three federal agencies are leading the effort in this program. They are the National Institute of Environmental Health Sciences, U.S. Environmental Protection Agency and the Agency for Toxic Substances and Disease Registry. As a result of their collaboration, a comprehensive program has been developed that ranges from basic to applied research with the aim of improving public health services and protection. This paper highlights the research within areas of toxicological investigation, exposure assessment, risk evaluation and engaging communities. Each of the agencies has developed strategies and initiatives to enhance the effectiveness of the Superfund research program. The continuation of research will contribute significantly towards achieving the Healthy People 2010 goals that have been set for the United States.     

Protecting disaster responder health: lessons (not yet?) learned

Recent developments at the National Institute for Occupational Safety and Health (NIOSH), the Occupational Safety and Health Administration (OSHA), and the National Institute for Environmental Health Sciences (NIEHS) indicate that each of these agencies is wrestling with how to better protect the health of disaster workers. This article urges increased reliance on comprehensive exposure assessments, more protective exposure benchmarks, the precautionary principle, and the hierarchy of controls of hazards. Additional issues, such as methods and content of worker training, as well as enforcement of applicable standards, are also considered. Finally, an effort is made to clarify the goals of disaster response.     

The developing brain and the environment: an introduction

mental retardation: timing and thresholds; (italic)b(/italic)) endocrine dysfunction and developmental disabilities: dose and target implications; (italic)c(/italic)) attention-deficit disorder-ADHD and learning disabilities; and (italic)d(/italic)) new horizons: extending the boundaries. Support for the Rochester conference came from both public and private sources. The National Institute of Environmental Health Sciences (NIEHS), the National Institute of Child Health and Human Development, and the EPA represented the federal government. The conference also received grants from several foundations: the Jennifer Altman Foundation, the Heinz Family Foundation, the National Alliance for Autism Research, the Violence Research Foundation, the Wacker Foundation, and the Winslow Foundation. The second of these conferences helped launch a new Center for Children's Health and the Environment at the Mount Sinai School of Medicine. It was held in New York City on 24-25 May 1999, and was convened specifically to consider the intersection between neurodevelopmental impairment, environmental chemicals, and prevention. Over 300 health scientists, pediatricians, and public health professionals examined the growing body of evidence linking environmental toxins to neurobehavioral disorders. The conference title was Environmental Influences on Children: Brain, Development, and Behavior. The conference began by reviewing well-known examples of deleterious effects of environmental chemicals, including lead and PCBs, on children's brains. The conferees then considered the potential impact of environmental chemicals on neurological disorders with particular focus on ADHD, autism, and Parkinson's disease. The inclusion of Parkinson's disease was intended to signal the notion that exposures in early life may have an influence on the evolution of neurological disease in later life. Support for the Mount Sinai conference came from the Superfund Basic Research Program (NIEHS); The Pew Charitable Trusts; the Institute for Health and the Environment at the University of Albany School of Public Health; the Agency for Toxic Substances and Disease Research (ATSDR); the Ambulatory Pediatric Association; Myron A. Mehlman, PhD; the National Center for Environmental Assessment (EPA); the National Center for Environmental Health (CDC); the National Institute of Child Health and Human Development; the Office of Children's Health Protection (EPA); Physicians for Social Responsibility; The New York Academy of Medicine; The New York Community Trust; and the Wallace Genetic Foundation. The impact of environmental toxins on children's health has become a topic of major concern in the federal government. Eight new research centers in children's environmental health have been established in the past 2 years with joint funding from EPA and NIEHS. Clinical units that specialize in the treatment of children with environmentally induced illness have been developed across the nation with grant support from ATSDR. The American Academy of Pediatrics has just published its (italic)Handbook of Pediatric Environmental Health (/italic)((italic)17(/italic)), the "Green Book," which is available to pediatricians throughout the Americas. Children's environmental health has climbed to a critical position as we launch the new millennium. This monograph marks a significant milestone in the evolution of this emerging discipline.     

Carcinogenicity of saccharin in laboratory animals and humans: letter to Dr. Harry Conacher of Health Canada

We appreciate this opportunity to provide input to the Health Protection Branch's (HPB's) review of the artificial sweetener saccharin. Concerns with regard to the safety of saccharin are of great public health significance and of great interest to the public because saccharin is consumed by tens of millions of people, including children and fetuses. Any evidence of carcinogenesis--and there is ample such evidence--of such a widely used chemical should spur health officials to minimize human exposure to it. It is worth noting that on October 31, 1997, the Board of Scientific Counselors of the National Toxicology Program, a unit of the National Institute of Environmental Health Sciences (NIEHS), voted not to delist saccharin from its Report on Carcinogens.     

Role of environmental chemicals in diabetes and obesity: a National Toxicology Program workshop review

Background: There has been increasing interest in the concept that exposures to environmental chemicals may be contributing factors to the epidemics of diabetes and obesity. On 11–13 January 2011, the National Institute of Environmental Health Sciences (NIEHS) Division of the National Toxicology Program (NTP) organized a workshop to evaluate the current state of the science on these topics of increasing public health concern.Objective: The main objective of the workshop was to develop recommendations for a research agenda after completing a critical analysis of the literature for humans and experimental animals exposed to certain environmental chemicals. The environmental exposures considered at the workshop were arsenic, persistent organic pollutants, maternal smoking/nicotine, organotins, phthalates, bisphenol A, and pesticides. High-throughput screening data from Toxicology in the 21st Century (Tox21) were also considered as a way to evaluate potential cellular pathways and generate -hypotheses for testing which and how certain chemicals might perturb biological processes related to diabetes and obesity.Conclusions: Overall, the review of the existing literature identified linkages between several of the environmental exposures and type 2 diabetes. There was also support for the “developmental obesogen” hypothesis, which suggests that chemical exposures may increase the risk of obesity by altering the differentiation of adipocytes or the development of neural circuits that regulate feeding behavior. The effects may be most apparent when the developmental exposure is combined with consumption of a high-calorie, high-carbohydrate, or high-fat diet later in life. Research on environmental chemical exposures and type 1 diabetes was very limited. This lack of research was considered a critical data gap. In this workshop review, we outline the major themes that emerged from the workshop and discuss activities that NIEHS/NTP is undertaking to address research recommendations. This review also serves as an introduction to an upcoming series of articles that review the literature regarding specific exposures and outcomes in more detail.     

Joining forces for children's health.

From airborne particulatesto pesticide-laden fruit, children probably encounter more pollutants than adults. Because their bodies are rapidly developing, children may react more strongly to these toxins, too. The NIEHS hopes to learn more about how several hazardous agents specifically affect kids. Together, the NIEHS and the EPA are spending $10 million to establish up to six Centers for Children's Environmental Health and Disease Prevention Research. The CDC, a third partner,will later help apply center research to public health.     

Carcinogenic effects of polychlorinated biphenyls

As part of its mandate, the Agency for Toxic Substances and Disease Registry (ATSDR) prepares toxicological profiles on hazardous chemicals found at Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) National Priorities List (NPL) sites that have the greatest public health impact. These profiles comprehensively summarize toxicological and environmental information. This article constitutes the release of an important section of the Toxicological profile for polychlorinated biphenyls [ATSDR. 2000: Toxicological profile for polychlorinated biphenyls. Atlanta, GA: US Department of Health and Human Services, Agency for Toxic Substances and Disease Registry.] into the scientific literature. This article focuses on the carcinogenic effects of this group of synthetic organic chemicals (polychlorinated biphenyls) in humans and animals. Information on other health effects, toxicokinetics, mechanisms of toxicity, biomarkers, interactions, chemical and physical properties, potential for human exposure, and regulations and advisories is detailed in the profile.     

ATSDR evaluation of potential for human exposure to zinc

As part of its mandate, the Agency for Toxic Substances and Disease Registry (ATSDR) prepares toxicological profiles on hazardous chemicals found at Comprehensive Environmental Response, Compensation and Liability Act (CERCLA) National Priorities List (NPL) sites that have the greatest public health impact. These profiles comprehensively summarize toxicological and environmental information. This article constitutes the release of portions of the toxicological profile for zinc. The primary purpose of this article is to provide interested individuals with environmental information on zinc that includes production data, environmental fate, potential for human exposure, analytical methods and a listing of regulations and advisories.     

ATSDR evaluation of potential for human exposure to tungsten

As part of its mandate, the Agency for Toxic Substances and Disease Registry prepares toxicological profiles on hazardous chemicals found at Comprehensive Environmental Response, Compensation and Liability Act, National Priorities List sites that have the greatest public health impact. These profiles comprehensively summarize toxicological and environmental information. This article constitutes the release of portions of the Toxicological Profile for Tungsten. The primary purpose of this article is to provide interested individuals with environmental information on tungsten that includes production data, environmental fate, potential for human exposure, analytical methods and a listing of regulations and advisories.     

Breathtaking research

Although the air we breathe is necessary for life, certain factors may make this same air detrimental to our health. For instance, a seemingly endless list of compounds can be toxic at certain concentrations, and inhaling such compounds may lead to damage in different parts of the body. To investigate the particular effects of inhaled toxicants, the NIEHS developed the Respiratory Toxicology Group. The group, which consists of toxicologist Dan Morgan, biologist Cassandra Shines, and engineer Michael Moorman, has been conducting experiments for about a decade at the NIEHS inhalation facility. Morgan says the group typically conducts studies of chemicals that have been nominated to the National Toxicology Program for investigation into their carcinogenic potential and other end points. "We provide research support and conduct special studies on these chemicals," he says. "We also do collaborative studies with other NIEHS investigators, other [federal] agencies such as the Environmental Protection Agency and the Department of Energy, universities, and industry."     

Toxicity characterization of environmental chemicals by the US National Toxicology Program: an overview

The US National Toxicology Program (NTP) is an interagency program whose mission is to evaluate agents of public health concern by developing and applying the tools of modern toxicology and molecular biology. Chemicals substances or physical agents selected for toxicology and carcinogenesis evaluations by the NTP are usually studied in a series of subacute (14-day exposure), subchronic (90-day exposure) and chronic (2-year exposure) studies in rodents. The NTP has published more than 500 reports of the findings and conclusions from its toxicology and carcinogenesis studies. In more specialized studies, the NTP also evaluates adverse effects on the structure and function of the immune, reproductive, nervous, and respiratory systems. The program attempts to evaluate and appropriately incorporate new technologies to improve the way we study the toxicity of chemicals. For example, the program has extensively evaluated several transgenic mouse models for their potential use as short-term cancer screens and has been a full participant in an international effort to examine their usefulness in pharmaceutical registration. Toxicogenomics, an emerging scientific field that examines the expression of thousands of genes simultaneously in response to chemical exposure, holds promise for future application to better understand the underlying mechanisms of chemical toxicity. A number of public health issues being addressed by the NTP are not only of national importance but also have global impact, such as the potential for endocrine disruptors to influence development and carcinogenesis and the safety of herbal medicines and dietary supplements. The program participates in the preparation of national and international toxicity testing guidelines and the findings from NTP studies are widely used for risk assessments by international organizations and federal agencies. The NTP maintains databases that contain toxicity, and health and safety information on a large number of chemicals. These databases are available from the NTP web site (http://ntp-server.niehs.nih.gov) and are accessed over 100000 times a month from around the world.     

Multidisciplinary research: strategies for assessing chemical mixtures to reduce risk of exposure and disease

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 bioinformatics to quantitative tools for an integrated science-based approach to chemical mixtures; 3) translate/disseminate these technologies into useable, practical means to reduce exposure and the risk of disease. Preventing adverse health effects from environmental exposures requires translation of research findings to affected communities and must include a high level of public involvement. Integrating these approaches are necessary to advance understanding of the health relevance of exposure to mixtures.     

Effects of polychlorinated biphenyls on development and reproduction

As part of its mandate, the Agency for Toxic Substances and Disease Registry (ATSDR) prepares toxicological profiles on hazardous chemicals found at Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) National Priorities List (NPL) sites that have the greatest public health impact. These profiles comprehensively summarize toxicological and environmental information. This article, which constitutes the release of an important section of the Toxicological Profile for Polychlorinated Biphenyls (ATSDR 2000) into the scientific literature, focuses on the developmental and reproductive effects of this group of synthetic organic chemicals (PCBs) in humans and animals. Information on other health effects, toxicokinetics, mechanisms of toxicity, biomarkers, interactions, chemical and physical properties, potential for human exposure, and regulations and advisories is detailed in the profile. Interested readers are encouraged to consult the original toxicological profile for more information. Profiles can be requested from ATSDR's Information Center by telephone (1-888-42-ATSDR [1-888-422-8737] or E-mail: (atsdric@cdc.gov).     

National exposure measurements for decisions to protect public health from environmental exposures

Protecting public health from environmental exposures requires four steps: detection of exposures known or expected to cause disease, assessment of health risk from exposure, implementation of an exposure intervention, and assurance that the exposure intervention is effective. To prioritize efforts in these four areas one must consider the size of the population affected, the seriousness of health effects, and the availability of cost-effective exposure interventions. Population exposure data is critical to each of these steps for protecting health. Biomonitoring data for the US population is now available to assist public health scientists and physicians in preventing disease from environmental exposures, and it complements that available for levels of chemicals in environmental media. The Second National Report on Human Exposure to Environmental Chemicals provides for the US population serum, blood and urine levels for 116 environmental chemicals over the years 1999 and 2000, with separate analyses by age, sex, and race/ethnicity. This national exposure information identifies which chemicals get into Americans in measurable quantities; determines whether exposure levels are higher among population subgroups; determines how many Americans have levels of chemicals above recognized health threshold levels (for chemicals with such threshold levels); establishes reference ranges that define general population exposure so unusual exposures can be recognized; assesses the effectiveness of public health efforts to reduce population exposure to selected chemicals; and tracks over time trends in US population exposure. Blood lead measurements in the population were important in identifying lead in gasoline as a significant source of human lead exposure and documenting the reduction in blood lead levels in the population as a result of removing lead from gasoline and other products in the United States. Serum cotinine levels in the early 1990s found more widespread exposure to environmental tobacco smoke (ETS) in the United States than previously thought and additional measurements in 1999 and 2000 documented major declines in exposure to ETS as a result of public health actions in the 1990s. A new biomonitoring assessment of the exposure of the US population will be released every 2 years as the "National Report on Human Exposure to Environmental Chemicals." These reports will include the current 116 chemicals and new chemicals added to monitor priority exposures of the population.     

Human genetics, environment, and communities of color: ethical and social implications

A conference titled "Human Genetics, Environment, and Communities of Color: Ethical and Social Implications" and a workshop symposium titled "Human Genetics and Environmental Justice" were held by West Harlem Environmental Action, Inc., with cosponsorship by the National Institute of Environmental Health Sciences (NIEHS), the Community Outreach and Education Program of the NIEHS P30 Center for Environmental Health at the Mailman School of Public Health at Columbia University, New York, and the U.S. Environmental Protection Agency. The conference and symposium took place at Columbia University in New York City on 4-5 February 2002. Expert panels composed of public health practitioners, genetic researchers, ethicists, lawyers, social scientists, and community organizations were assembled to explore how genetic research will affect communities of color, specifically in environmental health research. The goal of the conference was to educate participants on the science and ethics of genetic research and to explore the potential benefits and pitfalls of genetic research vis-à-vis new trends in environmental health research, specifically with reference to communities of color. The goal of the symposium was to discuss the major perceptions and concerns for community-based environmental justice advocates and other communities of color regarding environmental health genetic research. The conference and symposium drew more than 300 participants and articulated important perspectives on the opportunities and challenges for environmental justice advocates and other communities of color posed by rapid advances in environmental health genetic research and toxicogenomics.