Future directions of environmental public health research: ATSDR's 2002-2010 agenda for six priority focus areas

Additional research on human exposures to hazardous substances in community settings and resultant adverse health effects is needed to fill an extensive number of information gaps. For example, information is needed to answer specific public health questions about the toxic effects of specific chemicals, who has been exposed, what the health risks might be, and what interventions are effective. The Agency for Toxic Substances and Disease Registry (ATSDR) is the principal federal agency responsible for addressing issues of public health concerning the human health risks associated with hazardous waste sites and unplanned releases of hazardous substances into the environment. Research is a critical component in how effectively the agency can identify persons exposed, determine health risks, and intervene to reduce exposures and adverse health outcomes. ATSDR has recently developed an agenda for public health environmental research for 2002-2010, divided into the following six research focus areas: exposure assessment; chemical mixtures; susceptible populations; community and tribal involvement; evaluation and surveillance of health effects; and health promotion and intervention. This article discusses the agenda's development, the research issues within each of the six focus areas, and preliminary implementation plans.     

Findings and accomplishments of ATSDR's Superfund-mandated Substance-Specific Applied Research Program

Priority research needs determined by the Agency for Toxic Substances and Disease Registry (ATSDR) for the agencies top-ranked hazardous substances are being filled via regulatory mechanisms, private sector voluntarism, and university-based research. To date, 17 studies have been completed, 12 are ongoing, and 12 are currently planned. Under the direction of the Substance-Specific Applied Research Program (SSARP), ATSDR-supported research has filled research needs that significantly improved the information base available for making appropriate public health decisions. With the knowledge and understanding gained from this research, health professionals are better able to identify and interdict significant exposure and mitigate toxicity when exposure occurs. Thus, the SSARP has played, and continues to play, a vital role in contributing towards improving ATSDR's efforts to meet its mission and goals in environmental public health. In addition to addressing research needs of interest to ATSDR, findings from the program have contributed to the overall scientific knowledge about the effects of toxic substances in the environment.     

Evaluating toxicologic end points to derive minimal risk levels for hazardous substances

The Agency for Toxic Substances and Disease Registry (ATSDR) uses chemical-specific minimal risk levels (MRLs) to assist in evaluating public health risks associated with exposure to hazardous substances. MRLs are estimates of daily human exposure to a chemical that are likely to be without an appreciable risk of adverse noncancer health effects over a specified duration of exposure. MRLs serve as screening levels for health assessors to identify contaminants and potential health effects that may be of concern for populations living near hazardous waste sites and chemical releases. MRLs are derived from toxicologic data complied from a comprehensive literature search and are presented in ATSDR's toxicological profile for that substance. They are based on the most sensitive substance-induced end point considered to be of relevance to humans. MRLs for each substance are derived for acute (1-14 days), intermediate (15-364 days), and chronic (365 days and longer) exposure durations, and for the oral and inhalation routes of exposure. In this paper, we present an overview of the approach used for evaluating the toxicologic end points in deriving the MRLs. Examples are given to illustrate the agency's efforts to achieve increased understanding, reduced uncertainty and improved public health guidance.     

Chemical wastes, children''s health, and the Superfund Basic Research Program.

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.     

The impact of toxicology on public health policy and service: an update

The Division of Toxicology, Agency for Toxic Substances and Disease Registry (ATSDR) has a Congressional mandate to develop toxicological profiles for chemicals of greatest concern at hazardous waste sites. These chemical profiles provide a comprehensive evaluation and interpretation of the health effects, chemical and physical properties, production and use, potential for human exposure, analytical methodologies, and regulations and advisories for those chemicals. In addition, these profiles identify critical gaps in the knowledge base for these chemicals and identify levels of significant human exposure. Health assessors and other public health officials use this information to make critical decisions regarding the potential for adverse health effects at hazardous waste sites and other chemical-release events through such activities as public health assessments, chemical-specific and health-specific consultations, health-guidance-value derivations, database development, and emergency response actions. In a previous paper, we provided an overview of six specific public-health activities conducted by the ATSDR Division of Toxicology and examined how these activities have made unique impacts on public health policy and service. In this paper, we follow up on two of these, ATSDR polychlorinated biphenyls (PCBs) activities and ATSDR mercury activities, and examine their long-term, continually evolving impacts on public health policy and service.     

Polycyclic aromatic hydrocarbons in carcinogenesis

A symposium on "Polycyclic Aromatic Hydrocarbons (PAHs) in Carcinogenesis" was presented at the third International Congress of Pathophysiology held in Lathi, Finland, 28 June-3 July 1998. The congress was also sponsored by the International Union of Biological Sciences and the International Society of Free Radical Research. Institutional support for the symposium included the Electric Power Research Institute, National Center for Toxicological Research, and EPA/National Health and Environmental Effects Research Laboratory and the Office of Solid Waste and Emergency Response. The symposium focused on the sources, carcinogenicity, genotoxicity, and risk assessment of individual and mixtures of PAHs that are found in solid wastes, Superfund sites, and other hazardous waste sites. Based on the occurrence of PAHs at numerous Superfund sites and the significant data gaps on the toxic potential of certain PAHs, the information developed during this symposium would be of value in assessing health risks of these chemicals at Superfund and other hazardous waste sites.     

ATSDR evaluation of health effects of chemicals. VI. Di(2-ethylhexyl)phthalate. Agency for Toxic Substances and Disease Registry

Di(2-ethylhexyl)phthalate (also known as DEHP, bis(2-ethylhexyl)phthalate, or BEHP; CAS Registry Number 117-81-7) is a widely-used plasticizer. It is found in numerous plastic articles, such as paints, inks, floor tiles, upholstery, shower curtains, footwear, plastic bags, food-packaging materials, toys, and medical tubing. Not surprisingly, DEHP appears at many waste sites. As part of its mandate, the Agency for Toxic Substances and Disease Registry (ATSDR) prepares toxicological profiles on hazardous chemicals that are of greatest public health concern at Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) National Priority List (NPL) sites. These profiles comprehensively summarize toxicological and environmental information. This article constitutes the release of the bulk of ATSDR's profile for DEHP (ATSDR, 1993) into the mainstream scientific literature. An extensive listing of human and animal health effects, organized by route, duration, and endpoint, is presented. Toxicological information on toxicokinetics, biomarkers, interactions, sensitive subpopulations, reducing toxicity after exposure, and relevance to public health is also included. Environmental information encompasses physical properties, production and use, environmental fate, levels seen in the environment, analytical methods, and a listing of regulations. ATSDR, at the behest of Congress and therefore the citizenry, prepares these profiles to inform the public about site contaminants.     

The NIEHS Superfund Research Program: 25 Years of Translational Research for Public Health

Background

The Superfund Research Program (SRP) is an academically based, multidisciplinary, translational research program that for 25 years has sought scientific solutions to health and environmental problems associated with hazardous waste sites. SRP is coordinated by the National Institute of Environmental Health Sciences (NIEHS). It supports multi-project grants, undergraduate and postdoctoral training programs, individual research grants, and Small Business Innovation Research (SBIR) and Technology Transfer Research (STTR) grants.

Results

SRP has had many successes: discovery of arsenic’s toxicity to the developing human central nervous system; documentation of benzene toxicity to hematologic progenitor cells in human bone marrow; development of novel analytic techniques such as the luciferase expression assay and laser fragmentation fluorescence spectroscopy; demonstration that PCBs can cause developmental neurotoxicity at low levels and alter the genomic characteristics of sentinel animals; elucidation of the neurodevelopmental toxicity of organophosphate insecticides; documentation of links between antimicrobial agents and alterations in hormone response; discovery of biological mechanisms through which environmental chemicals may contribute to obesity, atherosclerosis, diabetes, and cancer; tracking the health and environmental effects of the attacks on the World Trade Center and Hurricane Katrina; and development of novel biological and engineering techniques to facilitate more efficient and lower-cost remediation of hazardous waste sites.

Conclusion

SRP must continue to address the legacy of hazardous waste in the United States, respond to new issues caused by rapid advances in technology, and train the next generation of leaders in environmental health science while recognizing that most of the world’s worst toxic hot spots are now located in low- and middle-income countries.

Citation

Landrigan PJ, Wright RO, Cordero JF, Eaton DL, Goldstein BD, Hennig B, Maier RM, Ozonoff DM, Smith MT, Tukey RH. 2015. The NIEHS Superfund Research Program: 25 years of translational research for public health. Environ Health Perspect 123:909–918; http://dx.doi.org/10.1289/ehp.1409247     

Hair analysis: exploring the state of the science

On 12-13 June 2001, the Agency for Toxic Substances and Disease Registry (ATSDR) convened a seven-member panel in Atlanta, Georgia, to review and discuss the current state of the science related to hair analysis, specifically its use in assessing environmental exposures in support of the agency's public health assessment activities. ATSDR invited scientific experts in the fields of hair analysis, toxicology, and medicine to participate in a discussion of such topics as analytical methods, factors affecting the interpretation of analytical results, toxicologic considerations, and data gaps and research needs. The goal of the panel was to determine the overall utility of hair analysis as a tool to evaluate exposure at hazardous waste sites. The principal lesson learned from the meeting was that, for most substances, data are insufficient to predict health effects from the concentration of the substance in hair. The presence of a substance in hair may indicate exposure (both internal and external) but does not necessarily indicate the source of exposure. Thus, before hair analysis can be considered a valid tool for assessing exposure and health impact of a particular substance, research is needed to establish standardized reference ranges, gain a better understanding of biologic variations of hair growth with age, gender, race and ethnicity, and pharmacokinetics, and further explore possible dose-response relationships. ATSDR intends to use the findings of this panel to develop educational materials to support its site work and to encourage researchers to continue to develop methods that may facilitate reliable exposure assessments.     

Overview of EPA Superfund human health research program

This paper presents major research needs for the Superfund program, and provides an overview of the EPA Office of Research and Development's (ORDs) current human health research program designed to fill some of those data gaps. Research is presented in terms of the risk paradigm and covers exposure, effects, and assessment activities directly funded by Superfund, as well as research not funded by Superfund but directly applicable to Superfund research needs. Research on risk management is not covered. Current research activities conducted by the Superfund program office are also included to provide a full picture of Superfund human health research activities being conducted by EPA.     

Sentinel human health indicators: to evaluate the health status of vulnerable communities

The presence of toxic substances in the Great Lakes (GL) basin continues to be a significant concern. In the United States, some 70,000 commercial and industrial compounds are now in use. More than 30,000 are produced or used in the Great Lakes ecosystem. These substances include organochlorines (e.g., polychlorinated biphenyls (PCBs), dioxins, furans, dieldrin, etc.), heavy metals such as methylmercury, and alkylated lead, and polycyclic aromatic hydrocarbons (e.g., benzo[a]pyrene). The IJC has identified 42 locations in the GL basin of the United States and Canada as Areas of Concern (AOCs) because of high concentrations of these toxic substances. In 1990 the U.S. Congress amended the Great Lakes Critical Programs Act to create The Agency for Toxic Substances and Disease Registry (ATSDR) Great Lakes Human Health Effects Research Program (GLHHERP) to begin to address these issues. This program characterizes exposures to contaminants via consumption of GL fish and investigates the potential for short- and long-term adverse health effects. This paper reviews the GLHHERP program and indicators established to monitor and address the risks posed by these substances to vulnerable populations in the Great Lakes ecosystem.     

Case studies--arsenic

Arsenic is found naturally in the environment. People may be exposed to arsenic by eating food, drinking water, breathing air, or by skin contact with soil or water that contains arsenic. In the U.S., the diet is a predominant source of exposure for the general population with smaller amounts coming from drinking water and air. Children may also be exposed to arsenic because of hand to mouth contact or eating dirt. In addition to the normal levels of arsenic in air, water, soil, and food, people could by exposed to higher levels in several ways such as in areas containing unusually high natural levels of arsenic in rocks which can lead to unusually high levels of arsenic in soil or water. People living in an area like this could take in elevated amounts of arsenic in drinking water. Workers in an occupation that involves arsenic production or use (for example, copper or lead smelting, wood treatment, pesticide application) could be exposed to elevated levels of arsenic at work. People who saw or sand arsenic-treated wood could inhale/ingest some of the sawdust which contains high levels of arsenic. Similarly, when pressure-treated wood is burned, high levels of arsenic could be released in the smoke. In agricultural areas where arsenic pesticides were used on crops the soil could contain high levels of arsenic. Some hazardous waste sites contain large quantities of arsenic. Arsenic ranks #1 on the ATSDR/EPA priority list of hazardous substances. Arsenic has been found in at least 1,014 current or former NPL sites. At the hazardous waster sites evaluated by ATSDR, exposure to arsenic in soil predominated over exposure to water, and no exposure to air had been recorded. However, there is no information on morbidity or mortality from exposure to arsenic in soil at hazardous waste sites. Exposure assessment, community and tribal involvement, and evaluation and surveillance of health effects are among the ATSDR future Superfund research program priority focus areas. Examples of exposures to arsenic in drinking water, diet and pesticide are given.     

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).     

Health effects of hazardous chemical waste disposal sites in New Jersey and in the United States: a review.

The hazardous chemical waste disposal issue is a widespread problem. Large quantities of chemical wastes have been produced by the chemical industries in the past forty years. Estimates now number disposal sites in the United States at least 30,000. The public and scientists have grown increasingly concerned about the effects of these waste disposal sites not only on the environment, but also on the human body. In this article, we review the number of hazardous chemical waste disposal sites (HCWDS), their construction, difficulties in defining their contents, and the establishment of the Superfund Act. We then discuss various studies in the literature that have attempted to define adverse health effects of HCWDS, particularly those examining Love Canal and sites in New Jersey. In our conclusions, we note the difficulties in establishing direct causal links between HCWDS and dangerous health effects. We suggest that more epidemiological studies are needed, with improved methodology for gathering complete data and studying large samples. Both positive and negative findings of epidemiological studies are important. Positive results will substantiate an association of health effects with HCWDS. Negative results may reduce the concerns of people living near HCWDS. Future investigators need sufficient information about HCWDS materials, possible routes of exposure, and measurements of exposure, as well as sufficient statistical power to detect even modest associations of health effects with HCWDS exposure.     

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.     

Surveillance of hazardous substance emergency events: identifying areas for public health prevention

The Hazardous Substances Emergency Events Surveillance (HSEES) system is a comprehensive, state-based surveillance system of hazardous substance releases and public health consequences. Maintained by the Agency for Toxic Substances and Disease Registry (ATSDR) since 1990, the system captures information on acute releases of hazardous substances that need to be cleaned up or neutralized according to federal, state, or local law. Information about threatened releases that result in public health action such as evacuation is also included. Of the 39,766 events reported to HSEES for 1996--2001, 8% resulted in deaths or injuries. Funded through a competitive program announcement, 15 states currently participate in HSEES. State coordinators actively collect data from multiple sources after an eligible event occurs and enter data about the event into a standardized ATSDR-provided web-based system. The information in HSEES describes the distribution and characteristics of hazardous substances emergencies and the morbidity and mortality experienced by employees, responders, and the general public as the result of hazardous substances releases. Analysis of HSEES data helps identify risk factors associated with hazardous substances releases. For example, although events in which chlorine was released account for only 1.6% of all events, they were 3.52 times more likely to result in injuries. Knowledge of these factors is useful in planning public safety interventions and can impact the formulation of guidelines and policies to help reduce the number of events (primary prevention) and the morbidity and mortality associated with these events (secondary prevention). Utilizing state-specific analyses of HSEES data, participating states have been able to develop prevention outreach activities such as awareness training of first responders, primary prevention of spills, and secondary prevention of related injuries and deaths caused by ammonia, chlorine, and mercury. Specific examples involving ammonia, chlorine, and mercury releases will be presented in detail.     

An overview of occupational safety and health guidelines for Superfund sites

An overview of the NIOSH occupational safety and health guidelines for Superfund activities is presented. Critical elements are outlined for site safety plans, site surveys and monitoring plans. The gathering of accurate and adequate information to prepare a plan of action to clean up abandoned hazardous waste sites is the first step and continues throughout any Superfund activity. Major emphasis is placed on selecting personal protective equipment with consideration for preventing heat stress. Decontamination is stressed to prevent exposure of other site workers as well as off-site personnel and the public. Worker training and medical monitoring are key components in a comprehensive occupational safety and health program for hazardous waste workers.     

Exposure to toxic waste sites: an investigative approach

Improper dumping and storage of hazardous substances and whether these practices produce significant human exposure and health effects are growing concerns. A sequential approach has been used by the Centers for Disease Control and the Agency for Toxic Substances and Disease Registry in investigating potential exposure to and health effects resulting from environmental contamination with materials such as heavy metals, volatile organic compounds, and pesticide residues at sites throughout the United States. The strategy consists of four phases: site evaluation, pilot studies of exposure or health effects, analytic epidemiology studies, and public health surveillance. This approach offers a logical, phased strategy to use limited personnel and financial resources of local, State, national, or global health agency jurisdictions optimally in evaluating populations potentially exposed to hazardous materials in waste sites. Primarily, this approach is most helpful in identifying sites for etiologic studies and providing investigative leads to direct and focus these studies. The results of such studies provide information needed for making risk-management decisions to mitigate or eliminate human exposures and for developing interventions to prevent or minimize health problems resulting from exposures that already have occurred.     

Evaluation of serum immunoglobulins among individuals living near six Superfund sites

Residents living in communities near Superfund sites have expressed concern that releases from these facilities affect their health, including adverse effects on their immune systems. We used data from six cross-sectional studies to evaluate whether people who live near several Superfund sites are more likely to have individual immunoglobulin test results (IgA, IgG, and IgM) below or above the reference range than those who live in comparison areas with no Superfund site. Study participants consisted of target-area residents who lived close to a Superfund site and comparison-area residents who were not located near any Superfund or hazardous waste sites. A consistent modeling strategy was used across studies to assess the magnitude of the relationship between area of residence and immunoglobulin test results, adjusting for potential confounders and effect modifiers. In all study areas, the results suggest that people who live near a Superfund site may have been more likely to have IgA test results above the reference range than comparison areas residents regardless of modeling strategy employed. The effect measures were larger for residents who lived in communities near military bases with groundwater contamination. For all analyses the wide confidence intervals reflect uncertainty in the magnitude of these effects. To adequately address the question of whether the immune system is affected by low-level exposures to hazardous substances, we recommend that more functional immunotoxicity tests be conducted in human populations where individual exposure information is available or when it can be reasonably estimated from environmental exposure measurements.     

Meeting Report: Methylmercury in Marine Ecosystems—From Sources to Seafood Consumers

Mercury and other contaminants in coastal and open-ocean ecosystems are an issue of great concern globally and in the United States, where consumption of marine fish and shellfish is a major route of human exposure to methylmercury (MeHg). A recent National Institute of Environmental Health Sciences–Superfund Basic Research Program workshop titled “Fate and Bioavailability of Mercury in Aquatic Ecosystems and Effects on Human Exposure,” convened by the Dartmouth Toxic Metals Research Program on 15–16 November 2006 in Durham, New Hampshire, brought together human health experts, marine scientists, and ecotoxicologists to encourage cross-disciplinary discussion between ecosystem and human health scientists and to articulate research and monitoring priorities to better understand how marine food webs have become contaminated with MeHg. Although human health effects of Hg contamination were a major theme, the workshop also explored effects on marine biota. The workgroup focused on three major topics: a) the biogeochemical cycling of Hg in marine ecosystems, b) the trophic transfer and bioaccumulation of MeHg in marine food webs, and c) human exposure to Hg from marine fish and shellfish consumption. The group concluded that current understanding of Hg in marine ecosystems across a range of habitats, chemical conditions, and ocean basins is severely data limited. An integrated research and monitoring program is needed to link the processes and mechanisms of MeHg production, bioaccumulation, and transfer with MeHg exposure in humans.