Applying genomic technologies in environmental health research: challenges and opportunities.

Recent discoveries in molecular biology and genetics have made it possible for environmental health researchers to examine how genetic characteristics affect response to environmental exposures. Understanding such gene-environment interactions offers exciting possibilities for the prevention and control of environmentally induced diseases. Despite these potential benefits, the collection and analysis of genetic information in environmental health research presents many of the same ethical, legal, and social (ELSI) challenges found in other types of genetic research. In this article, we describe a number of ELSI challenges in environmental genomic research and the opportunities and responsibilities that accompany this research.

Exposure to hazardous substances and male reproductive health: a research framework.

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.

A holistic approach to environmental health research.

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.

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.

Hazardous wastes in eastern and central Europe: technology and health effects.

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.

Peer reviewed: creating multidisciplinary research opportunities.

A unifying framework model helps researchers to address the complexities of environmental problems.

Children's health and the environment: a new agenda for prevention research.

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.

Genes and the environment: their impact on children's health.

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.

Environmental pollution and child health in central and Eastern Europe.

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 hazardous waste issues related to the U.S.-Mexico border.

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 of the maquiladoras (foreign-owned industries using imported raw materials) have intensified those concerns recently. Efforts to assess these issues are complicated by the fact that many of the issues affecting the border region are within federal jurisdiction, but the problems are regional and local in nature. Thus, state and local governments become involved with public concerns about real and potential problems. One major problem is that environmental health data from this region are lacking, particularly from Mexico. Some new agencies such as the Border Environment Cooperation Commission, the United States-Mexico Border Health Commission, and the North American Commission on Environmental Cooperation have joined several existing agencies at the federal and state level to address environmental quality and health. Several studies have been initiated to determine air and water quality, but little is being done in the areas of hazardous waste and health assessment. Several problems are anticipated in the generation of such data, such as its format and accessibility. Data gaps and research needs are discussed.

Human biomonitoring: research goals and needs.

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.

The development of an anchorage-independence assay using human lung tumor cells to screen potential chemopreventive agents.

Advances in tumor biology research have led to the possibility of early detection of cancers and rational intervention of cancer development using chemopreventive agents. A significant number of potential chemopreventive agents have been identified from epidemiological surveys, independent research efforts, clinical data or based on structural homology with known chemopreventive agents. We have developed a fast, reliable in vitro model for screening potential chemopreventive agents using inhibition of anchorage-independent growth of a human lung tumor cell line, A427.A427 cells were plated in soft agarose containing a known chemopreventive agent, 13-cis-retinoic acid as the test agent and allowed to develop colonies for 28 days. A cytotoxicity test was used concurrently with anchorage independent assay for measuring the relative survival of cells to ensure that any observed inhibition of anchorage independent growth is due to the biological activity of the chemopreventive agent and not due to cellular toxicity. At the end of 28 days of growth, the stained colonies were enumerated, and the inhibition of spontaneous colony formation was measured. 13-cis-Retinoic acid inhibited the growth of A427 colonies in a concentration dependent manner. Data from 25 successive experiments indicate that a concentration of 33 microM consistently inhibited colony formation by 66.2 +/- 16.5 percent, ranging from 27 to 96.1% inhibition. This assay is a useful tool for screening potential chemopreventive agents, as it uses human cells as substrates rendering the efficacy data feasible for direct extrapolation to humans.

Hazardous wastes in Eastern and Central Europe [meeting report].

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 in this region are stretched, awareness and concern about hazardous waste issues are a part of the new realities. At a recent conference sponsored in part by the National Institute of Environmental Health Sciences, representatives of seven countries in the region described the status of hazardous waste programs, issues of major concern, and steps being taken to protect human health. This report summarizes the deliberations, outlines some of the problems remaining in dealing with the legacy of the past, addressing the problems of the present, and providing a framework for future research and collaborative efforts.

The NIEHS Superfund Basic Research Program: overview and areas of future research directions.

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)

Application of molecular biomarkers in epidemiology.

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.

Assessment of human exposure to chemicals from Superfund sites.

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)