Significant Items in House & Senate Appropriations Committee Reports

FY 2005 House Appropriations Committee Report Language (H. Rpt. 108-636)

Item

Environmental exposures and lung disease - The Committee is pleased to note NIEHS's support of studies that establish epidemiological links between environmental exposures and the development of lung disease like asthma and COPD. The Committee encourages the Institute to enhance its research into how environmental stimuli interact with the lung to produce lung disease, with emphasis on cellular responses to inhaled pollutants and the subsequent cell signaling steps that lead to disease. (p. 88)

Action taken or to be taken

NIEHS agrees with the Committee that research on the cellular and molecular responses to inhaled environmental pollutants is an important priority. The Institute has long recognized the health consequences of environmental exposures to such pollutants as diesel exhaust particles, ozone, heavy metals, microbial products such as endotoxin and allergens, manufacturing chemicals such as toluene diisocyanante and dioxin, and environmental tobacco smoke. NIEHS continues to support investigator-initiated research and multi-disciplinary, multi-institutional program projects that encompass biochemical research to determine the toxic components of the exposure and pathobiologic research to examine cellular and molecular signaling pathways through which exposures cause oxidative stress, inflammation and injury, or immune system activation. Other NIEHS-supported efforts test the effect of fetal and childhood exposures to ozone and allergens on the structure and function of the developing lung, and the relationship of these changes to the development of childhood and adult lung disease. These studies employ state-of-the-art technologies, including genomics, to assess exposure-initiated changes in gene expression, proteomics to identify changes in the proteins that effect the response, and computer models to link in vitro and in vivo studies. The NIEHS lung disease portfolio includes asthma, chronic obstructive lung diseases such as fibrosis and emphysema, and granulomatous lung diseases.

The NIEHS has a major research effort to characterize the role of cellular responses and cell signaling steps that lead to lung diseases. Asthma is an immunologic lung disease of enormous public health importance that is exacerbated by exposure to environmental agents (e.g. allergens, endotoxins). NIEHS scientists are studying cyclooxygenase (COX) enzymes in normal lung physiology and in the pathogenesis of inflammatory lung diseases, and developing new animal models to facilitate studies on the biological role of these enzymes in the lung. New studies by NIEHS scientists, for instance, have shown that the functional roles in the lung of the two COX enzymes, COX-1 and COX-2, vary depending on the stimulus. COX-1 appears to play a more important role in airway inflammation and hyperresponsiveness following allergen challenge; in contrast, COX-2 plays a more critical role in acute inflammation and fibrosis following exposure to certain chemicals. One set of future experiments will focus on generating mice in which human COX-1 is overexpressed, an approach that should provide further insight into the functional role of COX-1 derived molecules in the lung in the response to environmental stimuli, and to determine the mechanisms responsible for altered airway function in these mice. It is expected that the NIEHS research effort in pulmonary disease will continue to be strong in future years. The area of gene-environment interactions in pulmonary disease, and of cellular mechanisms of lung disease and immunity, is a long-term research interest of the new Director of the NIEHS, Dr. David Schwartz, who will assume his position at NIEHS in April 2005.

 Back to top

Item

Juvenile diabetes. - The Committee commends NIEHS efforts on the Environmental Genome Project (EGP), which seeks to understand how individuals differ in their susceptibility to environmental agents and how these susceptibilities change over time. This project may help to identify environmental triggers for diseases such as Type 1 diabetes. The Committee encourages enhanced efforts to interact and coordinate EGP with efforts like NIDDK's Environmental Determinants of Diabetes in the Young (TEDDY) Study, to investigate genetic and gene-environment interactions in the development of prediabetic autoimmunity and Type 1 diabetes. (p. 88)

Action taken or to be taken

The Environmental Genome Project (EGP) has discovered over 14,000 new single polymorphisms in environmentally responsive genes in the DNA repair and cell cycle control genes. We are continuing to look at other pathways that affect one's susceptibility to environmental agents. Genes in the oxidative stress, apoptosis, metabolism, and signal transduction pathways are among those genes in the queue for resequencing this year. Future plans for the EGP include redirecting our single nucleotide polymorphisms (SNP) discovery activities to focus on environmentally related diseases. As there is a greater understanding that environmental and genetic factors likely work together to cause juvenile diabetes, this disease is a worthy candidate to consider in our future plans. NIEHS participated as a co-sponsor of the initiative leading to The Environmental Determinants of Diabetes in the Young (TEDDY) study and remains in contact with NIDDK staff about its progress. We will involve NIDDK staff as we develop the future directions for the EGP.

 Back to top

Item

Mercury - In order to properly research gaps in the area of mercury exposure and brain chemistry, and given recent hearings on mercury exposure and relationships between autism and Alzheimer's disease and mercury exposure, NIEHS is encouraged to pursue studies of how inorganic mercury and organic mercury compounds (including ethyl, methyl, and other forms of mercury from all sources) are processed in the bodies of children and adults. NIEHS is also encouraged to support studies of the toxic effects of inorganic mercury and organic mercury compounds on the nervous systems of young children, adults, and the elderly and methods of properly removing mercury and mercury-containing compounds from the brains of affected humans. (p. 89)

Action taken or to be taken

NIEHS is actively pursuing studies to characterize the distribution and effects of exposures to all forms of mercury (organic and inorganic) through multiple routes of exposure. In addition to the extensive work which has already been conducted on oral ingestion of methylmercury through dietary sources, NIEHS scientists are conducting evaluation of the tissue distribution of mercuricals (methylmercury, ethylmercury, and thimerosal) following intramuscular injection in mice. To date, the preliminary data suggest that the route of administration significantly influences the tissue distribution and levels of mercury. In comparison to oral methylmercury, minimal levels of mercury were found in blood, kidney, and brain for both methylmercury and ethylmercury intramuscular injections. Experiments were undertaken to replicate and extend findings from these initial studies, with additional measurements taken from the muscle tissue at the injection site. Final analysis of mercury levels in tissue samples from mice has been completed and the results submitted for publication. NIEHS is also collaborating with NIAID to conduct studies in adolescent and infant monkeys to compare the pharmacokinetics and tissue distribution of ethyl mercury (from thimerosal) and methyl mercury. These studies will provide information to address whether or not the guidelines for methyl mercury are also appropriate for ethyl mercury (from thimerosal).

With respect to development of methods for removal of mercury from the body, recent NIEHS-funded studies have identified a novel antidote for methylmercury, namely N-acetylcysteine. These investigators demonstrated that N-acetylcysteine added to drinking water of mice greatly increases the excretion of methylmercury from the body. The researchers are continuing to examine the mechanisms of methylmercury elimination and determine the role of N-acetylcysteine as an antidote.

 Back to top

Item

Toxic exposure and brain development. - Notwithstanding the Institute of Medicine May 2004 report on autism, the Committee believes it is important to develop a more complete understanding of the impact that toxic exposures may have on brain development. There is a convergence of findings from tissue culture studies, animal models, and clinical studies of immune dysfunction in children with autism that suggests a biological link between genetic sensitivity and damage to developing brains from certain toxins. It is important that NIH continue this research to better understand the impact that exposures to mercury (including thimerosal) and other toxins have on brain development. A more complete understanding of the impact of these exposures through research, including animal models, will help to develop more effective interventions. (p. 89)

Action taken or to be taken

The NIEHS agrees with the Committee that more research is needed to understand the effect of neurotoxic exposures on the developing brain. The NIEHS has long recognized that exposures affect fetuses and children differently from adults and that fetuses and children are more vulnerable than adults. Therefore, the NIEHS continues to fund a number of projects examining the effects of lead, mercury, pesticides, industrial chemicals and other neurotoxic exposure on brain development. These projects span the spectrum from very basic mechanistic studies on the developing brain to human-based studies. The NIEHS, in collaboration with EPA, supports a number of Children's Health Research Centers, several of which have research focused on developmental neurotoxicology. Within these Centers, as well as in our regular portfolio, are basic studies that explore how exposures can interfere with cell division, migration, differentiation formation and pruning of synapses, and other processes that are essential for normal brain development. The human-based studies that NIEHS supports have been instrumental in identifying the risk factors to be pursued in animal models.

The NIEHS sponsored a meeting April 28, 2004 on the " New Paradigms for Exploring Gene-Environment-Behavior Relationships" to examine the influences of early exposure to neurotoxicants on behavior. We hope to encourage research in the development of new animal models for behavioral toxicology that can be used to understand how exposure affects phenotype/genotype issues. The NIEHS is currently evaluating the latest solicitation of applications from the Fetal Basis of Adult Disease Program Announcement which includes neurotoxicology as one of the prime areas of interest. The NIEHS is pursuing, through the expansion of an ongoing study, the confirmation of an observation in the literature suggesting that immune dysfunction plays a role in the effect of thimerosal on the developing brain. The NIEHS will continue to encourage the expansion of research in developmental neurotoxicology by actively championing the field at appropriate scientific meetings.

 Back to top

Item

National Toxicology Program - In order for the Interagency Coordinating Committee for the Validation of Alternative Methods (ICCVAM) to carry out its responsibilities under the ICCVAM Authorization Act, the Committee encourages NIEHS to strengthen the resources provided for ICCVAM activities in order to ensure that new and alternative test methods used or recommended for federal regulatory agencies, and those under consideration or planned for use within the National Toxicology Program's toxicity testing project, are validated prior to their use. (p. 89)

Action taken or to be taken

ICCVAM is a permanent interagency committee of the NIEHS under the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM), which is charged with the technical review and evaluation of new, revised, and alternative test methods applicable for specific regulatory uses. NICEATM administers the ICCVAM and provides scientific support for ICCVAM and ICCVAM-related activities, including coordination of independent validation studies to evaluate the usefulness and limitations of proposed test methods. NICEATM has several new goals for FY2005, all of which are supported by the NIEHS: (1) Initiate validation studies on one or more non-animal/non-radioisotopic estrogen receptor binding and transcriptional activation test methods in FYO5 to determine if these test methods can replace current methods that require surgically- manipulated animals; (2) Initiate independent validation studies in FY05 based on expert panel recommendations; (3) Complete independent validation studies on two in vitro cytotoxicity methods in FY05 to determine if the non-animal methods will reduce the number of animals required for acute toxicity studies; and (4) Provide reference chemical data and coordination for a European Centre for the Validation of Alternative Methods (ECVAM) validation study on in vitro methods for estimating dermal irritation potential of chemicals.

In addition, a new Deputy Director for NICEATM will be appointed in either late 2004 or early 2005. This additional person will allow for expansion of NICEATM activities.

 Back to top

Item

Parkinson's Disease - The Committee encourages NIEHS in collaboration with NINDS to gain a greater understanding of the environmental underpinnings of Parkinson's disease. The Committee also encourages NIEHS to intensify its efforts in the Collaborative Centers for Parkinson's Disease Research Program. This initiative facilitates significant collaboration between, clinical medicine, epidemiology, and basic science so that the most promising leads may be investigated more quickly in pursuit of a cure or to reduce the incidence of harmful toxins. (p. 89)

Action taken or to be taken

The NIEHS supports several ongoing research initiatives to address environmental causation in PD and works closely with the NINDS to plan future initiatives in PD. In addition to the three Collaborative Centers for Parkinson's Disease Environmental Research (CCPDER), the NIEHS currently supports many individual investigator-initiated grants in PD. The scope of the NIEHS-funded research in Parkinson's Disease (PD) is considerable and spans studies from molecular epidemiology of environmental risk and protective factors for PD to basic laboratory investigations aimed at developing new animal models, understanding the role of mitochondrial oxidative damage in vulnerable cell populations and defining transport mechanisms for toxicant entry to brain. Understanding the causes of PD will require a synthesis of findings emerging across these disparate disciplines, diseases and experimental settings. NIEHS has taken several steps to encourage such synthesis. A meeting of NIEHS-supported researchers in PD and other neurodegenerative diseases was held in June, 2004 to promote cross-fertilization of ideas among researchers, diseases and disciplines and to identify and prioritize data gaps, future resource needs and research opportunities. The results of this meeting were used to re-fashion an ongoing NIEHS initiative in gene-environment interaction in PD to encourage submission of applications focused on the roles of non-neuronal cells and proteasomal function in environmentally-induced PD.

The NIEHS is also partnering with the NINDS to support a Parkinson's Disease Data Organizing Center (PD-DOC) that will include a repository for environmental exposure and other risk factor data collected from individuals with PD and from unaffected controls. This centralized database will facilitate data sharing and pooled analysis, providing increased power to detect associations between environmental exposures and genetic and clinical characteristics in persons with PD. To support more meaningful interactions among NIEHS Collaborative Centers for PD Environmental Research, the NIEHS has awarded supplemental funds for the purchase of behavioral testing equipment that will enable greater sharing and comparison of behavioral data collected across the Centers. The NIEHS provided a second supplemental award to these Centers to support a series of meetings that will be used to develop recommendations for standardized PD diagnosis and exposure assessment in epidemiology studies. Common guidelines will facilitate data sharing and interpretation across different Centers and studies. Most recently, the NIEHS provided an opportunity for each Center to apply for competitive supplemental funds to conduct cooperative studies across Centers.

 Back to top

FY 2005 Senate Appropriations Committee Report Language (S. Rpt. 108-345)

Item

Breastfeeding and Toxins - Recent reports on the presence of flame retardants and other environmental toxins in human breastmilk have given rise to concerns about the safety of breastfeeding. Recognizing that these reports may offer mixed messages about this public health concern, the Committee reaffirms the goal of Healthy People 2010 of AIncreasing the proportion of mothers who breastfeed their babies.@ The Committee also strongly urges the National Institute of Children's Health and Human Development, the National Institute of Nursing Research, the National Institute of Environmental Health Sciences, the Centers for Disease Control and Prevention, Department of Health and Human Services= Office of Women's Health to hold a consensus meeting with health professionals, to include nursing and breastfeeding and lactation professionals. The consensus meeting should focus on environmental toxins and breastfeeding and appropriate public risk communication. (p. 134)

Action taken or to be taken

NIEHS supports the current HHS recommendations on breastfeeding as outlined in the HHS Blueprint for Action on Breastfeeding (http://www.4woman.gov/Breastfeeding/bluprntbk2.pdf)   . A recent analysis by NIEHS scientists showed that breastfed babies had less risk of dying in the postneonatal period than children who had never been breastfed, and that breastfeeding has the potential to prevent hundreds of postneonatal deaths each year in the U.S. Periodically, however, we are reminded that industrial chemicals and pesticides appear in virtually all human milk, and have done so since DDT was first reported in human milk in 1951. For the last two decades, NIEHS has done and supported epidemiologic studies of the consequences of pollutants in breast milk. Those studies have found that polychlorinated biphenyls passed from mother to fetus while the child is in the womb result in subtle, detrimental effects on the mental and motor development of the child, but that exposure through breast milk does not appear to do further harm. Although this information is available in the scientific literature, in professional publications like those of the American Association for Pediatrics, in the HHS breastfeeding document, and periodically is the subject of reports in the lay press, the material is not much covered in clinical training and can be difficult for a new mother to find on her own or from her medical provider. NIEHS staff have had discussions with scientific staff at the HHS Office on Women's Health (OWH), who chair the interagency Committee on Women and the Environment. NIEHS will explore with OWH the best ways to bring interagency focus through this Committee to the issue of public communication and outreach on breastfeeding.

 Back to top

Item

Environmental Health and Nursing - According to the final report of the Nursing and Environmental Health Roundtable, held in the fall of 2002, there is a significant need to build a cadre of registered nurse researchers specializing in environmental health. During the last decade, increased emphasis has been placed on the impact of environment on human health and the need for nurses to engage in research to advance knowledge in this field. Several nurse researchers received funding for environmental health projects focused on prevention of lead exposures, environmental factors and asthma, pesticide exposures among workers and their families, environmental awareness, and occupational health. Despite these efforts, significant needs still exist. Environmental health nurse researchers bring knowledge in nursing research methods as well as more traditional areas of environmental health research, such as human disease manifestation, risk assessment, and risk management. Many of the priority areas of environmental health nursing research rely on methods of exposure assessment, risk assessment, and risk communication. This Committee urges the National Institute of Environmental Health Sciences to create specific nurse research fellowships with the goal of increasing the number of registered nurse researchers specializing in the area of environmental health. (p. 134)

Action taken or to be taken

The National Institute of Environmental Health Sciences (NIEHS) is currently working with representatives from the National Institute for Nursing Research, the Centers for Disease Control and Prevention (National Center for Environmental Health and Agency for Toxic Substances and Disease Registry), Health Resources and Services Administration, and the U.S. Environmental Protection Agency to address many of the recommendations outlined in the 2002 Roundtable Report and the IOM Report, "Nursing, Health and Environment." One of the primary objectives of this group is to encourage research training and career development opportunities for nurse researchers and practitioners in the field of environmental health. In coordination with these agencies, NIEHS is examining how to establish a research fellowship that best meets the needs for nurses interested in pursuing research in environmental health. NIEHS is also in contact with the American Public Health Association's newly established Environmental Health Task Force (a joint group between the Environment Section and Public Health Nursing Section) regarding issues of nurse training, research and translation to practice.

 Back to top

Item

Pacific Center for Environmental Health - The Committee encourages NIEHS to establish a Pacific Center for Environmental Health to further study the short-term and long-term health effects of volcanic emissions as well as other environmental issues. Such environmental concerns should include food and waterborne illness, fish contamination by pesticides and heavy metals, and pesticide residue in food and water. (p. 135)

Action taken or to be taken

In February 2004, NIEHS held a town meeting in Honolulu, Hawaii to hear the concerns of citizens and scientists on the environmental health problems on the islands of Hawaii. Approximately 100 members of the public were present to discuss environmental health concerns of the region. Presentations were given by University of Hawaii researchers on the respiratory health effects of volcanic emissions, interdisciplinary research on oceans and human health, and the effects of heptachlor contamination and the health effects in children and on the role of the environment in autism. In the discussion period we heard concerns from citizens on the effects of water contamination in waterways in Oahu on fish health and possible human health outcomes from eating contaminated fish and other environmental and land use issues. Members of two NIEHS Children's Environmental Health Centers discussed the concerns of parents of children with autism for several hours. In addition, it was announced that NIEHS and the National Science Foundation (NSF) made an award to the University of Hawaii for a Center for Oceans and Human Health, which will be one of four such Centers funded in the U.S. In follow-up, NIEHS staff spoke with Dr. Bruce Anderson, past health director and currently on the faculty at the School of Medicine, about the eligibility criteria for the development of an NIEHS Environmental Health Sciences Center in Hawaii and offered advice and assistance to the University if they decide to pursue such funding.

 Back to top

Item

Parkinson's Disease - The Committee urges NIEHS in collaboration with NINDS to gain a greater understanding of the environmental underpinnings of Parkinson's disease. The Committee also strongly urges NIEHS to intensify its efforts in the Collaborative Centers for Parkinson's Disease Research Program B as this initiative facilitates significant collaboration among genetics, clinical medicine, epidemiology, and basic science so that the most promising leads may be investigated more quickly in pursuit of a cure or to reduce the incidence of harmful toxins. (p. 135)

Action taken or to be taken

Please refer to Parkinson's Disease section of this document for the NIEHS response to this significant item regarding Parkinson's Disease.