Grantee Research Project Results
U.S. Environmental Protection Agency
Office of Research and Development
National Center for Environmental Research
Science to Achieve Results (STAR) Program
CLOSED - FOR REFERENCES PURPOSES ONLY
Children's Vulnerability to Toxic Substances in the Environment
October 30, 2000
Closing Date: February 28, 2001
Longitudinal Information on Exposure in Children
Children's Susceptibility to Toxic Chemicals
Standard Instructions for Submitting an Application
In this announcement the U.S. Environmental Protection Agency (EPA), Office of Research and Development (ORD), invites research grant applications on Children's Vulnerability to Toxic Substances in the Environment.
EPA's research programs focus on reduction of risks to human health and ecosystems and on the reduction of uncertainty associated with risk assessment. Through its laboratories and through grants to academic and other not-for-profit institutions, EPA promotes research in both domains, according the highest priority to those areas in which risk assessors are most in need of new concepts, methods, and data. EPA also fosters the development and evaluation of new risk reduction technologies across a spectrum, from pollution prevention through end-of-pipe controls to remediation and monitoring. In all areas, EPA is interested in research that recognizes issues relating to environmental justice, the concept of achieving equal protection from environmental and health hazards for all people without regard to race, economic status, or culture.
Over the past few years, public attention has increasingly focused on potential adverse health effects in children from exposure to toxic chemicals in their food, water, or environment. Public health officials and physicians are being asked to assess the significance of a plethora of possible risks for children. At the Federal level, recent actions by the President, the Congress, and the EPA Administrator have focused attention on environmental health threats to children. In 1997, President Clinton issued an Executive Order addressing protection of children from environmental health risks. The Food Quality Protection Act of 1996 and the Safe Drinking Water Act of 1996 both require consideration of infants and children in risk assessments used to determine acceptable levels of environmental contaminants in food and drinking water. In 1996, EPA Administrator Browner issued a report entitled Environmental Health Threats to Children and set a Children's Agenda for EPA, calling for consideration of children's risks in all Agency actions and a greater emphasis on research to support children's risk assessments.
The health impacts of most concern are respiratory diseases, childhood cancer, immune system effects, neurotoxicity, and developmental effects. From 1982 to 1993, the prevalence, morbidity, and age-adjusted mortality rates for asthma increased significantly despite improvements in asthma diagnosis and management and improved understanding of the biology and immunology of the disease. There are a limited number of studies that suggest age-related differences in cancer susceptibility. However, it is still difficult to assess the potential impact of these differences due to a lack of research. The immune system is of concern due to the known differences in immune structure and function between children and adults. Exposure to some toxic chemicals, such as lead, are well known to cause neurological effects in children. However, the potential neurological effects of other metals and chemicals such as solvents and pesticides are not as well understood. Finally, exposure to a variety of toxic chemicals in the environment can affect initial growth and development. In addition, exposure during crucial periods of development may have profound effects which may or may not be reversible in later life. These, among other concerns, support the need for additional research on possible environmental causes of childhood diseases.
In exploring the factors that affect health risk from exposure to toxic chemicals, it must be remembered that children are a unique sub-population. Depending on the circumstances, children may be more or less susceptible to the toxic effects of these chemicals than are adults. Risks to children may differ qualitatively or quantitatively from risks to adults because of differences in their immature physiology, metabolic processes, respiratory rates, and differing levels of exposure. Nutritional status, disease, and genetic variation can affect many of these processes, increasing or decreasing the risk from exposure to toxic substances. In response to this RFA the EPA will sponsor research to better understand how these factors affect risk to children from exposure to toxic chemicals in the environment. Of particular interest are pesticides such as pyrethroids and the triazine herbicides. Projects which explore the assessment of intermittent and time-varied exposures as well as the biological basis for increased susceptibility among children will be particularly valuable.
Proposals focusing exclusively on lead poisoning in children will be considered non-responsive to this RFA.
There are two areas of greatest interest to EPA, discussed below.
The exposure of children to potentially toxic chemicals is generally quite different from that to adults because of differences in physical environment, activity patterns, and diet. The assessment of exposure in children and adults depends on first being able to consider all relevant exposure pathways, including dietary, drinking water, respiratory, dermal, and non-dietary oral ingestion. Exposures that occur via some of these pathways may be relatively high, but are usually not persistent and often result from human activities that are relatively rare or intermittent. Many of the differences in exposure between children and adults are associated with these types of exposure and are most often linked with the unique behavior of children. Therefore, it is important that we better understand the temporal variation in the environmental and behavioral factors that influence exposure.
Children's daily activities, proximity to floors, carpets, lawns, and soils, the frequency and duration of hand to mouth behaviors, and many other factors combine to form a life environment that varies with age and from child to child. Studies suggest, for example, that children's normal activities may expose them to higher levels of pesticides applied in and around the home. Children also have greater average daily food consumption per unit body weight than do adults, and children differ in the specific foods eaten and in the relative proportions of various foods.
Proposals that are responsive to this RFA will identify specific pollutant chemicals, pollutant sources, environmental media, and exposure pathways and will attempt to develop novel methodologies for quantifying or assessing exposures to children and the associated temporal variability. The chemicals and pathways chosen should represent problems or issues of environmental relevance. These proposals might utilize currently employed techniques such as telephone surveys, lab experiments, or field studies. However, the development of new and untested approaches is also encouraged. Topics of interest include, but are not limited to:
- Methods to quantify children's
exposures that occur primarily through dermal contact and/or via
dietary and/or non-dietary ingestion and to quantify the temporal
variation associated with these exposures;
- Approaches for quantifying the
frequency, duration, and intra-individual variability of children's
activities in and around the home which might lead to significant
exposures, considering factors such as age, sex, culture, geography,
and climate; and
- Predictive models for estimating total human exposure which incorporate the unique factors associated with a childs physiology and activity patterns and account for sources of variability in these factors.
There are several interconnected factors that may contribute to increased vulnerability for children, depending on the toxic substance under consideration and the age of the child. Children's tissues, organs, and biological systems are still developing, with several stages of rapid growth and development occurring from infancy to adolescence. This rapid development and immaturity of body organs and systems predisposes children to potentially more severe consequences within certain age ranges and windows of vulnerability. Differences in the absorption, metabolism, distribution, storage, and elimination of toxic chemicals that enter the body at different ages may also contribute to increased vulnerability and higher doses to target organs and tissues.
Physiological differences influence the amount of chemical that is absorbed into the body. Children have a greater ratio of surface area to body weight than adults which may lead to increased dermal absorption. Comparisons of absorption through the respiratory and gastrointestinal tracts between children and adults are complex and could lead to either increased or decreased risk depending on the physicochemical properties of the toxic chemical. The rate at which a substance is distributed to various organs in the body may be influenced by developmental changes. For example, a child's greater volume of extracellular water may dilute substances in this compartment. Also, circulatory flow rates are generally higher in children and may impact the distribution of toxic chemicals, and reduced plasma binding may increase a child's susceptibility to toxic effects. The metabolism and excretion of toxic chemicals in a child's body may also differ from that of adults. Developmental changes occur in liver enzyme systems that may increase or decrease the toxicity of substances in children. These developmental changes occur at different rates in the various enzyme systems with some not being completed until puberty. The effects of these changes also depend on the chemical and how it is metabolized.
EPA will support research into novel methods for studying the susceptibility of children to environmentally induced disease. Proposals that are responsive to this RFA will incorporate information on biological and physiological characteristics of different age groups, the variability within particular age groups, and the mechanistic basis for increased susceptibility of children to the adverse health effects of environmental contaminants. Of particular interest are approaches that will provide a better understanding of these and other factors that contribute to increased susceptibility in children. This includes but is not limited to:
- The development of animal models
for studying the toxicity of environmental contaminants which
help us to understand the unique susceptibilities of children
to the adverse health effects that may result from exposure to
- Alternatives to animal testing
for studying the toxicity of environmental contaminants and which
help us to understand the unique susceptibilities of children
to the adverse health effects that may result from exposure to
- Research on approaches for extrapolating from animal or alternative models to children, including the development of physiologically based pharmacokinetic models for animals and humans.
Subject to the availability of funds, approximately $5 million is expected to be awarded in fiscal year 2001 in this program area. The projected award range is $150,000 to $250,000 per year total costs for up to 3 years.
Academic and not-for-profit institutions located in the U.S., and state or local governments, are eligible under all existing authorizations. Profit-making firms are not eligible to receive grants from EPA under this program. Federal agencies and national laboratories funded by federal agencies (Federally-funded Research and Development Centers, FFRDCs) may not apply.
Federal employees are not eligible to serve in a principal leadership role on a grant. FFRDC employees may cooperate or collaborate with eligible applicants within the limits imposed by applicable legislation and regulations. They may participate in planning, conducting, and analyzing the research directed by the principal investigator, but may not direct projects on behalf of the applicant organization or principal investigator. The principal investigator's institution may provide funds through its grant from EPA to a FFRDC for research personnel, supplies, equipment, and other expenses directly related to the research. However, salaries for permanent FFRDC employees may not be provided through this mechanism.
Federal employees may not receive salaries or in other ways augment their agency's appropriations through grants made by this program. However, federal employees may interact with grantees so long as their involvement is not essential to achieving the basic goals of the grant.1 The principal investigators institution may also enter into an agreement with a federal agency to purchase or utilize unique supplies or services unavailable in the private sector. Examples are purchase of satellite data, census data tapes, chemical reference standards, analyses, or use of instrumentation or other facilities not available elsewhere, etc. A written justification for federal involvement must be included in the application, along with an assurance from the federal agency involved which commits it to supply the specified service.
1EPA encourages interaction between its own laboratory scientists and grant principal investigators for the sole purpose of exchanging information in research areas of common interest that may add value to their respective research activities. However, this interaction must be incidental to achieving the goals of the research under a grant. Interaction that is incidental is not reflected in a research proposal and involves no resource commitments.Potential applicants who are uncertain of their eligibility should contact Dr. Robert E. Menzer in NCER, phone (202) 564-6849, email: firstname.lastname@example.org.
A set of special instructions on how applicants should apply for a STAR grant is found on the NCER web site, http://www.epa.gov/ncerqa. Standard Instructions for Submitting a STAR Application and the necessary forms for an application will be found on this web site.
The need for a sorting code to be used in the application and for mailing is described in the Standard Instructions for Submitting a STAR Application. The sorting code for applications submitted in response to this solicitation is 2001-STAR-H1
The deadline for receipt of applications by NCER is no later than 4:00 p.m. ET, February 28, 2001.
Further information, if needed, may be obtained from the EPA official indicated below. Email inquiries are preferred.