Overview of ORDs Research to Understand the Exposure, Susceptibility,

1
Overview of ORDs Research to Understand the
Exposure, Susceptibility, and Differential Risks
of Children to Pesticides Roy Fortmann1, Kacee
Deener2, Virginia Moser3, Daniel Stout1, and
Nicolle Tulve1 U.S. Environmental Protection
Agency, Office of Research and Development,
1National Exposure Research Laboratory, 2National
Center for Environmental Research, 3National
Health and Environmental Effects Laboratory
Results/Conclusions

• Research Output 2 Tools for Characterizing
  Exposures and Risks for Subpopulations
• Goals
• Determine why some children, or some groups, are
  more highly exposed to pesticides and other
  chemicals
• Determine why some children, or groups, are more
  susceptible to the effects of exposure
• Determine the most important pathways of exposure
  and the factors affecting exposure
• Approach
• A systematic approach was used to design
  laboratory studies, pilot scales studies, and
  large exposure assessment and environmental
  epidemiology studies to collect data to fill
  critical gaps in our understanding of childrens
  exposure and risk to pesticides
• The studies address a range of childrens ages
  and potentially susceptible subpopulations
• A number of different classes of pesticides and
  other chemicals are addressed in these studies
• Environmental samples, biological samples, and a
  large amount of ancillary data are collected
• The studies are being performed by ORD and by
  STAR grant children centers
• Highlights of Results
• Epidemiologic evidence suggests that recent EPA
  restrictions on the use of certain
  organophosphate (OP) pesticides in the home have
  reduced the exposure of both mothers and infants
  to these pesticides and that there is no longer a
  detectable impact on fetal growth
• Approximately 70 of the 386 women in the CEHDP
  study in East Harlem, New York City were exposed
  to indoor pesticides during pregnancy
• Dietary ingestion is the major route of exposure
  for many pesticides
• In a random sample of licensed child care centers
  in the U.S., 60 reported indoor applications of
  pesticides in the last year
• Childrens median pesticide urinary metabolite
  levels were higher in spring and summer when most
  agricultural pesticide applications occur in the
  Salinas Valley, CA

Science Question
Science Question

• Research Output 1 Tools for Identifying Highly
  Exposed Populations
• Goals
• Develop approaches, protocols, and tools for
  assessing the exposures and risks of children to
  pesticides
• Approach
• Develop sampling methods that are easy to use,
  efficient, and cost-effective for collection of
  environmental and biological samples
• Develop improved multi-residue analytical methods
  that facilitate collection of data simultaneously
  for large numbers of pesticides
• Develop improved methods for collection of
  time/activity data for children
• Evaluate these tools under realistic field
  conditions
• Highlights of the Results
• Draft Protocol for childrens exposure
  assessments
• Saliva biomonitoring method
• Visual child activity diary
• New GPS method
• Disposable diaper method for urine collection
• Cotton garment for assessing dermal exposure
• Multi-residue analytical methods for OPs and
  pyrethroids

Methods/Approach/Results

• There are many accomplishments from research
  performed by ORD and the Childrens Centers
• Many innovative tools and methods have been
  developed (e.g. the Draft Protocol, GPS methods,
  activity logs, diaper methods).
• Measurement studies have identified susceptible
  subpopulations, the pesticides, and levels of
  exposure for children.
• This research has produced data that is providing
  a better understanding of the important exposure
  pathways and the factors affecting exposure.
• ORD research has demonstrated the differential
  risk of the young to cholinesterase-inhibiting
  pesticides.
• Substantial progress has been made to reduce
  health risks through intervention and source
  management.

• One of the goals of ORDs human health research
  is to provide the scientific basis to understand
  and protect subpopulations that have differential
  risks. To meet that goal, ORD research must
  answer the following questions
• What subpopulations have differential risk to
  pesticides?
• What is the basis for differential risk?
• What is the risk to susceptible subpopulations?
  
• How can differential risk be mitigated?

Research Goals
Research to understand the exposure,
susceptibility, and differential risks of
children to pesticides is integral to ORDs
effort to provide scientific support for
conducting risk assessments that consider the
vulnerabilities of susceptible and highly exposed
life stages and subpopulations. The research on
childrens exposure to pesticides addresses the
requirements of the Food Quality Protection Act
of 1996 and the Safe Drinking Water Act
Amendments of 1996 that EPA consider children and
other potentially susceptible groups when setting
health-based standards. In response to these
requirements, ORD developed a systematic approach
to address the key science questions identified
in its research strategy documents. Key research
outputs that were identified included (1) tools
for identifying highly exposed populations, (2)
tools for characterizing exposures and risks for
subpopulations, (3) tools for describing the
biological basis for differential sensitivity,
and (4) tools that lead to reduced exposure (see
ORDs logic diagrams). The quality and quantity
of the available scientific data regarding
exposure and response and the existing data gaps
were evaluated and a conceptual model was
developed that was used to identify and
prioritize research needs. A set of highly
focused research studies were then performed to
collect data to fill critical data gaps. To
evaluate exposure, EPA researchers developed
innovative tools for assessing childrens
exposures, collected data on the pesticides to
which children are currently exposed, and
developed data on exposure factors. Basic
research within ORD was initiated to evaluate
differential responses to those pesticide
exposures to determine the magnitude and
biological basis for the differences. ORD also
awarded grants to eight Centers of Excellence in
Childrens Environmental Health and Disease
Prevention Research, where research has been, and
continues to be, performed that has contributed
substantially to developing the tools described
above, as well as to developing and implementing
effective intervention strategies.
EPAs Research Outputs (14) Address the
Conceptual Model of Childrens Exposure to
Pesticides
Impact and Outcomes
This program has already generated a substantial
number of research outputs, as shown in the body
of the poster. Tools developed in this research
program are being used by researchers in both the
public and private sector, which will further
collection of reliable data for use in future
risk assessments for pesticides and other
chemicals. The research program has developed a
data base that has contributed to a substantially
improved understanding of the exposures,
susceptibility, and risk of children to
pesticides. The data are being used by ORD, the
EPA Office of Pesticide Programs, industry, and
others to improve exposure and risk assessments
for children. The data are also being used to
develop risk intervention and source management
strategies.

• Research Output 3 Tools Describing the
  Biological Basis for Differential Sensitivity
• Goals
• Characterize the differential response of the
  young to the neurobehavioral and neurochemical
  effects of cholinesterase-inhibiting pesticides
  (e.g., carbamates and organophosphates) and
  determine the biological mechanisms for these
  differences.
• Approach
• Tests were performed to systematically compare
  dose-response data in young (preweaning) and
  adult rats. Hypotheses were then identified and
  tested to establish mechanisms, which would allow
  better extrapolation to the human population.
• Highlights of the Results
• The working hypothesis is that the young are more
  sensitive to pesticides which are detoxified via
  carboxylesterases and/or A-esterases. Therefore
  the young are more sensitive to some pesticides
  simply because the young are less efficient at
  detoxifying the pesticides. This allows
  predictions of which pesticides show differential
  toxicity, based on metabolic patterns.
• Impact
• This research has directly influenced risk
  assessment decisions for these pesticides. The
  Office of Pesticide Programs (OPP) has limited
  use of selected pesticides to decrease potential
  exposure in the young. A Data Call-In was issued
  to collect comparative sensitivity data for all
  registered organophosphate pesticides.
• This research has provided methods for, and
  identification of, pesticides which are more
  toxic to the young.
• Poster Differential Sensitivity of the Young to
  Cholinesterase-Inhibiting Pesticides

• Research Output 4 Tools that Lead to Reduced
  Exposures
• Goals
• Develop and evaluate approaches to reduce health
  risks from exposure to pesticides through source
  management, intervention, and community
  partnerships
• Develop community-based intervention projects
  designed to mitigate risk by reducing hazardous
  exposures and their potential health effects
• Approach
• EPA, in cooperation with NIEHS, has funded
  several childrens environmental health centers
  that are conducting basic and applied research
  that includes home-based and community-based
  intervention projects
• Relevant exposure pathways are identified and
  intervention methods are tailored for specific
  situations
• Home-based interventions are enhanced and taken
  to a broader audience through the development of
  community level programs
• Highlights of the Results
• Interventions have been implemented that are
  designed to break the take-home pathway
  (removing work boots and change out of work
  clothes before agricultural workers enter the
  home, etc.).
• The studies demonstrated that IPM is more
  effective at reducing cockroach populations than
  traditional pest control practices
• Impact
• The Centers are working with organizations such
  as the Central Coast Grower Shipper Association,
  the California Comprehensive Perinatal Services
  Program, the New York City Department of Health
  and Mental Hygiene, and the New York City Housing
  Authority to develop and implement intervention
  programs.
• Poster Children and Pesticides Approaches to
  Reducing Health Risks through Intervention,
  Source Management, and Community Partnerships

Future Directions
Work in this program is on-going. A number of
studies have been completed and the results
published. For recently completed studies, data
analysis and reporting will result in a
significant number of manuscripts during the
coming year. Work at the Childrens Centers is
continuing, with results been reported in the
scientific literature on a continuing basis. A
longitudinal study, the Childrens Environmental
Exposure Research Study (CHEERS) is scheduled to
begin in summer 2005 to collect more
comprehensive data on exposures of very young
children (ages 3 months to 3 years) to pesticides
in their homes.
References
Numerous manuscripts and reports have been
generated as a result of this research program.
The materials provided for this review highlight
important publications from this work.