Workshop to develop a framework for assessing risks to children from exposure to environmental agents.
"Children are not simply small adults but rather are a unique population for health risk assessment." So begins the summary of the International Life Sciences Institute (ILSI) Risk Science Institute's conference on Similarities and Differences Between Children and Adults: Implications for Risk Assessment, convened in Hunt Valley, Maryland, in November 1990 (Guzelian et al. 1992). That conference summary also recognized the need for further work on the "specific application of the information presented at this conference to risk assessment methodologies," thus setting the stage for the workshop that is the subject of this meeting report.
Nearly 11 years after the Similarities and Differences conference, the ILSI Risk Science Institute (RSI) held a workshop in Stowe, Vermont, 30 July-2 August 2001, to develop a framework for assessing risks to children from exposure to environmental agents. The 54 invited experts, working in three breakout groups (on toxicokinetics, toxicodynamics, and risk characterization), drafted a structured approach to identifying and assessing potential risks from exposures occurring during development. This meeting report briefly describes the workshop and summarizes the workshop conclusions.
The workshop was organized by a 16-member planning committee that drafted an outline for the framework, prepared and reviewed several background papers for the workshop, and nominated experts in the key scientific disciplines as potential workshop participants. Among the areas of expertise represented in the workshop were developmental biology and toxicology (neurologic, reproductive/developmental, immunologic, pulmonary, general), pediatrics, genetics, epidemiology, pharmacokinetics, modeling, exposure assessment, and risk assessment. Workshop participants were drawn from government, academia, industry, and the public health community. Most of the time was devoted to the work of the breakout groups.
The breakout group chairs (Ginsberg, Faustman, and Daston) and their rapporteurs were the keys to the success of the workshop, as they moved their respective groups through their tasks. With their leadership and the active participation of the breakout group members, the framework outline drafted by the planning committee was discussed, further developed and modified, and adopted by the workshop participants; focus questions were addressed; concepts, insights, conclusions, and recommendations developed in breakout groups were presented and discussed in plenary sessions and revised, as appropriate, by the breakout groups; and critical data needs for improving the assessment of children's risks were identified.
Following the workshop, the chairs and rapporteurs, in collaboration with their respective breakout groups, prepared the breakout group reports. These reports were compiled and synthesized into a workshop report by the overall workshop chair. This report was then circulated to all workshop participants and observers for comment, and a final workshop report was prepared.
The conceptual framework created by the workshop (Figure 1) is based on the Problem Formulation [right arrow] Analysis [right arrow] Risk Characterization paradigm that has been incorporated in many risk assessment frameworks over the past decade, and applies that paradigm to early life-stage exposures. The framework recognizes the potential significance of the timing of exposures in relation to the susceptibility of the developing human, from the perspective of both toxicokinetics and toxicodynamics. It offers a systematic approach to the consideration of factors that may influence risk during development, from conception through organ maturation (in adolescence). And it acknowledges that the complexity and unique insights of a risk assessment focusing on early life stages will depend critically on the data available and the scope of the assessment.
Among the conclusions from the workshop were the following:
* There are distinct life stages during development with both known and hypothesized "windows of susceptibility" in humans and in experimental animal models. These developmental life stages are defined by differences in relevant kinetic and dynamic processes occurring at the molecular, cellular, organ, and physiologic levels. Interspecies comparisons must consider differences in life stages and kinetic and dynamic processes, including timing and dosimetry.
* In addition to considerations of intrinsic sensitivity of the developing human, life-stage-specific behaviors, activity patterns, functions, and intakes often can lead to dramatic differences in exposures. Life-stage-linked exposure assessment is a critical component of any children's environmental health risk assessment.
* In Problem Formulation, in the context of the proposed framework (Figure 1), defining the overall scope and objectives of the risk assessment is important for the initial assessment of life stages, exposure scenarios, and toxic effects to be considered.
* Problem Formulation produces a conceptual model of the likely key relationships between exposures and the effects of the environmental agent(s) on host (exposed) populations, informed by the initial identification of exposure scenarios, exposed life stages, and the known or anticipated biologic effects of the environmental agent(s). The conceptual model for the risk assessment arises from and guides the collection of data in preparation for the Analysis phase.
* Toxicokinetic considerations in Analysis include agent/chemical-specific factors and life-stage/age-specific factors, both of which can include effects on absorption, distribution, metabolism, and excretion. Examination of these factors may reveal one or more age groups of particular toxicokinetic concern.
* Toxicodynamic considerations in Analysis include the identification of uniquely susceptible dynamic processes of concern and the functional consequences of altering these processes, and consideration of available data that may indicate differential toxicity from exposures during susceptible periods.
* Analysis of the timing of development and exposures and of the dosimetrics of the agent (including both kinetic and dynamic factors) links the characterization of life-stage-specific exposures with life-stage-specific effects.
* Risk Characterization for early life-stage exposures may be qualitative (e.g., when quantitative data are lacking or a quantitative analysis is unnecessary) or quantitative (e.g., incorporating a life-stage-specific physiologically based toxicokinetic or biologically based dose-response model) or some other semi-quantitative assessment.
* The full spectrum of potential developmental effects cannot be predicted from data on exposed adults. A core data set from studies in developing organisms is essential.
The workshop identified critical research needs for improved assessments. Among the highest research priorities are:
* Improved understanding of critical windows of developmental susceptibility and of comparative developmental schedules of animals and humans
* Characterization of' children's habits and practices (e.g., diet, behavior, time-activity patterns) at different stages of development
* Better methodology (e.g., in testing protocols), applied more often, on functional outcomes at relevant life stages in animal models and humans; the methods should be sensitive and specific and should account for variability in responses and norms
* Investigation of the temporal relationships between exposure and outcomes, particularly for delayed outcomes (latent sequelae)
* Understanding of host factors that contribute to susceptibility
* Monitoring of disease trends and exposures.
After the workshop, the ILSI Risk Science Institute formed a Children's Risk Assessment Framework Working Group to coordinate follow-up activities. Initial efforts have focused on developing the workshop observations and recommendations into a concise, pragmatic framework for assessing children's risks and refining, testing, and elaborating the framework by means of case studies. Other Working Group topics include coordinating the creation of a database on physiologic parameters for early life stages and comparing the timing of development of key organ/functional systems in different species.
Guzelian PS, Henry CJ. 1992. Conference summary. In: Similarities and Differences between Children and Adults: Impgcations for Risk Assessment (Guzelian PS, Henry C J, Olin SS, eds). Proceedings of the ILSI Conference on Similarities and Differences Between Children and Adults: Implications for Risk Assessment, 5-7 November 1990, Hunt Valley, Maryland. Washingtoll, DC:ILSI Press, 1-3.
Workshop to develop a framework for assessing risks to children from exposure to environmental agents. Toxicokinetics Toxicodynamics Chair: Gary Ginsberg (a) Chair: Elaine Faustman (a) Connecticut Department of University of Washington Public Health Rapporteur: William Breslin (a) Rapporteur: James Bruekner Eli Lilly & Co University of Georgia Breakout Group: Breakout Group: Richard Albertini Hugh Barton University of Vermont US EPA/ORD/NHEERL Adolfo Correa (a) Matthew Bogdanffy CDC DuPont Haskell Laboratory John DeSesso Harvey Clewell Mitretek Systems ICF Kaiser/KS Crump Group Rodney Dietert Karen Davis-Bruno (a) Cornell University U.S. FDA/CDER Joyce Donohue Dale Hattis U.S EPA/OW Clark University Jean Harry Dan Krewski NIEHS University of Ottawa Robert Kavlock Kannan Krishnan U.S EPA/ORD/NHEERL University of Montreal Gary Kimmel Stephen Olina U.S EPA/ORD/NCEA ILSI Risk Science Institute Bruce Lanphear Wayne Snodgrass University of Cincinnati University of Texas Medical Merle Paule Center FDA/NCTR Bob Sonawane (a) Kent Pinkerton U.S EPA/ORD/NCEA University of California, Davis Jennifer Seed U.S EPA/OPPT Michael Shelby NIEHS Diana Somers PMRA/Canada Tom Trautman (a) General Mills Isabel Walls ILSI Risk Science Institute Risk characterization Other participants Chair: George Daston (a) Robert Amler Procter & Gamble ATSDR Rapporteur: Penny Fenner-Crisp Nancy Beck ILSt Risk Science Institute U.S EPA/ORD/NCEA (AAAS Fellow) Breakout Group: Richard Becker John Adgate American Chemistry Council University of Minnesota Terri Damstra Sherlita Amler (a) WHO/IPCS ATSDR Michael Firestone Bob Chapin U.S. EPA/OCHP DuPont Pharmaceutical Steven Knott Vicki Dellarco U.S. EPA/ORD/NCEA U.S EPA/OPP Ray McAllister Brenda Eskenazi (a) American Crop Protection University of California, Association Berkeley LaRonda Morford Daniel Goldstein (a) Eli Lilly & Co Monsanto Vanessa Vu Elaine Cohen Hubal U.S. EPA/OPPTS/OSCP U.S EPA/ORD/NERL Carole Kimmel (a) U.S. EPA/ORD/NCEA Philip J. Landrigan (a) Mt. Sinai School of Medicine Melanie Marty CalEPA/OEHHA Butte Meek Health Canada Larry Sheets Bayer Corp. Tracey Zoetis Milestone Biomedical Associates Abbreviations: AAAS, American Association for the Advancement of Science; ATSDR, Agency for Toxic Substances and Disease Registry; CalEPA, California Environmental Protection Agency; CDC, Centers for Disease Control and Prevention; CDER, Center for Drug Evaluation and Research; FDA, U.S. Food and Drug Administration; NCTR, National Center for Toxicological Research; NERL, National Exposure Research Laboratory; NHEERL National Health and Environmental Effects Research Laboratory; IPCS, International Programme on Chemical Safety; NIEHS, National Institute of Environmental Hearth Sciences; OCHP, Office of Children's Health Protection; OEHHA, Office of Environmental Health Hazard Assessment; OPP, Office of Pesticide Programs; OPPT, Office of Pollution, Prevention, and Toxics; OPPTS, Office of Prevention, Pestecides, and Toxic Substances; OSCP, Office of Science Coordination and Policy; OW, Office of Water; PMRA, Pesticide Management Regulatory Agency; WHO, World Health Organization (a) Planning Committee; William Slikker (FDA/NCTR), Ralph Smialowicz (EPA/NHEERL), and Susan Kess (ATSDR) also participated in the Planning Committee.
Stephen S. Olin (1) and Babasaheb R. Sonawane (2)
(1) Risk Science Institute, International Life Sciences Institute, Washington, DC, USA; (2) National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC, USA
Address correspondence to S.S. Olin, Risk Science Institute, International Life Sciences Institute, One Thomas Circle, Ninth Floor, Washington, DC 20005-5802 USA. Telephone: (202) 659-3306. Fax: (202) 659-3617. E-mail: email@example.com
This project was conducted under a cooperative agreement (CR 82730801) with the U.S. Environmental Protection Agency (EPA), Office of Research and Development (ORD), National Center for Environmental Assessment, Washington, DC. Financial support from the U.S. EPA (the National Center for Environmental Assessment/ORD and the Office of Children's Health Protection), the American Chemistry Council, CropLife America, and the International Life Sciences Institute is gratefully acknowledged.
The views expressed by the authors do not necessarily reflect the views and policies of the U.S. Environmental Protection Agency or the International Life Sciences Institute, and mention of trade names of commercial products does not constitute endorsement or recommendation for use.
The authors declare they have no conflict of interest. Received 2 January 2003; accepted 7 April 2003.
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|Title Annotation:||Meeting Report|
|Author:||Sonawane, Babasaheb R.|
|Publication:||Environmental Health Perspectives|
|Date:||Sep 1, 2003|
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