PRINCIPLES FOR EVALUATING HEALTH RISKS IN CHILDREN ASSOCIATED WITH EXPOSURE TO CHEMICALS

Transcription

1 This report contains the collective views of an international group of experts and does not necessarily represent the decisions or the stated policy of the United Nations Environment Programme, the International Labour Organization or the World Health Organization. Environmental Health Criteria 237 PRINCIPLES FOR EVALUATING HEALTH RISKS IN CHILDREN ASSOCIATED WITH EXPOSURE TO CHEMICALS First drafts prepared by Dr Germaine Buck Louis, Bethesda, USA; Dr Terri Damstra, Research Triangle Park, USA; Dr Fernando Díaz- Barriga, San Luis Potosi, Mexico; Dr Elaine Faustman, Washington, USA; Dr Ulla Hass, Soborg, Denmark; Dr Robert Kavlock, Research Triangle Park, USA; Dr Carole Kimmel, Washington, USA; Dr Gary Kimmel, Silver Spring, USA; Dr Kannan Krishnan, Montreal, Canada; Dr Ulrike Luderer, Irvine, USA; and Dr Linda Sheldon, Research Triangle Park, USA Published under the joint sponsorship of the United Nations Environment Programme, the International Labour Organization and the World Health Organization, and produced within the framework of the Inter-Organization Programme for the Sound Management of Chemicals.

2 The International Programme on Chemical Safety (IPCS), established in 1980, is a joint venture of the United Nations Environment Programme (UNEP), the International Labour Organization (ILO) and the World Health Organization (WHO). The overall objectives of the IPCS are to establish the scientific basis for assessment of the risk to human health and the environment from exposure to chemicals, through international peer review processes, as a prerequisite for the promotion of chemical safety, and to provide technical assistance in strengthening national capacities for the sound management of chemicals. The Inter-Organization Programme for the Sound Management of Chemicals (IOMC) was established in 1995 by UNEP, ILO, the Food and Agriculture Organization of the United Nations, WHO, the United Nations Industrial Development Organization, the United Nations Institute for Training and Research and the Organisation for Economic Co-operation and Development (Participating Organizations), following recommendations made by the 1992 UN Conference on Environment and Development to strengthen cooperation and increase coordination in the field of chemical safety. The purpose of the IOMC is to promote coordination of the policies and activities pursued by the Participating Organizations, jointly or separately, to achieve the sound management of chemicals in relation to human health and the environment. WHO Library Cataloguing-in-Publication Data Principles for evaluating health risks in children associated with exposure to chemicals (Environmental health criteria ; 237) First drafts prepared by Dr Germaine Buck Louis... [et al.]. 1.Environmental health. 2.Risk assessment. 3.Child. 4.Organic chemicals - adverse effects. 5.Inorganic chemicals - adverse effects. 6.Environmental exposure. I.Louis, Germaine Buck. II.World Health Organization. III.Inter-Organization Programme for the Sound Management of Chemicals. IV.Series. ISBN X (NLM classification: WA 30.5) ISBN ISSN X World Health Organization 2006 All rights reserved. Publications of the World Health Organization can be obtained from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel: ; fax: ; bookorders@who.int). Requests for permission to reproduce or translate WHO publications whether for sale or for noncommercial distribution should be addressed to WHO Press, at the above address (fax: ; permissions@who.int). The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. All reasonable precautions have been taken by WHO to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either express or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall the World Health Organization be liable for damages arising from its use. The named authors alone are responsible for the views expressed in this publication. This document was technically and linguistically edited by Marla Sheffer, Ottawa, Canada, and printed by Wissenchaftliche Verlagsgesellschaft mbh, Stuttgart, Germany.

3 CONTENTS ENVIRONMENTAL HEALTH CRITERIA ON PRINCIPLES FOR EVALUATING HEALTH RISKS IN CHILDREN ASSOCIATED WITH EXPOSURE TO CHEMICALS PREAMBLE PREFACE ACRONYMS AND ABBREVIATIONS xi xvii xix 1. SUMMARY, CONCLUSIONS, AND RECOMMENDATIONS Summary Conclusions and recommendations 4 2. INTRODUCTION AND BACKGROUND Introduction Purpose and scope of document Global burden of disease in children Major environmental threats to children Economic and nutritional factors Social, cultural, demographic, and lifestyle factors Chemical hazards Intrinsic factors The significance of a developmental stage approach Summary and conclusions UNIQUE BIOLOGICAL CHARACTERISTICS OF CHILDREN General physical growth of children Body weight and height Organ weights/volumes Skin Anatomical and functional characteristics Physiological characteristics 26 iii

4 EHC 237: Principles for Evaluating Health Risks in Children iv Breathing rate Cardiac output Blood flow to organs Body composition Tissue composition Bone growth and composition Metabolic characteristics Toxicokinetics Absorption, distribution, metabolism, and elimination Physiological changes in mothers and their influence on toxicokinetics Pregnancy Lactation and breast milk Dose to target Normal development Basic principles of normal development Nervous system Reproductive system Endocrine system Hypothalamic pituitary axis Thyroid gland Adrenal glands Gonads Somatotropin (growth hormone), calcium homeostasis, and bone development Pancreas Cardiovascular system Immune system Respiratory system Kidney Summary and conclusions DEVELOPMENTAL STAGE SPECIFIC SUSCEPTIBILITIES AND OUTCOMES IN CHILDREN Introduction Mortality, growth restriction, and birth defects Mortality Growth restriction Birth defects (structural malformations) 64

5 Contents Etiology Functional developmental toxicity Specific organ systems Nervous system Periods of susceptibility and consequences of exposures Specific examples Reproductive system Periods of susceptibility Consequences of exposures Endocrine system Periods of susceptibility Consequences of exposures Cardiovascular system Periods of susceptibility Consequences of exposures Immune system Periods of susceptibility Consequences of exposures Respiratory system Periods of susceptibility Consequences of exposures Kidney Periods of susceptibility Consequences of exposures Cancer Childhood cancers that may have environmental causes Lymphoid tissues Liver Thyroid Brain and nervous system Other organ sites Adult cancers related to childhood exposures Brain and nervous system Thyroid Female breast Female reproductive tract Integument Other organ sites 123 v

6 EHC 237: Principles for Evaluating Health Risks in Children vi Chemical exposures of special concern Summary and conclusions EXPOSURE ASSESSMENT OF CHILDREN Introduction General principles of exposure assessments Methods for conducting exposure assessments Direct methods Biomarkers of exposure Modelling Unique characteristics of children that affect exposure Exposure as it relates to children around the world Sources/geographical location Pathways of exposure Ambient air exposure pathway Indoor exposure pathways Water exposure pathway Soil exposure pathway Food-chain exposure pathway Human to human exposure pathways Settings/microenvironments Residential School Child-care centres Recreational Special settings Environmental equity factors (vulnerable communities) Special considerations for children s exposure: case-studies Influence of activities Arsenic Insecticides Environmental tobacco smoke (ETS) Lead Hazardous waste sites Aggregate exposure Chlorpyrifos 164

7 Contents Smelter areas Malarious areas Cumulative exposure Summary and conclusions METHODOLOGIES TO ASSESS HEALTH OUTCOMES IN CHILDREN Introduction Methodological approaches for children s health studies Epidemiological methods Comparison of study designs Descriptive designs Analytic designs Unique methodological considerations Methodological approaches for animal studies Developmental stage susceptibility, dosing periods, and assessment of effects Dosing of fetuses and pups Growth and development Human studies Puberty Birth defects Animal studies Body weight and postnatal growth Pre-, peri-, and postnatal death Physical and functional developmental landmarks Birth defects and malformations Reproductive development and function Human studies Animal studies Malformations of reproductive organs Anogenital distance Nipple/areola retention Sexual maturation and puberty 204 vii

8 EHC 237: Principles for Evaluating Health Risks in Children viii Fertility Histopathology of reproductive organs Sperm quality and estrous cyclicity Neurological and behavioural effects Human studies Animal studies Motor activity Motor and sensory functions Learning and memory Evaluation of effects Cancer Human studies Animal studies Immune system effects Human studies Animal studies Respiratory system effects Human studies Animal studies Haematopoietic/cardiovascular, hepatic/renal, skin/musculoskeletal, and metabolic/endocrine system effects Human studies Animal studies Summary and conclusions IMPLICATIONS AND STRATEGIES FOR RISK ASSESSMENT FOR CHILDREN Introduction Problem formulation Hazard identification End-points and critical periods of exposure Human studies Relevance of animal studies for assessing potential hazards to children Reversibility and latency Characterization of the health-related database Dose response assessment Application of health outcome data 232

9 Contents Quantitative evaluation Tolerable daily intake (TDI) and reference dose (RfD)/reference concentration (RfC) approaches Benchmark dose (BMD)/benchmark concentration (BMC) approach Biologically based dose response models Duration adjustment Toxicokinetics Exposure assessment Age-specific exposures Assessment methods Risk characterization Summary and conclusions 244 REFERENCES 247 ANNEX 1: WORKING DEFINITIONS OF KEY TERMS 310 RESUME, CONCLUSIONS ET RECOMMANDATIONS 315 RESUMEN, CONCLUSIONES Y RECOMENDACIONES 323 ix

10 NOTE TO READERS OF THE CRITERIA MONOGRAPHS Every effort has been made to present information in the criteria monographs as accurately as possible without unduly delaying their publication. In the interest of all users of the Environmental Health Criteria monographs, readers are requested to communicate any errors that may have occurred to the Director of the International Programme on Chemical Safety, World Health Organization, Geneva, Switzerland, in order that they may be included in corrigenda. x