Principles for Evaluating Health Risks in Children Associated With Exposure to Chemicals (Environmental Health Criteria) (Environmental Health Criteria)

This new volume in the Environmental Health Criteria (EHC) Series provides a systematic analysis of the scientific principles to be considered in assessing health risks in children; taking into account their unique susceptibilities. The terms children and child as used in this report include the stages of development from conception through adolescence. This new EHC builds on previous volumes addressing methodologies for assessing risks in children: EHC 30, Principles for Evaluating Health Risks to Progeny Associated with Exposure to Chemicals During Pregnancy (WHO, 1984) and EHC 59, Principles for Evaluating Health Risks from Chemicals During Infancy and Early Childhood: The Need for a Special Approach (WHO, 1986). The central focus of this volume is on the child (developing embryo, fetus, infant, etc.) rather than on a specific environmental agent, target organ, or disease. Thus, it addresses the difficult task of integrating all what is known about both exposure information, toxicity data, and health outcome at different life stages, which is especially challenging when data are limited for particular life stages (e.g., during pregnancy). The book will be useful to public health officials, research and regulatory scientists, and risk assessors. TITLE......Page 1 COPYRIGHT......Page 2 CONTENTS......Page 3 NOTE TO READERS OF THE CRITERIA MONOGRAPHS......Page 10 PREAMBLE......Page 11 WHO TASK GROUP ON ENVIRONMENTAL HEALTH CRITERIA ON PRINCIPLES FOR EVALUATING HEALTH RISKS IN CHILDREN ASSOCIATED WITH EXPOSURE TO CHEMICALS......Page 15 PREFACE......Page 17 ACRONYMS AND ABBREVIATIONS......Page 19 1.1 Summary......Page 23 1.2 Conclusions and recommendations......Page 26 2.1 Introduction......Page 29 2.2 Purpose and scope of document......Page 31 2.3 Global burden of disease in children......Page 34 2.4 Major environmental threats to children......Page 36 2.4.1 Economic and nutritional factors......Page 37 2.4.2 Social, cultural, demographic, and lifestyle factors......Page 38 2.4.3 Chemical hazards......Page 39 2.5 Intrinsic factors......Page 41 2.6 The significance of a developmental stage approach......Page 42 2.7 Summary and conclusions......Page 43 3.1.1 Body weight and height......Page 44 3.1.2 Organ weights/volumes......Page 45 3.2 Anatomical and functional characteristics......Page 47 3.3.2 Cardiac output......Page 48 3.3.3 Blood flow to organs......Page 49 3.3.4 Body composition......Page 50 3.4 Metabolic characteristics......Page 51 3.5.1 Absorption, distribution, metabolism, and elimination......Page 53 3.5.2.1 Pregnancy......Page 55 3.5.2.2 Lactation and breast milk......Page 57 3.5.3 Dose to target......Page 58 3.6.1 Basic principles of normal development......Page 61 3.6.2 Nervous system......Page 62 3.6.3 Reproductive system......Page 64 3.6.4.1 Hypothalamic–pituitary axis......Page 66 3.6.4.2 Thyroid gland......Page 68 3.6.4.3 Adrenal glands......Page 69 3.6.4.6 Pancreas......Page 70 3.6.6 Immune system......Page 71 3.6.7 Respiratory system......Page 72 3.6.8 Kidney......Page 74 3.7 Summary and conclusions......Page 75 4.1 Introduction......Page 77 4.2.1 Mortality......Page 82 4.2.2 Growth restriction......Page 85 4.2.3 Birth defects (structural malformations)......Page 86 4.2.3.1 Etiology......Page 88 4.2.3.2 Functional developmental toxicity......Page 89 4.3.1 Nervous system......Page 90 4.3.1.1 Periods of susceptibility and consequences of exposures......Page 91 4.3.1.2 Specific examples......Page 94 4.3.2 Reproductive system......Page 100 4.3.2.1 Periods of susceptibility......Page 101 4.3.2.2 Consequences of exposures......Page 102 4.3.3.1 Periods of susceptibility......Page 107 4.3.3.2 Consequences of exposures......Page 114 4.3.4 Cardiovascular system......Page 117 4.3.4.2 Consequences of exposures......Page 118 4.3.5 Immune system......Page 119 4.3.5.1 Periods of susceptibility......Page 120 4.3.5.2 Consequences of exposures......Page 123 4.3.6.1 Periods of susceptibility......Page 127 4.3.6.2 Consequences of exposures......Page 128 4.3.7.1 Periods of susceptibility......Page 135 4.3.7.2 Consequences of exposures......Page 136 4.4 Cancer......Page 137 4.4.1.1 Lymphoid tissues......Page 138 4.4.1.3 Thyroid......Page 140 4.4.1.5 Other organ sites......Page 141 4.4.2.1 Brain and nervous system......Page 142 4.4.2.2 Thyroid......Page 143 4.4.2.5 Integument......Page 144 4.4.3 Chemical exposures of special concern......Page 145 4.5 Summary and conclusions......Page 148 5.2 General principles of exposure assessments......Page 151 5.3.1 Direct methods......Page 155 5.3.2 Biomarkers of exposure......Page 158 5.3.3 Modelling......Page 159 5.4 Unique characteristics of children that affect exposure......Page 161 5.5.1 Sources/geographical location......Page 166 5.5.2.1 Ambient air exposure pathway......Page 167 5.5.2.2 Indoor exposure pathways......Page 172 5.5.2.3 Water exposure pathway......Page 174 5.5.2.4 Soil exposure pathway......Page 175 5.5.2.5 Food-chain exposure pathway......Page 176 5.5.2.6 Human to human exposure pathways......Page 177 5.5.3 Settings/microenvironments......Page 178 5.5.3.3 Child-care centres......Page 179 5.5.3.4 Recreational......Page 180 5.5.3.5 Special settings......Page 181 5.5.4 Environmental equity factors (vulnerable communities)......Page 183 5.6.1.3 Environmental tobacco smoke (ETS)......Page 184 5.6.2 Hazardous waste sites......Page 185 5.6.3.1 Chlorpyrifos......Page 186 5.6.4 Cumulative exposure......Page 187 5.7 Summary and conclusions......Page 188 6.1.1 Methodological approaches for children’s health studies......Page 190 6.1.1.2 Comparison of study designs......Page 193 6.1.1.3 Descriptive designs......Page 198 6.1.1.4 Analytic designs......Page 200 6.1.1.5 Unique methodological considerations......Page 202 6.1.2 Methodological approaches for animal studies......Page 203 6.1.2.1 Developmental stage susceptibility, dosing periods, and assessment of effects......Page 206 6.2.1 Human studies......Page 212 6.2.1.1 Puberty......Page 216 6.2.2.1 Body weight and postnatal growth......Page 217 6.2.2.3 Physical and functional developmental landmarks......Page 218 6.3.1 Human studies......Page 220 6.3.2.1 Malformations of reproductive organs......Page 224 6.3.2.2 Anogenital distance......Page 225 6.3.2.5 Fertility......Page 226 6.3.2.6 Histopathology of reproductive organs......Page 228 6.4.1 Human studies......Page 229 6.4.2.1 Motor activity......Page 230 6.4.2.3 Learning and memory......Page 231 6.4.2.4 Evaluation of effects......Page 232 6.5.1 Human studies......Page 233 6.6.1 Human studies......Page 234 6.7.2 Animal studies......Page 235 6.9 Summary and conclusions......Page 236 7.1 Introduction......Page 239 7.2 Problem formulation......Page 242 7.3 Hazard identification......Page 243 7.3.1 End-points and critical periods of exposure......Page 245 7.3.2 Human studies......Page 246 7.3.3 Relevance of animal studies for assessing potential hazards to children......Page 247 7.3.4 Reversibility and latency......Page 251 7.4 Dose–response assessment......Page 252 7.4.1 Application of health outcome data......Page 254 7.4.2.1 Tolerable daily intake (TDI) and reference dose (RfD)/reference concentration (RfC) approaches......Page 255 7.4.2.3 Biologically based dose–response models......Page 258 7.4.2.5 Toxicokinetics......Page 259 7.5.1 Age-specific exposures......Page 260 7.5.2 Assessment methods......Page 262 7.6 Risk characterization......Page 264 7.7 Summary and conclusions......Page 266 REFERENCES......Page 269 ANNEX 1: WORKING DEFINITIONS OF KEY TERMS......Page 332 RESUME, CONCLUSIONS ET RECOMMANDATIONS......Page 337 RESUMEN, CONCLUSIONES Y RECOMENDACIONES......Page 345 Conclusions, and recommendations -- Introduction and background -- Unique biological characteristics of children -- Developmental stage-specific susceptibilities and outcomes in children -- Exposure assessment of children -- Methodologies to assess health outcomes in children -- Implications and strategies for risk assessment for children