| | PRINCIPLES FOR EVALUATING HEALTH RISKS IN CHILDREN |
| | 3,14 | | MB | ASSOCIATED WITH EXPOSURE TO CHEMICALS |
| | 302 | | stron |
| | 3669 | | ID | World Health Organization |
| | 2006 | | rok |
| | TABLE OF CONTENTS |
| | CHAPTER 1 – Executive Summary, Conclusions, and Recommendations |
| | 1.1 Introduction |
| | 1.2 Conclusions |
| | CHAPTER 2 – Introduction and Background |
| | 2.1 Introduction |
| | 2.2 Purpose and Scope of Document |
| | 2.3 Global Burden of Disease in Children |
| | 2.4 Major Environmental Threats to Children |
| | 2.4.1 Economic and nutritional factors |
| | 2.4.2 Social, cultural, demographic, and lifestyle factors |
| | 2.4.3 Chemical hazards |
| | 2.5 Intrinsic Factors |
| | 2.6 The Significance of a Developmental Stage Approach |
| | CHAPTER 3 – Unique Biological Characteristics of Children |
| | 3.1 Growth and Development |
| | 3.1.1 Body weight and height |
| | 3.1.2 Organ weights/volumes |
| | 3.1.3 Skin |
| | 3.2 Anatomical and Functional Characteristics |
| | 3.3 Physiological Characteristics |
| | 3.3.1 Breathing rate |
| | 3.3.2 Cardiac output |
| | 3.3.3 Blood flow to organs |
| | 3.3.4 Body composition |
| | 3.3.5 Tissue composition |
| | 3.3.6 Bone growth and composition |
| | 3.4 Metabolic Characteristics |
| | 3.5 Toxicokinetics |
| | 3.5.1 Absorption, distribution, metabolism and elimination |
| | 3.5.2 Physiological changes in mother and their influences on toxicokinetics |
| | 3.5.3 Dose to target |
| | 3.6 Normal Development |
| | 3.6.1 Basic principles of normal development |
| | 3.6.2 Nervous system |
| | 3.6.3 Reproductive system |
| | 3.6.4 Endocrine system |
| | 3.6.5 Cardiovascular system |
| | 3.6.6 Immune system |
| | 3.6.7 Respiratory system |
| | 3.6.8 Kidney |
| | 3.7 Conclusions |
| | CHAPTER 4 – Developmental Stage Specific Susceptibilities and Outcomes in Children |
| | 4.1 Introduction |
| | 4.2 Mortality, Growth Restriction, and Birth Defects |
| | 4.2.1 Mortality |
| | 4.2.2 Growth restriction |
| | 4.2.3 Birth defects (structural malformations) |
| | 4.2.3.1 Etiology |
| | 4.2.3.2 Functional developmental toxicity |
| | 4.3 Specific Organ Systems |
| | 4.3.1 Nervous system |
| | 4.3.1.1 Periods of vulnerability and consequences of exposure |
| | 4.3.1.2 Specific Examples |
| | 4.3.2 Reproductive system |
| | 4.3.2.1 Periods of vulnerability |
| | 4.3.2.2 Consequences of exposure to chemicals |
| | 4.3.3 Endocrine and metabolic disorders |
| | 4.3.3.1 Periods of vulnerability |
| | 4.3.3.2 Consequences of exposures |
| | 4.3.4 Cardiovascular system |
| | 4.3.5 Immune system |
| | 4.3.5.1 Periods of vulnerability |
| | 4.3.5.2 Consequences of early exposure |
| | 4.3.6 Normal development respiratory system |
| | 4.3.6.1 Periods of vulnerability |
| | 4.3.6.2 Consequences of exposures |
| | 4.3.7 Kidney |
| | 4.3.7.1 Periods of vulnerability |
| | 4.3.7.2 Consequences of exposure |
| | 4.4 Cancer |
| | 4.4.1 Childhood cancers that may have environmental causes |
| | 4.4.2 Adult cancers related to childhood exposures |
| | 4.4.3 Chemical exposures of special concern |
| | 4.5 Conclusions |
| | CHAPTER 5 – Exposure Assessment of Children |
| | 5.1 Introduction |
| | 5.2 General Principles of Exposure Assessments |
| | 5.3 Methods for Conducting Exposure Assessments |
| | 5.3.1 Direct methods |
| | 5.3.2 Biomarkers of exposure |
| | 5.3.3 Modeling |
| | 5.4 Unique Characteristics of Children that Affect Exposure |
| | 5.5 Exposure as It Relates to Children Around the World |
| | 5.5.1 Sources/geographical location |
| | 5.5.2 Pathways of exposure |
| | 5.5.2.1 Ambient air exposure pathway |
| | 5.5.2.2 Indoor exposure pathways |
| | 5.5.2.3 Water exposure pathway |
| | 5.5.2.4 Soil exposure pathway |
| | 5.5.2.5 Food-chain exposure pathway |
| | 5.5.2.6 Human exposure pathways |
| | 5.5.3 Settings/microenvironments |
| | 5.5.3.1 Residential |
| | 5.5.3.2 School |
| | 5.5.3.3 Child care centers |
| | 5.5.3.4 Recreational |
| | 5.5.3.5 Special settings |
| | 5.5.4 Environmental equity factors (vulnerable communities) |
| | 5.6 Special Considerations for Children’s Exposure: Case Studies |
| | 5.6.1 Influence of activities |
| | 5.6.2 Environmental equity |
| | 5.6.3 Aggregate exposure |
| | 5.6.4 Cumulative exposure |
| | 5.7 Conclusions |
| | CHAPTER 6 – Methodologies to Assess Health Outcomes in Children |
| | 6.1 Introduction |
| | 6.1.1 Methodologic approaches for children’s health |
| | 6.1.2 Methodologic approaches for animal studies |
| | 6.2 Growth and Development |
| | 6.2.1 Human studies |
| | 6.2.2 Animal studies |
| | 6.3 Reproductive Development and Function |
| | 6.3.1 Human studies |
| | 6.3.2 Animal studies |
| | 6.4 Neurological and Behavioral Effects |
| | 6.4.1 Human studies |
| | 6.4.2 Animal studies |
| | 6.5 Cancer |
| | 6.5.1 Human studies |
| | 6.5.2 Animal studies |
| | 6.6 Immune |
| | 6.6.1 Human studies |
| | 6.6.2 Animal studies |
| | 6.7 Respiratory |
| | 6.7.1 Human studies |
| | 6.7.2 Animal studies |
| | 6.8 Hemopoeitic/Cardiovascular, Hepatic/Renal, Skin/Musculoskeletal, Metabolic/Endocrine |
| | 6.8.1 Human studies |
| | 6.8.2 Animal studies |
| | 6.9 Conclusions |
| | CHAPTER 7 – Implications and Strategies for Risk Assessment for Children |
| | 7.1 Introduction |
| | 7.2 Problem Formulation |
| | 7.3 Hazard Identification |
| | 7.3.1 Endpoints and critical periods of exposure |
| | 7.3.2 Human studies |
| | 7.3.3 Relevance of animal studies for assessing potential hazards to children |
| | 7.3.4 Reversibility and latency |
| | 7.3.5 Characterization of the health related data base |
| | 7.4 Dose Response Assessment |
| | 7.4.1 Application of health outcome data |
| | 7.4.2 Quantitative evaluation |
| | 7.4.2.1 Tolerable daily intake (TDI) and reference dose (RfD/reference concentration (RfC) |
| | approaches |
| | 7.4.2.2 Benchmark dose (BMD) – benchmark concentration (BMC) approach |