| | A Model for Establishing Upper Levels of Intake for Nutrients |
| | 2,93 | | MB | and Related Substances |
| | 257 | | stron |
| | 3674 | | ID | World Health Organization |
| | 2006 | | rok |
| | Contents |
| | Acronyms and abbreviations ix |
| | Key terms x |
| | Acknowledgements xi |
| | Preface xi |
| | Executive summary xii |
| | 1. INTRODUCTION 1 |
| | 1.1 Reasons for the Workshop 1 |
| | 1.2 Organization of the Workshop 3 |
| | 1.2.1 Preparation 3 |
| | 1.2.2 Identification of scientific experts 3 |
| | 1.2.3 Conduct of the Workshop 4 |
| | 1.3 Charge to the Workshop 4 |
| | 2. BACKGROUND 5 |
| | 2.1 Classic non-nutrient risk assessment 5 |
| | 2.2 National/regional reports on nutrient risk assessment 8 |
| | 2.2.1 Terms of reference (problem statements) for the three national/regional reports 9 |
| | 2.2.2 Nutrient hazard identification and characterization 9 |
| | 2.2.3 Nutrient exposure/intake assessment 10 |
| | 2.2.4 Nutrient risk characterization 11 |
| | 2.3 Application of nutrient risk assessment outcomes 11 |
| | 2.3.1 Nutrient risk management decisions about the need to take action 11 |
| | 2.3.2 Nutrient risk management decisions about interventions or regulatory options 12 |
| | 2.3.3 Other applications 14 |
| | 2.3.4 Role of problem formulation 14 |
| | 2.4 Summary 14 |
| | 3. CONSIDERATIONS FOR NUTRIENT RISK ASSESSMENT 15 |
| | 3.1 An international approach 15 |
| | 3.1.1 Global application 15 |
| | 3.1.2 Inadequately nourished and ‘diseased’ populations 16 |
| | 3.2 Terminology 16 |
| | 3.2.1 Adverse health effects 17 |
| | 3.2.2 Hazard 17 |
| | 3.2.3 Habitual intake 18 |
| | 3.2.4 Upper level of intake 19 |
| | 3.2.5 Other terminology 19 |
| | 3.3 Homeostatic mechanisms for nutrient substances 20 |
| | 3.4 Adverse health effects and biomarkers of effect 21 |
| | 3.4.1 Adverse health effects 21 |
| | 3.4.2 Biomarkers of effect 23 |
| | 3.5 Summary 25 |
| | 4. NUTRIENT HAZARD IDENTIFICATION AND CHARACTERIZATION 26 |
| | 4.1 Data search and evaluation for hazard identification and characterization: an iterative process |
| | 26 |
| | 4.1.1 Nature of approach 26 |
| | 4.1.2 Evidence-based systematic review 27 |
| | 4.1.3 Summary of approach to data search and evaluation 29 |
| | 4.2 Step 1: identifying adverse health effects associated with intake 29 |
| | 4.2.1 Combining data to link intakes and adverse health effects 29 |
| | 4.2.2 Identification and selection of data 32 |
| | 4.2.3 Initial review of data 33 |
| | 4.2.4 Summarizing and presenting results 36 |
| | 4.3 Step 2: selecting the critical adverse health effect 37 |
| | 4.4 Step 3: quantifying the upper level 39 |
| | 4.4.1 Intake–response assessment 40 |
| | 4.4.2 Specification of the NOAEL, LOAEL, or BI 41 |
| | 4.4.3 Dealing with uncertainties and setting the upper level 43 |
| | 4.4.4 Adjustment of upper level of intake for unstudied age/sex/lifestage subpopulations 46 |
| | 4.4.5 Summary: setting an upper level of intake 47 |
| | 4.5 Step 4: characterizing the hazard and identifying vulnerable subgroups 47 |
| | 4.6 Summary 48 |
| | 5. DIETARY INTAKE ASSESSMENT 49 |
| | 5.1 Overview: definitions, principles, and harmonization 49 |
| | 5.1.1 Definitions 49 |
| | 5.1.2 Objectives and key principles for dietary intake assessment 49 |
| | 5.1.3 Harmonization of methods for dietary intake assessment 50 |
| | 5.2 Step 1: specifying the type of dietary intake assessment 52 |
| | 5.2.1 Specification of intake of interest 52 |
| | 5.2.2 Specification of time frame of interest 52 |
| | 5.3 Step 2: use of composition data 53 |
| | 5.3.1 Sources of data 53 |
| | 5.3.2 Modifying and adjusting composition data 55 |
| | 5.4 Step 3: use of consumption data 56 |
| | 5.4.1 Data on individuals 57 |
| | 5.4.2 Aggregated availability data and marketing/sales data 57 |
| | 5.4.3 Combining consumption data to estimate intake from all sources 59 |
| | 5.4.4 Strategies to obtain additional consumption data 62 |
| | 5.5 Step 4: methods for estimation of intake 63 |
| | 5.5.1 Intake estimation using data on individuals 63 |
| | 5.5.2 Intake estimation using other types of data 65 |
| | 5.6 Uncertainties associated with assessments 68 |
| | 5.6.1 Composition data 69 |
| | 5.6.2 Consumption data 69 |
| | 5.6.3 Analytical methods and corrections 70 |
| | 5.7 Reporting the dietary intake assessment 70 |
| | 5.8 Summary 71 |
| | 6. NUTRIENT RISK CHARACTERIZATION 72 |
| | 6.1 Overview 72 |
| | 6.2 Examples of nutrient risk assessment 72 |
| | 6.3 Components of nutrient risk characterization 73 |
| | 6.3.1 Basic components 73 |
| | 6.3.2 Considerations to foster an improved interface between assessor and manager 75 |
| | 6.4 Summary 76 |
| | 7. THE MODEL FOR NUTRIENT RISK ASSESSMENT 77 |
| | 7.1 The general model 77 |
| | 7.2 Key questions and activities associated with the model 78 |
| | 7.3 Implications of a data-driven model 80 |
| | 7.4 Summary 82 |
| | 8. APPLICABILITY OF THE MODEL TO THE RANGE OF NUTRIENT SUBSTANCES 83 |
| | 8.1 General applicability and ‘test nutrients’ 83 |
| | 8.2 Special applications 84 |
| | 8.2.1 Nutrient substances with no identified adverse health effects: highest observed intake values |
| | 84 |
| | 8.2.2 Inherent macronutrient substances with no known intake levels without risk 85 |
| | 8.2.3 Apparent overlap between level of intake associated with risk and ‘health benefit’ 85 |
| | 8.3 Summary 86 |
| | 9. APPLICABILITY OF THE MODEL TO INADEQUATELY NOURISHED (SUB)POPULATIONS 87 |
| | 9.1 Overview 87 |
| | 9.2 Homeostatic considerations 88 |
| | 9.3 Establishing upper levels for inadequately nourished (sub)populations 89 |
| | 9.4 Impact of infectious disease 89 |
| | 9.5 Summary 90 |
| | 10. IDENTIFIED RESEARCH/DATA GAPS, NEEDED DISCUSSIONS, AND |
| | NEXT STEPS 91 |
| | 10.1 Nutrient hazard identification and characterization 91 |
| | 10.1.1 General metabolism of nutrient substances 91 |
| | 10.1.2 Nature of adverse health effects, including biomarkers of effect 92 |
| | 10.1.3 Data evaluation and uncertainties 92 |
| | 10.2 Dietary intake assessment 93 |
| | 10.3 Risk characterization 94 |
| | 10.4 Applicability of the model 94 |
| | 10.5 Next steps 95 |
| | 11. REFERENCES 96 |
| | ANNEXES 101 |
| | A Model for Establishing Upper Levels of Intake for Nutrients and Related Substances |
| | List of annexes |
| | Annex 1 List of Workshop participants 101 |
| | Annex 2 Discussion paper 1: An evidence-based approach to nutrient hazard identification 102 |
| | Annex 3 Discussion paper 2: Uncertainty and adjustment 123 |
| | Annex 4 Discussion paper 3: Estimating the distribution of usual nutrient exposures in populations |
| | 157 |
| | Annex 5 Discussion paper 4: Nutrient risk characterization: key considerations 177 |
| | Annex 6 Key elements of hazard identification/hazard characterization for vitamin A, summarized |
| | from reports by three national/regional authorities 192 |
| | Annex 7 Comparison of approaches to considering adverse health effects in setting upper levels, |
| | summarized from reports by three national/regional authorities 198 |
| | Annex 8 Comparison of scientific review of data on vitamin A and bone density, summarized from |
| | reports by three national/regional authorities 204 |
| | Annex 9 Comparison of national/regional nutrient intake assessments, summarized from reports by |
| | three national/regional authorities 214 |
| | Annex 10 Comparison of selected risk characterization information, summarized from reports by |
| | three national/regional authorities 236 |