PRINCIPLES FOR EVALUATING CHEMICAL EFFECTS ON THE AGED

0,63

MB

POPULATION

117

stron

3686

ID

World Health Organization

2006

rok

CONTENTS

INTRODUCTION

1. SCOPE OF THE PROBLEM

1.1. Objectives

1.2. Definitions

1.2.1. Aging versus senescing

1.2.2. Aging of individuals and populations

1.2.3. Chemicals of concern

1.2.4. Time and dose of exposure

1.3. Chemical exposure

1.4. Aged population

1.4.1. Demographic consideration

1.4.2. Life expectancy

1.4.3. Life-style in aged populations

1.5. Theories of aging

2. STRUCTURAL AND PHYSIOLOGICAL CHANGES IN THE AGED

2.1. Changes in gene structure and function in aging

2.1.1. Chromatin structure

2.1.2. DNA repair

2.1.3. Transcription

2.1.4. Translation

2.2. Changes in tissues, organs and systems in aging

2.2.1. Nervous system

2.2.1.1 Structural changes

2.2.1.2 Biochemical changes

2.2.1.3 Functional changes

2.2.2. Sensory organs

2.2.2.1 Vision

2.2.2.2 Hearing

2.2.2.3 Olfaction

2.2.2.4 Taste

2.2.2.5 Somatic sensations

2.2.3. Endocrine system

2.2.3.1 The pituitary-thyroid axis and the basal metabolism

2.2.3.2 The pituitary-adrenal axis

2.2.3.3 The endocrine pancreas and carbohydrate metabolism

2.2.4. Reproductive system

2.2.4.1 Female aging

2.2.4.2 Male aging

2.2.5. Immune system

2.2.5.1 Aging of lymphoid organs

2.2.5.2 Aging of cellular constituents

2.2.5.3 Neuroendocrine-immune

2.2.6. Cardiovascular system

2.2.6.1 Heart

2.2.6.2 Blood vessels

2.2.6.3 Characteristics of atherosclerotic lesions

2.2.6.4 Theories of atherosclerosis

2.2.7. Respiratory function

2.2.7.1 Gas-exchange organs

2.2.7.2 Erythropoietic activity

2.2.8. Kidney and body fluid distribution

2.2.8.1 Renal function

2.2.8.2 Lower urinary tract

2.2.9. Gastrointestinal function

2.2.9.1 Gastrointestinal tract

2.2.9.2 Pancreas

2.2.9.3 Liver

2.2.10. Musculo-skeletal system

2.2.10.1 Bones

2.2.10.2 Joints

2.2.10.3 Skeletal muscles

2.2.11. Skin

3. BASIS OF ALTERED SENSITIVITY TO ENVIRONMENTAL CHEMICALS

3.1. Pharmacokinetics

3.1.1. Absorption

3.1.2. Distribution

3.1.3. Metabolism

3.1.4. Excretion

3.2. Pharmacodynamics

3.2.1. Central nervous system

3.2.2. Endocrine system

3.2.2.1 Changes in hormonal availability with age

3.2.2.2 Changes with age in the reception of the signal by the target cells

3.2.2.3 Changes in the nature of the hormonal message with age

3.2.3. Kidney

3.2.4. Immune system

3.2.5. Other tissues and systems

3.3. Modifying factors

3.3.1. Nutrition

3.3.2. Alcohol intake

3.3.3. Smoking

3.4. Interactions of chemicals and diseases

3.4.1. Cancer

3.4.2. Other diseases

4. APPROACHES TO EXAMINING THE EFFECTS OF CHEMICALS ON THE AGED POPULATION

4.1. Experimental approaches

4.1.1. Principles for testing chemicals in the aged population

4.1.2. Animal models

4.1.2.1 Animal species

4.1.2.2 Animal strain

4.1.2.3 Animal sex

4.1.2.4 Selection of age groups for comparison

4.1.2.5 Underlying pathology of animals of different ages

4.1.2.6 Transgenic animals

4.1.2.7 Animal husbandry

4.1.3. Chemical exposure

4.1.3.1 Dose level

4.1.3.2 Route of administration

4.1.3.3 Duration of exposure

4.1.4. Non-mammalian models

4.1.5. In vitro studies

4.1.6. Statistical considerations

4.1.7. Extrapolation of animal data to humans

4.2. Epidemiological and clinical approaches

4.2.1. Disease pattern of aged population

4.2.2. Assessment of effects of environmental chemicals in the elderly population

4.2.3. Acute episodes

4.2.4. Concerns for the aged population

4.3. Biomarkers of aging

5. CONCLUSIONS

6. FURTHER RESEARCH

REFERENCES

APPENDIX 1