Table of Contents

Preface

Foreword: Outlook

List of Contributors

List of Reviewers

Chapter 1

Introduction—General Considerations and International Perspectives   Gunnar F. Nordberg, Bruce A. Fowler, Monica Nordberg, and Lars T. Friberg

1

Metals and Health—An International Perspective

2

Current Concerns Related to the Toxicology of Metals

2.1

Expanding Current Industrial New Technological Uses of Metals

2.2

Ecological and Natural Environmental Mobilization Processes

2.3

Routes of Exposure

2.4

Essentiality of Metals

2.5

Human Health Effects

2.6

Metal Carcinogenesis and Reproductive Toxicology

2.7

Toxicokinetics and Metabolism

2.8

Biological Monitoring

2.9

Risk Assessment

2.10

Interactions Among Metals

Chapter 2

General Chemistry Sampling Analytical Methods and Speciation   Rita cornelis and Monica Nordberg

1

Definition of Metals

2

The Periodic Table

3

Compounds of Metallic Elements

3.1

Covalent and Ionic Bonds

3.2

Oxidation Number

3.3

Inorganic Compounds

3.4

Metal Complexes

3.5

Organometallic Compounds

4

Solubility

5

Properties of Metal Irons

5.1

Formation of Metal Irons

5.2

Redox Potential

5.3

Metal Irons as Lewis Acids

5.4

Hydrolysis

6

Other Aspects of Metal Chemistry of Biological and Toxicological Interest

6.1

Main Group and Transition Metals

6.2

Metal-Containing Biological Molecules

6.2.1

Metalloporphyrins

6.2.2

Non-Heme Iron Proteins

6.2.3

Cobalt-Containing Biological Molecules

6.2.4

Metalloenzymes and Metal-Activated Enzymes

6.2.5

Metallothioneins

6.2.6

Lead-Containing Biological MolecuIes

7

Total Element Analysis, Elemental Speciation, and Metallomics

8

Sampling and Sample Preparation

8.1

General Considerations

8.2

Air Water and Food

8.2.1

Air

8.2.2

Water

8.2.3

Food

8.3

Biological Monitoring

9

Separation Techniques

9.1

Liquid Chromatography

9.2

Gas Chromatography

9.3

Capillary Electrophoresis

9.4

Gel Electrophoresis

9.5

Precautionary Measures in Elemental Speciation

10

Detection Methods

10.1

General Aspects

10.2

Current Methods for the Detection of Metals

10.2.1

Atomic Absorption Spectrometry

10.2.2

Atomic Fluorescence Spectrometry

10.2.3

Atomic Emission Spectrometry

10.2.4

Mass Spectrometry

10.2.5

Electrochemical Methods

10.2.6

Spectrophotometry

10.2.7

Biosensors for Monitoring Metal Irons

10.2.8

Direct Measurement of Metals in Solid Samples (Particle Characterization)

10.2.9

Neutron Activation Analysis

10.2.10

Spark Source Mass Spectrometry

11

Calibration

12

Reference Materials

13

Quality Assurance

13.1

Definitions

13.2

Sources of Error

13.3

Results of Interlaboratory Testing

13.4

Elements of Quality Assurance

13.5

Statistical Considerations

13.6

Reporting of Quality Assurance Data

14

Conclusions

Chapter 3

Routes of Exposure, Dose, and Metabolism of Metals   William S. Beckett Gunnar F Nordberg and Thomas W. Clarkson

1

Introduction

2

Exposure

2.1

General Aspects

2.2

Exposure by Inhalation

2.3

Exposure Through Food and Drinking Water

3

Deposition and Absorption

3.1

Deposition and Absorption After Inhalation

3.1.1

Absorption of Gases and Vapors

3.1.2

Deposition of Particles

3.1.3

Clearance of Particles from the Respiratory System

3.2

Absorption After Ingestion

3.4

Total Absorption

4

Transport, Biotransformation, and Distribution

5

Pathways and Mechanisms of Excretion

5.1

Gastrointestinal Excretion

5.2

Renal Excretion

5.3

Excretion Rate—Biological Half-Time

6

Toxicokinetic Models and Their Use for Establishment of Dose-Response and Dose-Effect Relationships

6.1

One-Compartment Model

6.1.1

Description

6.1.2

Use of One-Compartment Model for Toxicokinetic (TK)-Toxicodynamic (TD) Modeling of Dose-Response or Dose-Effect Relationships

6.2

Multicompartment Models and Physiologically Based Models

6.2.1

Description of a Multicompartment Model for Cadmium

6.2.2

Use of Multicompartment and Physiologically Based Models for TK/TD Modeling

7

Use of Indicator Media for Estimation of Exposure or Critical Organ Concentration

Chapter 4

Biological Monitoring and Biomarkers   Antero Aitio Alfred Bernard Bruce A. Fowler and Gunnar F. Nordberg

1

Introduction

2

Sources of Preanalytical and Analytical Error

3

Quality Assurance Reference Materials

4

Specimens in Use; Urine Sample Standardization

4.1

Urine

4.2

Blood

5

Reference Values

6

Ethical Considerations

7

Biomarkers of Exposure

7.1

Analytical Approaches

7.2

Speciation in Biomonitoring

7.3

Kinetics and Sampling: Timing and Frequency

7.4

Interpretation of Results

7.5

Biomarkers of Exposure as a Complement to Industrial Hygiene Measurements

8

Biomarkers of Effects

8.1

Renal Toxicity Biomarkers

8.2

Neurotoxicity Biomarkers

8.3

Lung Toxicity Biomarkers

8.4

Biomarkers for Other Target Organs

8.5

Genotoxicity Biomarkers

9

Future Trends

Chapter 5

Selected Molecular Mechanisms of Metal Toxicity and Carcinogenicity   Todd Davidson Qingdong Ke and Max Costa

1

Transport of Toxic Metals by Molecular/Ionic Mimicry of Essential Compounds

1.1

Introduction

1.2

Iron

1.3

Zinc

1.4

Phosphate and Sulfate Mimics

1.5

Organic Complexes

1.6

Metal-Anion Complexes

1.7

Calcium Channels

1.8

Summary

2

Interference with the Functions of Essential Metals by Toxic Metals

2.1

Introduction

2.2

Calcium

2.3

Zinc

2.4

Magnesium

2.5

Iron

2.6

Copper

3

Toxic Metal-Binding Molecules

3.1

Introduction

3.2

Metallothioneins (MTs)

3.3

Glutathione

3.4

Summary

4

Mutagenic and Genotoxic Effects of Metals

4.1

Introduction

4.2

Mutagenicity and Genotoxicity of Nickel Compounds

4.3

Mutagenicity and Genotoxicity of Chromium Compounds

4.4

Mutagenicity and Genotoxicity of Arsenic

4.5

Mutagenicity and Genotoxicity of Cadmium

5

Epigenetic Effects of Metal Compounds

5.1

Introduction

5.2

Epigenetic Events in the Development of Cancer

5.2.1

DNA Methylation

5.2.2

Histone Modifications

5.3

Impacts of Metal Compounds on Epigenetics

5.3.1

As

5.3.2

Cd

5.3.3

Ni

6

Effects of Metals on Cell Signaling Pathways and Gene Expression

6.1

Introduction

6.2

Signal Transduction Pathways Affected by Metal Compounds

6.2.1

ROS

6.2.2

MAPK

6.2.3

PI3K/Akt

6.2.4

HIF-1

6.2.5

NF-kB

6.2.6

NFAT

6.2.7

AP-1

6.3

Impacts of Metal Compounds on Signal Transduction Pathways and Gene Expression

6.3.1

As

6.3.2

Cd

6.3.3

Cr

6.3.4

Co

6.3.5

Ni

6.3.6

Other Metals

Chapter 6

General Considerations of Dose-Effect and Dose-Response Relationships   Daphne B. Moffett Hisham A. El-Masri and Bruce A. Fowler

1

General Aspects of Dose-Response Relationships

1.1

Use of the Terms Effect and Response

1.2

Interrelationships Among Dose, Effect, and Response

1.3

Definitions of Dose and Response

2

Modeling of Dose-Response Relationships

2.1

The Shape of Dose-Response Curves: S, Hormesis, U-Shaped

2.2

The Sigmoid Curve

2.3

Hormesis—Inverted U- or J-Shaped Curves

2.4

U-Shaped Curves and Essentiality

3

Modeling the Data

3.1

Biological Basis for Modeling

4

Species-to-Species Extrapolations

5

Risk Assessment and Dose-Response Relationships

5.1

NOAEL/LOAEL

5.2

Benchmark Dose

5.3

Data Types and Benchmark Dose

6

Dose-Response in an Era of -Omics

Chapter 7

Interactions in Metal Toxicology   Gunnar F. Nordberg, Lars Gerhardsson, Karin Broberg Moiz Mumtaz Patricia Ruiz and Bruce A. Fowler

1

Introduction

2

Age, Sex, Drugs, and Some Other Factors

2.1

Influence of Drugs, Alcohol, and Tobacco on Metal Metabolism and Toxicity

2.1.1

Drugs

2.1.2

Alcohol and Tobacco

2.2

Influence of Age and Sex on Metal Toxicity

2.2.1

Age

2.2.2

Sex

2.3

Influence of Some Other Factors on Metal Metabolism and Toxicity

3

Gene–Environment Interactions for Metals

3.1

Genes of Concern

3.2

Design of Gene–Environment Interaction Studies

3.3

Interactions for Specific Metals

3.3.1

Arsenic

3.3.2

Beryllium and Cobalt

3.3.3

Cadmium

3.3.4

Lead

3.3.5

Mercury

3.3.6

Nickel

3.3.7

Platinum

3.4

Conclusions

4

Metal-Metal Interactions (Noncarcinogenic Effects)

4.1

Arsenic and Other Metals

4.2

Interactions Between Cadmium and Other Metals

4.3

Interactions Between Lead and Other Metals

4.4

Hg and Other Metals

4.5

Molybdenum-Copper-Zinc Interactions

4.6

Interactions Between Thallium and Potassium

5

Metal-Metal Interactions in Carcinogenesis

5.1

Arsenic

5.2

Chromium

5.3

Iron

5.4

Lead

5.5

Nickel

5.6

Selenium

5.7

Zinc

6

Risk Assessment of Mixtures of Metals

6.1

Introduction

6.2

Toxicity Assessment of Mixtures

6.2.1

The Mixture of Concern

6.2.2

The Similar Mixture Approach

6.2.3

The Hazard Index Approach

6.2.4

The Target-Organ Toxicity Dose(TTD)

6.3

A Weight-of-Evidence (WOE) Method

6.3.1

Direction of Interaction

6.3.2

Mechanistic Understanding

6.3.3

Toxicological Significance

6.4

Perspectives and Future Needs

Chapter 8

Epidemiological Methods for Assessing Dose-Response and Dose-Effect Relationships   Tord Kjellstrom and Philippe Grandjean

1

Epidemiological Measurement of Occurrence of Health Effects

2

Observational Studies and Modeling Studies of Dose-Response Relationships

3

Study Design

4

Data Collection

4.1

Measurement of Dose

4.2

Measurement of Effect and Response

5

Data Analysis

6

Inference

Chapter 9

Essential Metals: Assessing Risks from Deficiency and Toxicity   George C. Becking, Monica Nordberg, and Gunnar F. Nordberg

1

Introduction

2

Basic Concepts

2.1

Definition of an AROI (Acceptable Range of Oral Intake)

2.1.1

Groups with Special Sensitivity/Resistance

2.2

Other Concepts Used in Risk Assessment of Essential Metals

2.2.1

Toxicological Terms

2.2.2

Nutritional Terms: Definitions and Approaches Used to Assess Individual and Population Requirements for Ems

3

Effects of Deficiency and Toxicity

3.1

Factors Affecting Dose-Response Relationships

3.1.1

Homeostatic Mechanisms

3.1.2

Bioavailability, Speciation, and Interactions

3.2

Basic Principles for Classifying Effect

3.3

Examples of Effects of Varying Severity

3.3.1

Lethal Deficiency

3.3.2

Deficiency—Clinical Disease

3.3.3

Subclinical Biomarkers of Deficiency with or without Clinical Significance

3.3.4

Lethal Toxic Effects

3.3.5

Toxic Effects with Clinical Significance

3.3.6

Subclinical Toxic Effects with or without Functional Significance— Biomarkers of Critical Effect

4

Summary of Principles for Human Risk Assessment of Exposures to EMs

4.1

Application of Principles for Determination of AROI

5

Estimation of AROI

6

Conclusions

Chapter 10

Carcinogenicity of Metal Compounds   Qingdong Ke, Max Costa, and George Kazantzis

1

Principal Metals Showing Carcinogenic Effects

1.1

Nickel

1.1.1

Epidemiological Observations

1.1.2

Animal Models

1.1.3

Evaluation

1.2

Chromium

1.2.1

Epidemiological Observations

1.2.2

Animal Models

1.2.3

Short-Term Tests

1.2.4

Evaluation

1.3

Arsenic

1.3.1

Epidemiological Observations

1.3.2

Animal Models

1.3.3

Short-Term Tests

1.3.4

Evaluation

1.4

Cadmium

1.4.1

Epidemiological Observations

1.4.2

Animal Models

1.4.3

Short-Term Tests

1.4.4

Evaluation

1.5

Beryllium

1.5.1

Epidemiology Observations

1.5.2

Animal Models

1.5.3

Evaluation

1.6

Lead

1.6.1

Epidemiological Observations

1.6.2

Animal Models and Short-Term Tests

1.6.3

Evaluation

1.7

Cobalt

1.8

Iron

1.9

Manganese

1.10

Platinum

1.11

Titanium

2

Principal Metals Showing Mutagenic Effects

2.1

Nickel

2.2

Chromium

2.3

Arsenic

2.4

Cadmium

Chapter 11

Immunotoxicology of Metals   Per Hultman

1

Introduction

1.1

Development of the Concept Metal Lmmunotoxicology

1.2

Overview of Mechanisms in Immunotoxicology

1.3

Dose-Response Considerations in Metal Immunotoxicology

2

Immunosuppression Induced by Metals

2.1

General Considerations

2.2

In Vitro Studies

2.3

In Vivo Studies

2.4

Experimental Host-Resistance Challenge Systems

2.5

Clinical Immunosuppressive Effects

3

Essential Metals and the Immune System

4

Hypersensitivity Induced by Metals

4.1

General Considerations

4.2

Type I Hypersensitivity (Anaphylacticor Immediate Hypersensitivity)

4.3

Type II Hypersensitivity (Antibody-Mediated—IgG or IgM—Reactions Against Cells or Matrix)

4.4

Type III Hypersensitivity (Immune-Complex Mediated Reactions)

4.5

Type IV Hypersensitivity (Cell-Mediated Reactions)

4.6

Relation Between Atopy and Metal Hypersensitivity

5

Metals Causing Hypersensitivity Reactions

5.1

Beryllium

5.2

Chromium

5.3

Cobalt

5.4

Gold

5.5

Mercury

5.6

Nickel

5.7

Multiple Metal Exposure Relatedto Prosthetic Devices

5.8

The Platinum Group of Elements (Palladium, Platinum, Rhodium)

6

Interaction Between Metals and Proteins

6.1

Introduction

6.2

Mechanisms of Interaction Between T Cells and Metal Irons

7

Other Interactions Between Metals and Proteins— Implications for Autoimmunity

8

Nonspecific Immunostimulation Induced by Metals: The Examples of Pb and Hg

9

Metal-Induced Autoimmunity

10

Acceleration and Aggravation of Autoimmunity by Xenobiotics

10.1

General Considerations

10.2

Acceleration of Spontaneous Autoimmune Diseases by Hg

10.3

Acceleration of Spontaneous Autoimmune Diseases by Cadmium and Lead

10.4

Comments on the Autoimmune Effects of Metals

Chapter 12

Reproductive and Developmental Toxicity of Metals   Pietro Apostoli, Spomenka Tellsman and Polly R. Sager

1

Introduction

2

Male Reproductive Effects

2.1

Lead

2.2

Mercury

2.3

Cadmium

2.4

Manganese

2.5

Chromium

2.6

Nickel

2.7

Arsenic

3

Female Reproductive Effects

3.1

Lead

3.2

Mercury

3.3

Cadmium

3.4

Manganese

3.5

Chromium

3.6

Nickel

3.7

Arsenic

3.8

Platinum

3.9

Mixed Metal Exposure

4

Developmental Effects of Prenatal Exposure

4.1

Lead

4.2

Mercury

4.3

Cadmium

4.4

Chromium

4.5

Nickel

4.6

Arsenic

4.7

Vanadium

4.8

Uranium

4.9

Aluminum

4.10

Lithium

5

Developmental Effects from Neonatal Exposure

5.1

Lead

5.2

Mercury

5.3

Cadmium

5.4

Nickel

5.5

Arsenic

5.6

Aluminum

5.7

Mixed Metal and Multichemical Exposure

Chapter 13

Ecotoxicology of Metals—Sources Transport, and Effects in the Ecosystem   Poul Bjerregaard and Ole Andersen

1

Sources for Metal Emission

1.1

Direct Emissions of Metals into Nature

1.1.1

Emissions to the Atmosphere

1.1.2

Emissions into Water

1.1.3

Emissions to Soil

1.2

Indirect Mobilization of Metals

1.2.1

Acid Rain

1.2.2

Oxygen Depletion

1.2.3

Pyrite Oxidation

2

The BiogeochemicaI Transport of Metals

2.1

Atmospheric Transport

2.2

Metal Speciation in Water

2.3

Metal Transport in the Ocean

2.4

Transport of Metals in Freshwater and Estuaries

2.5

Metals in Sediments

3

Uptake and Accumulation of Metals

3.1

Bioavailability, Uptake, Accumulation, and Elimination

3.2

Metal Transport in Aquatic Food Chains

4

Defense Against and Storage of Metals

4.1

Metal Toxicity and Defense Systems in Plants

5

Toxicity of Metals in Ecosystems

6

Risk Assessment of Metals

6.1

The Aim of Ecotoxieological Risk Assessment

6.2

Integrated Risk Assessment

6.3

Methods of Ecotoxicology

6.4

Practical Risk Management

6.5

Biomarkers as Hazard Indicators in Ecotoxicological Risk Assessment

7

Monitoring Metal Pollution—Biomonitoring

7.1

Mussel Watch

7.2

Other Monitoring Organisms

8

Ecotoxicology of Individual Metals

8.1

Alumina

8.2

Antimony

8.3

Arsenic

8.3

Cadmium

8.3.1

Background Levels and Emissions

8.3.2

Uptake in Organisms

8.3.3

Contamination with Cadmium

8.3.4

Cadmium’s Toxicity in Water

8.3.5

Cadmium in Agricultural Soil and Uptake of Cadmium into Plants

8.3.6

Implication for Human Health

8.4

Cobalt

8.5

Chromium

8.6

Copper

8.7

Iron

8.8

Lead

8.8.1

Lead in Ammunition

8.8.2

Effects in Birds and Mammals

8.9

Manganese

8.10

Mercury

8.10.1

Background Concentrations, Uses, and Emissions

8.10.2

The Transformation of Mercury in Nature

8.10.3

The Global Mercury Flux

8.10.4

Uptake of Mercury in Organisms and Transport in Food Webs

8.10.5

Effects of Mercury in Wildlife

8.10.6

Implications for Human Health

8.11

Molybdenum

8.12

Nickel

8.13

Selenium

8.14

Silver

8.15

Tin

8.15.1

Inorganic Tin

8.15.2

Tributyltin (TBT)

8.16

Vanadium

8.17

Zinc

8.18

Radioactive Metals

8.18.1

Cesium

8.18.2

Polonium

8.18.3

Strontium

8.18.4

Transuranic Metals

Chapter 14

Risk Assessment   Gunnar F. Nordberg And Bruce A. Fowler

1

Introduction

2

Exposure and Dose Assessment

2.1

Exposure and Dose Terminology

2.2

Exposure, Applied/Inhaled Dose, Daily Intake

2.3

Absorbed Dose, Internal Dose

2.4

Dose/Concentration in Critical Organ and Critical Target

2.5

Use of Biomarkers in Estimating Concentration in Critical Organ and Critical Target Dose

3

Hazard Identification

3.1

Speciation

3.2

Human Data

3.3

Data from Studies on Acute and Chronic Toxicity in Animals, Cells, and Molecular Systems in Vitro

3.3.1

IARC Group 2

3.3.2

IARC Group 2A: The Agent is Probably Carcinogenic to Humans

3.3.3

IARC Group 2B: The Agent is Possibly Carcinogenic to Humans

3.4

Classification According to the European Union

3.5

Classification According to the USEPA

3.6

Classification According to the American Conference of Governmental Industrial Hygienists Inc.

4

Dose-Effect and Dose-Response Assessment

4.1

Concepts in Quantitative Toxicological Analysis

4.1.1

Dose Effect and Dose Response

4.1.2

Critical Concentration, Critical Organ, Critical Effect, and No-Observed-Effect Level

4.1.3

Benchmark Dose

4.1.4

The Critical Concentration on a Population Basis

4.2

Based on Short-Term and Long-Term Studies in Animals

4.2.1

Threshold-Type Critical Effects

4.2.2

Carcinogenesis and Other Nonthreshold Effects

4.3

Probabilistic Estimation of Dose-Response Relationships by Toxicokinetic (TK) and Toxicodynamic (TD) Modeling

4.3.1

Deterministic or Threshold-Type Effects

4.3.2

Stochastic or Nonthreshold Effects

4.4

Based on Epidemiological Studies

4.4.1

Sensitive Groups

4.4.2

Carcinogenic Effects

4.5

Simplified Approach as an Alternative to Risk Assessment

5

Risk Characterization

6

Risk Management and Risk Communication

6.1

Managing Human Exposures by Emission Control, Substitution, Labeling, or Restrictions in Use

6.2

Controlling Human Exposures by Guidelines and Legislated Permissible Exposure Levels

6.3

Risk Communication

Chapter 15

Diagnosis and Treatment of Metal Poisoning—General Aspects   George Kazantzis

1

Clinical Effects

1.1

General Considerations

1.2

Exposure Pattern and Clinical Effect

1.3

Acute Clinical Effects of Metals

1.3.1

Gastrointestinal Effects

1.3.2

Respiratory Effects

1.3.3

Cardiovascular Effects

1.3.4

Effects on the Central Nervous System

1.3.5

Renal Effects

1.3.6

Hemopoietic Effects

1.4

Chronic Clinical Effects of Metal Toxicity

1.4.1

Gastrointestinal Effects

1.4.2

Hepatic Effects

1.4.3

Respiratory Effects

1.4.4

Effects on the Nervous System

1.4.5

Renal Effects

1.4.6

Hemopoietic Effects

2

Diagnosis of Metal Poisoning

2.1

History of Exposure

2.2

Clinical Features

2.3

Toxicological Analysis

2.4

Biochemical Investigation

2.5

Physiological Investigation

3

Treatment

3.1

Prevention of Further Absorption

3.1.1

Removal from Exposure

3.1.2

Minimizing Absorption from the Gastrointestinal Tract

3.2

General Supportive Therapy

3.2.1

Maintenance of Respiration and Circulation

3.2.2

Maintenance of Water and Electrolyte Balance

3.2.3

Control of Nervous System Effects

3.3

Elimination of Absorbed Poison

3.3.1

Diuresis

3.3.2

Biliary Excretion

3.3.3

Dialysis

3.3.4

Exchange Transfusion

3.4

Inactivation of the Absorbed Poison

3.5

Chelation Therapy

3.5.1

Dimercaprol

3.5.2

Calcium Disodium Edetate (Calcium EDTA)

3.5.3

Penicillamine (Cuprimine)

3.5.4

Triethylene Tetramine (Trien, TETA)

3.5.5

Desferrioxamine (DFOA)

3.5.6

Deferiprone(LI)

3.5.7

Diethylenetriaminepentaacetic Acid (DTPA)

3.5.8

Diethyldithiocarbamate(DEDTC)

3.5.9

Combinations of chelating Agents

3.6

Modification of Response

3.6.1

Modification of Tissue Response

3.6.2

Modification of Biochemical Status

Chapter 16

Principles for Prevention of the Toxic Effects of Metals   Philip J. Landrigan, David Kotelchuck, and Philippe Grandjean

1

Introduction

2

General Principles for Prevention of the toxic Effects of metals

2.1

Hazard Identification

2.1.1

Lead

2.1.2

Methylmercury

2.1.3

Arsenic

2.2

Reduction of Exposure

3

Prevention of the Effects of Metal Toxicity in the Work Environment

3.1

General considerations

3.2

Reduction of Exposure

3.2.1

Elimination of Unnecessary Uses and Substitution of Safer Materials

3.2.2

Reduced Use of Toxic Metals in Plant and Manufacturing Design

3.2.3

Other Technical Control Measures

3.2.4

Local Exhaust Ventilation

3.2.5

General Room Ventilation

3.2.6

Housekeeping

3.2.7

Influence of Personal Hygiene on Metal Absorption and Toxicity

3.2.8

Reduction of Worker Contact with Toxic Metals and Personal Protective Equipment

3.3

Monitoring of the Work Environment

3.3.1

Air Sampling Strategy in the Workspace

3.3.2

Sampling Technique

3.3.3

Analysis

3.3.4

Biological Monitoring

3.3.5

Health Examinations

3.4

Training

3.5

Authority

4

Prevention of the Effects of Metal Toxicity in the General Environments

4.1

General Considerations

4.2

The Unique Vulnerability of Infants and Children to Poisoning by Metals

4.3

Reduction of Exposure

4.3.1

Elimination or Reduction of Use

4.3.2

Source Control

4.3.3

Routes of Environmental Contamination by Metals

4.4

Environmental Monitoring

4.5

Public Education

4.6

Regulatory Authority

5

Perspectives on Precaution and Prevention

5.1

Populations at Risk

5.2

Widening Implications of Subclinical Toxicity

5.3

Precautionary Approaches

Chapter 17

Aluminum   Bengtsjögren, Anders Iregren, Carl-Gustaf Elinder, and Robert A. Yokel

1

Physical and Chemical Propertiea

2

Methods and Problems of Analysis

3

Production and Use

4

Dietary, Environmental, and Occupational Exposure

5

Metabolism

5.1

Absorption

5.2

Distribution

5.3

Excretion

5.4

Biological Monitoring

6

EFFECTS

6.1

Gastrointestinal Symptoms

6.2

Restrictive Pulminory Disease

6.3

Obstructive Pulminory Disease

6.4

Central Nervous System

6.4.1

Dialysis Encephalopathy

6.4.2

Other Medical Aluminum Exposures

6.4.3

Neurobehavioral Effects of Occupational Aluminum Exposure

6.4.4

Alzheimer’s Disease

6.5

Bone

6.6

Hematopoietic Tissue

6.7

Skin

6.8

Allergic Effects

6.9

Coronary Heart Disease

6.10

Carcinogenic Effects

7

Other Aluminum Compounds

8

Recommendations

Chapter 18

Antimony   Carolyn A Tylenda and Bruce A Fowler

1

Physical and Chemical Properties

2

Methods and Problems of Analysis

3

Production and Uses

3.1

Historical Background

3.2

Production

3.3

Uses

4

Environmental Levels and Exposures

4.1

General Environment

4.1.1

Food and Daily Intake

4.1.2

Air, Soil, and Water

4.1.3

Tobacco

4.2

Working Environment

5

Metabolism

5.1

Absorption

5.1.1

Inhalation

5.1.2

Indigestion

5.2

Distribution

5.2.1

Animals

5.2.2

Humans

5.3

Excretion

5.3.2

Animals

5.3.2

Humans

5.4

Biological Half-Life

5.4.1

Animals

5.4.2

Humans

6

Biological Monitoring

7

Effects and Dose-Response Relationships

7.1

Animals

7.1.1

Local Effects and Dose-Response Relationships

7.1.2

Systemic Effects and Dose-Response Relationships

7.2

Humans

7.2.1

Local Effects and Dose-Response Relationships

7.2.2

Systemic Effects and Dose-Response Relationships

7.2.3

Adverse Effects During Antimony Treatment

8

Carcinogenic and Genotoxic Effects

Chapter 19

Arsenic   Bruce A. Fowler C.H. Selene J. Chou Robert L. and J. Chien

1

Physical and Chemical Properties

2

Methods and Problems of Analysis

3

Production and Uses

3.1

Production

3.2

Uses

4

Environmental Levels and Exposures

4.1

Food and Daily Intake

4.2

Water

4.3

Soil

4.4

Air

4.5

Tobacco

5

Metabolism

5.1

Absorption

5.1.1

Inhalation

5.1.2

Ingestion

5.1.3

Skin Absorption

5.2

Transport and Distribution

5.3

Biotransformation

5.4

Excretion

5.5

Biological Half-Time

5.6

Mechanisms of Arsenical Toxicity

5.6.1

Mechanisms of Arsenical Metabolism and Toxicity

5.6.2

Metabolism

5.6.3

Mechanisms of Arsenical Toxicity

6

Biological Monitoring

6.1

Organs

6.2

Urine

6.3

Blood

6.4

Hair

7

Effects

7.1

Lethality

7.2

Acute and Subacute Effects

7.3

Chronic Noncardiovascular Effects

7.3.1

Dermal Effects

7.3.2

Gastrointestinal Effects

7.3.3

Neural Effects

7.3.4

Hepatic Effects

7.3.5

Hematological Effects

7.3.6

Respiratory Effects

7.3.7

Metabolic Effects

7.3.8

Immunological Effects

7.3.9

Ophthalmic Effects

7.4

Chronic Cardiovascular Effects

7.4.1

Cardiac Effects

7.4.2

Peripheral Vascular Diseases

7.4.3

Ischemic Heart Diseases

7.4.4

Stroke

7.4.5

Carotid Atherosclerosis

7.4.6

Hypertension

7.4.7

Microcirculation Abnormality

7.5

Carcinogenic Effects

7.5.1

Skin Cancer

7.5.2

Lung Cancer

7.5.3

Urothelial Cancer

7.5.4

Liver Cancer

7.5.5

Other Internal Cancers

7.5.6

Lifetime Cancer Risk Induced by Arsenic

7.6

Experimental System Cancer Studies

7.6.1

Developmental and Reproductive Effects

7.6.2

Genetoxic Effects and Mutagenicity

7.7

Interaction Between Arsenic and Other Compounds

8

Dose-Effect and Dose-Response Relationship in Arsenic Poisoning

9

Diagnosis, Treatment, and Prognosis

9.1

Acute Poisoning

9.1.1

Inhalation Diagnosis

9.1.2

Ingestion Diagnosis

9.2

Chronic Poisoning

9.2.1

Diagnosis

9.2.2

Treatment and Prognosis

10

Arsine

10.1

Experimental Model Studies

Chapter 20

Barium   Agneta Oskarsson and Andrew L Reeves

1

Physical and Chemical Properties

2

Methods and Problems of Analysis

3

Production and Uses

3.1

Production

3.2

Uses

4

Environmental Levels and Exposures

4.1

General Environment

4.1.1

Soil, Water, and Air

4.1.2

Plants, Animals, and Dietary Intake

4.2

Working Environment

5

Kinetics

5.1

Absorption

5.1.1

Inhalation

5.1.2

Ingestion

5.1.3

Parenteral Administration

5.2

Transport and Distribution

5.3

Excretion

6

Biological Monitoring

7

Effects and Dose-Response Relationships

7.1

Humans

7.1.1

Acute Effects

7.1.2

Chronic Effects

7.2

Animals

7.2.1

inhalation

7.2.2

Ingestion

8

Treatment

Chapter 21

Beryllium   Marek Jakubowski and Cezary Palczynski

1

Physical and Chemical Properties

2

Methods and Problems of Analysis

3

Production and Uses

3.1

Production

3.2

Uses

4

Environmental Levels and Exposures

4.1

General Environment

4.1.1

Soil, Water, and Air

4.1.2

Plants, Animals, and Dietary Intake

4.1.3

Estimates of Daily Exposure

4.2

Working Environment

5

Kinetics

5.1

Absorption

5.1.1

Dermal Exposure

5.1.2

Inhalation

5.1.3

Ingestion

5.2

Transport, Distribution, and Excretion

6

Levels in Tissues and Biological Fluids—Biological Monitoring

7

Effects and Dose-Response Relationships

7.1

Local Effects

7.1.1

Skin Contact

7.1.2

Inhalation

7.2

Systemic Effects

7.2.1

Acute Effects

7.2.2

Chronic Beryllium Disease (CBD, Chronic Pulmonary Granulomatosis, Berylliosis)

7.2.3

Other Chronic Systemic Effects

7.3

Carcinogenic Effects

7.3.1

Humans

7.3.2

Animals

7.4

Genotoxic Effects

7.5

Mechanisms of Toxic Action