- •CONTENTS
- •Preface
- •Contributors
- •1 Introduction to Toxicology
- •1.1 Definition and Scope, Relationship to Other Sciences, and History
- •1.1.2 Relationship to Other Sciences
- •1.1.3 A Brief History of Toxicology
- •1.3 Sources of Toxic Compounds
- •1.3.1 Exposure Classes
- •1.3.2 Use Classes
- •1.4 Movement of Toxicants in the Environment
- •Suggested Reading
- •2.1 Introduction
- •2.2 Cell Culture Techniques
- •2.2.1 Suspension Cell Culture
- •2.2.2 Monolayer Cell Culture
- •2.2.3 Indicators of Toxicity in Cultured Cells
- •2.3 Molecular Techniques
- •2.3.1 Molecular Cloning
- •2.3.2 cDNA and Genomic Libraries
- •2.3.3 Northern and Southern Blot Analyses
- •2.3.4 Polymerase Chain Reaction (PCR)
- •2.3.5 Evaluation of Gene Expression, Regulation, and Function
- •2.4 Immunochemical Techniques
- •Suggested Reading
- •3.1 Introduction
- •3.2 General Policies Related to Analytical Laboratories
- •3.2.1 Standard Operating Procedures (SOPs)
- •3.2.2 QA/QC Manuals
- •3.2.3 Procedural Manuals
- •3.2.4 Analytical Methods Files
- •3.2.5 Laboratory Information Management System (LIMS)
- •3.3 Analytical Measurement System
- •3.3.1 Analytical Instrument Calibration
- •3.3.2 Quantitation Approaches and Techniques
- •3.4 Quality Assurance (QA) Procedures
- •3.5 Quality Control (QC) Procedures
- •3.6 Summary
- •Suggested Reading
- •4 Exposure Classes, Toxicants in Air, Water, Soil, Domestic and Occupational Settings
- •4.1 Air Pollutants
- •4.1.1 History
- •4.1.2 Types of Air Pollutants
- •4.1.3 Sources of Air Pollutants
- •4.1.4 Examples of Air Pollutants
- •4.1.5 Environmental Effects
- •4.2 Water and Soil Pollutants
- •4.2.1 Sources of Water and Soil Pollutants
- •4.2.2 Examples of Pollutants
- •4.3 Occupational Toxicants
- •4.3.1 Regulation of Exposure Levels
- •4.3.2 Routes of Exposure
- •4.3.3 Examples of Industrial Toxicants
- •Suggested Reading
- •5 Classes of Toxicants: Use Classes
- •5.1 Introduction
- •5.2 Metals
- •5.2.1 History
- •5.2.2 Common Toxic Mechanisms and Sites of Action
- •5.2.3 Lead
- •5.2.4 Mercury
- •5.2.5 Cadmium
- •5.2.6 Chromium
- •5.2.7 Arsenic
- •5.2.8 Treatment of Metal Poisoning
- •5.3 Agricultural Chemicals (Pesticides)
- •5.3.1 Introduction
- •5.3.3 Organochlorine Insecticides
- •5.3.4 Organophosphorus Insecticides
- •5.3.5 Carbamate Insecticides
- •5.3.6 Botanical Insecticides
- •5.3.7 Pyrethroid Insecticides
- •5.3.8 New Insecticide Classes
- •5.3.9 Herbicides
- •5.3.10 Fungicides
- •5.3.11 Rodenticides
- •5.3.12 Fumigants
- •5.3.13 Conclusions
- •5.4 Food Additives and Contaminants
- •5.5 Toxins
- •5.5.1 History
- •5.5.2 Microbial Toxins
- •5.5.3 Mycotoxins
- •5.5.4 Algal Toxins
- •5.5.5 Plant Toxins
- •5.5.6 Animal Toxins
- •5.6 Solvents
- •5.7 Therapeutic Drugs
- •5.8 Drugs of Abuse
- •5.9 Combustion Products
- •5.10 Cosmetics
- •Suggested Reading
- •6 Absorption and Distribution of Toxicants
- •6.1 Introduction
- •6.2 Cell Membranes
- •6.3 Mechanisms of Transport
- •6.3.1 Passive Diffusion
- •6.4 Physicochemical Properties Relevant to Diffusion
- •6.4.1 Ionization
- •6.5 Routes of Absorption
- •6.5.1 Extent of Absorption
- •6.5.2 Gastrointestinal Absorption
- •6.5.3 Dermal Absorption
- •6.5.4 Respiratory Penetration
- •6.6 Toxicant Distribution
- •6.6.1 Physicochemical Properties and Protein Binding
- •6.7 Toxicokinetics
- •Suggested Reading
- •7 Metabolism of Toxicants
- •7.1 Introduction
- •7.2 Phase I Reactions
- •7.2.4 Nonmicrosomal Oxidations
- •7.2.5 Cooxidation by Cyclooxygenases
- •7.2.6 Reduction Reactions
- •7.2.7 Hydrolysis
- •7.2.8 Epoxide Hydration
- •7.2.9 DDT Dehydrochlorinase
- •7.3 Phase II Reactions
- •7.3.1 Glucuronide Conjugation
- •7.3.2 Glucoside Conjugation
- •7.3.3 Sulfate Conjugation
- •7.3.4 Methyltransferases
- •7.3.7 Acylation
- •7.3.8 Phosphate Conjugation
- •Suggested Reading
- •8 Reactive Metabolites
- •8.1 Introduction
- •8.2 Activation Enzymes
- •8.3 Nature and Stability of Reactive Metabolites
- •8.4 Fate of Reactive Metabolites
- •8.4.1 Binding to Cellular Macromolecules
- •8.4.2 Lipid Peroxidation
- •8.4.3 Trapping and Removal: Role of Glutathione
- •8.5 Factors Affecting Toxicity of Reactive Metabolites
- •8.5.1 Levels of Activating Enzymes
- •8.5.2 Levels of Conjugating Enzymes
- •8.5.3 Levels of Cofactors or Conjugating Chemicals
- •8.6 Examples of Activating Reactions
- •8.6.1 Parathion
- •8.6.2 Vinyl Chloride
- •8.6.3 Methanol
- •8.6.5 Carbon Tetrachloride
- •8.6.8 Acetaminophen
- •8.6.9 Cycasin
- •8.7 Future Developments
- •Suggested Reading
- •9.1 Introduction
- •9.2 Nutritional Effects
- •9.2.1 Protein
- •9.2.2 Carbohydrates
- •9.2.3 Lipids
- •9.2.4 Micronutrients
- •9.2.5 Starvation and Dehydration
- •9.2.6 Nutritional Requirements in Xenobiotic Metabolism
- •9.3 Physiological Effects
- •9.3.1 Development
- •9.3.2 Gender Differences
- •9.3.3 Hormones
- •9.3.4 Pregnancy
- •9.3.5 Disease
- •9.3.6 Diurnal Rhythms
- •9.4 Comparative and Genetic Effects
- •9.4.1 Variations Among Taxonomic Groups
- •9.4.2 Selectivity
- •9.4.3 Genetic Differences
- •9.5 Chemical Effects
- •9.5.1 Inhibition
- •9.5.2 Induction
- •9.5.3 Biphasic Effects: Inhibition and Induction
- •9.6 Environmental Effects
- •9.7 General Summary and Conclusions
- •Suggested Reading
- •10 Elimination of Toxicants
- •10.1 Introduction
- •10.2 Transport
- •10.3 Renal Elimination
- •10.4 Hepatic Elimination
- •10.4.2 Active Transporters of the Bile Canaliculus
- •10.5 Respiratory Elimination
- •10.6 Conclusion
- •Suggested Reading
- •11 Acute Toxicity
- •11.1 Introduction
- •11.2 Acute Exposure and Effect
- •11.3 Dose-response Relationships
- •11.4 Nonconventional Dose-response Relationships
- •11.5 Mechanisms of Acute Toxicity
- •11.5.1 Narcosis
- •11.5.2 Acetylcholinesterase Inhibition
- •11.5.3 Ion Channel Modulators
- •11.5.4 Inhibitors of Cellular Respiration
- •Suggested Reading
- •12 Chemical Carcinogenesis
- •12.1 General Aspects of Cancer
- •12.2 Human Cancer
- •12.2.1 Causes, Incidence, and Mortality Rates of Human Cancer
- •12.2.2 Known Human Carcinogens
- •12.3 Classes of Agents Associated with Carcinogenesis
- •12.3.2 Epigenetic Agents
- •12.4 General Aspects of Chemical Carcinogenesis
- •12.5 Initiation-Promotion Model for Chemical Carcinogenesis
- •12.6 Metabolic Activation of Chemical Carcinogens and DNA Adduct Formation
- •12.7 Oncogenes
- •12.8 Tumor Suppressor Genes
- •12.8.1 Inactivation of Tumor Suppressor Genes
- •12.8.2 p53 Tumor Suppressor Gene
- •12.9 General Aspects of Mutagenicity
- •12.10 Usefulness and Limitations of Mutagenicity Assays for the Identification of Carcinogens
- •Suggested Reading
- •13 Teratogenesis
- •13.1 Introduction
- •13.2 Principles of Teratology
- •13.3 Mammalian Embryology Overview
- •13.4 Critical Periods
- •13.5 Historical Teratogens
- •13.5.1 Thalidomide
- •13.5.2 Accutane (Isotetrinoin)
- •13.5.3 Diethylstilbestrol (DES)
- •13.5.4 Alcohol
- •13.6 Testing Protocols
- •13.6.1 FDA Guidelines for Reproduction Studies for Safety Evaluation of Drugs for Human Use
- •13.6.3 Alternative Test Methods
- •13.7 Conclusions
- •Suggested Reading
- •14 Hepatotoxicity
- •14.1 Introduction
- •14.1.1 Liver Structure
- •14.1.2 Liver Function
- •14.2 Susceptibility of the Liver
- •14.3 Types of Liver Injury
- •14.3.1 Fatty Liver
- •14.3.2 Necrosis
- •14.3.3 Apoptosis
- •14.3.4 Cholestasis
- •14.3.5 Cirrhosis
- •14.3.6 Hepatitis
- •14.3.7 Oxidative Stress
- •14.3.8 Carcinogenesis
- •14.4 Mechanisms of Hepatotoxicity
- •14.5 Examples of Hepatotoxicants
- •14.5.1 Carbon Tetrachloride
- •14.5.2 Ethanol
- •14.5.3 Bromobenzene
- •14.5.4 Acetaminophen
- •14.6 Metabolic Activation of Hepatotoxicants
- •Suggested Reading
- •15 Nephrotoxicity
- •15.1 Introduction
- •15.1.1 Structure of the Renal System
- •15.1.2 Function of the Renal System
- •15.2 Susceptibility of the Renal System
- •15.3 Examples of Nephrotoxicants
- •15.3.1 Metals
- •15.3.2 Aminoglycosides
- •15.3.3 Amphotericin B
- •15.3.4 Chloroform
- •15.3.5 Hexachlorobutadiene
- •Suggested Reading
- •16 Toxicology of the Nervous System
- •16.1 Introduction
- •16.2 The Nervous system
- •16.2.1 The Neuron
- •16.2.2 Neurotransmitters and their Receptors
- •16.2.3 Glial Cells
- •16.3 Toxicant Effects on the Nervous System
- •16.3.1 Structural Effects of Toxicants on Neurons
- •16.3.2 Effects of Toxicants on Other Cells
- •16.4 Neurotoxicity Testing
- •16.4.1 In vivo Tests of Human Exposure
- •16.4.2 In vivo Tests of Animal Exposure
- •16.4.3 In vitro Neurochemical and Histopathological End Points
- •16.5 Summary
- •Suggested Reading
- •17 Endocrine System
- •17.1 Introduction
- •17.2 Endocrine System
- •17.2.1 Nuclear Receptors
- •17.3 Endocrine Disruption
- •17.3.1 Hormone Receptor Agonists
- •17.3.2 Hormone Receptor Antagonists
- •17.3.3 Organizational versus Activational Effects of Endocrine Toxicants
- •17.3.4 Inhibitors of Hormone Synthesis
- •17.3.5 Inducers of Hormone Clearance
- •17.3.6 Hormone Displacement from Binding Proteins
- •17.4 Incidents of Endocrine Toxicity
- •17.4.1 Organizational Toxicity
- •17.4.2 Activational Toxicity
- •17.4.3 Hypothyroidism
- •17.5 Conclusion
- •Suggested Reading
- •18 Respiratory Toxicity
- •18.1 Introduction
- •18.1.1 Anatomy
- •18.1.2 Cell Types
- •18.1.3 Function
- •18.2 Susceptibility of the Respiratory System
- •18.2.1 Nasal
- •18.2.2 Lung
- •18.3 Types of Toxic Response
- •18.3.1 Irritation
- •18.3.2 Cell Necrosis
- •18.3.3 Fibrosis
- •18.3.4 Emphysema
- •18.3.5 Allergic Responses
- •18.3.6 Cancer
- •18.3.7 Mediators of Toxic Responses
- •18.4 Examples of Lung Toxicants Requiring Activation
- •18.4.1 Introduction
- •18.4.2 Monocrotaline
- •18.4.3 Ipomeanol
- •18.4.4 Paraquat
- •18.5 Defense Mechanisms
- •Suggested Reading
- •19 Immunotoxicity
- •19.1 Introduction
- •19.2 The Immune System
- •19.3 Immune Suppression
- •19.4 Classification of Immune-Mediated Injury (Hypersensitivity)
- •19.5 Effects of Chemicals on Allergic Disease
- •19.5.1 Allergic Contact Dermatitis
- •19.5.2 Respiratory Allergens
- •19.5.3 Adjuvants
- •19.6 Emerging Issues: Food Allergies, Autoimmunity, and the Developing Immune System
- •Suggested Reading
- •20 Reproductive System
- •20.1 Introduction
- •20.2 Male Reproductive Physiology
- •20.3 Mechanisms and Targets of Male Reproductive Toxicants
- •20.3.1 General Mechanisms
- •20.3.2 Effects on Germ Cells
- •20.3.3 Effects on Spermatogenesis and Sperm Quality
- •20.3.4 Effects on Sexual Behavior
- •20.3.5 Effects on Endocrine Function
- •20.4 Female Reproductive Physiology
- •20.5 Mechanisms and Targets of Female Reproductive Toxicants
- •20.5.1 Tranquilizers, Narcotics, and Social Drugs
- •20.5.2 Endocrine Disruptors (EDs)
- •20.5.3 Effects on Germ Cells
- •20.5.4 Effects on the Ovaries and Uterus
- •20.5.5 Effects on Sexual Behavior
- •Suggested Reading
- •21 Toxicity Testing
- •21.1 Introduction
- •21.2 Experimental Administration of Toxicants
- •21.2.1 Introduction
- •21.2.2 Routes of Administration
- •21.3 Chemical and Physical Properties
- •21.4 Exposure and Environmental Fate
- •21.5 In vivo Tests
- •21.5.1 Acute and Subchronic Toxicity Tests
- •21.5.2 Chronic Tests
- •21.5.3 Reproductive Toxicity and Teratogenicity
- •21.5.4 Special Tests
- •21.6 In vitro and Other Short-Term Tests
- •21.6.1 Introduction
- •21.6.2 Prokaryote Mutagenicity
- •21.6.3 Eukaryote Mutagenicity
- •21.6.4 DNA Damage and Repair
- •21.6.5 Chromosome Aberrations
- •21.6.6 Mammalian Cell Transformation
- •21.6.7 General Considerations and Testing Sequences
- •21.7 Ecological Effects
- •21.7.1 Laboratory Tests
- •21.7.2 Simulated Field Tests
- •21.7.3 Field Tests
- •21.8 Risk Analysis
- •21.9 The Future of Toxicity Testing
- •Suggested Reading
- •22 Forensic and Clinical Toxicology
- •22.1 Introduction
- •22.2 Foundations of Forensic Toxicology
- •22.3 Courtroom Testimony
- •22.4.1 Documentation Practices
- •22.4.2 Considerations for Forensic Toxicological Analysis
- •22.4.3 Drug Concentrations and Distribution
- •22.5 Laboratory Analyses
- •22.5.1 Colorimetric Screening Tests
- •22.5.2 Thermal Desorption
- •22.5.6 Enzymatic Immunoassay
- •22.6 Analytical Schemes for Toxicant Detection
- •22.7 Clinical Toxicology
- •22.7.1 History Taking
- •22.7.2 Basic Operating Rules in the Treatment of Toxicosis
- •22.7.3 Approaches to Selected Toxicoses
- •Suggested Reading
- •23 Prevention of Toxicity
- •23.1 Introduction
- •23.2 Legislation and Regulation
- •23.2.1 Federal Government
- •23.2.2 State Governments
- •23.2.3 Legislation and Regulation in Other Countries
- •23.3 Prevention in Different Environments
- •23.3.1 Home
- •23.3.2 Workplace
- •23.3.3 Pollution of Air, Water, and Land
- •23.4 Education
- •Suggested Reading
- •24 Human Health Risk Assessment
- •24.1 Introduction
- •24.2 Risk Assessment Methods
- •24.2.2 Exposure Assessment
- •24.2.3 Dose Response and Risk Characterization
- •24.3 Noncancer Risk Assessment
- •24.3.1 Default Uncertainty and Modifying Factors
- •24.3.2 Derivation of Developmental Toxicant RfD
- •24.3.3 Determination of RfD and RfC of Naphthalene with the NOAEL Approach
- •24.3.4 Benchmark Dose Approach
- •24.3.5 Determination of BMD and BMDL for ETU
- •24.3.6 Quantifying Risk for Noncarcinogenic Effects: Hazard Quotient
- •24.3.7 Chemical Mixtures
- •24.4 Cancer Risk Assessment
- •24.5 PBPK Modeling
- •Suggested Reading
- •25 Analytical Methods in Toxicology
- •25.1 Introduction
- •25.2 Chemical and Physical Methods
- •25.2.1 Sampling
- •25.2.2 Experimental Studies
- •25.2.3 Forensic Studies
- •25.2.4 Sample Preparation
- •25.2.6 Spectroscopy
- •25.2.7 Other Analytical Methods
- •Suggested Reading
- •26 Basics of Environmental Toxicology
- •26.1 Introduction
- •26.2 Environmental Persistence
- •26.2.1 Abiotic Degradation
- •26.2.2 Biotic Degradation
- •26.2.3 Nondegradative Elimination Processes
- •26.3 Bioaccumulation
- •26.4 Toxicity
- •26.4.1 Acute Toxicity
- •26.4.2 Mechanisms of Acute Toxicity
- •26.4.3 Chronic Toxicity
- •26.4.5 Abiotic and Biotic Interactions
- •26.5 Conclusion
- •Suggested Reading
- •27.1 Introduction
- •27.2 Sources of Toxicants to the Environment
- •27.3 Transport Processes
- •27.3.1 Advection
- •27.3.2 Diffusion
- •27.4 Equilibrium Partitioning
- •27.5 Transformation Processes
- •27.5.1 Reversible Reactions
- •27.5.2 Irreversible Reactions
- •27.6 Environmental Fate Models
- •Suggested Reading
- •28 Environmental Risk Assessment
- •28.1 Introduction
- •28.2 Formulating the Problem
- •28.2.1 Selecting Assessment End Points
- •28.2.2 Developing Conceptual Models
- •28.2.3 Selecting Measures
- •28.3 Analyzing Exposure and Effects Information
- •28.3.1 Characterizing Exposure
- •28.3.2 Characterizing Ecological Effects
- •28.4 Characterizing Risk
- •28.4.1 Estimating Risk
- •28.4.2 Describing Risk
- •28.5 Managing Risk
- •Suggested Reading
- •29 Future Considerations for Environmental and Human Health
- •29.1 Introduction
- •29.2 Risk Management
- •29.3 Risk Assessment
- •29.4 Hazard and Exposure Assessment
- •29.5 In vivo Toxicity
- •29.6 In vitro Toxicity
- •29.7 Biochemical and Molecular Toxicology
- •29.8 Development of Selective Toxicants
- •Glossary
- •Index
SUGGESTED READING |
477 |
assessing the integrity of the immune system in the seals. Seals fed the contaminated fish did indeed have impaired immune responses lending credence to the hypothesis that organochlorine contaminants in the marine environment are rendering some species immunodeficient. Mortality occurs, not as a direct result of chemical toxicity, but due to increased susceptibility to pathogens.
26.5CONCLUSION
Environmental toxicologists have learned a great deal about the effects of chemicals in the environment and the characteristics of chemicals that are responsible for the hazards they pose. Much of the information gained has been due to retrospective analyzes of the environmental consequences of the deposition of chemicals into the environment. Such analyzes have resulted in curtailing the release of demonstrated hazardous chemicals into the environment and provide benchmark information upon which the regulation of chemicals proposed for release into the environment can be based. The recognition that environmentally hazardous chemicals commonly share characteristics of persistence, potential to bioaccumulate, and high toxicity has resulted in development and use of chemicals that lack one or more of these characteristics yet fulfill societal needs previously served by hazardous chemicals. For example, recognition that persistence and propensity to bioaccumulate were largely responsible for the environmental hazards posed by many organochlorine pesticides led to the development and use of alternative classes of pesticides such as organophosphates, carbamates, and pyrethroids. While these chemicals all possess the toxicity necessary to function as pesticides, their lack of persistence and reduced propensity to bioaccumulate makes them more suitable for use in the environment.
Such advances in our understanding of the fate and effects of chemicals in the environmental does not imply that the role of environmental toxicologists in the twentyfirst century will diminish. A dearth of information persist in areas vital to continued protection of natural resources against chemical insult. These include understanding
(1) the unique susceptibilities of key species to the toxicity of different classes of chemicals, (2) the interactions of chemical contaminants with abiotic components of the environment that lead to increased toxicity, (3) the toxicological consequences of exposure to complex chemical mixtures, and (4) the consequences of toxicant effects on individuals with respect to ecosystem viability. Additionally continued research is needed to develop molecular and cellular biomarkers of toxicant exposure and effect that could be used to predict dire consequences to ecosystem before such effects are manifested at higher levels of biological organization. The role of the environmental toxicologist undoubtedly will increase in prospective activities aimed at reducing the risk associated with chemical contaminants in the environments before problems arise, and hopefully will decrease with respect to assessing damage caused by such environmental contaminants.
SUGGESTED READING
Persistence
Burns, L. A., and G. L. Baughman. Fate modeling. In Fundamentals of Aquatic Toxicology, G. M. Rand, and S. R. Petrocelli, eds. New York: Hemisphere, 1985, pp. 558–586.
478 BASICS OF ENVIRONMENTAL TOXICOLOGY
Larson, R. A., and E. J. Weber. Reaction Mechanisms in Environmental Organic Chemistry. Boca Raton, FL: Lewis Publishers, 1994.
Bioaccumulation
Banerjee, S., and G. A. Baughman. Bioconcentration factors and lipid solubility. Environ. Sci. Technol. 25: 536–539, 1991.
Barron, M. G. Bioconcentration. Environ. Sci. Technol. 24: 1612–1618, 1990.
Barron, M. G. Bioaccumulation and bioconcentration in aquatic organisms. In Handbook of Ecotoxicology, D. J. Hoffman, B. A. Rattner, G. A. Burton Jr., and J. Cairns Jr., eds. Boca Raton, FL: Lewis Publishers, 1995, pp. 652–666.
LeBlanc, G. A. Trophic-level differences in the bioconcentration of chemicals: Implications in assessing environmental biomagnification. Environ. Sci. Technol. 28: 154–160, 1995.
Acute Toxicity
Kelso, D. D., and M. Kendziorek. Alaska’s response to the Exxon Valdez oil spill. Environ. Sci. Technol. 25: 183–190, 1991.
Parrish, P. R. Acute toxicity tests. In Fundamentals of Aquatic Toxicology, G. M. Rand, and S. R. Petrocelli, eds. New York: Hemisphere, 1985, pp. 31–57.
Stansley, W. Field results using cholinesterase reactivation techniques to diagnose acute anticholinesterase poisoning in birds and fish. Arch. Environ. Contam. Toxicol. 25: 315–321, 1993.
van Wezel, A. P., and A. Opperhuizen. Narcosis due to environmental pollutants in aquatic organisms: residue-based toxicity, mechanisms, and membrane burdens. Crit. Rev. Toxicol. 25: 255–279, 1995.
Wilson, V. S., and G. A. LeBlanc. Petroleum pollution. Rev. Toxicol. 3: 1–36, 1999.
Chronic Toxicity
Adams, W. J. Aquatic toxicology testing methods. In Handbook of Ecotoxicology, D. J. Hoffman, B. A. Rattner, G. A. Burton Jr., and J. Cairns Jr., eds. Boca Raton, FL: Lewis Publishers, 1995, pp. 25–46.
Blaustein, A. R., P. D. Hoffman, D. G. Hokit, J. M. Kiesecker, S. C. Walls, J. B. Hays. UV repair and resistance to solar UV-B in amphibian eggs: A link to population declines? Proc. Nat. Acad. Sciences. USA 91: 1791–1795, 1994.
Colborn, T., and C. Clement, eds. Chemically-Induced Alterations in Sexual and Functional Development: The Wildlife/Human Connection. Princeton, NJ: Princeton Scientific, 1992.
LeBlanc, G. A., and L. J. Bain. Chronic toxicity of environmental contaminants: Sentinels and biomarkers. Environ. Health Perspect. 105(suppl. 1): 65–80, 1997.
Hayes, T. B., A. Collins, M. Lee, M. Mendoza, N. Noriega, A. A. Stuart, and A. Vonk. Hermaphroditic, demasculinized frogs after exposure to the herbicide atrazine at low ecologically relevant doses. Proc. Nat. Acad. Sciences. 99: 5476–5480, 2002.
CHAPTER 27
Transport and Fate of Toxicants
in the Environment
DAMIAN SHEA
27.1INTRODUCTION
More than 100,000 chemicals are released into the global environment every year through their normal production, use, and disposal. To understand and predict the potential risk that this environmental contamination poses to humans and wildlife, we must couple our knowledge on the toxicity of a chemical to our knowledge on how chemicals enter into and behave in the environment. The simple box model shown in Figure 27.1 illustrates the relationship between a toxicant source, its fate in the environment, its effective exposure or dose, and resulting biological effects. A prospective or predictive assessment of a chemical hazard would begin by characterizing the source of contamination, modeling the chemical’s fate to predict exposure, and using exposure/dose-response functions to predict effects (moving from left to right in Figure 27.1). A common application would be to assess the potential effects of a new waste discharge. A retrospective assessment would proceed in the opposite direction starting with some observed effect and reconstructing events to find a probable cause. Assuming that we have reliable dose/exposure-response functions, the key to successful use of this simple relationship is to develop a qualitative description and quantitative model of the sources and fate of toxicants in the environment.
Toxicants are released into the environment in many ways, and they can travel along many pathways during their lifetime. A toxicant present in the environment at a given point in time and space can experience three possible outcomes: it can be stationary and add to the toxicant inventory and exposure at that location, it can be transported to another location, or it can be transformed into another chemical species. Environmental contamination and exposure resulting from the use of a chemical is modified by the transport and transformation of the chemical in the environment. Dilution and degradation can attenuate the source emission, while processes that focus and accumulate the chemical can magnify the source emission. The actual fate of a chemical depends on the chemical’s use pattern and physical-chemical properties, combined with the characteristics of the environment to which it is released.
A Textbook of Modern Toxicology, Third Edition, edited by Ernest Hodgson
ISBN 0-471-26508-X Copyright 2004 John Wiley & Sons, Inc.
479
480 TRANSPORT AND FATE OF TOXICANTS IN THE ENVIRONMENT
Transport and fate model
Environmental factors Exposure – response model that modify exposure
Toxicant source(s) Toxicant exposure Toxicant effects
Figure 27.1 Environmental fate model. Such models are used to help determine how the environment modifies exposure resulting from various sources of toxicants.
Conceptually and mathematically, the transport and fate of a toxicant in the environment is very similar to that in a living organism. Toxicants can enter an organism or environmental system by many routes (e.g., dermal, oral, and inhalation versus smoke stack, discharge pipe, or surface runoff). Toxicants are redistributed from their point of entry by fluid dynamics (blood flow vs. water or air movement) and intermedia transport processes such as partitioning (blood-lipid partitioning vs. water-soil partitioning) and complexation (protein binding vs. binding to natural organic matter). Toxicants are transformed in both humans and the environment to other chemicals by reactions such as hydrolysis, oxidation, and reduction. Many enzymatic processes that detoxify and activate chemicals in humans are very similar to microbial biotransformation pathways in the environment.
In fact, physiologically based pharmacokinetic models are similar to environmental fate models. In both cases we divide a complicated system into simpler compartments, estimate the rate of transfer between the compartments, and estimate the rate of transformation within each compartment. The obvious difference is that environmental systems are inherently much more complex because they have more routes of entry, more compartments, more variables (each with a greater range of values), and a lack of control over these variables for systematic study. The discussion that follows is a general overview of the transport and transformation of toxicants in the environment in the context of developing qualitative and quantitative models of these processes.
27.2SOURCES OF TOXICANTS TO THE ENVIRONMENT
Environmental sources of toxicants can be categorized as either point sources or nonpoint sources (Figure 27.2). Point sources are discrete discharges of chemicals that are usually identifiable and measurable, such as industrial or municipal effluent outfalls, chemical or petroleum spills and dumps, smokestacks and other stationary atmospheric discharges. Nonpoint sources are more diffuse inputs over large areas with no identifiable single point of entry such as agrochemical (pesticide and fertilizer) runoff, mobile sources emissions (automobiles), atmospheric deposition, desorption or leaching from very large areas (contaminated sediments or mine tailings), and groundwater inflow. Nonpoint sources often include multiple smaller point sources, such as septic tanks or automobiles, that are impractical to consider on an individual basis. Thus the identification and characterization of a source is relative to the environmental compartment or system being considered. For example, there may be dozens of important toxicant sources to a river, each must be considered when assessing the hazards of toxicants to aquatic life in the river or to humans who might drink the water or consume the
Farm
SOURCES OF TOXICANTS TO THE ENVIRONMENT |
481 |
Lake
Mine
Wet or dry fallout
Agricultural |
runoff |
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Siltation above dam
Dam
Air emissions |
Mine drainage |
Leachate, runoff
Lead shot in pond
Landfill
Plant discharge (Point Source)
City |
Dam |
Sewage treatment plant
Confined disposal area for dredged spoils
Sewage treatment plant outfall
Location of in-place pollutants
Runoff |
Boat channels |
Old chemical |
dump site |
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Berths |
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Marina |
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Harbor |
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Old dump site |
p |
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d |
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Open dredge |
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Spoil disposal area |
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r |
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Ship wastes |
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Offshore oil well |
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Spills |
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Ocean |
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Drill muds and |
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cuttings, oil |
Figure 27.2 Entry of toxicants into environment through many point and nonpoint sources.
fish and shellfish. However, these toxicant sources can be well mixed in the river, resulting in a rather homogeneous and large point source to a downstream lake or estuary (Figure 27.2).
The rate (units of g/h) at which a toxicant is emitted by a source (mass emission rate) can be estimated from the product of the toxicant concentration in the medium (g/m3) and the flow rate of the medium (m3/h). This would appear to be relatively simple for point sources, particularly ones that are routinely monitored to meet environmental
482 TRANSPORT AND FATE OF TOXICANTS IN THE ENVIRONMENT
regulations. However, the measurement of trace concentrations of chemicals in complex effluent matrices is not a trivial task (see Chapter 25). Often the analytical methods prescribed by environmental agencies for monitoring are not sensitive or selective enough to measure important toxicants or their reactive metabolites. Estimating the mass emission rates for nonpoint sources is usually very difficult. For example, the atmospheric deposition of toxicants to a body of water can be highly dependent on both space and time, and high annual loads can result from continuous deposition of trace concentrations that are difficult to measure. The loading of pesticides from an agricultural field to an adjacent body of water also varies with time and space as shown in Figure 27.3 for the herbicide atrazine. Rainfall following the application of atrazine results in drainage ditch loadings more than 100-fold higher than just two weeks following the rain. A much smaller, but longer lasting, increase in atrazine loading occurs at the edge of the field following the rain. Again, we see the need to define the spatial scale of concern when identifying and characterizing a source. If one is concerned with the fate of atrazine within a field, the source is defined by the application rate. If one is concerned with the fate and exposure of atrazine in an adjacent body of water, the source may be defined as the drainage ditch and/or as runoff from the edge of field. In the latter case one either needs to take appropriate measurements in the field or model the transport of atrazine from the field.
Atrazine concentration (ng/L)
2000
Large rain events
1500
1000
Period of atrazine application
Drainage ditch
500
Edge of field
0
April |
May |
June |
July |
Aug |
Sept |
Figure 27.3 Loading of atrazine from an agricultural field to an adjacent body of water. The loading is highly dependent on rainfall and the presence of drainage ditches that collect the chemical and focus its movement in the environment.
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