- •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
54 CLASSES OF TOXICANTS: USE CLASSES
Table 5.1 Examples of Chelating Drugs Used to Treat Metal Toxicity
British antilewisite (BAL[2,3–dimercaptopropanol]), dimercaprol
DMPS (2,3-dimercapto-1-propanesulfonic acid)
DMSA (meso-2,3-dimercaptosuccinic acid)
EDTA (ethylenediaminetetraacetic acid, calcium salt)
DTPA (diethylenetriaminepentaacetic acid, calcium salt)
DTC (dithiocarbamate)
Penicillamine (β-β-dimethylcysteine), hydrolytic product of penicillin
and burning esophageal pain. Vasodilatation, myocardial depression, cerebral edema, and distal peripheral neuropathy may also follow. Later stages of poisoning include jaundice and renal failure. Death usually results from circulatory failure within 24 hours to 4 days.
Chronic exposure results in nonspecific symptoms such as diarrhea, abdominal pain, hyperpigmentation, and hyperkeratosis. A symmetrical sensory neuropathy often follows. Late changes include gangrene of the extremities, anemia, and cancer of the skin, lung, and nasal tissue.
5.2.8Treatment of Metal Poisoning
Treatment of metal exposure to prevent or reverse toxicity is done with chelating agents or antagonists. Chelation is the formation of a metal ion complex, in which the metal ion is associated with an electron donor ligand. Metals may react with O-, S-, and N-containing ligands (e.g., –OH, –COOH, –S–S–, and –NH2). Chelating agents need to be able to reach sites of storage, form nontoxic complexes, not readily bind essential metals (e.g., calcium, zinc), and be easily excreted.
One of the first clinically useful chelating drugs was British antilewisite (BAL [2,3-dimercaptopropanol]), which was developed during World War II as an antagonist to arsenical war gases. BAL is a dithiol compound with two sulfur atoms on adjacent carbon atoms that compete with critical binding sites involved in arsenic toxicity. Although BAL will bind a number of toxic metals, it is also a potentially toxic drug with multiple side effects. In response to BAL’s toxicity, several analogues have now been developed. Table 5.1 lists some of the more common chelating drugs in therapeutic use.
5.3AGRICULTURAL CHEMICALS (PESTICIDES)
5.3.1Introduction
Chemicals have been used to kill or control pests for centuries. The Chinese used arsenic to control insects, the early Romans used common salt to control weeds and sulfur to control insects. In the 1800s pyrethrin (i.e., compounds present in the flowers of the chrysanthemum, Pyrethrum cineraefolium) was found to have insecticidal properties. The roots of certain Derris plant species, (D. elliptica and Lonchocarpus spp.) were used by the Chinese and by South American natives as a fish poison. The active ingredient, rotenone, was isolated in 1895 and used for insect control. Another material
AGRICULTURAL CHEMICALS (PESTICIDES) |
55 |
developed for insect control in the 1800s was Paris Green, a mixture of copper and arsenic salts. Fungi were controlled with Bordeaux Mixture, a combination of lime and copper sulfate.
However, it was not until the 1900s that the compounds we identify today as having pesticidal properties came into being. Petroleum oils, distilled from crude mineral oils were introduced in the 1920s to control scale insects and red spider mites. The 1940s saw the introduction of the chlorinated hydrocarbon insecticides such as DDT and the phenoxy acid herbicides such as 2,4-D). Natural compounds such as Red Squill, derived from the bulbs of red squill, Urginea (Scilla) maritima, were effective in controlling rodents. Triazine herbicides, such as atrazine, introduced in the late 1950s, dominated the world herbicide market for years. Synthetic pyrethrins or pyrethroid insecticides (e.g., resmethrin) became and continue to be widely used insecticides due to their low toxicity, enhanced persistence compared to the pyrethrins and low application rates. New families of fungicides, herbicides, and insecticides continue to be introduced into world markets as older compounds lose their popularity due to pest resistance or adverse health effects.
Pesticides are unusual among environmental pollutants in that they are used deliberately for the purpose of killing some form of life. Ideally pesticides should be highly selective, destroying target organisms while leaving nontarget organisms unharmed. In reality, most pesticides are not so selective. In considering the use of pesticides, the benefits must be weighed against the risk to human health and environmental quality. Among the benefits of pesticides are control of vector-borne diseases, increased agricultural productivity, and control of urban pests. A major risk is environmental contamination, especially translocation within the environment where pesticides might enter both food chains and natural water systems. Factors to be considered in this regard are persistence in the environment and potential for bioaccumulation.
5.3.2Definitions and Terms
The term “agricultural chemicals” has largely been replaced by the term “pesticides,” defined as economic poisons, regulated by federal and state laws, that are used to control, kill, or repel pests. Depending on what a compound is designed to do, pesticides have been subclassified into a number of categories (Table 5.2). The primary classes of pesticides in use today are fumigants, fungicides, herbicides, and insecticides with total US production of 1.2 billion pounds (1997: US Environmental Protection Agency’s latest figures) and production of some 665 million pounds of wood preservatives. Table 5.3 describes the relative use of different classes of pesticides in the United States.
Generally, it takes some five to seven years to bring a pesticide to market once its pesticidal properties have been verified. Many tests must be conducted to determine such things as the compound’s synthesis, its chemical and physical properties, and its efficacy. In addition, in order for registration for use by the US EPA, numerous toxicity tests are undertaken including those for acute toxicity, those for chronic effects such as reproductive anomalies, carcinogenesis, and neurological effects and those for environmental effects.
The mandated pesticide label contains a number of specified items, including the concentration and/or percentage of both the active (A.I.) and inert ingredients; proper mixing of the formulation with water to obtain the application rate of A.I., what the A.I.
56 |
CLASSES OF TOXICANTS: USE CLASSES |
|
|
Table 5.2 Classification of Pesticides, with Examples |
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||
|
|
|
|
Class |
|
Principal Chemical Type |
Example, Common Name |
|
|
|
|
Algicide |
Organotin |
Brestar |
|
Fungicide |
Dicarboximide |
Captan |
|
|
|
Chlorinated aromatic |
Pentchlorophenol |
|
|
Dithiocarbamate |
Maneb |
|
|
Mercurial |
Phenylmercuric acetate |
Herbicide |
Amides, acetamides |
Propanil |
|
|
|
Bipyridyl |
Paraquat |
|
|
Carbamates, thiocarbamates |
Barban |
|
|
Phenoxy |
2,4-D |
|
|
Dinitrophenol |
DNOC |
|
|
Dinitroaniline |
Trifluralin |
|
|
Substitute urea |
Monuron |
|
|
Triazine |
Atrazine |
Nematocide |
Halogenated alkane |
Ethylene dibromide (EDB) |
|
Molluscicide |
Chlorinated hydrocarbon |
Bayluscide |
|
Insecticide |
Chlorinated hydrocarbons |
|
|
|
|
DDT analogous |
DDT |
|
|
Chlorinated alicyclic |
BHC |
|
|
Cyclodiene |
Aldrin |
|
|
Chlorinated terpenes |
Toxaphene |
|
|
Organophosphorus |
Chlorpyrifos |
|
|
Carbamate |
Carbaryl |
|
|
Thiocyanate |
Lethane |
|
|
Dinitrophenols |
DNOC |
|
|
Fluoroacetate |
Nissol |
|
|
Botanicals |
|
|
|
Nicotinoids |
Nicotine |
|
|
Rotenoids |
Rotenone |
|
|
Pyrethroids |
Pyrethrin |
|
|
Synthetic pyrethroids |
Fenvalerate |
|
|
Synthetic nicotinoids |
Imidacloprid |
|
|
Fiproles |
Fipronil |
|
|
Juvenile hormone analogs |
Methroprene |
|
|
Growth regulators |
Dimilin |
|
|
Inorganics |
|
|
|
Arsenicals |
Lead arsenate |
|
|
Fluorides |
Sodium fluoride |
|
|
Microbials |
Thuricide, avermectin |
Insecticide synergists |
Methylenedioxyphenyl |
Piperonyl butoxide |
|
|
|
Dicarboximides |
MGK-264 |
Acaricides |
Organosulfur |
Ovex |
|
|
|
Formamidine |
Chlordimeform |
|
|
Dinitrophenols |
Dinex |
|
|
DDT analogs |
Chlorbenzilate |
Rodenticides |
Anticoagulants |
Warfarin |
|
|
|
Botanicals |
|
|
|
Alkaloids |
Strychine sulfate |
|
|
Glycosides |
Scillaren A and B |
|
|
Fluorides |
Fluoroacetate |
|
|
Inorganics |
Thallium sulfate |
|
|
Thioureas |
ANTU |
|
|
|
|
AGRICULTURAL CHEMICALS (PESTICIDES) |
57 |
will control, and how and when to apply it. In addition the label describes environmental hazards, proper storage of the material, re-entry intervals (REIs) for application sites, and the personal protective equipment (PPE) that must be worn during application or harvesting.
Depending on the toxicity, formulation concentration, and use patterns, pesticides can be classified as “general” or “restricted” use. A general use pesticide will cause no unreasonable, adverse effects when used according to the label and can be purchased and applied by anyone. A restricted use pesticide, defined as generally causing undesirable effects on the environment, applicator, or workers can only be purchased and applied by an individual who is licensed by the state.
The US EPA has developed “category use” definitions based on toxicity. Category I pesticides are highly hazardous, are classified as restricted use and have an oral LD50 less than or equal to 1.0/kg of body weight; category II pesticides are moderately toxic and have an oral LD50 less than or equal to 500 mg/kg; category III pesticides are generally nontoxic and have an oral LD50 less than or equal to 15,000 mg/kg. In addition the US EPA has developed a “carcinogenicity categorization” to classify pesticides for carcinogenicity.
5.3.3Organochlorine Insecticides
The chlorinated hydrocarbon insecticides were introduced in the 1940s and 1950s and include familiar insecticides such as DDT, methoxychlor, chlordane, heptachlor, aldrin, dieldrin, endrin, toxaphene, mirex, and lindane. The structures of two of the more familiar ones, DDT and dieldrin, are shown in Figure 5.1. The chlorinated hydrocarbons are neurotoxicants and cause acute effects by interfering with the transmission of nerve impulses. Although DDT was synthesized in 1874, its insecticidal properties were not noted until 1939, when Dr. Paul Mueller, a Swiss chemist, discovered its effectiveness as an insecticide and was awarded a Nobel Prize for his work. During World War II the United States used large quantities of DDT to control vector-borne diseases, such as typhus and malaria, to which US troops were exposed. After the war DDT use became widespread in agriculture, public health, and households. Its persistence, initially considered a desirable attribute, later became the basis for public concern. The publication of Rachel Carson’s book The Silent Spring in 1962 stimulated this concern and eventually led to the ban of DDT and other chlorinated insecticides in the United States in 1972.
Table 5.3 Use Patterns of Pesticides in the United
States
|
Percentage of Total |
Class |
Pesticide Use |
|
|
Herbicides |
47 |
Insecticides |
19 |
Fungicides |
13 |
Othersa |
21 |
Note: Most recent data: for 1997, published by US EPA in 2001. a Includes fumigants and wood preservates.
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