Toxicology of Organophosphate and Carbamate Compounds

This text/reference book provides the most comprehensive coverage of anticholinesterase compounds (Organophosphates and Carbamates), which constitute the largest number of chemicals that are primarily used as insecticides in agriculture, industry, and around the home/garden. Some OPs (nerve agents) have been used in chemical warfare and terrorist attacks, while some OPs and CMs have been recommended as therapeutic agents in human medicine as well as in veterinary medicine. Many chemicals of both classes are extremely toxic and lack selectivity, thus their inadvertent/accidental use continues to pose a threat to human and animal health, aquatic systems and wildlife. These anticholinesterase agents produce a variety of toxicological effects in target and nontarget organs.

In light of this complexicity, this multi-authored book is written by the well known scientists from many countries. The book is organized into nine sections, with a total of 49 chapters, to provide in-depth knowledge on various aspects of OP and CM compounds, including their use, classification, mechanism-based toxicity, and prophylactic and therapeutic measurements. Several chapters are written with special emphasis to cover timely topics, such as chemical warfare agents, physiologically-based pharmacokinetic modeling, structure and function of cholinesterases, paraoxonase, carboxylesterases; developmental neurotoxicity, the intermediate syndrome, oxidative stress, endocrine disruption, and DNA damage/gene expression and carcinogenesis. Section-VI with 5 chapters is specifically devoted to risk assessment, and safety and regulatory guidelines for pesticides.

• Describes everything you need to know about Organophosphates and Carbamates
• Extensively covers pesticides, nerve agents, therapeutic drugs, and flame retardants
• Describes epidemiology of the world's major disasters involving Organophosphates and Carbamates
• Covers animal, human, aquatic, and wildlife toxicity of Anticholinesterases
• Insights into in-depth cholinergic and noncholinergic mechanisms of toxicity
• Describes recent advancements in cholinesterases, paraoxonases, carboxylesterases, oxidative stress, endocrine disruption, cardiac and pulmonary toxicity, and carcinogenesis
• Provides in vitro and in vivo models for neurotoxicity testing
• Integrates knowledge of studies in lab animals and humans
• Offers risk/safety assessment and national/international guidelines for permissible levels of pesticide residues
• Describes management of Anticholinesterase poisoning in humans

Toxicologists, Pharmacologists, Biologists/Neurochemists, Physicians, and Libraries

Foreword
Section-I Uses, Abuses & Epidemiology

1. Introduction
2. Classification and Uses of Organophosphates and Carbamates
3. Therapeutic Uses of Cholinesterase Inhibitors in Neurodegenerative Diseases
4. Co-administration of Memantine with Acetylcholinesterase Inhibitors: Preclinical and Clinical Evidence
5. Cholinesterase Inhibitors as Chemical Warfare Agents: Community Preparedness Guidelines
6. Organophosphates and the Gulf War Syndrome
7. The Bhopal Accident and Methyl Isocyanate Toxicity
8. Global Epidemiology of Organophosphates and Carbamates Poisonings

Section-II Pharmacokinetics & Metabolism

1. Physiologically Based Pharmacokinetic Modeling of Organophosphorus and Carbamate Pesticides
2. Metabolism of Organophosphorus and Carbamate Pesticides
3. Interspecies Variation in Toxicity of Cholinesterase inhibitors

Section-III Esterases, Receptors, Mechanisms & Tolerance Development

1. Structure and Function of Cholinesterases
2. Cholinesterase Pharmacogenetics
3. Methods for Measuring Cholinesterase Activities in Human Blood
4. Interactions of Organophosphorus and Carbamate Compounds with Cholinesterases
5. Structure, Function and Regulation of Carboxylesterases
6. Non-Cholinesterase Mechanisms of Central and Peripheral Neurotoxicity: Muscarinic Receptors and Other Targets
7. Paraoxonase (PON1) Polymorphisms and Toxicity of Organophosphates
8. Tolerance Development to Toxicity of Cholinesterase Inhibitors

Section-IV Organ Toxicity

1. CNS Effects and Neurotoxicity
2. Developmental Neurotoxicity of Organophosphates: A Case Study of Chlorpyrifos
3. In Vitro Models for Testing Organophosphate-Induced Neurotoxicity and Remediation
4. Electrophysiological Mechanisms in Neurotoxicity of Organophosphates and Carbamates
5. Behavioral Toxicity of Cholinesterase Inhibitors
6. PNS Effects and Delayed Neuropathy
7. The Intermediate Syndrome in Organophosphate Poisoning
8. Cardiovascular Toxicity of Cholinesterase Inhibitors
9. Pulmonary Toxicity of Cholinesterase Inhibitors
10. Approaches in Defining and Evaluating the Inhalation Pharmacology and Toxicology Hazards of Anticholinesterases
11. Dermal Absorption/Toxicity of Organophosphates and Carbamates
12. Local and Systemic Ophthalmic Pharmacology and Toxicology of Organophosphate and Carbamate Anticholinesterases
13. Reproductive Toxicity of Organophosphate and Carbamate Pesticides
14. Placental Toxicity of Organophosphate and Carbamate Pesticides
15. Endocrine Disruption by Organophosphate and Carbamate Pesticides
16. Organophosphates, Carbamates and the Immune System

Section-V Non-Specific Toxic Effects

1. Oxidative Stress in Anticholinesterase Induced Excitotoxicity
2. DNA Damage, Gene Expression and Carcinogenesis by Organophosphates and Carbamates
3. Temperature Regulation in Experimental Mammals and Humans Exposed to Organophosphate and Carbamate Agents
4. Occupational Toxicology and Occupational Hygiene Aspects of Organophosphate and Carbamate Anticholinesterases with Particular Reference to Pesticides

Section-VI Risk Assessment & Regulations

1. Public Health Impacts of Organophosphates and Carbamates
2. Cumulative Effects of Organophosphorus or Carbamate Pesticides
3. Federal Regulations and Risk Assessment of Organophosphate and Carbamate Pesticides
4. Regulatory Considerations in Developmental Neurotoxicity of Organophosphorus and Carbamate Pesticides
5. WHO/FAO Guidelines for Cholinesterase Inhibiting Pesticide Residues in Food

Section-VII Aquatic & Wildlife

1. Aquatic Toxicity of Carbamates and Organophosphates
2. Toxicity of Organophosphorus and Carbamate Insecticides Using Birds as Sentinels for Terrestrial Vertebrate Wildlife

Section-VIII Analytical & Biomarkers

1. Analysis of Organophosphate and Carbamate Pesticides and Anticholinesterase Therapeutic Agents
2. Biomarkers of Organophosphate Exposure

Section-IX Therapeutic Measures

1. Management of Organophosphorus Pesticide Poisoning