Industrial guide to chemical and drug safety

CONTENTS Foreword xxiii Preface xxv Acknowledgments xxvii Chapter 1 Introduction to Chemical and Drug Safety 1 Introduction 1 Chemicals and Their Impact 2 Pesticides 5 Toxic Chemicals and Eggshell Thinning 6 Heavy Metals 7 Endocrine-Disrupting Chemicals 8 Polychlorinated Biphenyls, Polycyclic Aromatic Hydrocarbons, Dioxins, Toxic Gases, Vapors, and Their Pollutants 10 Greenhouse Gases 12 Ozone Depletion 13 Motor Vehicle–Emitted Pollutants 14 Need of the Time 15 Conclusion 15 References 15 Chapter 2 Principles of Toxicity and Safety 19 Introduction 19 History of Toxicology 22 Hazard and Risk 24 Branches of Toxicology 25 The Elements in Toxicology 26 Pathways of Toxicity 26 Factors Influencing Toxicity 28 v vi CONTENTS Extrinsic Factors 36 Types of Toxicological Tests 37 Conclusion 50 References 51 Chapter 3 Heavy Metals 59 Introduction 59 Metals and Toxicity 61 Aluminum 62 Arsenic 63 Barium 65 Beryllium 65 Cadmium 66 Chromium 67 Cobalt 68 Lead 68 Manganese 73 Mercury and Methyl Mercury 75 Nickel 78 Zinc 79 Conclusion 80 References 80 Appendix 3-1 Lead Levels Are Considered Elevated in Humans 88 Chapter 4 Organochlorine Pesticides 89 Introduction 89 Growth and Production 90 Use Pattern of Pesticides 90 Use of Pesticides in Tanzania 91 Benefits from Pesticides 92 Adverse Effects from Pesticides 92 Cyclodienes 93 Chlordane 102 Heptachlor and Heptachlor Epoxide 103 Heptachlor Epoxide 104 Aldrin, Dieldrin, and Endrin 104 DDT 107 CONTENTS vii Dicofol 109 Endosulfan 109 Hexachlorocyclohexane 110 Lindane (gamma-HCH) 111 Methoxychlor 112 Mirex and Chlordecone 113 Pentachlorophenol 114 Toxaphene 115 Conclusion 116 References 116 Appendix 4-1 Organochlorinated Pesticides and Carcinogenicity 122 Chapter 5 Organophosphorus Pesticides 123 Introduction 123 Neurotoxicity 124 Cholinergic Receptor Sites 125 Signs and Symptoms of Poisoning 125 Neurotoxicity 127 Synergism, Antagonism, Additive Effects 128 Azinphos-Methyl 130 Carbophenothion 131 Chlorpyrifos 131 Coumaphos 132 Demeton-S-Methyl 133 Diazinon 134 Dichlorvos 135 Dimethoate 136 Disulfoton 137 Ethion 138 Fenamiphos 138 Fenitrothion 139 Fenthion 140 Fonophos 141 Isofenphos 142 Malathion 142 Methamidophos 144 Methyl Parathion 145 viii CONTENTS Mevinphos 145 Parathion 146 Phosphamidon 147 Propetamphos 148 Temephos 149 Trichlorfon 149 Conclusion 150 References 151 Appendix 5-1 Selected List of Organophosphorus Pesticides 156 Chapter 6 Herbicides and Fungicides 157 Introduction 157 Herbicides 160 Alachlor 160 Amitrole 161 Triazines 162 Atrazine 162 Bromacil 162 Butachlor 163 Dicamba 164 Glyphosate 164 Simazine 165 Picloram 165 2,4-D 166 Fluazifop-p-Butyl 167 Napropamide 168 Dalapon 169 Diquat 170 Paraquat 171 Fungicides 172 Benomyl 172 Chlorothalonil 173 Folpet 174 Mancozeb 175 Thiram 176 Zineb 177 Ziram 178 Conclusion 179 References 179 CONTENTS ix Chapter 7 Carbamates 184 Introduction 184 Carbamates 184 Aldicarb 184 Bendiocarb 186 Carbaryl 187 Carbofuran 189 Methomyl 190 Propoxur 192 Aminocarb 194 Isoprocarb 195 Pirimicarb 195 References 196 Chapter 8 Synthetic Pyrethroids, Fumigants, and Rodenticides 198 Introduction 198 Synthetic Pyrethroids 198 Bifenthrin 199 Deltamethrin 200 Permethrin 200 Fumigants 201 Phosphine 201 Ethylene Dibromide 203 Methyl Bromide 203 Other Chemicals 204 Rodenticide 204 Strychnine 204 References 205 Chapter 9 Industrial Solvents 207 Introduction 207 Aliphatic Hydrocarbons 208 Methane 209 Ethane 209 Propane 209 Butane 209 n-Pentane 209 n-Hexane 210 n-Heptane 210 x CONTENTS Aromatic Hydrocarbons 210 Benzene 211 Toluene 211 Xylene 212 Styrene 212 Petroleum Products 213 Crude Oil 213 Gasoline 214 Petroleum Ether 214 Kerosene 215 Aliphatic and Alicyclic Amines 215 Methylamine 215 Dimethylamine 216 Ethylamine 216 Diethylamine 216 Butylamines 217 n-Butylamine 217 Allylamines 217 Allylamine 218 Cyclohexylamine 218 Ethylenediamine 219 Triethanolamine 219 Aromatic Nitro and Amino Compounds 220 Picric Acid 220 Aniline 220 Diphenylamine 221 4-Aminophenyl Ether 221 Nitrobenzene 222 Benzidine 222 O-Toluidine 222 O-Nitrotoluene 223 Dinitrotoluene 223 Ethylene Glycol Dinitrate 224 Nitroglycerin 224 Other Organic Solvents 224 Alicyclic Hydrocarbons 225 1,3-Butadiene 225 CONTENTS xi Naphtha 226 Paraffin 226 Turpentine 226 Alcohols 227 Allyl Alcohol 227 Amyl Alcohol 227 n-Butyl Alcohol 228 Ethyl Alcohol 228 Methyl Alcohol 228 Propyl Alcohol 229 Phenol and Phenolic Compounds 229 Cresol 230 Creosote 230 Hydroquinone 230 Phenol 231 Quinone 231 Benzyl Chloride 232 Chlorodiphenyls 232 Chlorobenzenes 232 Chlorinated Naphthalenes 233 1,1,1-Trichloroethane 233 Carbon Tetrachloride 234 Conclusion 234 References 234 Chapter 10 Food Additives and Food Contaminants 242 Introduction 242 Food Additives 243 Anticaking Agents 243 Antioxidants 244 Bleaching and Maturing Agents 244 Buffering and Sequestering Agents 244 Flavoring Agents and Flavor Boosters 244 Food Colorants 245 Nonnutritive Dietary Sweeteners 246 Nutrient Supplements 246 Preservatives 246 xii CONTENTS Food Contaminants 246 Mycotoxins 246 Food Allergy 247 Food Poisoning 247 Food Storage 248 Dry Storage of Food 248 Food Preparation and Management 249 Food Handling 249 Conclusion 250 References 250 Chapter 11 Industrial Gases and Fumes 252 Introduction 252 Kinds of Gases and Adverse Effects 252 Ammonia 252 Carbon Dioxide 254 Carbon Monoxide 254 Hydrogen Cyanide 254 Hydrogen Sulfide 255 Nitrogen Oxides 255 Ozone 256 Phosgene 256 Sulfur Dioxide 257 References 257 Chapter 12 Drugs: Discovery and Development 259 Introduction 259 Safety Evaluation 261 Consideration in Toxicity Testing 263 Choice of Test Animals 264 Animal Care 264 Number and Size of Groups 264 Blood Collection 265 Termination of Animals 266 Issues Involved in Toxicity Testing 267 New Avenues in Drug Development and Safety 268 Techniques of Discovery 268 Proteins as Medicines 268 CONTENTS xiii Genetic Medicines 269 Immunopharmacology 269 Drug Delivery Systems 269 Preclinical Studies in Animals 269 Pharmaceutical Evaluation of New Drugs 271 New Thinking in Research 273 References 274 Chapter 13 Drugs and Human Diseases 275 Introduction 275 Analgesics and Antiinflammatory Agents 275 Aspirin 276 Paracetamol 276 Diclofenac 277 Sedatives, Hypnotics, and Antipsychotics 277 Drugs Used in Gout 278 Colchicine 278 Allopurinol 278 Vitamins 279 Vitamin A 279 Vitamin D 279 Vitamin E 280 Vitamin K 281 Vitamin B1 281 Vitamin B2 281 Vitamin B3 281 Vitamin B6 282 Vitamin C 282 Diabetes 282 Insulin 283 Glibenclamide 283 Acarbose 284 Troglitazone 284 Drugs for Malaria 284 Chloroquine 284 Quinine 285 Artemisinin 285 xiv CONTENTS Bronchodilators and Antiasthmatic Drugs 285 Aminophylline 285 Salbutamol 286 Adrenocortical Steroids 286 Anticancer Drugs 287 Cardiovascular Drugs 287 Cardiac Glycosides 287 Glyceryltrinitrates 288 Angiotensin-Converting Enzyme Inhibitors 288 Beta-Blockers 288 Diseases of the Central Nervous System 289 Alzheimer’s Disease 289 Parkinson’s Disease 289 Huntington’s Disease 290 Antimicrobial Drugs 290 Sulfonamides 291 Penicillins 291 Cephalosporins 291 Tetracyclines 292 Aminoglycosides 292 Antiviral Drugs 293 Human Immunodeficiency Virus 293 Acyclovir 293 Indinavir Sulfate 294 Interferon 294 Antifungal Agents 294 Amphotericin B 294 Fluconazole 295 Ketoconazole 295 Anthelmintics 295 Albendazole 295 Levamisole Hydrochloride 296 Lipid-Lowering Agents 296 Clofibrate 296 Simvastatin 297 Probucol 297 CONTENTS xv Sex Hormones 297 Hormone Replacement Therapy 298 Clomiphene Citrate 298 Antiulcer Agents 299 Cimetidine 299 Omeprazole 299 Antiepileptic Drugs 300 Carbamazepine 300 Phenobarbitone 301 Acute Barbiturate Poisoning 301 Vaccines 301 Over-the-Counter Drugs 303 Drugs and the Elderly 304 Sedatives, Hypnotics, and Analgesics 305 Antipsychotics, Antidepressants, and Drugs for Alzheimer’s Disease 305 Cardiovascular Drugs 305 Drugs and Obesity 305 Adipogenesis and Obesity 306 Contrast Media 306 Barium Sulfate 306 Coloring Agents Radiopharmaceuticals Therapeutic Gases 307 Oxygen 308 Carbon Dioxide 308 Nitric Oxide 309 Helium 309 Disinfectants and Preservatives 309 Disinfectants 309 Preservatives 309 Disinfection of Water 310 Chlorhexidine 310 Formaldehyde Solutions 311 Drug Poisoning 311 Poisoning by Biologic Substances 313 Treatment of Plant Poisoning 313 References 313 30 307 7 xvi CONTENTS Chapter 14 Nonmedical Use of Drugs 320 Introduction 320 Drug Use and Misuse 320 Drug Abuse 320 Drug Dependence 320 Physical Dependence 321 Drug Habituation 321 Drug Addiction 321 Nicotine 322 Opioids 323 Cocaine 324 Marijuana 325 Lysergic Acid Diethylamide 325 Phencyclidine 326 Methamphetamine 326 Alcohol 327 Sports and Misuse of Drugs 329 Drugs Used for Torture, Interrogation, and Judicial Execution 330 References 330 Chapter 15 Drugs and Pharmaceuticals: Safety Considerations 332 Introduction 332 Antimicrobial Agents 333 Antibacterials 333 Antifungals 336 Antiprotozoals 337 Antivirals 337 Autocoids: Drugs Used for Inflammatory-Related Diseases 338 Analgesic, Antipyretic, and Antiinflammatory Drugs 338 Antigout Drugs 344 Antihistamines 345 Bronchodilators and Antiasthma Drugs 345 Cardiovascular Drugs 345 Beta-Blockers 346 Glyceryl Trinitrate 346 Quinidine 346 Verapamil 347 CONTENTS xvii Warfarin 347 Amiodarone 347 Amrinone Lactate 347 Diltiazem Hydrochloride 347 Digitoxin 348 Dobutamine 348 Dopamine 348 Flecainide 348 Frusemide 348 Glyceryl Trinitrate 348 Heparin 349 Hydralazine 349 Isosorbide Dinitrate 349 Labetalol Hydrochloride 349 Mannitol 349 Nicardipine Hydrochloride 349 Procainamide 350 Nitroprusside 350 Trimetaphan Camsylate 350 Verapamil Hydrochloride 350 Warfarin Sodium 350 Drugs Acting on the Nervous System and Related Dysfunctions 351 Antidepressants 351 Antimigraine Drugs 352 Antimuscarinics 353 Anxiolytics, Sedatives, Hypnotics, and Antipsychotics 353 Drugs Used for Gastrointestinal Tract Disorders 355 Bismuth Compounds 356 Cimetidine 356 Diphenoxylate 356 Metoclopramide 356 Sucralfates 356 Drugs Used for Parasitic Diseases 357 Anthelmintics 357 Antimalarials 357 Hormones and Hormone-Regulating Drugs 357 Antidiabetics 357 Bone-Modulating Drugs 359 xviii CONTENTS Miscellaneous 359 Anticancer Agents and Immunosuppressants 359 Blood Products, Plasma Expanders, and Hemostatics 363 Corticosteroids 363 General Anesthetics 363 Antidotics 364 References 365 Chapter 16 Target Organ Toxicity 377 Introduction 377 Skin 378 Skin Sensitization 382 Skin and Phototoxicity 382 Primary Skin Irritants 382 Ocular Irritation 383 Selected List of Primary Skin Irritants 387 The Respiratory System 387 Respiratory Irritants 387 Asthma 390 The Nervous System 392 Hepatotoxicty 395 Nephrotoxicity 399 Fetotoxicity 400 The Cardiovascular System 403 References 403 Chapter 17 Disposal of Hazardous Chemicals 408 Introduction 408 Laboratory Materials: Explosive Chemicals 409 Laboratories and Waste Management Systems 411 Waste Management Plan 412 Responsibility for the Waste Management System 412 Generation of Waste: Reduction in Volumes 413 Storage and Shelf Life of Reagents 413 Reagent Labeling and Maintenance 414 CONTENTS xix Avoiding Orphan Reaction Mixtures 414 The Waste Management System 414 Initial Survey 414 Waste Management Manual 415 Peroxide-Forming Chemicals 415 References 419 Appendix 17-1 Shock-Sensitive Chemicals 420 Appendix 17-2 Potentially Explosive Combination of Some Common Reagents 421 Appendix 17-3 Chemicals Generally Incompatible 422 Appendix 17-4 Specific Chemicals with Incompatibles 423 Appendix 17-5 Quick Guide to Chemical Toxicity and Safety 425 Appendix 17-6 Nonhazardous Organic and Inorganic Chemicals Suitable for Sanitary Sewer Disposal 427 Chapter 18 Good Laboratory Practice 429 Introduction 429 Good Laboratory Practice 430 International Organizations 430 International Program on Chemical Safety 431 Harmonization 432 Harmonization of Environmental Measurement 432 Good Laboratory Practice Mind-Set 433 Good Laboratory Practice Provisions 434 Organization, Management, and the Testing Facility 435 Responsibilities of the Test Facility Management 435 Study Purpose 436 Study Director, Qualifications, and Responsibilities 436 Quality Assurance Unit 438 Facilities 439 Standard Operating Procedure 439 Protocol 440 Protocol Development and Amendment 440 Performance of the Study 441 Study Plan 442 Study Deviations 443 Documentation Requirements 443 Data Storage and Retrieval, Archiving, Raw Data Availability 444 Final Report 444 xx CONTENTS Conclusion 447 References 447 Appendix 18-1 Protocol Checklist 449 Appendix 18-2 Animals Dosing and Observations 451 Appendix 18-3 Facility Inspection Report 453 Appendix 18-4 Method Development and Validation (Analytical Chemistry Audit Form) 456 Appendix 18-5 Stability of Test Substance in Sample Matrix 457 Appendix 18-6 Analytical Reference Standards 458 Appendix 18-7 Standard Reference Solutions and Instrument Calibration 459 Appendix 18-8 Sample Preparation, Extraction, and Clean Up 460 Appendix 18-9 Sample Analysis 461 Appendix 18-10 Quality Control Practices 462 Appendix 18-11 Quality Assurance Checklist 463 Chapter 19 Safety Evaluation: Methods and Procedures 465 Introduction 465 Acute Oral Toxicity 465 Acute Dermal Toxicity 469 Acute Dermal Irritation/Corrosion Test 471 Sensitization Studies (Skin and Mucous Membranes) 472 Acute Eye Irritation Test 474 Irritation of Mucous Membrane Test 476 Acute Inhalation Toxicity 477 Short-Term Toxicity Studies 479 Repeated-Dose, Oral Toxicity (14- and 28-Day Study) 479 Subchronic Oral Toxicity (90-Day Study) 482 Test System 482 Repeated-Dose Dermal Toxicity Test (21- and 28-Day Study) 485 Subchronic Dermal Toxicity (90-Day Study) 488 Repeated Inhalation Toxicity (14- and 28-Day Study) 490 Subchronic Inhalation Toxicity (90-Day Study) 493 Chronic Toxicity Studies 495 Test System 495 Animal Care, Diet and Water Supply 496 Test Conditions 498 Oral Toxicity Studies 498 CONTENTS xxi Dermal Toxicity Studies 499 Inhalation Toxicity Studies 499 References 503 Chapter 20 Guidance for Laboratory Students and Occupational Workers 504 Introduction 504 General Safety Guidelines 505 Chemical Safety Guidelines 505 General Principles 507 Health and Hygiene 507 Food Handling 508 Housekeeping 508 Equipment Maintenance 509 Guarding for Safety 509 Shielding for Safety 509 Glassware 510 Flammability Hazards 510 Cold Traps and Cryogenic Hazards 511 Closed Systems Under Positive or Negative Pressure 511 Waste Disposal Procedures 511 Warning Signs and Labels 511 Unattended Operations 512 Working Alone 512 Accident Reporting 512 Evacuation 513 Everyday Hazards 513 Identification 513 Classification 514 Segregation 515 Labeling 515 Disposal of Wastes in Sewer Systems 515 Accumulating Wastes for Disposal 515 Using Liquefied Petroleum Gas Safely 518 xxii CONTENTS Safety When Accepting Door Delivery 518 Safety When Changing Cylinders 518 Safe Usage 518 If You Suspect Leakage 519 Appendixes 521 Glossary 597 Index 617