Encyclopedia of

TOXICOLOGY

THIRD EDITION

EDITOR-IN-CHIEF

PHILIP WEXLER

US National Library of Medicine, Bethesda, MD, USA

ASSOCIATE EDITORS

MOHAMMAD ABDOLLAHI

Tehran University of Medical Sciences (TUMS), Tehran, Iran

ANN DE PEYSTER

San Diego State University, San Diego, CA, USA

SHAYNE C. GAD

Gad Consulting Services, Cary, NC, USA

HELMUT GREIM

Technical University of Munich, Freising-Weihenstephan, Germany

STACEY HARPER

Oregon State University, Corvallis, OR, USA

VIRGINIA C. MOSER

US Environmental Protection Agency, Research Triangle Park, NC, USA

SIDHARTHA RAY

Manchester University College of Pharmacy, Fort Wayne, IN, USA

JOSE TARAZONA

European Chemicals Agency (ECHA), Helsinki, Finland

TIMOTHY J. WIEGAND

University of Rochester Medical Center and Strong Memorial Hospital, Rochester, NY, USA

VOLUME 3

ELSEVIER

Amsterdam • Boston • Heidelberg • London • New York • Oxford

Paris • San Diego • San Francisco • Singapore • Sydney • Tokyo

Academic Press is an imprint of Elsevier

CONTENTS

Foreword Ixvii

Preface ixix

Preface to The Second Edition Ixxiii

Preface to The First Edition Ixxv

Editor-in-Chief Ixxvii

Associate Editors hcxix

List of Contributors Ixxxiii

How to Use The Encyclopedia cix

Acknowledgments cxi

Dedication cxiii

VOLUME 3

Itai Itai Disease

H Horiguchi

IUCLID (International Uniform Chemical Information Database)M Sobanska and F Le Goff

IVERMECTINS see Avermectin

J

Jet Fuels

U Apte

Joint FAO/WHO Expert Meetings (JECFA and JMPR)O Sabzevari and A Tritscher

K

Kava

L R Olsen and C Skonberg

Kerosene

S C Gad and T Pham

KidneyG O Rankin and M A Valentovic

Killer Lakes

G Karimi andM Vahabzadeh

xxxviii Contents

Lanthanide Series of Metals 43

C E Lambert and M-L Ledrich

Law and Toxicology 48

A G Hopp and T Stedeford

LD50/LC50 (Lethal Dosage 50/Lethal Concentration 50) 58

SCGad

Lead 61

S C Gad and T Pham

LETHAL, DOSAGE, OR COMMUNICATION see LD50/LC5o (Lethal Dosage 50/Lethal Concentration 50)

Levels of Effect in Toxicology Assessment 66

M L Dourson and S Poumourmohammadi

Lewisite 68

D / Angelini, S D Cole, R M. Dorsey, and H Salem

Lidocaine 71

Y L Leung

Life Cycle Assessment 74

G Finnveden and J Potting

LIGROINE see Petroleum Ether

Limonene 78

S Nikfar and A F Behboudi

Linuron 83

G Chen

Lipid Metabolism Modifying (Statins, Cholesterol) 85

/ Fain and SCGad

Lipid Peroxidation 89

S N Desai, F F Farris, and S D Ray

Lithium 94

S C Gad and T Pham

Liver 96

/ E Kester

Lotronex 107

SCGad

Love Canal 109

M A Kamrin

Low-Dose Effects of Environmental Chemicals: Bisphenol A as a Case Study 111

L N Vandenberg

LOWEST-OBSERVED-ADVERSE EFFECT LEVEL see Levels of Effect in Toxicology Assessment

LOWEST-OBSERVED-EFFECT LEVEL see Levels of Effect in Toxicology Assessment

Loxapine 118

F L Cantxell

Lysergic Acid DiethylamideC M Stork and B Henriksen

LUBRICATING OIL see Lubricating Oils

LUNG see Respiratory Tract Toxicology

LyeSEGad

Lyme Disease

M A Kamrin

M

MagnesiumS C Gad and T Pham

MAK Committee

A Hartwig and H Greim

Malathion

N R Reed and A L Rubin

Maleic AnhydrideD Hernandez-Moreno, I de la Casa Resino, and F Soler-Rodriguez

MALE REPRODUCTIVE SYSTEM see Reproductive System, Male

Malonitrile

CPope

Mancozeb

/ R Roede and G W Miller

Maneb

IR Roede and G W Miller

ManganeseS C Gad and T Pham

MARCAR

Margin of Exposure (MOE)U Apte

Marijuana/ Pereira and T Wiegand

Marine Venoms and Toxins

WRKem

Maximum Tolerated Dose

SCGad

Mechanisms of ToxicityS Betharia, F F Farris, G B Corcoran, and S D Ray

MecopropP Gomez-Ramirez and A ] Gartia-Femdndez

Medical Surveillance

C P Holstege and L S Hardison

xl Contents

Medical Textiles 182

KGad

Melphalan 191

A L Oropesa Jimenez, D Hemdndez-Moreno, and F Soler-Rodriguez

Mephedrone 194

F Carvalho, H Carmo, P Guedes de Pinho, F Remiao, M de Lourdes Bastos, and M Carvalho

Mercaptans 197

R Munday

Mercaptoethanol, 2- 201

A Foroumadi and M Saeedi

Mercuric Chloride (HgCl2) 203

V S Vaidya and H M Mehendale

Mercury 207

SCGadandTPham

Mercury Tragedies: Incidents and Effects 211

S G Gilbert

Merphos 217

E Vilanova

Mescaline 221

/ D Slothower and TJ Wiegand

Mesocosms and Microcosms (Aquatic) 223

K R Solomon and M Hanson

Metaldehyde 227

WK Rumbeiha

Metallothionein 230

SCGad

Metals 231

SCGad

Methamidophos 232

KN Baer and B } Marcel

Methane 235

S R Clough

Methanol 238

P Richter

Methomyl 242

S R Mortensen and T L Serex

Methoprene 246

/ P Monteiro and A S Jurado

Methoxyaniline, 2-; o-Anisidine 250

S N Desai

Methoxychlor 254

G Chen

MethoxyethanolG S Wang

Methoxypsoralen, 8-

S E Gad

Methyl AcrylateR ] Parod

MethylamineG L Kennedy

Methyl Bromide

N R Reed and L Urn

Methylcholanthrene, 3-

H Robles

Methyl-CCNU (Semustine)/ Chilakapati, HM Mehendale, N Rezvani, and D L Bolduc

Methyl Disulfide

A de Peyster

Methylenedianiline and Its DihydrochlorideM Perez-Lopez, F Soler-Rodriguez, O Giouleme, and P Paschos

Diphenylmethane diisocyanate (MDI), 4,4'-

R } Parod

MethylenedioxymethamphetamineL J Schep and R } Slaughter

Methyl Ethyl Ketone

S E Gad and D W Sullivan, Jr.

Methylfentanyl-aFFFarris

MethylglyoxalM S Parmar

Methyl IsocyanateP Limaye

Methyl IsothiocyanateB Gadagbui, M Vincent, and A Willis

Methyl MethacrylateJ de la Casa-Resino, M Perez-Lopez, and F Soler-Rodriguez

MethylmercurySCGad

MethylnitrosoureaA Tsubura, K Yoshizawa, and T Sasaki

Methyl Parathion

CPope

Metribuzin

C R Armenddriz, A H dela Torre, A] G Fernandez, and G L Gonzdlez

xlii Contents

Metronidazole 330

M. H Bucklin, C M. Groth, and B Henriksen

Mevinphos 332

P Raman

Microarray Analysis 336

K Shankar and H M Mehendale

Micronudeus Assay 338

RCGuy

Minamata 340

T Yorifuji and T Tsuda

Mirex 345

CPope

Mithramycin 347

C P Holstege

Mitochondrial Toxicity 349

/ A Dykens and Y Will

Mitomycin C 354

SEGad

Mixtures, Toxicology, and Risk Assessment 357

G Rice, L K Teuschler, } E Simmons, and R C Hertzberg

Mode of Action 361

L T Haber, A Willis, and P Nance

MODELS see Animal Models

Modifying Factors of Toxicity 365

SCGad

Molecular Toxicology: Recombinant DNA Technology 374

E A Thackaberry

Molinate 381

C S Wood

Molybdenum 383

R WKappJr.

Monoamine Oxidase Inhibitors 389

PM Wax

MONOMETHYLHYDRAZINE see Mushrooms, Monomethylhydrazine (MMH) - Generating

Monosodium Glutamate (MSG) 391

A Campbell

Monte Carlo Analysis 393

N Rezvani and D L Bolduc

MOTHBALL see Naphthalene

Mouse Lymphoma Assay 397

RCGuy

Multispecies Environmental Testing Designs

P / van den Brink and M A Daam

MUSCARINE see Mushrooms, Muscarine

Musculoskeletal SystemM ) Fedoruk and S Hong

Mushrooms, CoprineT R Peredy

Mushrooms, CydopeptideS M Schneider

Mushrooms, Ibotenic Acid

T Peredy and R D Bruce, III

Mushrooms, Monomethylhydrazine (MMH) - GeneratingTR Peredy

Mushrooms, Muscarine

T Peredy and H Bradford

Mushroom, Psilocybin

T Peredy and H Bradford

MUTAGENICITY TESTS see Sister Chromatid Exchanges; Ames Test

MUTAGENICITYTOXICITY TESTS see Toxicity Testing, Mutagenicity

MyclobutanilF Soler-Rodriguez and A L Oropesa Jimenez

MycotoxinsC R Armenddriz, A J G Fernandez, M C LR Girones, and AH dela Torre

N

Nails (of the Fingers and Toes)A Hosseini-Tabatabaei

Naled

G M Pent

NanotoxicologyD WHdbson and R C Guy

NaphthaleneH Robles

Naphthylamine, 2-

G Talaska and N B Hopf

NaphthylisothiocyanateSEGad

Naphthylthiourea, <x-

VModyand S D Ray

National Center for Environmental Health-ATSDR

S S Devi and H M Mehendale

xiiv Contents

National Center for Toxicological Research, US 451

L Sheppard

National Environmental Polity Act, USA 453

S E Gad and S C Gad

National Institute for Occupational Safety and Health 454

M E Kiersma

The National Institute of Environmental Health Sciences 456

V Mody and S D Ray

National Institutes of Health 458

R D Beckett

National Library of Medicine and Its Toxicology and Environmental Health Information Program 460

P Wexler

National Toxicology Program 464

N } Walker, L D White, and M S Wolfe

Natural Products 468

S R Eagle and S C Gad

n-Butyl Alcohol 470

A S Bale and } A Weaver

Nematicides 473

SCGad

Neon 475

L M Ewers

Neonicotinoids 477

/ Seifert

NEOPLASIA see Carcinogenesis

NEPHROTOXICITY see Kidney

Nerve Agents 483

R A Moyer, F R Sidell, and H Salem

Neurotoxicity 489

P S Spencer and P J Lein

NEW DRUG APPLICATION see Investigative New Drug Application

Next Generation Sequencing 501

S Beedanagari and KJohn

Niacin 504

C L Sledge and B W Morgan

Nickel and Nickel Compounds 506

SCGad

Nickel Chloride 511

SCGad

Nicotine 514

A C Holloway

Nithiazine

/ Seifert

NitrapyrinS Espin and A } Garcta-Femdndez

Nitrate

AM Fan

Nitric Oxide

SCGad

Nitrite Inhalants

F L Cantrell

Nitrites

A / Gutierrez, C Rubio, } M Cdballero, and A Hardisson

Nitrobenzene

Q / Zhao and C H Hsu

Nitrocellulose

DHKim

Nitroethane

A Shafiee and M Khoobi

Nitrofuran, 2-

M Abdollahi and A H Abdolghaffari

Nitrofuran CarboxaldehydeM Abdollahi and A H Abdolghaffari

Nitrofurfuryl Alcohol

M Abdollahi and P Mahdaviani

Nitro-2-Furoic Acid, 5-

M Abdollahi and M Baeeri

Nitrofuroyl Chloride, 5-

M Abdollahi, Z Bayrami, and S Hassani

Nitrogen Dioxide (Formerly Nitrogen Oxides)P Kovacic and R Somanathan

Nitrogen Mustards

R Jabbour, H Salem, and F R Sidell

Nitrogen TetraoxideS E Gad and D W Sullivan, Jr.

NitroglycerinM Abdollahi and A F Behboudi

Nitromethane

/ Lord-Garcia

Nitrophenol, 4-

M Abdollahi and A Mohammadirad

Nitropropane, 2-

M Abdollahi and S Karami-Mohajeri

xlvi Contents

Nitropyrene, 1- 581

M Abdollahi and S Karami-Mohajeri

Nitrosamines 584

H Robles

Nitrous Oxide 586

SCGad

N-Methylpyrrolidone 588

M. R Heidari

HN-Dimethylacetamide 594

A R Ghazali and S H Inayat-Hussain

Dimethylnitrosamine 598

S D Ray, D Brown, and N Yang

N-Nitrosopyrrolidine 601

M Abdollahi, R Solgi, and S Karami-Mohajeri

NON-IONIZING RADIATION see Radiation Toxicology, Ionizing and Nonionizing

Nonlethal Weapons 603

M Balali-Mood, M Moshiri, and L Etemad

Nonmammalian Models in Toxicology Screening 609

S R Das, K S Saili, and R L Tanguay

NONSTEROIDAL ANTIINFLAMMATORY AGENTS see Acetaminophen; Acetylsalicylic Acid; Ibuprofen

NO-OBSERVED-ADVERSE-EFFECT LEVEL see Levels of Effect in Toxicology Assessment

NO-OBSERVED-EFFECT LEVEL see Levels of Effect in Toxicology Assessment

Nonylphenol 614

ST Kim

Norbormide 617

L P Weber

NOREPINEPHRINE see Catecholamines

Norethisterone (Norethindrone) 619

M Abdollahi and S Mostafalou

Notorious Poisoners and Poisoning Cases 622

HA Borek, V R Hall, K N Sibbald, and C P Holstege

Nutmeg 630

M Smith

Obesogens 633

F FFarris

Occupational Exposure Limits 637

S Nikfar and A A Malekirad

Occupational Safety and Health Act, US 641

M A Kamrin

Occupational Safety and Health Administration

M E Kiersma

Occupational ToxicologyE V Wattenberg

Octachlorostyrene

TNakajima and Y Yanagiba

Octane

S R Clough

OECD see Organisation for Economic Cooperation and Development (OECD)

eChemPortal — The Global Portal to Information on Chemical Substances

S de Marcellus

OCULAR TOXICOLOGY see Eye Irritancy Testing

Oil, Crude

J Marigdmez

Lubricating Oils

J Mangos, M A Sogorb, and E Vilanova

Oil SpillsS Othumpangat and V Castranova

Okadaic Acid

V Valdiglesias, B Laffon, J Femdndez-Tajes, and J Mendez

OLFACTION see Sensory Organs

Oleander

R Gorodetsky

Omics and Related Recent TechnologiesE van Vliet

TheOPCW

D Feakes and S Mogl

Opium and the Constituent OpiatesA Fields and T J Wiegand

Oral/Dermal Reference Dose (RfD)/Inhalation Reference Concentration (RfC)M Abdollahi, S Karami-Mohajeri, and B Gadagbui

Organization for Economic Cooperation and Development (OECD)S Nikfar, A Farshchi, and R Visser

Organochlorine Insecticides

W-T Tsai

Organophosphorus CompoundsR } Richardson and G F Makhaeva

Organotin CompoundsH K Okoro, O S Fatoki, F A Adekola, B J Ximba, and R G Snyman

Otto Fuel II

K L Mumy and N R Webber

xlviii Contents

Oxalates 730

A } Garcia-Ferndndez, S Espin, P Gomez-Ramirez, and E Martinez-Lopez

Oxidative Stress 735

K Sharikar and H M Mehendale

Oxydemeton-methyl 738

M Abdollahi and S Mostafalou

Oxygen 741

SCGad

OXYGENATES see Fuel Oxygenates

Oxymetholone 744

M Abdollahi and M Pakzad

Ozone 747

SCGad

Palladium 751

SCGad

Paraldehyde 754

M Abdollahi and A Nili-Ahmadabadi

Paraquat 756

/ R Roede and G W Miller

Parathion 759

CPope

PBT (Persistent, Bioaccumulative, and Toxic) Chemicals 762

TM Murray

Pendimethalin 765

S Ramasahayam

Penicillins 768

G G Dumancas, R S Hikkaduwa Koralege, E-R E Mojica, B S Murdianti, and P J Pham

Pentachlorobenzene 773

/ Liu

Pentachloroethane 775

M Abdollahi and A F Behboudi

Pentachloronitrobenzene 778

/ Liu

Pentane 780

S R Clough

Pentobarbital Sodium 783

M Abdollahi and A Baghaei

Peptide Coupling Agents 786

S-T Kim

Peracetic Acid 788

SCGad

Contents xlix

Perchlorate 791

G Karimi and R Rezaee

Perchloric Acid 796

KPBaran and S Gad

PERFLUORINATED CHEMICALS see Perfluorooctanoic Acid

Perfluoroisobutylene 799

SCGad

Perfluorooctanoic Acid 802

P de Voogt

Periodic Acid 806

S E Gad and S C Gad

Permethrin 808

D WGammon

PERMISSIBLE EXPOSURE LIMIT see Occupational Exposure Limits

Peroxisome Proliferator-Activated Receptors (PPARs) 812

K P Baran

Peroxisome Proliferators 815

M Jiang and N Yang

Persistent Organic Pollutants 820

L Fitzgerald and D S Wikoff

PERSONAL CARE PRODUCTS see Cosmetics and Personal Care Products

PESTICIDE RESIDUES: Joint FAO/WHO Meeting see Joint FAO/WHO Expert Meetings (JECFA and JMPR)

Pesticides 826

CPope

Petroleum Distillates 828

M A Sogorb, I Mangos, and E Vilanova

Petroleum Ether 834

R E Nalliah

PETROLEUM NAPHTHA see Petroleum Ether

Petroleum Hydrocarbons 838

SCGad

Peyote 841

CM Stork and S M Schreffler

Pharmaceuticals Effects in the Environment 844

C Fernandez, E M Beltrdn, and J V Tarazona

Pharmacokinetics 849

P Hinderliter and S A Saghir

Pharmacokinetic and Toxicokinetic Modeling 856

R W Seabury and C M Stork

PHARMACOLOGY AND SAFETY see Safety Pharmacology

Phenacetin 862

SCGad

Contents

Phenanthrene 865

S E Gad

Phencyclidine 868

A C Puran, C P Holstege, K P Jamison, and T J Wiegand

PHENELZINE see Monoamine Oxidase Inhibitors

PHENOBARBETAL see Barbiturates

Phenol 871

M. Abdollahi, S Hassani, andM Derakhshani

Phenol, 4-(l,l(3,3-tetramethylbutyl) 874

E P Hines

Phenolphthalein 877

S Saeidnia and A Manayi

Phenothiazines 881

M. M Dougherty and f M Marraffa

Phenothrin 884

S C Gad and T Pham

Phenylmercuric Acetate 887

L P Weber

Phenylphenol 889

SCGad

Phenylpropanolamine 893

R Gorodetsky

Phenytoin 895

A L Inselman and D K Hansen

Pheromones 898

A M Fan and D Ting

Phorbol Esters 902

S E Gad and S C Gad

Phosgene 904

SCGad

Phosgene Oxime 907

D R Wallace

Phosphate Ester Flame Retardants 909

SCGad

Phosphine 913

C S Wood

Phosphoric Acid 916

C B Spainhour

Phosphorus 920

H Robles

Photoallergens 922

SCGad

Contents li

Photochemical Oxidants 926

SCGad

Phthalates 928

S Saeidnia

Phthalic Anhydride 934

SCGad

Physical Hazards 937

G Rider, R Alikorn, X Chen, and D Stool

Picloram 948

G G Dumancas

Picric Acid 952

SCGad

Piperazine 955

A M Molina Lopez and M R Moyano Salvago

Piperonyl Butoxide 958

D Maples

Plants, Poisonous (Animals) 960

M I San Andres Larrea, M D San Andres Larrea, and C Rodriguez Fernandez

Plants, Poisonous (Humans) 970

M Banasik and T Stedeford

PLASTICIZERS see Phthalates

Platinum 979

SCGad

Plutonium 982

Y R Rodriguez

Poisoning Emergencies in Humans 986

C P Holstege and E Holstege

Pollutant Release and Transfer Registers 991

H Aizawa and M Oi

Pollution, Air in Encyclopedia ofToxicology 995

T Gordon, L W Stanek, and J Brown

Pollution, Indoor Air 1003

D Schwela

Pollution Prevention Act, United States 1018

SCGad

Pollution, Soil 1019

/ V Tarazona

Pollution, Water 1024

/ V Tarazona

Polybrominated Biphenyls (PBBs) 1028

S A Saghir

Polybrominated Diphenyl Ethers 1032

L G Costa and G Giordano

lii Contents

Polychlorinated Biphenyls (PCBs) 1035

S / Stohs

Polycyclic Aromatic Amines 1038

SCGad

Polycydic Aromatic Hydrocarbons (PAHs) 1040

S C Gad and S E Gad

Polyethylene Glycol 1043

H-W Leung

Polymers 1045

SEGad

Potassium 1051

SCGad

Potassium Hydroxyoctaoxodizincatedichromate 1053

FFFarris

Potassium Iodide 1057

N Barton and T } Wiegand

POTENTIATION see Chemical Interactions

Predicted No Effect Concentration (PNEC) 1061

A Finizio and M Vighi

Primidone 1066

S R Rose

Hazard Ranking 1068

A Maier and M L Dourson

PROBABILISTIC ANALYSIS see Monte Carlo Analysis

Procainamide 1070

C P Holstege and W Rushton

Progesterone and Progestin Mimics 1073

7 L Wittliffand S A Andres

Prometryn 1077

D Dikic

Propachlor 1082

P Gomez-Ramirez and A } Garcia-Ferndndez

Propane 1086

S R Clough

Propane Sultone 1089

SCGad

Propanil 1092

J Liu

Propargite 1094

/ Liu

Propazine 1096

R D Maples

PropeneH M Bolt

PropiconazoleS C Gad and T Pham

Propionic Acid

SCGad

Proposition 65, California

S E Gad and D W Sullivan, }r.

Propoxur

L G Costa

Propylene GlycolK McMartin

Propylene Oxide

H A Shojaei Saadi

ProstaglandinsSEGad

PseudoephedrineR Gorodetsky

PSILOCYBIN see Mushroom, Psilocybin

PSORALEN (P) AND LONG-WAVE ULTRAVIOLET RADIATION (UVA) see PUVA

Psychological Indices of Toxicity

B Weiss

PTFE (Polytetrafluoroethylene; Teflon®)L L Radulovic and Z W Wojcinski

Publishing Trends in ToxicologyHM Bolt

PuromycinM C Korrapati

PUVA

M Tsai-Turton

Pyrene/ Mangos and E Vilanova

Pyrethrins/PyrethroidsD E Ray and S A Burr

PyridineG G Dumancas, R S Hikkaduwa Koralege, E-R E Mojica, B S Murdianti, and P } Pham

PyridostigmineT Dodd-Butera and M Broderick

PyridoxineD B McCormick

PyriminilL P Weber

liv Contents

Pyrrolizidine Alkaloids 1170

H Wiedenfeld