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 ofRochester Medical Center and Strong Memorial Hospital, Rochester, NY, USA

VOLUME 2

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

Preface

Preface to The Second Edition

Preface to The First Edition

Editor-in-Chief

Associate Editors

List of Contributors

How to Use The Encyclopedia

Acknowledgments

Dedication

hcvii

ixix

Ixxiii

Ixxv

Ixxvii

Ixxix

Ixxxiii

cix

cxi

cxiii

v

xxii Contents

VOLUME 2

Department of Energy, US 1

/ A Handler

Derived Minimal Effect Level (DMEL) 4

R Roy and R Skoglund

Derived No-Effect Level (DNEL) 7

R Roy and R Skoglund

DERMAL TOXICITY TESTING see Toxicity Testing, Dermal

DESFEROXAMINE see Deferoxamine

DESIPRAMINE see Tricyclic Antidepressants

Detergent 10

Z Cai and P } Hakkinen

Developmental Toxicology 14

C C Willhite and P E Mirkes

DEVELOPMENT TOXICITY TESTING see Toxicity Testing, Developmental

Dextromethorphan 45

/ M Marraffa

Diacetyl 47

V Schaeffer and A Iannucci

Diaminotoluenes 51

A R Gohari, A bAanayi, and S Saeidnia

Diazinon 55

S Karanth

Diazoaminobenzene 57

E Martinez-Lopez and A J Garda-Femdndez

Diazoxide 60

F F Farris

Dibenz[d,/i]anthracene 62

S Bhattacharya, P Chakraborty, and S S Roy

Dibenzofuran 67

K N Thakore and H M Mehendale

Dibromochloropropane 70

D M Naistat

DIBUTHYL ETHER see Diethyl Ether

Dicamba

X Song

Dicarboxylic Acid

M S Parmar

Dichlone

XSong

Dichlorobenzene

E M Udarbe Zamora

Dichloroethane, 1,2-

I Syed and S D Ray

1,1-Dichloroethane

I Syed

1,2-Dichloroethylene

S S Devi and H M Mehendale

Dichloromethane

N Yang

Dichloropropene

J Liu

Dichlorvos

S Karanth

Dieldrin

M. Honeycutt and S Shirley

Diesel Exhaust

M } Wemke

Diesel Fuel

SCGad

Dietary Restriction

UApte

Dietary Sugar: Public Health PerspectiveN P Steyn and N } Temple

Dietary SupplementsJC P Baran

Diethylamine/ M McKee

Diethyl Ether

F Monticelli

Diethylene Glycol/ M. Marraffa

DiethylstilbestrolM S Mitra and B K Philip

Diflubenzuron

N Jin

xxiv Contents

Difluoroethylene, 1,1- 149

K N Thakore and H M Mehendale

Digitalis Glycosides 151

M P Emswiler and B K Wills

Dimethoate 155

N S Mirajkar

Dimethylaminoazobenzene 158

H Robles

Dimethyl Ether 160

G L Kennedy

Dimethyl Sulfate 162

SAsha

Dimethyl Sulfoxide (DMSO) 166

S E Gad and D W Sullivan, Jr.

Dimethylmercury 169

S G Gilbert

Dinitroanilines 172

R A Young

1,3-Dinitrobenzene 175

S } Klein

Dinitrophenols 177

D M Janz

Dinitrotoluene 179

R A Young

Dinoseb 183

M Badanthadka and HM Mehendale

Dioxane, 1,4- 186

J Stickney and H Carlson-Lynch

Dioxins 190

R A Young

Diphenhydramine 195

S M Miller and K L Cumpston

Diphenylamine 198

S / Klein

Diphenylhydrazine 200

R A Young

Diquat 202

/ R Roede and G W Miller

Distribution 205

S A Saghir

Disulfiram 208

L Qian and F L Cantrell

Contents xxv

Disulfoton 210

G M Fent

Dithiocarbamates 212

D M Janz

Diuron 215

J Liu

DNA see Aneuploidy; Carcinogen—DNA Adduct Formation and DNA Repair; Chromosome Aberrations; DNA

Phosphoramidites; Genetic Toxicology; MOLECULARTOXICOLOGY: Recombinant DNA Technology; ToxicityTesting, Mutagenicity

DNA ADDUCT see Carcinogen-DNA Adduct Formation and DNA Repair

DNA Phosphoramidites 217

N Rezvani and D L Bolduc

DNA REPAIR see Carcinogen—DNA Adduct Formation and DNA Repair

Dominant Lethal Assay 220

KPBaran and S C Gad

Donora: Air Pollution Episode 222

M A Kamrin

Dose—Response Relationship 224

E } Calabrese

Drinking-Water Criteria (Safety, Quality, and Perception) 227

HH Dieter

Drug and Poison Information Centers 236

SLHon

Drug Regulations, Europe 240

M I de San Andres Larrea, M Escribano, and A Gonzdlez-Canga

Drugs of Abuse 248

/M Marraffa

Dyes and Colorants 252

S Nikfar and M Jaberidoost

ECHA (The European Chemicals Agency) 263

European Chemicals Agency

Echinacea 265

S A Meyer and S Ramasahayam

Ecological Exposure Limits and Guidelines 268

/ V Tarazona

Ecological Quality Standards (EQS) Global 272

7 V Tarazona

Ecotoxicology 276

/ V Tarazona and M J Ramos-Peralonso

Ecotoxicology, Aquatic 281

B Versonnen, M Sobanska, and R Cesnaitis

xxvi Contents

Ecotoxicology, Aquatic Invertebrates 284

A Chaumot, B Ferrari, O Geffard, and J Game

Ecotoxicology, Avian 289

A J Garda-Femdndez

Ecotoxicology, Genetic 295

B Pina and C Barata

Ecotoxicology, Terrestrial 301

/ V Tarazona and M J Ramos-Peralonso

Ecotoxicology, Wildlife 306

/ V Tarazona and M } Ramos-Peralonso

EDTA (Ethylenediaminetetraacetic Acid) 310

C Barton

EDUCATION AND CAREERS IN TOXICOLOGY see Toxicology, Education and Careers

Effluent Biomonitoring 312

1 Michalak and K Chojnacka

Electromagnetic Fields 316

/ R Salvatore

Emergency Planning and Community Right-to-Know Act (EPCRA) 320

Emergency Response and Preparedness 321

G C Millner, PM Brady, and T L Murta

Endocrine System 332

K Chou and } Henderson

Endosulfan 341

P Singh, B Volger, and E Gordon

Endrin 344

M Honeycutt and L Jones

Environmental & Health Laws, Europe 348

M I Szynkowska and A Pawlaczyh

Environmental Advocacy (Non US) 353

M Lloyd-Smith

ENVIRONMENTAL CHANGE see Global Climate Change and Environmental Toxicology

Environmental Exposure Assessment 366

A Di Guardo

Environmental Fate and Behavior 372

A Covad

Environmental Health 375

S Harper

Environmental Hormone Disruptors 378

L R Rhomberg, M Seeley, T Verslycke, and J E Goodman

Environmental Justice 381

K Sexton

Environmental Processes

C Theodorakis and T D Walker

Environmental Protection Agency, US

Environmental Risk Assessment, AquaticR Cesnaitis, B Versonnen, and M Sobanska

Environmental Risk Assessment, Cosmetic and Consumer Products

/ V Tarazona

Environmental Risk Assessment, Marine

/ Marigomez

Environmental Risk Assessment, Pesticides and Biocides

F Pellizzato

Environmental Risk Assessment, Secondary Poisoning/ V Tarazona and M f Ramos-Peralonso

Environmental Risk Assessment, Terrestrial

/ V Tarazona and M J Ramos-Peralonso

Environmental ToxicologyM I Szynkowska and A Pawlaczyk

Eosinophilia—Myalgia Syndrome/ A Allen and } Varga

EphedraV S Vaidya and HM Mehendale

EPHEDRINE see Amphetamines

EpichlorohydrinB Hirakawa

EpidemiologySCGad

EpigeneticsR E Watson

EPINEPHRINE see Catecholamines

ErgotC P Holstege and S A Traven

Erionites

N Rezvani and D L Bolduc

ErythromycinD / Roberts

Escherichia coli

J Robbens, L Devriese, K Verstraete, and M Heyndrickx

Estrogens I: Estrogens and Their Conjugates/ L Wittliffand S A Andres

Estrogens II: Catechol Estrogens/ L Wittliffand S A Andres

xxviii Contents

Estrogens III: Phytoestrogens and Mycoestrogens 471

/ L Wittliff and S A Andres

Estrogens IV: Estrogen-Like Pharmaceuticals 475

/ L Wittliff and S A Andres

Estrogens V: Xenoestrogens 480

/ L Wittliff and S A Andres

Ethane 485

S R Clough

Ethanol 488

B Strohm

Ethanolamine 492

S C Gad

Ethene 496

H M Bolt

ETHER see Diethyl Ether

Ethics: Ethical Issues in Toxicology 498

S G Gilbert

Ethionine 501

F-M Menn

2-Ethoxyethanol 503

B Stanard

Ethyl Acetate 506

C Estevan and E Vilanova

Ethyl Acrylate 511

R } Parod

Ethylamine 514

G L Kennedy

Ethylbenzene 516

M Banton

Ethyl Bromide 519

M J Wemke

Ethyl Methanesulfonate 522

M Amini

Ethylene Glycol 525

/ / Devlin and M Schwartz

Ethylene Glycol Mono-n-Butyl Ether 528

B Strohm

Ethyleneimine 532

SCGad

Ethylene Oxide 535

R } Parod

EU see European Union and Its European Commission

EugenolR Sellamuihu

EU Risk Assessment Committees

/ V Tarazona

European Association of Poisons Centres and Clinical Toxicologists (EAPCCT), TheH Persson and P Hulten

European Centre for Ecotoxicology and Toxicology of Chemicals

N Carmichael

European Classification and Labeling (C&L) Inventory, The

E Luschiitzky, } M Kilpinen, P Atlason, and C Comu

European Food Safety Authority (EFSA)M } Ramos-Peralonso

European Medicines Agency (EMA), The

European Medicines Agency

European Union and Its European CommissionS Nikfar, S Golbabaei, A Abdolahi, and ] van der Kolk

EUROTOX

A Tsatsakis and C Tsitsimpikou

Evidence-Based ToxicologyS Hoffmann, M Stephens, and T Hartung

Electronic Waste

V Dissanayake

Excretion

S A Saghir

Exposome, The

A4 T Smith

Eye Irritancy TestingKPBaran and S C Gad

F

FAO see Food and Agriculture Organization of the United Nations

Federal Insecticide, Fungicide, and Rodenticide Act, US

P Krishnan

FEMALE REPRODUCTIVE SYSTEM see Reproductive System, Female

Fenthion

V C Moser

Fenvalerate

E Martinez-Lopez and A J Garcia-Ferndndez

Fetal Alcohol Spectrum Disorders

K Shankar and HM Mehendale

xxx Contents

Fexofenadine 593

S R Clough

Fipronil 596

G M Fent

Fish Consumption Advisory 598

/ M Gohlke and D Doke

FLAME RETARDANTS see Polybrominated Diphenyl Ethers

Flavor and Extract Manufacturers Association 602

Fluometuron 603

E Ki Udarbe Zamora

Fluoride 606

M Abdollahi and F tAomen-Heravi

Fluorine 611

R WKapp, Jr.

Folic Acid 616

D K Hansen and A L Inselman

Folpet 619

P Singh, S M Cohen, and E Gordon

FOOD see Dietary Restriction; Algae; Dietary Supplements; Food Additives; Food Quality Protection Act;

Food Safety and Toxicology; Food, Drug, and Cosmetic Act, US; Food and Agriculture Organization of the

United Nations; Genetically Modified Food/Organism; Monosodium Glutamate (MSG)

Food Additives 622

/ C Griffiths and J F Borzelleca

FOOD ADDITIVES: Joint FAO/WHO Expert Committee see Joint FAO/WHO Expert Meetings(JECFA and JMPR)

Food and Agriculture Organization of the United Nations 628

A Wennberg

Food and Drug Administration, US 631

R D Beckett

Food, Drug, and Cosmetic Act, US 633

R W Kapp, Jr.

Food Quality Protection Act 637

tA Rajabi

Food Safety and Toxicology 639

C D Carrington and PM Bolger

Foreign Body Response 645

SCGad

Forensic Toxicology 647

FKAdatsi

Formaldehyde 653

M Abdollahi and A Hosseini

Formamide

G L Kennedy

657

Formic Acid

/ Liesivuori

FrackingS L Thornton

Freons

M ) Wemke

Fuel Oils

B Laffon

Fuel OxygenatesD McGregor

Furan

H Robles

Furfural

N R Reed andESC Kwok

G

Galactosamine

UApte

Gallium

SCGad

Gap Junctional Intercellular Communication

/ E Trosko and R J Ruch

Gasoline

M A Kamrin

Gastrointestinal SystemM } Fedoruk and S Hong

Generally Recognized as Safe (GRAS)S E Gad and D W Sullivan, Jr.

Genetically Modified Food/OrganismM Rabiei and S Sardari

GENETIC ECOTOXICOLOGY see Genetic Ecotoxicology

Genetic Toxicology! R Landolph, Jr.

Cyclosarin (GF)K Willis, H Salem, and F R Sidell

Ginger Jake

RCGuy

GI TRACT see Gastrointestinal System

Global Chemicals Policy/ van der Kolk

Global Climate Change and Environmental ToxicologyABA Boxall

xxxii Contents

Globally Harmonized System for Classification and Labeling of the GHS 741

/ van der Kolk

Global Public Health and Toxicology 746

/ A Romano and P L Knechtges

GLOBAL WARMING see Global Climate Change and Environmental Toxicology

Glutathione 751

S C Gad

Glyceraldehyde 752

S R Clough

Glycerol 754

M } Wernke

Glycidol 757

A Foroumadi and S Emami

Glycol Ethers 762

A Shafiee, M Khoobi, and H Nadri

Glyphosate 767

KN Baer and B } Marcel

Gold 770

SCGad

Good Clinical Practice (GCP) 772

S P Sawant, H S Parihar, H M Mehendale, and KM Hanson

Good Laboratory Practices 778

RCGuy

Gossypol 782

A de Peyster

Graphical Depictions ofToxicological Data 786

G M Woodall

Great Smog of London 796

Y R Rodriguez

Green Chemistry 798

T A Lewandowski

G-Series Nerve Agents 800

M Abdollahi and S Mostafalou

Guaifenesin 806

P Richter

HI-Blockers

C M. Groth and N M Acquisto

Hair

S Nikfar and M Jaberidoost

809

813

HALLUCINOGENS see Belladonna Alkaloids; Lysergic Acid Diethylamide

Hamner Institutes for Health Sciences, The

S S Devi and H M Mehendale

Hazard Identification

M A Kamrin

Import/Export of Hazardous Chemicals

/ van der Kolk

Hazardous Waste

M V Pablos

Health Assessments

C Barton

HEARING see Sensory Organs

Heat-Shock Proteins

K Shankar and HM Mehendale

Helium

M L Hultin

HemocompatibilityK Rodgers

HeparinN M Acquisto

HEPATOTOXICOLOGY see Liver

HeptachlorN R Reed and S Koshlukova

HeptaneS R Clough

HeptanoneM Badanthadka and HM Mehendale

HERBICIDES see Chlorophenoxy Herbicides

hERG (Human Ether-a-Go-Go Related Gene)/ Steidl-Nichols

Heterocyclic Aromatic Amines

K John and S Beedanagari

HexabromocyclododecaneD T Szabo

Hexachlorobenzene

E M Udarbe Zamora

Hexachlorobutadiene

D M Janz

Hexachlorocyclohexanes Including Lindane

G Chen

HexachlorocyclopentadieneM Badanthadka and HM Mehendale

xxxiv Contents

Hexachloroethane 882

S B Jazayeri, R Bazl, M Biglar, and M Amanlou

Hexachloronaphthalene 890

D T Szabo and A E Loccisano

Hexachlorophene 894

R W Lange and B K Philip

Hexamethylene Diisocyanate 897

R N Shiotsuka

Hexane 900

S R Clough

2-Hexanone 905

A S Persad

High Production Volume (HPV) Chemicals 908

S Nikfar, A F Behboudi, } van der Kolk, and A Benson

High Temperature Cooked Meats 912

A Gevaart-Durkin and A de Peyster

High Throughput Screening 916

M S Attene-Ramos, C P Austin, and M Xia

History of the US Environmental Movement (Revised 10 January 2012) 918

P Montague andM B Pellerano

HISTORY OF TOXICOLOGY see Toxicology, History of

Hormesis 944

S D Ray, F F Farris, and A C Hartmann

HORMONE DISRUPTORS see Environmental Hormone Disruptors

HORMONES see Anabolic Steroids; Androgens; Estrogens I: Estrogens and their Conjugates;

Estrogens II: Catechol Estrogens; ESTROGENS III: Phytoestrogens and Mycoestrogens;ESTROGENS IV: Estrogen-Like Pharmaceuticals; ESTROGENS V: Xenoestrogens

Host-Mediated Assay 949

D A Eastmond

Hydraulic Fluids 951

/ Lord-Garcia

Hydrazine 953

C E Lambert

Hydrobromic Acid 957

A Foroumadi and M Saeedi

Hydrochloric Acid 960

M Abdollahi and S Nikfar

Hydrofluoric Acid 964

S E Gad and D W Sullivan, Jr.

HYDROGEN CYANIDE see Cyanide

Hydrogen Peroxide 967

M Abdollahi and A Hosseini

Hydrogen Sulfide

M Abdollahi and A Hosseini

Hydroiodic Acid

C P Holstege and HA Borek

Hydroperoxide, tert-ButylSEGad

HydroquinoneS C Gad and T Pham

HydroxylamineS C Gad

HymenopteraG W Everson

Hypersensitivity, Delayed TypeL A Burns-Naas

Hypoglycemics, Oral

H A Spiller

I

IBOTENIC ACID see Mushrooms, Ibotenic Acid

IbuprofenA Garrard

Idiopathic Environmental Intolerances

K Rodgers

ImidaclopridL P Sheets

Immune System/ Descotes

Implant Studies

SCGad

IMPORT AND EXPORT OF CHEMICALS see Import/Export of Hazardous Chemicals

INDOOR AIR POLLUTION see Indoor Air Pollution

INHALATION see Respiratory Tract Toxicology

INHALATION TESTING see Toxicity Testing, Inhalation

INSECT see Hymenoptera

INSECTICIDES see Permethrin

In Silico Methods

L G Valerio, Jr.

INTERACTIONS see Interactive Toxicity

INTERCELLULAR COMMUNICATION see Gap Junctional Intercellular Communication

Indole

D W Sullivan, Jr. and S E Gad

XXXVI Contents

Industrial Hygiene 1032

D L Dahlstrom, S Nikfar, A A Malekirad, and A F Behboudi

Information Resources in Toxicology 1036

F W Berman

Integrated Pollution Prevention and Control (IPPC) 1058

M J Ramos-Peralonso

Interactive Toxicity 1061

S S Anand, B K Philip, and H M Mehendale

Intergovernmental Forum on Chemical Safety 1065

/ van der Kolk

International Agency for Research on Cancer 1067

C P Wild

International Conference on Harmonisation 1070

RCGuy

International Fragrance Association (IFRA) 1073

S Nikfar and S Kharabaf

International Labor Organization (ILO) 1075

S Nikfar and S Kharabaf

International Life Sciences Institute Health and Environmental Sciences Institute (ILSI-HESI) 1077

M R Embry

International Organization of the Flavor Industry 1078

N Rezvani and D L Bolduc

International Society for the Study of Xenobiotics 1080

V Mody and S D Ray

International Society of Exposure Science 1082

DB Ban-

International Union of Pure and Applied Chemistry 1084

JHDuffus

International Union of Toxicology 1088

E Corsini

Inter-Organization Programme for Sound Management of Chemicals 1090

/ van der Kolk

Investigative New Drug Application 1093

SCGad

In Vitro—In Vivo Extrapolation 1096

H } Clewell and M Yoon

In Vitro Tests 1101

SCGad

In Vivo Tests

SCGad

1103

Iodine

SCGad

1105

Contents xxxvii

IONIZING RADIATION see Radiation Toxicology, Ionizing and Nonionizing

Iron 1108

SCGad

Islip Garbage Barge 1111

T Canedy

Isocyanates 1112

R WKapp,Jr.

Isodrin 1132

; E Kester

Isoniazid 1135

N M Accjuisto

Isophorone 1138

SCGad

Isoprene 1141

M ] Wemke

Isopropanol 1144

M Punja