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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