Ebook The toxicologist’s pocket handbook (3/E): Part 1

Third Edition

The Toxicologist's
Pocket Handbook
Michael J. Derelanko


The Toxicologist’s
Pocket Handbook
Third Edition



The Toxicologist’s
Pocket Handbook
Third Edition

Michael J. Derelanko


CRC Press
Taylor & Francis Group
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Contents
Preface..............................................................................................xxvii
Acknowledgments.......................................................................... xxxi
Author.............................................................................................xxxiii
1. Lab Animals..................................................................................1

Table 1
Guiding Principles in the Use of Animals in
Toxicology...................................................................1
Table 2
Guiding Principles for Humane Treatment of
Animals in Toxicology Studies................................2
Table 3
Signs Indicative of Pain, Suffering, and
Distress in Animals...................................................3
Table 4
Signs of Moribundity as Criteria for
Humane Sacrifice.......................................................4
Table 5
General Information Sources for the Care
and Use of Research Animals..................................5
Table 6
Approximate Daily Food and Water
Requirements for Various Species...........................6
Table 7
Common Stocks and Strains of Laboratory
Mice..............................................................................7
Table 8
Common Stocks and Strains of Laboratory
Rats...............................................................................9
Table 9
Physical and Physiological Parameters
of Mice....................................................................... 10
Table 10 Physical and Physiological Parameters
of Rats........................................................................ 11
Table 11 Physical and Physiological Parameters

of Dogs.......................................................................12
vii


viii

Contents
Table 12
Table 13
Table 14
Table 15
Table 16
Table 17
Table 18
Table 19
Table 20
Table 21
Table 22
Table 23

Physical and Physiological Parameters of
Rabbits.......................................................................13
Physical and Physiological Parameters
of Guinea Pigs.......................................................... 14
Physical and Physiological Parameters of
Miniature Swine......................................................15
Physical and Physiological Parameters of
Old World Monkeys ............................................... 16
Physical and Physiological Parameters of
New World Monkeys ..............................................17

Body Weight and Food Consumption—
CD-1 Mice..................................................................18
Body Weight and Food Consumption—
Sprague-Dawley Rats..............................................20
Body Weight and Food Consumption—
Fischer 344 Rats........................................................22
Typical Routes and Dosages of Several
Sedative, Analgesic, and Anesthetic Agents........24
Guiding Principles for Animal Euthanasia.........25
Acceptable and Conditionally Acceptable
Agents and Methods of Euthanasia......................26
Summary of the Characteristics of Several
Euthanasia Methods................................................28

2. General Toxicology.....................................................................31
Table 24 Minimum Requirements for an Acceptable
Toxicology Study......................................................31
Table 25 Typical Contents of a GLP Protocol.......................32
Figure 1 Animal Number and Predictive Probability.......33
Table 26 Suggested Dose Volumes for Test Material
Administration.........................................................34
Table 27 Suggested Dosing Apparatus/Needle Sizes
for Test Material Administration...........................35


Contents
Table 28
Table 29
Table 30
Table 31

Table 32
Table 33
Table 34
Table 35
Table 36
Table 37
Table 38
Table 39
Table 40
Table 41
Table 42
Table 43

ix
Guidelines for Dose Administration for
Intravenous Infusion Studies.................................36
Body Weight: Surface Area Conversion...............37
Equivalent Surface Area Dosage Conversion
Factors........................................................................37
Comparison of Dosage by Weight and
Surface Area..............................................................38
Approximate Diet Conversion Factors
(ppm to mg/kg)........................................................38
Clinical Signs of Toxicity........................................39
Autonomic Signs......................................................45
Clinical Chemistry Parameters of
Subchronic and Chronic Studies—
Standard Study Guidelines....................................46
Hematology Parameters of Subchronic and
Chronic Studies—Standard Study Guidelines....47

Urinalysis Parameters of Subchronic and
Chronic Studies—Standard Study
Guidelines.................................................................48
Organ Weight Requirements—Standard
Study Guidelines......................................................49
Microscopic Pathology Requirements—
Standard Study Guidelines—Tissues Most
Often Recommended for Chronic Studies...........50
Microscopic Pathology Requirements—Tissues
Occasionally Recommended for Chronic
Studies—Standard Study Guidelines...................52
Effect of Decreased Body Weights on
Relative Organ Weights of Rats.............................53
Common Abbreviations and Codes Used
in Histopathology....................................................54
Examples of Frequently Used Grading
Schemes for Histopathology Findings..................55


x

Contents

3. Inhalation Toxicology................................................................57
Table 44 Body Weight and Lung Volumes in
Fischer-344 Rats at Various Ages...........................57
Table 45 Body Weight and Lung Volumes in Adult
and Older Hamsters................................................58
Table 46 Ventilatory Parameters in Fischer-344 Rats
at Various Ages.........................................................58

Table 47 Ventilatory Parameters in Hamsters at
Various Ages.............................................................58
Table 48 Morphometric Values in Sprague-Dawley
Rats at Various Ages................................................59
Table 49 Normal Cytology of BALF......................................59
Table 50 Normal Biochemical Content of BALF.................60
Table 51 Tracheal Mucociliary Clearance............................ 61
Table 52 Nasal Mucociliary Clearance.................................62
Table 53 Ammonia Concentrations in an Inhalation
Chamber....................................................................63
Table 54 Conversion Table for Gases and Vapors...............64
Table 55 Calculations Used in Inhalation Toxicology........70
4. Dermal Toxicology.....................................................................73
Table 56 Relative Ranking of Skin Permeability in
Different Animal Species........................................73
Table 57 Common Materials Used as Positive
Controls.....................................................................73
Table 58 Draize Dermal Irritation Scoring System.............75
Table 59 Human Patch Test Dermal Irritation
Scoring System.........................................................75
Table 60 Chamber Scarification Dermal Irritation
Scoring System......................................................... 76
Table 61 Magnusson Sensitization Scoring System............ 76
Table 62 Split Adjuvant Sensitization Scoring System....... 76
Table 63 Buehler Sensitization Scoring System...................77


Contents
Table 64
Table 65

Table 66
Table 67

Table 68

Table 69
Table 70
Table 71
Table 72
Table 73
Table 74
Table 75
Table 76

xi
Contact Photosensitization Scoring
System........................................................................77
Local Lymph Node Ear Scoring System...............77
Human Patch Test Sensitization Scoring
System........................................................................78
Environmental Protection Agency
(EPA) Method of Calculating the Primary
Irritation Index (PII) for Dermal Irritation
Studies.......................................................................78
Federal Hazardous Substances Act (CPSCFHSA) Method of Calculating the Primary
Irritation Index (PII) for Dermal Irritation
Studies.......................................................................79
European Economic Community’s (EEC)
Method of Calculating the Primary Irritation
Index (PII) for Dermal Irritation Studies..............79

Environmental Protection Agency (EPA)
Dermal Classification System................................80
Environmental Protection Agency (EPA)
Standard Evaluation Procedure Dermal
Classification System...............................................80
Federal Fungicide, Insecticide, and
Rodenticide Act (EPA-FIFRA) Dermal
Classification System...............................................81
European Economic Community (EEC)
Dermal Classification System................................81
Federal Hazardous Substances Act (CPSCFHSA) Dermal Classification System....................82
Draize Dermal Classification System....................82
Environmental Protection Agency (EPA)
Design for the Environment Dermal
Classification System Based on Skin
Irritation/Corrosivity..............................................82


xii

Contents
Table 77
Table 78

Table 79
Table 80
Table 81
Table 82
Table 83

Table 84

United Nations Globally Harmonized
System (GHS) for Dermal Classification
Based on Skin Irritation/Corrosivity....................83
Department of Transportation (DOT),
Occupational Safety and Health
Administration (OSHA), and International
Maritime Organization (IMO) Packing
Group Classification System..................................84
Maximization Sensitization Classification
System........................................................................85
Optimization Sensitization Classification
System........................................................................85
OECD and EPA Sensitization Classification
Systems......................................................................85
Local Lymph Node Classification Systems..........86
Environmental Protection Agency (EPA)
Design for the Environment Dermal
Classification System Based on Skin
Sensitization.............................................................86
United Nations Globally Harmonized
System (GHS) for Dermal Classification
Based on Skin Sensitization...................................87

5. Ocular Toxicology.......................................................................91
Table 85 Scale of Weighted Scores for Grading the
Severity of Ocular Lesions......................................91
Table 86 Grades for Ocular Lesions......................................93
Table 87 Classification of Compounds Based on Eye

Irritation Properties.................................................94
Table 88 NAS Classification Method Based on
Severity and Persistence.........................................96
Table 89 Modified NAS Classification Method...................97


Contents
Table 90

Table 91
Table 92
Table 93
Table 94
Table 95
Table 96

xiii
Environmental Protection Agency
(EPA) Design for the Environment
Classification System Based on Eye
Irritation/Corrosivity..............................................98
United Nations Globally Harmonized
System (GHS) for Classification Based on
Eye Irritation/Corrosivity.......................................99
Categorization of Substances Using the Slit
Lamp Biomicroscope and Fluorescein................100
Categorization and Labeling of Pesticides......... 101
Considerations in Selecting In Vitro Assays
to Support Product Development Programs..... 103
Advantages and Disadvantages of DilutionBased Assays for Ocular Irritation...................... 106

Advantages and Disadvantages of Topical
Application Assays for Ocular Irritation............ 107

6. Genetic Toxicology/Carcinogenesis...................................... 109
Table 97 Mutagenicity Assay Bacteria Strains
Overview................................................................. 109
Table 98 The Genetic Code................................................... 110
Table 99 Genetic Toxicology Assays................................... 111
Table 100 Characteristics of Initiation, Promotion,
and Progression..................................................... 119
Table 101 Classification of Carcinogenic Chemicals
Based on Mode of Action......................................120
Table 102 Reported Percentage Incidence of
Spontaneous Tumor Formation in
Various Mouse Strains..........................................123
Table 103 Reported Percentage Incidence of
Spontaneous Tumor Formation in
Various Rat Strains................................................ 124


xiv

Contents
Table 104 Frequency of Carcinogenic Response
to Chemicals by Organ/System—Rats
and Mice..................................................................126
Table 105 Capacity of Tissues to Undergo Hyperplasia..... 128
Table 106 Selected Taxonomy of Neoplasia.........................129
Table 107 Selected Examples of Presumptive
Preneoplastic Lesions............................................130

Table 108 Animal Neoplastic Lesions of Questionable
Significance to Humans........................................ 131
Table 109 Comparative Features of Benign and
Malignant Neoplasms........................................... 132
Table 110 Criteria for Determining the Human
Relevance of Animal Bioassay Results...............134
Table 111 Known Human Carcinogens...............................135

7.Neurotoxicology........................................................................ 139
Table 112 Examples of Potential Endpoints of
Neurotoxicity.......................................................... 139
Table 113 Examples of Parameters Recorded in
Neurotoxicity Safety Studies................................ 140
Table 114 Summary of Measures in the Functional
Observational Battery and the Type of Data
Produced by Each.................................................. 141
Table 115 Measures of the FOB, Divided by
Functional Domain................................................ 142
Table 116 Chemicals Commonly Used as Positive
Control Materials for the FOB.............................. 142
Table 117 Toxic Signs of Acetylcholinesterase Inhibition..... 143
Table 118 Representative Areas of the Nervous System
for Histopathological Evaluations....................... 144
8.Immunotoxicology................................................................... 147
Figure 2 Cellular Elements of the Immune System.......... 147


Contents

xv

Table 119 Examples of the Four Types of Hypersensitivity
Responses................................................................. 148
Table 120 Examples of Antemortem and Postmortem
Findings That May Include Potential
Immunotoxicity If Treatment Related................. 149
Table 121 National Toxicology Program Panel for
Detecting Immune Alterations in Rodents........ 151
Table 122 Immunotoxicology Functional Assays............... 152
9. Reproductive/Developmental Toxicology........................... 159
Figure 3 A General Scheme of Mammalian
Spermatogenesis.................................................... 159
Figure 4 A General Scheme of Mammalian
Oogenesis................................................................ 160
Table 123 Reproductive Parameters for Various
Species.....................................................................161
Table 124 Breeding Characteristics of Female
Laboratory Mammals Compared with the
Human..................................................................... 162
Table 125 Species Variability in Parameters Involving
Spermatogenesis.................................................... 163
Table 126 Species Variability in Parameters Involving
Oogenesis................................................................ 165
Figure 5 Graphic Representation of an
Animal’s Reproductive Life-Cycle and
Corresponding Relationship to the ICH
Reproductive Life Stages...................................... 167
Table 127 Fertility and Reproductive Indices Used in
Single and Multigeneration Studies.................... 168
Table 128 Basic Developmental Toxicity Testing

Protocol.................................................................... 170
Figure 6 Developmental Stages and Timelines in the
Human, Rat, and Rabbit........................................ 171


xvi

Contents
Figure 7

Critical Periods of Embryogenesis in the
Human, Rat, and Rabbit........................................172
Table 129 Signs of Overt Maternal Toxicity......................... 173
Table 130 Signs of Overt Embryofetal Toxicity................... 173
Table 131 End Points of Developmental Toxicity in
Female Rodents and Rabbits................................ 174
10. Clinical Pathology....................................................................177
Table 132 Approximate Blood Volumes in Animals
Typically Used in Nonclinical Toxicology
Research..................................................................177
Table 133 Recommended Maximum Allowable Blood
Collection Volumes for Animals.........................177
Table 134 Common Sites for Blood Collection and
Blood Volumes in Various Species...................... 178
Table 135 Erythrocyte Life Span in Various
Animals................................................................... 179
Table 136 Mean Control Ranges of Typical Serum
Clinical Chemistry Measurements in
B6C3F1 Mice............................................................180
Table 137 Mean Control Ranges of Typical Serum

Clinical Chemistry Measurements
in CD-1 and BALB/c Mice of Various
Ages......................................................................... 182
Table 138 Mean Control Ranges of Typical Serum
Clinical Chemistry Measurements in CD®
Rats...........................................................................183
Table 139 Mean Control Ranges of Typical Serum
Clinical Chemistry Measurements in
F-344 Rats................................................................185
Table 140 Mean Control Ranges of Typical Serum
Clinical Chemistry Measurements
in Beagle Dogs........................................................ 187


Contents

xvii

Table 141 Mean Control Ranges of Typical Serum
Clinical Chemistry Measurements in
Nonhuman Primates of Various Ages................ 189
Table 142 Mean Control Ranges of Typical Serum
Clinical Chemistry Measurements in
New Zealand White Rabbits................................ 191
Table 143 Control Ranges of Typical Clinical
Chemistry Measurements in Minipigs............... 192
Table 144 Mean Control Ranges of Typical
Hematology Measurements in B6C3F1 Mice...... 193
Table 145 Mean Control Ranges of Typical Hematology
Measurements in CD-1 and BALB/c Mice of

Various Ages........................................................... 194
Table 146 Mean Control Ranges of Typical
Hematology Measurements in CD® Rats........... 195
Table 147 Mean Control Ranges of Typical
Hematology Measurements in F-344 Rats......... 196
Table 148 Mean Control Ranges of Typical
Hematology Measurements in Beagle Dogs...... 197
Table 149 Mean Control Ranges of Typical Hematology
Measurements in Nonhuman Primates of
Various Ages........................................................... 198
Table 150 Mean Control Ranges of Typical
Hematology Measurements in
New Zealand White Rabbits................................199
Table 151 Control Ranges of Typical Hematology
Measurements in Minipigs...................................200
Table 152 24-hr Mean Urinalysis Data in Adult
Male Rats: Fischer-344, Sprague-Dawley,
and Wistar...............................................................201
Table 153 24-hr Mean Urinalysis Data in Adult
Female Rats: Fischer-344, Sprague-Dawley,
and Wistar...............................................................202


xviii

Contents

Table 154 Comparison of Biochemical Components in
Urine of Normal Experimental Animals...........203
Table 155 Normal Human Laboratory Values....................205

11. Risk Assessment....................................................................... 215
Figure 8 The Four Major Elements of Risk Assessment.....215
Table 156 Typical Factors Considered in a Risk
Assessment............................................................. 216
Table 157 Major Factors That Influence a Risk
Assessment............................................................. 217
Table 158 Human Data Commonly Used in Risk
Assessment............................................................. 218
Table 159 Epidemiological Measures (Rates and Ratios)...... 219
Figure 9 Exposure Pathways to an Environmental
Pollutant..................................................................220
Figure 10 Diagrammatic Representation of the Possible
Pharmacokinetic Fate of a Chemical after
Exposure by Inhalation, Dermal Contact, and
Ingestion..................................................................221
Figure 11 Representation of the Relationships between
Ambient Exposure and Critical Target Dose
and the Progressive Decrease in Effective
Exposure due to Various Biological Barriers...... 222
Figure 12 Relationship between the Degree of
Uncertainty Associated with the Risk
Assessment of a Chemical, the Concern
for Human Exposure, and the Toxicological
Information Available on the Chemical.............223
Figure 13 Typical Sigmoid Cumulative Dose-Response
Curve for a Toxic Effect.........................................224
Figure 14 A Dose–Response Curve from a Typical
toxicology Study Showing Dose-Related
Indices Commonly Used in Risk Assessment.....225

Contents

xix

Table 160 The Duration of Studies in Experimental
Animals and Time Equivalents in Humans......226
Table 161 Comparative Mammalian Reference Values
for Relative Dose Calculations.............................227
Table 162 Reference Comparative Physiological
Values.......................................................................228
Table 163 Typical Human Exposure Values Useful
in Risk Assessments..............................................230
Table 164 Comparative Mammalian Organ Weights.........232
Table 165 Body Fluid Volumes for Men and Women.........233
Table 166 Relationship between Body Weight and Body
Surface Area in a Number of Vertebrates...........233
Table 167 Constants for Estimating Surface Area of
Mammals................................................................234
Table 168 Median Total Body Surface Area for
Humans by Age.....................................................234
Table 169 Summary of Human Inhalation Rates
for Men, Women, and Children by
Activity Level.........................................................235
Table 170 Summary of Drug Absorption in Neonates,
Infants, and Children............................................236
Table 171 Drug Metabolism in the Neonate, Infant,
and Child................................................................237
Table 172 Renal Function in the Neonate, Infant, and
Child........................................................................238

Table 173 Plasma Protein Binding and Drug
Distribution in Neonates, Infants, and
Children..................................................................239
Table 174 Developmental Patterns for the Ontogeny
of Important Drug-Metabolizing Enzymes
in Humans..............................................................240
Table 175 Frequency of Selected Adverse Pregnancy
Outcomes in Humans........................................... 241


xx

Contents
Table 176 Probabilities of Spontaneous Abortion in
Humans...................................................................242
Table 177 Risk Assessment Calculations.............................243

12. Human Clinical Toxicology....................................................255
Table 178 Some Common Clinical Presentations and
Differential Diagnoses in Overdose....................255
Table 179 Toxicological Syndromes by Class of Drugs......257
Table 180 Common Drugs Included on Most
Toxicology Screens.................................................260
13. Industrial Chemical Toxicology............................................ 261
Table 181 Combined Tabulation of Toxicity Classes.......... 261
Figure 15 Classifications Based on Rat Acute
Oral LD50.................................................................262
Figure 16 Classification Based on Rabbit or Rat Acute
Dermal LD50............................................................263
Figure 17 Classification Based on Rat Acute

Inhalation LC50.......................................................264
Figure 18 Classification Based on Rat Acute
Inhalation LC50.......................................................265
Figure 19 Classification Based on Fish Acute LC50. ...........266
Table 182 Classification Based on Mutagenicity/
Genotoxicity............................................................ 267
Table 183 Classification Based on Carcinogenicity............268
Table 184 Classification Based on Repeated Dose
Target Organ Toxicity............................................272
Table 185 Classification Based on Reproductive and
Developmental Toxicity........................................ 274
Table 186 Classification Based on Eye and Skin
Irritation/Corrosivity, Skin Sensitization
and Respiratory Sensitization.............................. 276


Contents

xxi

Table 187 EPA Categories of Toxicological Concerns.........278
Table 188 Criteria Defining “High-Exposure”
Chemicals................................................................284
Table 189 Selected OECD Guidelines for Testing of
Chemicals................................................................285
Table 190 Risk (R) Phrases Previously Used in the
European Community (EU).................................288
Table 191 GHS Hazard (H) Statements................................293
Table 192 Information Disclosed on a Safety Data
Sheet (SDS)..............................................................295

14. Pharmaceutical and Related Toxicology..............................299
Figure 20 An Overview of the Drug Development
Process in the United States.................................299
Table 193 Typical Timing of Nonclinical Toxicology
and Safety Pharmacology Studies in Drug
Development...........................................................300
Table 194 Biopharmaceuticals versus Small
Molecules: Major Differences That
Affect Testing Strategy..........................................301
Table 195 Minimal Duration for Repeated Dose
Toxicology Studies to Support Drug Clinical
Trials and Marketing.............................................302
Figure 21 A simplistic Method for Assessing “Safety
Ratios’’ for Drugs...................................................303
Table 196 Content of an Investigational New Drug
(IND) Application..................................................304
Table 197 Order for Reporting Toxicology Data for
an IND/NDA..........................................................305
Table 198 Content of the Common Technical
Document (CTD)....................................................307
Table 199 Pharmacokinetics: Basic Overview.....................308


xxii

Contents
Table 200 Comparative Physiological Values for
Frequently Used Pharmacokinetic
Determinations......................................................309
Table 201 Table for Predicting Human Half-Life of

Xenobiotics from Rat Half-Life............................ 310
Table 202 Table for Predicting Human Volume of
Distribution from Rat Volume of 
Distribution.............................................................313
Table 203 Animal/Human Dose Conversions.................... 315
Table 204 FDA Pregnancy Categories.................................. 316
Table 205 DEA Controlled Substances Schedules.............. 317
Table 206 Respiratory Function Parameters Collected
by Whole-Body Plethysmograph in the
Sprague-Dawley Rat.............................................. 318
Table 207 Respiratory Function Parameters Collected
by Whole-Body Plethysmograph in the
CD-1 Mouse............................................................ 318
Table 208 Respiratory Function Parameters Collected
by Whole-Body Plethysmograph in the
Guinea Pig...............................................................319
Table 209 Respiratory Function Parameters Collected
by Head Plethysmograph in the Beagle Dog..... 319
Table 210 Respiratory Function Parameters Collected
by Head Plethysmograph in the Nonhuman
Primate (Cynomolgus Macaque).........................320
Table 211 Cardiovascular Parameters Collected by
Implanted Telemetry in the Beagle Dog............. 321
Table 212 Cardiovascular Parameters Collected by
Implanted Telemetry in the Nonhuman
Primate (Cynomolgus Macaque).........................322
Table 213 Cardiovascular Parameters Collected
by Implanted Telemetry in the Gottingen
Minipig....................................................................323

Contents

xxiii

Figure 22 Correlation between the Cardiac Action
Potential and the QT Interval of the Surface
Electrocardiogram (ECG)..................................... 324
Table 214 Substances Generally Recognized as Safe
(GRAS).....................................................................325
Table 215 The ISO Standard 10993-1 Guidance for
Selection of Biocompatibility Tests as
Modified by the FDA.............................................328
15. Miscellaneous Information....................................................331
Table 216 Comparison of Physiological Parameters for
Different Human Body Organs...........................331
Table 217 Comparison of the Blood Flow/Perfusion
and Oxygen Consumption of Liver, Lung,
Intestine, and Kidney of the Rat In Vivo and
in Organ Perfusion................................................332
Table 218 Comparison of Physiological Characteristics
of Experimental Animals and Humans.............333
Table 219 Comparison of Certain Physiological Values
of Experimental Animals and Humans.............334
Table 220 Overview of Major Mammalian Hormones......335
Figure 23 A Generalized Schematic of Mammalian
Hormonal Regulation Showing Major Points
for Potential Disruption/Modulation.................337
Table 221 Tissue Localization of XenobioticMetabolizing Enzymes.........................................338
Table 222 Metabolic Phase I and Phase II Reactions..........338

Table 223 Major Cytochrome P450 Enzymes......................339
Table 224 Xenobiotic Steady State and Half-Life................342
Table 225 Greek Alphabet......................................................342
Table 226 Prefixes and Symbols for Decimal
Multiples and Submultiples.................................343
Table 227 Table of Equivalents...............................................344


xxiv

Contents

Table 228 Approximate Metric and Apothecary
Weight Equivalents................................................345
Table 229 Conversion Factors: Metric to English................346
Table 230 Conversion Factors: English to Metric................347
Table 231 Temperature Conversion Factors.........................348
Table 232 Temperature Conversions.....................................349
Table 233 Conversion of Hematological Values from
Conventional Units into SI Units.........................350
Table 234 Conversion of Clinical Laboratory Values
from Conventional Units into SI Units...............351
Table 235 Transformation of Percentages into Logits........352
Table 236 Transformation of Percentages into Probits.......352
Table 237 Molarity, Molality, Normality, Osmolarity
Calculations............................................................353
Table 238 Solution Calculations............................................354
Table 239 pH Calculations.....................................................355
Table 240 Mammalian Toxicology Tests—Cost and
Material Requirements..........................................356

Table 241 Genetic Toxicology Tests—Cost and
Material Requirements..........................................358
Table 242 Aquatic/Ecotoxicology Tests—Cost and
Material Requirements..........................................359
Table 243 Chemical Functional Groups...............................360
Table 244 Standard Atomic Weights.....................................369
Table 245 Frequently Encountered Acronyms....................373
16. Glossary—by Subject..............................................................387
Carcinogenesis............................................................................387
Clinical Pathology......................................................................392
Dermal Toxicology.....................................................................394
Ecotoxicology.............................................................................397
Genetic Toxicology.....................................................................400
Immunotoxicology....................................................................401