A Practical Approach, Second Edition=Ronald D. Ho.pdf

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424 DEVELOPMENTAL REPRODUCTIVE TOXICOLOGY: A PRACTICAL APPROACH, SECOND EDITION174. U.S. Environmental Protection Agency, Health Effects Test Guidelines; Reproduction and FertilityEffects, Office of Prevention, Pesticides and Toxic Substances (OPPTS) 870.3800, 1998b.175. ICH Expert Working Group, ICH Harmonised Tripartite Guideline, Detection of Toxicity to Reproductionfor Medicinal Products, S5A, International Conference on Harmonisation, Geneva, Switzerland,1994.176. ICH Expert Working Group, Maintenance of the ICH Guidelines on Toxicity to Male Fertility, anAddendum to the ICH Harmonised Tripartite guideline, Detection of Toxicity to Reproduction forMedicinal Products, S5B(M), International Conference on Harmonisation, Geneva, Switzerland, 1994.© 2006 by Taylor & Francis Group, LLC
CHAPTER 10Testing for Reproductive Toxicity*Robert M. ParkerCONTENTSI. Introduction ........................................................................................................................428A. Brief Overview of DART Study Guidelines.............................................................4281. Fertility Studies....................................................................................................4292. Developmental Toxicity Studies..........................................................................4303. Reproduction Studies...........................................................................................4304. Reproductive Assessment by Continuous Breeding ...........................................4315. Developmental Neurotoxicity Study ...................................................................4326. Combined Repeated Dose Toxicity Study with the Reproduction andDevelopmental Toxicity Screening Test..............................................................4337. Dominant Lethal Study .......................................................................................435B. Endpoints for Reproductive Studies..........................................................................4361. Couple-Mediated Endpoints ................................................................................4362. Male-Specific Endpoints and Paternally Mediated Effects ................................4363. Female-Specific Endpoints and Maternally Mediated Effects ...........................436II. Reproductive Performance.................................................................................................437A. Overview....................................................................................................................437B. Treatment Duration for Males in Fertility and Reproduction Studies .....................437C. Cohabitation and Evidence of Mating ......................................................................4381. Vaginal Plugs .......................................................................................................4382. Vaginal Smears ....................................................................................................438D. Reproductive Indices .................................................................................................4391. Male Mating and Fertility Index .........................................................................4392. Female Fertility Index .........................................................................................4403. Mean Gestational Length ....................................................................................4424. Litter Size ............................................................................................................4425. Live-Birth Index ..................................................................................................4436. Survival Index......................................................................................................4437. Sex Ratio..............................................................................................................444III. Male Reproductive Toxicology..........................................................................................444A. Biology.......................................................................................................................444B. Observations ..............................................................................................................445C. Male Body Weight and Food Consumption..............................................................445D. Male Necropsy...........................................................................................................445* The views expressed in this chapter are those of the author and do not necessarily reflect the views of <strong>Ho</strong>ffmann-LaRoche, Inc.425© 2006 by Taylor & Francis Group, LLC
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Second EditionDEVELOPMENTALandREPRO
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Published in 2006 byCRC PressTaylor
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Chapter 12Chapter 13Chapter 14Chapt
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The EditorRonald D. Hood, Ph.D., is
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Alan M. HobermanArgus ResearchHorsh
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APPENDIX ATerminology of Anatomical
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TERMINOLOGY OF ANATOMICAL DEFECTS 9
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Organ/StructureCodeNumberObservatio
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Organ/Structure10145 Ocular colobom
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Organ/StructurePulmonaryarteryPulmo
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Terminology of developmental abnorm
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Organ/StructureCervicalcentrumCodeN
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Organ/Structure10689 Misshapen thor
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Organ/StructureSacralcentrumSacralv
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968 DEVELOPMENTAL REPRODUCTIVE TOXI
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1000 DEVELOPMENTAL REPRODUCTIVE TOX
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Table 1Human Non-human Primate Rat
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Table 1 (continued)Sertoli CellsHum
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Table 2 (continued) Landmarks in th
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Table 2 (continued) Landmarks in th
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POSTNATAL DEVELOPMENTAL MILESTONES
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PART IPrinciples and Mechanisms© 2
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4 DEVELOPMENTAL REPRODUCTIVE TOXICO
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10 DEVELOPMENTAL REPRODUCTIVE TOXIC
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Table 2.6Receptor(Official Name a )
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Clearly, more research needs to be
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CHAPTER 6Comparative Features of Ve
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COMPARATIVE FEATURES OF VERTEBRATE
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Table 6.2Comparative reproductive a
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Maturation andRelease ofGametesSper
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Amniotic cavity 9.5 1.5 1-4 1-4,6,9
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Posteriorcardinal veinsestablishedT
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PosteriorcardinaldegenerationRight
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StomachappearsThirdpharyngealpouch;
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Table 6.6DescriptionComparative ges
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ParathyroidParathyroids 12.5 6.2 41
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Table 6.8DescriptionComparative ges
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Formation ofchoroid plexusof latera
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Optic nervefibers presentDifferenti
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Table 6.10DescriptionMuscular Syste
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Distalphalanges offingersseparatedF
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Table 6.11DescriptionIntermediateme
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Table 6.12DescriptionComparative ge
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CHAPTER 7Developmental Toxicity Tes
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DEVELOPMENTAL TOXICITY TESTING —
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Female 0.00-0.69 0.004-0.39 0.00-0.
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Figure 8.11775Pott DescribesScrotal
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The underlying physiology of juveni
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Table 8.5Total body composition by
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Table 8.6Serum chemistry values for
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Table 8.7Parameter bHematology valu
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CHAPTER 9Significance, Reliability,
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DEVELOPMENTAL AND REPRODUCTIVE TOXI
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Prior to the early 1980s, numerous
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Figure 9.51906Food andDrugs Act2000
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Table 9.18Selected comparison point
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TESTING FOR REPRODUCTIVE TOXICITY 4
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We would like to acknowledge the ef
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CHAPTER 12Role of Xenobiotic Metabo
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ROLE OF XENOBIOTIC METABOLISM IN DE
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y ESR spectrometry. 122 Further ESR
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CHAPTER 13Use of Toxicokinetics in
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USE OF TOXICOKINETICS IN DEVELOPMEN
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CHAPTER 17Statistical Analysis for
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STATISTICAL ANALYSIS FOR DEVELOPMEN
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CHAPTER 19Perspectives on the Devel
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PERSPECTIVES ON THE DEVELOPMENTAL A
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Guideline OECD 415 (One Generation)
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The Office of Prevention, Pesticide
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CHAPTER 20Human Studies — Epidemi
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HUMAN STUDIES 801I. INTRODUCTIONEpi
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HUMAN STUDIES 803is actively trying
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HUMAN STUDIES 829B. The Formation o
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CHAPTER 21Developmental and Reprodu
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There are six factors that may affe
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