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

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232 DEVELOPMENTAL REPRODUCTIVE TOXICOLOGY: A PRACTICAL APPROACH, SECOND EDITIONTable 7.7Summary and statistical analysis of control rat fetal malformationsand variationsGestational Days of DosingParameter 6–15 6–19No. fetuses examined a 2723 1932No. litters examined b 178 136MalformationsNo. fetuses with external malformations/litter c,d 0.02 ± 0.01 0.02 ± 0.01Percent fetuses with external malformations/litter c,d 0.16 ± 0.08 0.13 ± 0.08No. (percent) fetuses with external malformations d 4 (0.1) 3 (0.2)No. (percent) litters with external malformations e 4 (2.2) 3 (2.2)No. fetuses with visceral malformations/litter c,d 0.55 ± 0.10 0.11 ± 0.04Percent fetuses with visceral malformations/ litter c,d,f 6.92 ± 1.36 1.41 ± 0.49No. (percent) fetuses with visceral malformations d 98 (6.4) 15 (1.6)No. (percent) litters with visceral malformations e 43 (24.2) 9 (6.6)No. fetuses with skeletal malformations/litter c,d 0.04 ± 0.02 0.05 ± 0.02Percent fetuses with skeletal malformations/litter c,d 0.89 ± 0.42 0.77 ± 0.03No. (percent) fetuses with skeletal malformations d 8 (0.4) 7 (0.7)No. (percent) litters with skeletal malformations e 7 (3.9) 7 (5.1)No. fetuses with any malformations/litter c,d 0.61 ± 0.10 0.18 ± 0.05Percent fetuses with malformations/litter c,d,f 4.73 ± 0.87 1.22 ± 0.30No. (percent) fetuses with malformations d 109 (4.0) 25 (1.3)No. (percent) litters with malformations e 53 (29.8) 17 (12.5)VariationsNo. fetuses with external variations/litter c,d 0.02 ± 0.01 0.0 ± 0.0Percent fetuses with external variations/litter c,d 0.10 ± 0.07 0.0 ± 0.0No. (percent) fetuses with external variations d 3 (0.01) 0 (0.0)No. (percent) litters with external variations e 2 (1.1) 0 (0.0)No. fetuses with visceral variations/litter c,d 3.62 ± 0.23 1.15 ± 0.11Percent fetuses with visceral variations/litter c,d,f 44.9 ± 2.89 16.04 ± 1.54No. (percent) fetuses with visceral variations d 645 (41.9) 157 (16.3)No. (percent) litters with visceral variations e 140 (78.7) 79 (58.1)No. fetuses with skeletal variations/litter c,d 0.97 ± 0.10 1.00 ± 0.11Percent fetuses with skeletal variations/litter c,d 10.87 ± 1.21 14.40 ± 1.58No. (percent) fetuses with skeletal variations d 172 (9.4) 136 (14.1)No. (percent) litters with skeletal variations e 94 (52.8) 74 (54.4)No. fetuses with variations/litter c,d 4.46 ± 0.24 2.15 ± 0.015Percent fetuses with variations/litter c,d,f 29.09 ± 1.50 15.26 ± 1.05No. (percent) fetuses with variations d 793 (29.1) 293 (15.2)No. (percent) litters with variations e 160 (89.9) 113 (83.1)aOnly live fetuses were examined for malformations and variationsbIncludes only litters with live fetusescReported as the mean ± S.E.M.dFetuses with one or more malformations or variationseLitters with one or more fetuses with malformations or variationsfp ≤ 0.001; significant difference between the two groupsSource: Marr, M.C., Myers, C.B., Price, C.J., Tyl, R.W., and Jahnke, G.D., Teratology,59, 413, 1999 (tables provided by the authors).Technicians should make notations regarding spilled feeders, feed in bottom of cage, etc., to accountfor “outlying” values not appropriate for inclusion in summarization and analysis (statistical testsfor outliers can also be used to identify suspect values). Water consumption should be assessed inexactly the same way as feed consumption. If the animals are dosed via feed or water, the actualintake of test material in grams or milligrams per kilogram of body weight per day can be easilycalculated. This is done by using the value for consumption in grams per kilogram per day multipliedby the percentage of test material in the diet or water.© 2006 by Taylor & Francis Group, LLC
DEVELOPMENTAL TOXICITY TESTING — METHODOLOGY 233Table 7.8Summary of morphological abnormalities in control CD ® rat fetuses:listing by defect type aGestational Days of DosingParameter 6–15 6–19Fetal Malformations and VariationsTotal no. fetuses examined externally b 2723 1932Total no. fetuses examined viscerally b 1538 d 966Total no. fetuses examined skeletally b 1838 d 965 eTotal no. litters examined c 178 136External MalformationsAnasarca 1 (1)Cleft palate 1 (1)Anal atresia 1 (1) 2 (2)Agenesis of the tail 1 (1)Short, thread-like tail 2 (2)Short tail 1 (1)Umbilical hernia 1 (1)Visceral MalformationsAbnormal development of the cerebral hemispheres 1 (1)Abnormally shaped heart 1 (1)Hydronephrosis:Bilateral 2 (2) 6 (4)Left 3 (2) 3 (2)Right 1 (1)Hydroureter:Bilateral 54 (28) 4 (3)Left 36 (19) 2 (2)Right 3 (3) 3 (3)Skeletal MalformationsUnossified frontals, parietals, and interparietals 1 (1)Discontinuous rib 1 (1)Discontinuous rib cartilage 1 (1)Fused rib cartilage 1 (1)Fused cartilage: thoracic centrum 1 (1)Bipartite cartilage, bipartite ossification center: thoracic centrum 6 (5) 6 (6)External VariationsHematoma:Neck 2 (1)Forelimb 1 (1)Visceral VariationsEnlarged lateral ventricle of brain (full):Bilateral 100 (43) 18 (15)Left 20 (13) 8 (7)Right 19 (14) 4 (4)Enlarged lateral ventricle of brain (half):Bilateral 129 (52) 48 (28)Left 12 (9) 21 (15)Right 11 (10) 7 (5)Enlarged lateral ventricle of brain (partial):Bilateral 283 (63)Left 14 (11)Right 14 (13)© 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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Table 8.5Total body composition by
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Table 8.6Serum chemistry values for
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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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Table 9.33Selected comparison point
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Table 9.48What do regulatorswant to
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CHAPTER 10Testing for Reproductive
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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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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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CHAPTER 21Developmental and Reprodu
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There are six factors that may affe
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