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

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1010 DEVELOPMENTAL REPRODUCTIVE TOXICOLOGY: A PRACTICAL APPROACH, SECOND EDITIONNormal Values of Glomerular Filtration Rate for Humans by AgeAge GFR (ml/min/1.73m 2 )Preterm infant (gestation weeks 25–28)1 week 11.0 ± 5.42–8 weeks 15.5 ± 6.2Preterm infant (gestation weeks 29–34)1 week 15.3 ± 5.62–8 weeks 28.7 ± 13.8Term infant5–7 days 50.6 ± 5.81–2 months 64.6 ± 5.83–4 months 85.8 ± 4.85–8 months 87.7 ± 11.99–12 months 86.9 ± 8.42–12 years 133 ± 27From: Gomez et al. 1999 (2)The kidney is a well-perfused organ, receiving approximately 20% of cardiac output at rest.Glomerular filtration delivers filtered plasma to the proximal tubule. Small molecules (~5000daltons) pass through the glomerular barrier and restriction increases as molecular mass increasesto where molecules the size of albumin (~68,000 daltons) do not pass the barrier. Glomerularfiltration rate (GFR) is determined using clearance studies comparing urine volume excreted withamount of excreted inulin or some other metabolically inert material not reabsorbed or secreted bythe renal tubules. A normal GFR for newborn infants is less than 50 mL/min/1.73m 2 , rises to 100to 140 mL/min/1.73m 2 in humans over 1 year of age, and reaches an adult level by the age of 2years (1, 7, 8). After birth the rapid rise in glomerular filtration rate is attributed to several factorsincluding increased mean arterial blood pressure and glomerular hydraulic pressure, a sharp declinein renal vascular resistance, with a redistribution of intrarenal blood flow from the juxtamedullaryto the superficial cortical nephrons (25).Immature glomeruli are present for months after birth and glomerular maturation and filtrationincreases during early infancy. Glomerular size follows a regular growth curve in childhood, withan average diameter of 100 µm at birth, progressing to 300 µm (1). <strong>Ho</strong>wever, glomerular filtrationrate does not increase proportionally with body size. Prior to gestation week 34, body size increasesbut glomerular filtration rate does not; after that time glomerular filtration rate increases morerapidly than body weight (26). Immature glomeruli are functional once capillary function has beenestablished (1).Comparative SpeciesThree stages of glomerular filtration rate development have been identified by studying variousspecies (13). The first stage is characterized by equivalent rates of increase in GFR and kidneymass. The second stage is characterized by a greater rate of increase in GFR than kidney growth.In the final stage, GFR increases at the same rate as that of kidney mass. These three stages do notnecessarily correlate with anatomical development across species. In addition to empirical measurements,allometric scaling has been used to predict GFR for various species (27).Changes in glomerular filtration rate parallel those for renal blood flow. Intrarenal blood flowoccurs at different rates for the inner and outer cortexes. Thus glomerular filtration developmentoccurs during different time periods as intra renal blood flow distributes between inner and outercortexes (13).Dogs — Inner cortical blood flow begins to increase with age about postnatal Day 12 in dogs.This results in a sharp decline in the ratio between inner and outer cortical blood flow, that has© 2006 by Taylor & Francis Group, LLC
POSTNATAL DEVELOPMENTAL MILESTONES 1011been reported as ~0.95 on Day 1 to 0.3 on Day 12 and throughout adulthood (13). In the case ofthe neonatal dog the developmental change in intra renal blood flow distribution correlates withthe period of nephrogenesis. An illustration of the timing of maturation of the inner cortical andouter cortical blood flow in dogs is presented below.130110IC/OC Flow Ratio90705030102 6 10 14 18 22 26 30 34 38Age (days)From: Kleinman, 1982. (13)Glomerular filtration rate increases with age postnatally in dogs. Based on clearance studiesusing small to large molecules, an increase in glomerular capillary surface area and pore densityoccurs between postnatal weeks 1 and 6 in dogs (28).Rats — Glomerular filtration rate sharply increases in rats during the first six weeks of postnatallife (29). A comparison of early postnatal glomerular filtration rates in rats and dogs is presentedbelow.Glomerular Filtration Rate(ml.min −1 /g Kidney)0.90.60.31 2 3Postnatal Age (months)Glomerular filtration rate in rat () and canine () kidney during postnatal maturation. From: <strong>Ho</strong>rster, 1977. (29)© 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/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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1060 DEVELOPMENTAL REPRODUCTIVE TOX
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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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100 DEVELOPMENTAL REPRODUCTIVE TOXI
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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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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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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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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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HUMAN STUDIES 837with spina bifida
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CHAPTER 21Developmental and Reprodu
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