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

CHAPTER 1Principles of DevelopmentalToxicology RevisitedRonald D. HoodCONTENTSI. Introduction ............................................................................................................................3II. Basic Principles......................................................................................................................5A. Some Basic Terminology ..............................................................................................5B. Wilson’s Principles ........................................................................................................61. Susceptibility to Teratogenesis Depends on the Genotype of the Conceptusand the Manner in Which This Interacts with Adverse Environmental Factors....62. Susceptibility to Teratogenesis Varies with the Developmental Stageat the Time of Exposure to an Adverse Influence ..................................................73. Teratogenic Agents Act in Specific Ways (Mechanisms) on DevelopingCells and Tissues to Initiate Sequences of Abnormal DevelopmentalEvents (Pathogenesis)..............................................................................................84. The Access of Adverse Influences to Developing Tissues Dependson the Nature of the Influence (Agent)...................................................................85. The Four Manifestations of Deviant Development Are Death, Malformation,Growth Retardation, and Functional Deficit...........................................................96. Manifestations of Deviant Development Increase in Frequency and Degreeas Dosage Increases, from the No-Effect to the Totally Lethal Level.................10III. Who Will Conduct the Tests, and Who Will Interpret the Results?...................................11IV. Where Do We Go from Here?.............................................................................................12References ........................................................................................................................................12I. INTRODUCTIONDevelopmental toxicology has been evolving as a discipline for decades with only modest initialrecognition despite the early knowledge that an excess of certain nutrients (e.g., vitamin A) 1 oradministration of various chemicals could cause developmental defects in various animal species. 2–4As has been stated many times, it took the revelation in the early sixties that thalidomide, a drugpromoted as a relatively innocuous sedative and antiemetic, was a potent human teratogen 5 to arouse3© 2006 by Taylor & Francis Group, LLC