Risk Assessment of Prenatally-Induced Adverse Health Effects

ISBN-13: 9783642777554 / Angielski / Miękka / 2011 / 565 str.

Diether Neubert; Robert J. Kavlock; Hans-Joachim Merker

Opis

Since the thalidomide (Contergan) tragedy about 30 years ago the induction of prenatally-induced morphological or functional defects has been an area of extensive research. Risk assessment of prenatally-induced adverse health effects is still a difficult task from both experimental data as well asfrom observations in humans. In the contributions to this book three major aspects are dealt with: - Quantitative extrapolations of experimental data to the situation possibly relevant for man. - The significance for a risk assessment with respect to man of minor or rare structural abnormalities observed in experimental studies - The future need to assess congenital dysfunctions (e.g. of the hormone or the immune system) beside the present evaulation of structural defects. Limitations as well as gaps of the present knowledge in this area of basic and applied research are pointed out. Since the results of prenatally-induced lesions may manifest themselves not only pre- but often not before late postnatally, numerous aspects of structural and functional abnormaldevelopment must be studied in experimental and clinical investigations.

Spis treści

Risk Assessment for Pharmaceutical Products.- Reproductive Toxicity Risk Assessment — Some Questions.- Biomarkers of Developmental Neurotoxicity.- A Call for Increased Flexibility in Current Teratogenicity Testing.- Specific and Non-Specific Developmental Effects.- Assessment of Reproductive Toxicology of Drugs at the Food and Drug Administration.- New Approaches to Developmental Toxicity Risk Assessment at the U.S. Environmental Protection Agency.- Scientific Basis for Risk Assessment (Reproductive Toxicity) for Pesticides as Practiced by the Bundesgesundheitsamt (BGA).- Scientific Basis for Risk Assessment (Reproductive Toxicity) in Ecotoxicology as Practiced by the Federal Environmental Agency (Umweltbundesamt).- General Discussion: Choice of Species.- Scientific Basis for Risk Assessment (Reproductive Toxicity) for Medicinal Products as Practiced in Germany and the European Community (EC).- Risk Assessment in Reproductive Toxicology as Practiced in South America.- Reproductive Hazard Evaluation and Risk Assessment under California’s Proposition 65.- General Discussion: Risk Assessment.- Statistical Problems (and Some Solutions) Associated with Testing for Effects in Developmental Toxicology.- Aspects of Concentration-Response Analysis.- Dose-Response Relationships in Reproductive Toxicology: Importance of Skeletal Variations.- Prenatal-Toxic Risk Estimation Based on Dose-Response Relationships and Molecular Dosimetry.- Kinetic Problems Arising in a Multigeneration Study.- Application of Mathematical Dose-Response Models vs. Physiological Models in Risk Assessment in Reproductive Toxicology.- General Discussion: Use of Biologically Based Models.- Pharmacoknetics and Drug Metabolism in the Design and Interpretation of Developmental Toxicity Studies.- Feasibility of Studying Effects on the Immune System in Non-Human Primates.- Marmosets (Callithrix jacchus) as Useful Species for Toxicological Risk Assessments.- Planning and Performance of Segment I, II and III Experiments: Practical Aspects and General Comments.- Significance of Postnatal Manifestations of Prenatally-Induced Effects (Behaviour).- Significance of Prenatally or Early Postnatally-Induced Organ Dysfunctions — Other than CNS Defects.- Quantitative Morphological Tests for Evaluation of Testicular Toxicity.- Morphological Changes in Cultures of Hippocampus Following In Vitro Irradiation.- Possible Contribution of In Vitro Methods to Risk Assessment in Reproductive and Developmental Toxicology.- Morphological Endpoints in In Vitro Testing.- Significance of Epidemiological Studies for Risk Assessment in Prenatal Toxicity.- Maternal Thyroid Autoantibodies and Fetal Thyroid Growth.- Pre- and Postnatal Risk Factors for the Development of Atopy in Childhood.- Does Smoking During Pregnancy Alter Brain Perfusion in the Neonate? A Doppler Study.- Risk Assessment of Tocolytic Therapy in Pregnancy.- Histochemical and Immunocytochemical Investigations of the Fetal Extravascular and Vascular Contractile System in the Normal Placenta and During Preeclampsia.- Some Data on the Pattern of Lymphocyte Subsets in Blood During the Perinatal Period.