1. Suspected Causes of Human Birth Defects Suspected Cause% of Total Genetic Autosomal genetic disease15-20 Cytogenetic5 Environmental Maternal conditions4 Maternal infections3 Mechanical Problems1-2 Chemicals/drugs/radiation/hyperthermia<1 Unknown65

2. Human Developmental Toxicants I Radiation –Therapeutic –Radionuclide –Atomic fallout Infection –Rubella virus –Cytomegalovirus –Toxoplasmosis –Venezuelan equine encephalitis virus –Syphilis –Parvovirus B-19 –Varicella virus Maternal Trauma/Metabolic Imbalance –Alcoholism –Amniocentesis (early) –CVS before day 60 –Cretinism –Diabetes –Folic acid deficiency –Hyperthermia –Phenylketonuria –Rheumatic disease –Sjogren’s syndrome –Virilizing tumors

3. Human Developmental Toxicants II Drugs/Chemicals –Androgens –ACE inhibitors Enalapril, captopril –Antibiotics Tetracycline –Anticancer drugs Cycloposphamide, busulfan –Anticonvulsants Diphenylhydantoin, trimethadione, valproic acid –Antithyroid drugs Methimazole –Chelators Penicillamine –Chlorobiphenyls –Cigarette smoke –Cocaine –Coumarin (warfarin) –Ethanol –Ethylene oxide –Fluconazole –Diethylstilbesterol –Iodides –Lithium –Metals Hg, Pb –Methylene blue –Misoprostol –Retinoids 13-cis retinoic acid, etretinate –Thalidomide –Toluene abuse

4. Critical Periods of Susceptibility (Wilson)

5. Critical Periods for Malformations in Humans MalformationTime of Induction Cyclopia23 days Anencephaly26 days Transposition of great vessels34 days Cleft lip36 days Aplasia of radius38 days Ventricular septal defects6 weeks Syndactyly6 weeks Cleft palate8-9 weeks Bicornurate uterus10 weeks Hypospadias12 weeks Cryptorchidism7-9 months