Susceptibility in utero and upon neonatal exposure.
Important determinants or principles in developmental toxicology are: (1) genotype; (2) developmental stage when an insult is hitting; (3) mechanisms of action; (4) pharmacokinetics of the drug in the mother, conceptus and the neonate; (5) the manifestations of embryo/foeto- and neonatal toxicity such as death, malformations, growth inhibition and functional disturbances; and (6) dose-effect and dose-response relationships. The present paper will give a broad review of some important developmental events and sensitivity periods, such as the preimplantation period, the period of gastrulation, organogenesis and placental formation, the foetal and neonatal period during which xenobiotics can cause perturbation in the normal development. Mostly pharmaceuticals are used as examples due to their often well documented effects and sometimes known sensitivity periods. For the postnatal period, some neurotoxic pesticides and environmental pollutants, known to affect adult behaviour in experimental animals after perinatal exposure, are given as examples.
Dencker
L
L
Uppsala University, Department of Pharmaceutical Biosciences, Faculty of Pharmacy, Biomedical Centre, Sweden.
Eriksson
P
P
D000014:Abnormalities, Drug-Induced; D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects; D001755:Blastocyst / Q000187:drug effects; D004054:Diethylstilbestrol / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000009:adverse effects; D005838:Genotype; D005865:Gestational Age; D006801:Humans; D015474:Isotretinoin / Q000009:adverse effects; D051379:Mice; D051381:Rats; D013792:Thalidomide / Q000009:adverse effects
D000927:Anticonvulsants; D000431:Ethanol; D013792:Thalidomide; D004054:Diethylstilbestrol; D015474:Isotretinoin