||Contemporary Issues in Toxicology: A New Frontier in Understanding the Mechanisms of Developmental Abnormalities.
Kimmel, C. A. ;
Generoso, W. M. ;
Thomas, R. D. ;
Bakshi, K. S. ;
||Environmental Protection Agency, Washington, DC. Office of Health and Environmental Assessment.
Congenital abnormalities ;
Embryo development ;
Risk assessment ;
Preimplantation phase ;
Ovum implantation ;
Newborn animals ;
||Some EPA libraries have a fiche copy filed under the call number shown.
||The paper reviews some of the important issues that may lead to understanding basic developmental processes and mechanisms by which toxic agents may interfere with normal and abnormal development. Approximately 70% of developmental defects are of unknown etiology. Historically, it has been assumed that these defects were most likely to be induced by exposure to chemical or physical agents during organogenesis. There is now convincing evidence that exposure during preorganogenesis developmental stages to certain agents can also lead to fetal abnormalities as a result of direct damage to the exposed early conceptus. Thus, pre- or post-implantation exposure of the developing conceptus to toxicants may result in a 'derailment' in the genetic control of development and the coordinated cascade of events that occur during normal development. For example, developmental abnormalities may be induced by disrupting the coordinated expression of developmental genes involved in genomic imprinting, cell lineage specification, cell mixing and recognition, cell-cell interaction, cell migration and differentiation, and segmentation. The study of mechanisms of normal and abnormal development and the pharmacokinetic-pharmacodynamic relationships in humans and experimental animals are key to the development of appropriate risk assessment assumptions and dose-response models for characterizing the risk for developmental toxicity in humans.
||Pub. in Toxicology and Applied Pharmacology, v119 p159-165 1993.
|NTIS Title Notes
||Reprint: Contemporary Issues in Toxicology: A New Frontier in Understanding the Mechanisms of Developmental Abnormalities.
||PC A02/MF A01