Bridging the Gap from Short-Term Teratogenesis Assays to Human Health Hazard Assessment by Understanding Common Modes of Teratogenic Action / JA. Bantle, DJ. Fort, DA. Dawson
- Conference Author:
- Aquatic Toxicology and Hazard Assessment: 12th Volume (12th : 1988 : Sparks, Nevada)
- Physical Description:
- 1 online resource (13 pages) : illustrations, figures, tables
- Additional Creators:
- Bantle, JA., Dawson, DA., Fort, DJ., American Society for Testing and Materials, and ASTM International
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- License restrictions may limit access. and Subscription required for access to full text.
- Embryonic development depends on the timely expression of genetic information. As development proceeds, embryonic cells undergo processes such as cell division, interaction (induction), migration, differentiation, and selective death. Developmental toxicants affect one or more of these mechanisms. Whole embryo teratogenesis screening assays are best suited for hazard identification because all the developmental mechanisms are represented in the test. Cell culture and biochemical tests are better suited for determining which biochemical or cellular mechanisms are adversely affected by the toxicant. By combining data from a validated whole embryo teratogenesis test with data from cellular and biochemical tests in a battery format, a better indication of the potential human health hazard is afforded. We have tried this approach in the case of DNA synthesis inhibitors. These inhibitors are teratogenic in virtually all species tested regardless of where in the metabolic pathway they inhibit replication. DNA synthesis inhibitors, such as hydroxyurea, cytosine arabinoside, and 5-fluorouracil, were teratogenic in the Frog Embryo Teratogenesis Assay Xenopus (FETAX). These substances also inhibited DNA synthesis in a fluorometric assay using cleaving Xenopus eggs. However, they did not inhibit gene expression as measured by their inability to prevent the expression of the cloned herpes thymidine kinase gene microinjected into Xenopus Stage 6 oocytes. The combined data not only show that malformations are caused by these agents but pinpoint the developmental mechanism affected. This suggests that all species, including man, may be affected. A battery of simple tests could be developed which measures effects on the developmental mechanisms shared by all species. Risk assessment studies would still be necessary to consider dose levels and types of exposure needed to observe an effect in man.
- Dates of Publication and/or Sequential Designation:
- Volume 1989, Issue 1027 (January 1989)
- 080311253X, 9780803112537, and 9780803150881 (e-ISBN)
- Digital File Characteristics:
- text file PDF
- Bibliography Note:
- Includes bibliographical references 33.
- Other Forms:
- Also available in PDF edition., Also available online via the World Wide Web. Tables of contents and abstracts freely available; full-text articles available by subscription., and Full text article also available for purchase.
- Reproduction Note:
- Electronic reproduction. W. Conshohocken, Pa. : ASTM International, 1989. Mode of access: World Wide Web. System requirements: Web browser. Access may be restricted to users at subscribing institutions.
- Technical Details:
- Mode of access: World Wide Web.
- Source of Acquisition:
- ASTM International PDF Purchase price USD25.
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