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Key Event Title
Increased, Structural malformations
Key Event Components
Key Event Overview
AOPs Including This Key Event
Key Event Description
In utero vascular disruptions are thought to be associated with a variety of birth defects [Husain et al., 2008]. Vascular disruption was identified as one of 6 teratogenic mechanisms linked with medications [van Gelder et al., 2010]. In humans, the most common apparent cause of limb deficiencies was found to be vascular disruption defects [Gold et al., 2011]. Susceptibility to Thalidomide linked to the disruption of immature angiogenic network at time of exposure [Therapontos et al., 2009]. Predicted vascular disrupting chemicals in ToxCast correlate with developmental toxicity [Kleinstreuer et al., 2011]. Many genetic and environmental factors alter molecular pathways regulating angiogenesis [Knudsen and Kleinstreuer, 2011].
How It Is Measured or Detected
OECD Test Guidelines:
Test No. 414: Prenatal Development Toxicity Study Test No. 415: One-Generation Reproduction Toxicity Study Test No. 416: Two-Generation Reproduction Toxicity
Domain of Applicability
Gold NB, Westgate MN, Holmes LB. Anatomic and etiological classification of congenital limb deficiencies. American journal of medical genetics Part A. 2011 Jun;155A(6):1225-35. PubMed PMID: 21557466.
Husain T, Langlois PH, Sever LE, Gambello MJ. Descriptive epidemiologic features shared by birth defects thought to be related to vascular disruption in Texas, 1996-2002. Birth defects research Part A, Clinical and molecular teratology. 2008 Jun;82(6):435-40. PubMed PMID: 18383510.
Kleinstreuer NC, Judson RS, Reif DM, Sipes NS, Singh AV, Chandler KJ, et al. Environmental impact on vascular development predicted by high-throughput screening. Environmental health perspectives. 2011 Nov;119(11):1596-603. PubMed PMID: 21788198. Pubmed Central PMCID: PMC3226499.
Knudsen TB, Kleinstreuer NC. Disruption of embryonic vascular development in predictive toxicology. Birth defects research Part C, Embryo today : reviews. 2011 Dec;93(4):312-23. PubMed PMID: 22271680.
Therapontos C, Erskine L, Gardner ER, Figg WD, Vargesson N. Thalidomide induces limb defects by preventing angiogenic outgrowth during early limb formation. Proceedings of the National Academy of Sciences of the United States of America. 2009 May 26;106(21):8573-8. PubMed PMID: 19433787. Pubmed Central PMCID: 2688998.
van Gelder MM, van Rooij IA, Miller RK, Zielhuis GA, de Jong-van den Berg LT, Roeleveld N. Teratogenic mechanisms of medical drugs. Human reproduction update. 2010 Jul-Aug;16(4):378-94. PubMed PMID: 20061329.