IngentaConnect The future of teratology research is in vitro

Authors: Bailey, Jarrod; Knight, Andrew; Balcombe, Jonathan

Source: Biogenic Amines, Volume 19, Number 2, 2005 , pp. 97-145(49)

Abstract:

Birth defects induced by maternal exposure to exogenous agents during pregnancy are preventable, if the agents themselves can be identified and avoided. Billions of dollars and manhours have been dedicated to animal-based discovery and characterisation methods over decades. We show here, via a comprehensive systematic review and analysis of this data, that these methods constitute questionable science and pose a hazard to humans. Mean positive and negative predictivities barely exceed 50%; discordance among the species used is substantial; reliable extrapolation from animal data to humans is impossible, and virtually all known human teratogens have so far been identified in spite of, rather than because of, animal-based methods. Despite strict validation criteria that animal-based teratology studies would fail to meet, three in vitro alternatives have done so. The embryonic stem-cell test (EST) is the best of these. We argue that the poor performance of animal-based teratology alone warrants its cessation; it ought to be replaced by the easier, cheaper and more repeatable EST, and resources made available to improve this and other tests even further.

Keywords: TERATOGEN; TERATOLOGY; DEVELOPMENTAL TOXICOLOGY; BIRTH DEFECTS; THALIDOMIDE; ANIMAL; MODEL

Document Type: Research article

DOI: 10.1163/1569391053722755

The full text electronic article is available for purchase. You will be able to download the full text electronic article after payment.

$25.00 plus tax Refund Policy