Critical evaluation of current developmental toxicity testing strategies: a case of babies and their bathwater
Version of Record online: 18 JUL 2011
© 2011 Wiley Periodicals, Inc.
Birth Defects Research Part B: Developmental and Reproductive Toxicology
Special Issue: Developmental Toxicology: New Directions
Volume 92, Issue 5, pages 395–403, October 2011
How to Cite
Carney, E. W., Ellis, A. L., Tyl, R. W., Foster, P. M.D., Scialli, A. R., Thompson, K. and Kim, J. (2011), Critical evaluation of current developmental toxicity testing strategies: a case of babies and their bathwater. Birth Defects Research Part B: Developmental and Reproductive Toxicology, 92: 395–403. doi: 10.1002/bdrb.20318
- Issue online: 17 OCT 2011
- Version of Record online: 18 JUL 2011
- Manuscript Accepted: 3 JUN 2011
- Manuscript Received: 17 MAY 2011
- safety testing;
- maternal toxicity;
- alternatives to animal testing
This review is the second in a series of four papers emanating from a workshop entitled “Developmental Toxicology—New Directions,” which was sponsored by the ILSI Health and Environmental Sciences Institute's (HESI) Developmental and Reproductive Toxicology Technical Committee. The present review analyzes the strengths and weaknesses of current developmental safety testing approaches in an effort to identify those strengths that should be retained in the future versus the weaknesses that should be eliminated. Workshop participants considered the following to be key strengths of current testing approaches: the integrated biology of pregnant animal models including pharmacokinetic and pharmacodynamic processes, the ability to detect low incidence malformations as well as maternally mediated toxicity, and the long history of use coupled with extensive historical data. A number of weaknesses were related to the resource-intensive nature of developmental toxicity testing (e.g., large number of animals, high costs, low throughput, the inability to keep pace with the demand for more toxicity data). Other weaknesses included the use of very high dose levels that often far exceed human exposure levels, the confounding influence of maternal toxicity, sparse understanding of basic developmental mechanisms and genetics of standard animal models relative to mouse or lower organisms, difficulties interpreting low incidence findings, and issues surrounding the interpretation of minor skeletal variations. An appreciation of these strengths and weaknesses is critical for the design of new approaches to developmental toxicity testing in the 21st century. Birth Defects Res (Part B) 92:395–403, 2011. © 2011 Wiley Periodicals, Inc.