Loading…

Relative parameter sensitivity in prenatal toxicity studies with substances classified as developmental toxicants

► Relative parameter sensitivity in 22 developmental toxicity studies was analyzed. ► Maternal and fetal weight effects were most often affected at dLOAEL. ► Skeletal malformations were the most often affected specific developmental effects. ► Classified developmental toxicants show similar effect p...

Full description

Saved in:
Bibliographic Details
Published in:Reproductive toxicology (Elmsford, N.Y.) N.Y.), 2012-09, Vol.34 (2), p.284-290
Main Authors: Rorije, E., van Hienen, F.J.W., Dang, Z.C., Hakkert, B.H., Vermeire, T., Piersma, A.H.
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:► Relative parameter sensitivity in 22 developmental toxicity studies was analyzed. ► Maternal and fetal weight effects were most often affected at dLOAEL. ► Skeletal malformations were the most often affected specific developmental effects. ► Classified developmental toxicants show similar effect patterns as general chemicals. Developmental toxicity testing according to the globally standardized OECD 414 protocol is an important basis for decisions on classification and labeling of developmental toxicants in the European Union (EU). This test requires relatively large animal numbers, given that parental and offspring generations are involved. In vitro assay designs and systems biology paradigms are being developed to reduce animal use and to improve prediction of human hazard. Such approaches could benefit from the long-term experience with animal protocols and more specifically from information on the relevance of effects observed in these tests for developmental toxicity. Therefore, we have analyzed relative parameter sensitivity in 22 publicly available developmental toxicity studies, representing about one third of all classified developmental toxicants under European legislation. Maternal and fetal weight effects and fetal survival were most often affected parameters at the developmental Lowest Observed Adverse Effect Level (dLOAEL), followed by skeletal malformations. Specific end points such as cleft palate were observed in fewer studies at dLOAEL, but if observed may have been crucial in classification and labeling decisions. These results are similar to earlier studies using different selections of chemicals, indicating that in general classified developmental toxicants have a similar pattern of effects at the dLOAEL as chemicals in general. These findings are discussed within the perspective of the development of innovative alternative approaches to developmental hazard assessment.
ISSN:0890-6238
1873-1708
DOI:10.1016/j.reprotox.2012.05.092