| Interpretation of skeletal variations for human risk assessment: delayed ossification and wavy ribs. | |
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MedLine Citation:
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PMID: 18157903 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Delayed (or incomplete) ossification of developing fetal bones and wavy ribs are some of the most common skeletal variations encountered in regulatory guideline developmental toxicity studies. Although they tend to be regarded as minor effects, they can be quite sensitive and consequently may influence the study lowest-observed-adverse-effect levels (LOAELs), and thus, impact classification, labeling, and risk assessment. In this study, we review the underlying mechanisms of these skeletal variations, evaluate different scenarios in which they have been observed, offer guidance for their interpretation, and comment on their use for risk assessment. Both minor delays in ossification and wavy ribs seem to be readily repairable via postnatal skeletal remodeling, are not mechanistically linked to malformation, and often are seen in the presence of maternal or fetal toxicity. As such, these minor variations would not generally be considered adverse in and of themselves but should be interpreted in the context of other maternal and fetal findings, information available on normal skeletogenesis patterns, mode of action of the test agent, and historical control incidence using a weight of evidence approach. |
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Authors:
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Edward W Carney; Carole A Kimmel |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Birth defects research. Part B, Developmental and reproductive toxicology Volume: 80 ISSN: 1542-9741 ISO Abbreviation: Birth Defects Res. B Dev. Reprod. Toxicol. Publication Date: 2007 Dec |
Date Detail:
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Created Date: 2007-12-27 Completed Date: 2008-02-05 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101155115 Medline TA: Birth Defects Res B Dev Reprod Toxicol Country: United States |
Other Details:
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Languages: eng Pagination: 473-96 Citation Subset: IM |
Copyright Information:
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(c) 2007 Wiley-Liss, Inc. |
Affiliation:
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Toxicology & Environmental Research and Consulting, The Dow Chemical Company, Midland, Michigan 48674, USA. EWCarney@dow.com |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Abnormalities, Drug-Induced* Animals Humans Osteogenesis / drug effects* Rats Ribs / abnormalities, drug effects* Risk Assessment / methods Skull / abnormalities, drug effects* Teratogens / classification, toxicity* Time Factors Toxicity Tests / methods Xenobiotics / classification, toxicity* |
| Chemical | |
Reg. No./Substance:
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0/Teratogens; 0/Xenobiotics |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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