ToxSci Advance Access originally published online on April 10, 2009
Toxicological Sciences 2009 110(1):181-190; doi:10.1093/toxsci/kfp080
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Published by Oxford University Press 2009.
Profiling the Reproductive Toxicity of Chemicals from Multigeneration Studies in the Toxicity Reference Database
* National Center for Computational Toxicology, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711
Health Effects Division, Office of Pesticide Programs, U.S. Environmental Protection Agency, Washington, District of Columbia 20460
1 To whom correspondence should be addressed at National Center for Computational Toxicology, Office of Research and Development, U.S. Environmental Protection Agency, MD D343-03, 109 TW Alexander Drive, Research Triangle Park, NC 27711. Fax: (919) 685-3399. E-mail: martin.matt{at}epa.gov.
Received January 26, 2009; accepted April 8, 2009
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Abstract |
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Multigeneration reproduction studies are used to characterize parental and offspring systemic toxicity, as well as reproductive toxicity of pesticides, industrial chemicals and pharmaceuticals. Results from 329 multigeneration studies on 316 chemicals have been digitized into standardized and structured toxicity data within the Toxicity Reference Database (ToxRefDB). An initial assessment of data quality and consistency was performed prior to profiling these environmental chemicals based on reproductive toxicity and associated toxicity endpoints. The pattern of toxicity across 75 effects for all 316 chemicals provided sets of chemicals with similar in vivo toxicity for future predictive modeling. Comparative analysis across the 329 studies identified chemicals with sensitive reproductive effects, based on comparisons to chronic and subchronic toxicity studies, as did the cross-generational comparisons within the multigeneration study. The general pattern of toxicity across all chemicals and the more focused comparative analyses identified 19 parental, offspring and reproductive effects with a high enough incidence to serve as targets for predictive modeling that will eventually serve as a chemical prioritization tool spanning reproductive toxicities. These toxicity endpoints included specific reproductive performance indices, male and female reproductive organ pathologies, offspring viability, growth and maturation, and parental systemic toxicities. Capturing this reproductive toxicity data in ToxRefDB supports ongoing retrospective analyses, test guideline revisions, and computational toxicology research.
Key Words: pesticides; relational database; reproductive toxicity; toxicity profiling.
Disclaimer: The United States Environmental Protection Agency through its Office of Research and Development funded and managed the research described here. It has been subjected to Agency administrative review and approved for submission and peer review.