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Annual Report for Fiscal Year 2016

Annual Report for Fiscal Year 2016

NICEATM Support of Tox21

NICEATM will make curated data from Tox21 and the U.S. Environmental Protection Agency ToxCast program available through its Integrated Chemical Environment resource to be launched in FY 2017. Future resource development plans include the addition of tools such as in vitro to in vivo extrapolation workflows.

The Tox21 and the U.S. Environmental Protection Agency’s (EPA) ToxCast programs are investigating the use of the zebrafish model as a screening tool for hazard identification. A Collaborative Workshop on Aquatic Models and 21st Century Toxicology identified the lack of standardized husbandry and testing protocols as a challenge to broader use. These issues will be addressed by the NTP Systematic Evaluation of the Application of Zebrafish in Toxicology initiative supported by NICEATM.

Using the collective results of 16 Tox21 and ToxCast estrogen receptor pathway related assays, NICEATM developed and applied one-compartment or physiologically based pharmacokinetic models to a workflow that quantitatively correlates in vitro and in vivo dosimetry for estrogen receptor reference chemicals. The approach highlighted the importance of pharmacokinetic considerations in assessing and ranking endocrine-active chemicals based on in vitro high throughput screening assays. This work is described in several publications. The first version of the workflow was published in December 2014 in Applied In Vitro Toxicology. A manuscript describing the application of an improved approach to a larger chemical set will be submitted to Environmental Health Perspectives in FY 2017 and a poster describing open-source workflows to conduct these analyses will be presented at the 2017 Society of Toxicology annual meeting.

Using data from nine Tox21 and ToxCast assays, NICEATM built a model to predict androgen receptor pathway activity and evaluated it using a list of reference chemicals developed from high-quality in vitro data from androgenic activity assays. The model and evaluation are described in a manuscript submitted to Chemical Research in Toxicology.

From these data and the androgen receptor pathway predictions, NICEATM also developed predictive quantitative structure-activity relationship models for androgen receptor binding and activity. These models were presented in a poster (Zang et al.) at the 2016 Society of Toxicology annual meeting.

Related Annual Report Pages:

Zebrafish Screening