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. 2016 Jan;32(1):9-14.
doi: 10.5487/TR.2016.32.1.009. Epub 2016 Jan 31.

Advances in the Development and Validation of Test Methods in the United States

Warren M Casey  1
Affiliations

Advances in the Development and Validation of Test Methods in the United States

Warren M Casey. Toxicol Res. 2016 Jan.

Abstract

The National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) provides validation support for US Federal agencies and the US Tox21 interagency consortium, an interagency collaboration that is using high throughput screening (HTS) and other advanced approaches to better understand and predict chemical hazards to humans and the environment. The use of HTS data from assays relevant to the estrogen receptor signaling data pathway is used as an example of how HTS data can be combined with computational modeling to meet the needs of US agencies. As brief summary of US efforts in the areas of biologics testing, acute toxicity, and skin sensitization will also be provided.

Keywords: Alternative; HTS; Tox21; Toxicity; US; Validation.

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Figures

Fig. 1
Fig. 1
16 ER pathway assays from ToxCast. These include three cell-free biochemical radioligand ER binding assays from NovaScreen (human, mouse, bovine); a set of three protein complementation assays from Odyssey Thera that measure formation of ER dimers and test for activity against ER-alpha and ER-beta, (each homo- and hetero-dimer measured at two separate times for a total of six assay readouts); two Odyssey Thera assays measuring interaction of the transcription factor with DNA; two transactivation assays from Atta-gene measuring RNA transcript levels; two transactivation assays measuring reporter protein level readouts, conducted at NIH-NCGC; and an ER-sensitive cell proliferation assay from ACEA. The assay sources refer to the company or laboratory where the assays were performed. Cell line and tissue of origin are also provided for each assay.
Fig. 2
Fig. 2
Flow diagram illustrating the curation of the uterotrophic database (UTDB) and identification of high-quality guideline like (GL) studies.
See this image and copyright information in PMC

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