ICE: Integrated Chemical Environment
Successful computational toxicology projects depend on high-quality data that are freely available and formatted for use in computational workflows. The Integrated Chemical Environment (ICE) addresses the data needs frequently expressed by NICEATM stakeholders. Launched in March 2017, ICE provides curated data from NICEATM, its partners, and other resources, as well as tools to facilitate the safety assessment of chemicals. An article in published in November 2022 in Frontiers in Toxicology (Daniel et al. 2022) provides the most recent detailed overview of ICE.
In August 2023, NICEATM released ICE 4.0.1, which implemented these features:
- Availability of population-level exposure predictions across multiple pathways through the ICE Search tool in addition to the ICE REST API and IVIVE tool.
- Functional use categories added to ICE Chemical Characterization tool.
- A new "Curated Product Use Explorer" in the ICE Chemical Characterization tool that expands and improves upon the former "Consumer Use Explorer."
- Improved support for chemical name searching in all ICE tools.
- Harmonization of structure and data fields in the dermal irritation/corrosion data set to make data computationally accessible and facilitate interoperability on the ICE user interface.
- New Chemical Quick Lists:
- Mixtures and Formulations in ICE.
- ToxCast Phase I, Phase II, and e1k.
- Further development of data visualizations and query summaries for Search tool results (beta version).
A training event organized by PCRM shortly after the ICE 3.6 update featured NICEATM developers demonstrating how to use ICE tools for data and assay exploration. Videos from the training are available on the PCRM website.
A oral presentation at the 12th World Congress on Alternatives and Animal Use in the Life Sciences (Unnikrishnan et al., Session S452, "On the Runway: Interactive Predictive Tox Models") will describe the ICE 4.0.1 updates. Posters to be presented at World Congress describe features to be included in ICE version 4.0.1 and future releases:
- Hull et al. (Human-Centered Biomedical Research session) describes how future versions of ICE will integrate variability in metabolic enzyme activity into physiologically based kinetic models.
- Hull et al. (Next-Gen Education session) describes how future ICE releases will incorporate flags alerting users to potential technological interference.
- Unnikrishnan et al. (21st Century Predictive Toxicology session) describes expansion of PBPK models to predict chemical distribution in brain and adipose tissue.
ICE Data and Curation
ICE includes data from animal and non-animal tests that measure toxic effects described in chemical safety regulations. These effects include acute oral toxicity, skin and eye irritation, skin sensitization, and endocrine activity. ICE also contains curated HTS data from the EPA ToxCast program and the Tox21 consortium and physicochemical property data about chemicals including solubility, melting point, and molecular weight.
Inclusion of data from Mansouri et al. 2018) means that ICE tools can utilize predictions of physicochemical and ADME properties and toxicity endpoints for thousands of chemicals lacking experimental data. ICE REST APIs, implemented in version 3.7 (July 2022), allow users to access ICE data more easily via database searches outside of the ICE graphical user interface environment.(
Curation by NICEATM of all data that go into ICE (described in Daniel et al. 2022) is paramount to ensuring that robust data are available to users. NICEATM staff critically curate, review, and harmonize all ICE data. Curation of HTS data for ICE first retrieves Tox21 and ToxCast data from EPA’s invitrodb, which houses all HTS data analyzed using the ToxCast Pipeline (tcpl) package. NICEATM then applies curation steps to minimize low-confidence hit calls, providing a processed version of the HTS data, referred to as cHTS, that is ready for any application. Factors considered in the curation include chemical purity, quality control data, concentration-response curve fits, and testing range. To facilitate targeted access of cHTS data by ICE tools, NICEATM also maps assay endpoints to mechanistic targets, facilitating interpretation of assay readouts based on biological processes, and to modes of action relevant to toxicity endpoints of regulatory concern.
The ICE Search tool enables users to easily query and integrate data streams and explore the results interactively.
Assays selected in one ICE tool can be used to query other ICE tools. Various ICE tools support uploads of custom data, results visualizations, and results filtering options. Outputs provide publication-quality graphics and downloadable data files.
ICE IVIVE and PBPK tools leverage EPA’s httk package to provide users with an approachable, easy-to-use interface for running analyses. Users can leverage curated datasets in ICE or upload their own data. Furthermore, the IVIVE outputs can be visualized with in vivo or predicted exposure data overlays to provide additional context to results.
The ICE Chemical Quest tool conducts chemical similarity searches based on Saagar fingerprints (Sedykh et al. 2021) to help ICE users identify similar chemicals based on their own input chemicals. This tool allows users to draw novel structures or in put any chemical descriptor as input. The ICE Chemical Characterization tool allows the user to comprehensively evaluate a chemical or chemical list or compare two chemical lists, and review their chemicals' physicochemical properties, chemical product use information, and bioactivity across cHTS data backgrounds.