ChemTunes.ToxGPS - Toxicity Database, Knowledgebase and Read-Across

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ChemTunes is a unique cheminformatics platform and expert QC'ed database to store, manage, search and retrieve chemical substances along with their in vitro and in vivo toxicity, safety evaluation and metabolism data designed to facilitate and support the safety and risk assessment process for chemical substances.

ChemTunes offers an easy-to-use user interface to retrieve relevant information, combining chemistry and toxicity searches tailored to the needs of toxicologists working in the area of safety and risk assessment.

Key Facts

Approximately 100,000 chemical compounds
Over 32,000 toxicity studies and 70 endpoints
Diverse chemical space and regulatory use types, including food-related substances, drugs, cosmetics, industrial chemicals and pesticides

ChemTunes database is now available with an optionally integrated version of the RepDose database from Fraunhofer ITEM (more info)

ToxGPS® provides a reliable toxicity knowledgebase including workflows and predictions for a series of in vivo and in vitro human health and regulatory-relevant endpoints. The predictions are based on mechanistically-informed, probabilistic QSAR models and endpoint-specific structural knowledge (expert rules) which are combined to provide a weight-of-evidence prediction together with an estimate of the associated uncertainty. Nearest neighbors of the query compounds in the training sets are identified and linked to the experimental study data in the ChemTunes databases.

ToxGPS Predictions

ToxGPS® predictions are also suited for the assessment of genotoxic impurities in drug products under the ICH M7 guideline.

ToxGPS®also features the ToxGPS Read-Across workflow for data gap filling by identifying structural, physicochemical and biological analogs from the ChemTunes databases. The system offers tools to line up diverse evidence sources, either experimental or in silico, and to combine them to obtain an overall outcome with estimated uncertainty. Users can interactively explore how the read-across outcome varies depending on which evidence sources are used and the reliability assigned to each source.

References

[1]	Cherkasov A, et al. QSAR modeling: where have you been? Where are you going to? J. Med. Chem. 2014, 57(12), 4977-5010.
[2]	Leist M, Yang C, et al. Novel Technologies and an Overall Strategy to Allow Hazard Assessment and Risk Prediction of Chemicals, Cosmetics, and Drugs with Animal-Free Methods. Altex 2012, 29, 4/12, 373-388.
[3]	Yang C, et al. Computational Toxicology Approaches at the US Food and Drug Administration. ATLA 2009, 37, 523-531.
[4]	Rathman JF, et al. Uncertainty Estimation and Quantitative Combination-of-Evidence using Dempster-Shafer Theory. Comp. Tox. 2018, 6, 16-31.

Key Features

The ChemTunes Toxicity Database provides reliable in vitro, in vivo toxicity and regulatory information.

Overview

Endpoint-specific, comprehensive safety evaluation and risk assessment information
Safety assessment including MoS, MoE, RfD, NOAEL, ADI, uncertainty factor, target site, critical effect, regulatory body, year
Expert-assigned data reliability and quality scores
Data mining capabilities to perform hypothesis-driven queries, e.g., combined search for chemical structure, toxicity endpoint and effect site
Data location for ToxGPS read-across workflow

Retrieval Process

ChemTunes ToxGPS Retrieval

Regulatory Data Sources

US EPA IRIS, EFSA, SCCS/SCCP/SCCNFP, US FDA, JECFA/WHO, NITE Japan, COSMOS and Munro database

Toxicological Data Sources

NTP, US EPA ToxRefDB, US FDA, EFSA, HESS Japan and REACH
RepDose database from Fraunhofer ITEM (optional, more info)

ToxGPS provides a reliable toxicity prediction system for a series of in vivo and in vitro human health and regulatory-relevant endpoints as well as workflows to support the safety and risk assessment of chemical compounds.

Available Prediction Endpoints

Available endpoints

Overview

QSAR outcomes by global and local mode-of-action (mechanistic) models
Chemotype alerts (structure knowledge) including severity scores (odds ratios)
Nearest neighbors of query compound including experimental study calls and link to ChemTunes Toxicity Database
Weight of evidence for combined final outcome based on decision theory approach minimizing and assigning uncertainties of predictions

Data Sources

US NTP, CPDB, US EPA ToxRefDB, US FDA, ILSI DevTox, EFSA, SCCS/SCCP/SCCNFP, ECETOC, HESS, Substance Registration database (ECHA) and scientific literature