Profiling chemicals based on chronic toxicity results from the U.S. EPA ToxRef Database

Area of Science:

• Toxicology
• Environmental Health
• Data Science

Background:

• Historical pesticide toxicity data (30 years) were unstructured, stored as hardcopy and scanned documents by the U.S. Environmental Protection Agency (EPA).
• Significant data have been processed into the standardized Toxicity Reference Database (ToxRefDB), encompassing chronic, cancer, developmental, and reproductive studies.
• ToxRefDB provides accessible, mineable data validating the EPA's ToxCast research program in predictive toxicology.

Purpose of the Study:

• To profile in vivo toxicities for 310 chemicals using ToxRefDB.
• To generate detailed anchoring endpoints for the development of ToxCast predictive signatures.

Main Methods:

• Generated toxicity profiles from ToxRefDB using query and structured data-mining approaches.
• Analyzed chronic/cancer data from long-term rodent bioassays for suitability as anchoring endpoints (incidence, target organ, severity, potency, significance).

Main Results:

• Pathologies observed in 273 of 310 chemicals, predominantly in liver, kidney, thyroid, lung, testis, and spleen (>90%).
• Proliferative lesions observed in 225 chemicals; 167 chemicals showed progression to cancer-related pathologies.

Conclusions:

• Selected 26 primarily tissue-specific pathology endpoints based on incidence, severity, and potency to classify the 310 chemicals.
• Structured legacy toxicity data in ToxRefDB facilitates computation for ToxCast and other predictive toxicology applications.