Screening industrial chemicals for human developmental toxicity in the DevTox Germ Layer Reporter platform

Area of Science:

• Toxicology
• Developmental Biology
• Chemical Safety Assessment

Background:

• The Toxic Substances Control Act (TSCA) requires efficient review of new chemicals.
• Existing screening methods for developmental toxicity are insufficient for rapid hazard identification.
• New Approach Methods (NAMs) offer promising alternatives for chemical safety evaluation.

Purpose of the Study:

• To screen a diverse set of chemicals using the DevTox Germ Layer Reporter (GLR)-Endo assay.
• To assess the assay's performance and predictivity for developmental toxicants.
• To evaluate chemicals relevant to the EPA's New Chemicals Collaborative Research Program (NCCRP).

Main Methods:

• Screening of 171 TSCA chemicals and 54 in vitro assay reference chemicals using the DevTox GLR-Endo assay.
• Evaluation of assay performance metrics and predictivity against 16 reference developmental toxicants.
• Analysis of chemical activity and selective activity for specific assay endpoints (e.g., SOX17).

Main Results:

• The DevTox GLR-Endo assay demonstrated acceptable performance and predictivity.
• Of 38 previously unevaluated reference chemicals, 25 were active, with 13 showing selective activity.
• 60 of 165 tested TSCA chemicals were active, and 29 exhibited selective activity.

Conclusions:

• The DevTox GLR-Endo assay is a viable tool for rapid screening of developmental toxicity.
• Results support the development of NAM-based hazard assessment strategies for new chemicals.
• This study provides critical toxicological data for chemicals relevant to the NCCRP.