Profiling 58 compounds including cosmetic-relevant chemicals using ToxRefDB and ToxCast

Area of Science:

• Toxicology
• Cosmetic Science
• Regulatory Science

Background:

• European Union regulations restrict animal testing for cosmetics, necessitating alternative safety assessment methods.
• New Approach Methodologies (NAMs) are crucial for predicting chemical toxicity and ensuring cosmetic product safety.
• Cosmetic-Relevant Chemicals (CRCs) include ingredients and trace contaminants requiring robust safety evaluations.

Purpose of the Study:

• To evaluate the utility of NAMs for assessing the systemic toxicity of CRCs.
• To demonstrate how in vitro bioactivity data can inform in vivo toxicity estimations.
• To support the development of NAMs for cosmetic safety assessments in alignment with regulatory changes.

Main Methods:

• Surveyed in vitro bioactivity (ToxCast) and in vivo systemic toxicity (ToxRefDB) data for 58 CRCs.
• Analyzed Lowest Effect Level (LEL) doses from ToxRefDB for CRCs and other chemicals.
• Utilized high-throughput toxicokinetic data to calculate Administered Equivalent Doses (AEDs) for 17 CRCs.

Main Results:

• CRCs showed diverse use categories.
• Median LEL doses for CRCs were comparable to other chemicals, with similar ranges.
• Calculated AEDs from in vitro bioactivity served as conservative estimates for in vivo LELs.

Conclusions:

• NAMs utilizing bioactivity data can provide conservative estimates for systemic toxicity of CRCs.
• This approach supports the safety assessment of diverse CRCs without animal testing.
• NAMs are valuable tools for ensuring cosmetic product safety under evolving regulatory landscapes.