Making safety decisions for a sunscreen active ingredient using next-generation risk assessment: Benzophenone-4 case...

Area of Science:

• Toxicology
• Risk Assessment
• Dermatology

Background:

• Benzophenone-4 (BP-4) is a UV filter used in body lotions.
• Traditional safety assessments often rely on animal data.
• Evaluating BP-4 safety using non-animal methods is crucial for regulatory compliance and ethical considerations.

Purpose of the Study:

• To conduct a next-generation risk assessment (NGRA) for BP-4.
• To compare a non-animal approach with traditional safety assessment methods.
• To evaluate the safety of BP-4 in a body lotion at a 5% concentration.

Main Methods:

• Physiologically-based kinetic (PBK) modeling to predict BP-4 absorption, metabolism, and excretion.
• In silico and in vitro new approach methodologies (NAMs) to characterize bioactivity.
• Calculation of bioactivity:exposure ratios (BERs) using in vitro points of departure (PoDNAM) and predicted plasma Cmax.

Main Results:

• PBK modeling predicted low systemic exposure to BP-4 (plasma Cmax of 1.27 µM).
• Most calculated BERs were above 11, indicating a sufficient safety margin.
• Lowest BERs (3.3 and 4.3) were linked to adaptive gene transcription changes, not adverse effects.

Conclusions:

• NGRA provides a robust, non-animal approach for evaluating UV filter safety.
• BP-4 demonstrates a favorable safety profile at 5% in body lotion.
• This study supports the regulatory acceptance of NAMs in chemical safety assessments.