Applying a next generation risk assessment framework for skin sensitisation to inconsistent new approach methodology...

Area of Science:

• Cosmetic Science
• Toxicology
• Risk Assessment

Background:

• Regulatory bans on animal testing drive adoption of New Approach Methodologies (NAMs) like in silico, in chemico, and in vitro methods.
• Defined Approaches (DAs) integrate NAMs to assess skin sensitization hazard and potency, with some adopted by OECD Test Guideline 497.
• Deriving quantitative points of departure from DAs for Next Generation Risk Assessment (NGRA) remains a challenge.

Purpose of the Study:

• To update a previously published NGRA framework.
• To present hypothetical consumer risk assessment scenarios for rinse-off and leave-on products using a case study ingredient.
• To evaluate the use of DAs in deriving quantitative risk assessment conclusions.

Main Methods:

• Applied seven Defined Approaches (DAs) to Diethanolamine (DEA), a case study ingredient.
• Utilized existing NAM data for DEA, noting discrepancies between in silico predictions and in chemico/in vitro data.
• Conducted hypothetical risk assessments for rinse-off and leave-on consumer exposure scenarios.

Main Results:

• Divergent DA outcomes were observed due to discrepancies in NAM data for DEA, impacting confidence in hazard and potency predictions.
• Risk assessment concluded safety for rinse-off exposure across all applied DAs.
• Risk assessment for leave-on exposure yielded mixed conclusions: safe for some DAs, unsafe for others.

Conclusions:

• The study highlights the challenges in achieving consistent risk assessment conclusions with current DAs, particularly for leave-on products.
• Identified reasons for divergent outcomes and inherent uncertainties associated with NAMs and DAs.
• Provided insights for further refinement of the NGRA framework to enhance reliability and confidence in safety assessments.