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

Abstract

Cosmetic products must be safe for their intended use. Regulatory bans on animal testing for new ingredients has resulted in a shift towards the use of new approach methodologies (NAM), such as in silico predictions and in chemico/in vitro data. Defined Approaches (DA) have been developed to interpret combinations of NAM to provide information on skin sensitisation hazard and potency, three having been adopted within OECD Guideline 497. However, the challenge remains as to how DA can be used to derive a quantitative point of departure for use in next generation risk assessments (NGRA). Here we provide an update to our previously published NGRA framework and present two hypothetical consumer risk assessment scenarios (rinse-off and leave-on) on one case study ingredient. Diethanolamine (DEA) was selected as the case study ingredient based upon the existing NAM information demonstrating differences with respect to the outcomes from in silico predictions and in chemico / in vitro data. Seven DA were applied, and these differences resulted in divergent DA outcomes and reduced confidence with respect to the hazard potential and potency predictions. Risk assessment conclusion for the rinse-off exposure led to an overall decision of safe for all DA applied. Risk assessment conclusion for the higher leave-on exposure was safe when based upon some DA but unsafe for others. The reasons for this were evaluated, as well as the inherent uncertainty from the use of each NAM and DA in the risk assessment, enabling further refinement of our NGRA framework.