International Collaboration on Cosmetic Safety: Skin Sensitization Assessment Using NAMs

The International Collaboration on Cosmetic Safety (ICCS) recently published its Best Practice Guidance (BPG) Document for skin sensitization assessment using New Approach Methods (NAMs) for substances in cosmetics and personal care products¹. This BPG reflects the cosmetics industry’s commitment to inform hazard and safety assessments without conducting new animal testing. In the following discussion, we examine the use of Leadscope to support the principles and procedures outlined in the BPG.

Key Elements of the ICCS Framework

The ICCS BPG outlines six (6) steps in a proposed workflow for skin sensitization assessments. These steps cover defining the scope and context of decision making, gathering existing data and characterizing the substance, and identifying the use scenario. Additionally, an evaluation of the weight of evidence derived from the existing data for adequacy to inform the assessment is described.

Substance characterization

Substance characterization includes the need to gather experimental or predicted physical and chemical properties in addition to the reaction mechanism whereby a covalent bond with amino acids in skin proteins initiates the sensitization reaction.  Such reaction mechanisms include direct and pro-electrophiles covering the following reactivity domains: Michael acceptors, SNAr electrophiles, SN2, Schiff base formers, and acylating agents. These reaction domain categories are systematically captured and profiled within Leadscope’s predictive toxicology platform.

Literature review: accessing curated databases

Additionally, existing data should be sourced from authoritative sources such as government and scientific advisory agencies, followed by literature reviews for outstanding data, for example, in vivo experimental animal data (e.g., LLNA; GPMT), and in chemico and in vitro studies, and human exposure studies (e.g., HRIPT, HMT).  Leadscope’s curated databases complement these sources by providing access to collections of regulatory and literature data to support hazard and potency assessments.

Applying in silico tools and approaches

In silico tools such as the Leadscope Model Applier could also be used as part of the data gathering process and can help fill gaps in hazard and potency assessments. Additionally, read-across is suggested for substances with limited or conflicting data. In read-across assessments, justifying analogue selection through demonstrating the presence of shared mechanistic features, such as those that will covalently bind with skin proteins or undergo metabolism to reactive species, is important to document. To ensure that the read-across is transparent, documentation of analogues excluded as well as included is recommended. The in silico profiling capability, built into the Leadscope Read-across tool, supports such transparent assessments, while also allowing for in-tool management and documentation of analogues.

Following the collection of data, a review of the adequacy of the totality of the information is necessary. Where data are adequate based on the context of use, no additional data generation is required. An organized data collection framework also helps define a targeted testing strategy.  

Leadscope’s contribution to ICCS Framework

The ICCS Best Practice Guidance Document for skin sensitization highlights the use of New Approach Methods (NAMs) for the assessment of skin sensitization in cosmetics and personal care products. Leadscope contributes to these assessments by offering transparent, reproducible, and scientifically developed silico approaches, along with comprehensive databases, that can be used in research and regulatory submissions. Our tools are designed to meet the evolving needs of safety assessors and toxicologists to support research, development, and regulatory needs.