The capability to perform animal-free risk assessment for a wide range of consumer products and their ingredients is at our doorstep, yet there remain some significant barriers to wide implementation of these methods globally. At Humane Society International, we are joining hands with collaborative stakeholders to provide solutions at numerous levels, including legislative and regulatory, scientific and, most recently, in education and training. With the ongoing changes to cosmetics and chemicals legislations in the EU under the Chemical Strategy for Sustainability, these solutions are more necessary and more timely than ever.
Great strides have been made in recent decades regarding the science available to assess chemical safety. State-of-the-art science involves advances in cell-culturing techniques to the point where it is now possible to grow tissues that quite closely resemble organs in a petri dish. Our ability to query complex cellular processes is also advancing through the use of ’omics technologies (genomics, proteomics, etc.) and high-content imaging. Computer scientists, are making extraordinary advances, with ever-accumulating data being used to generate accurate, predictive models of biological outcomes.
These approaches have the capacity to completely revolutionize chemical safety They provide information that is quite different from what traditional animal testing provides. Not only is the information different, but its application in chemical safety is a relatively new field, with few published examples and few practitioners around the world. To help familiarize stakeholders with these new types of information and their application to chemical safety, we have brought together a large team of experts to share their knowledge and experience as part of the Animal-Free Safety Assessment Collaboration. This course will be available to all, free of charge, via AFSAcollaboration.org website, beginning in January 2023.
The course is focused on the safety assessment of cosmetic products and ingredients without new animal data and covers all aspects of the process for internal company decisions and regulatory safety assessments. What makes this course unique is that it focuses on understanding the information generated from these tools and how it is used in decision-making. It is designed to complement other courses and trainings that focus on how to perform or build the individual methods. The ultimate purpose is to support capacity-building in animal-free risk assessment within the regulated and regulatory communities globally.
The basic structure of traditional animal data-based and animal-free data-based risk assessment is quite similar: both rely on measurements or estimates of exposure, as well as estimation of a chemical’s intrinsic bioactivity, to determine the risk associated with a particular use or exposure. The main differences are in how and when exposure comes into the process, the types of information used to estimate a chemical’s hazard and risk, and in the application of a tiered assessment framework. In traditional risk assessment, a set of standard animal tests is performed and the lowest dose causing an effect, or the highest dose causing no effect, in any of these tests is taken as the biological activity data point for performing the risk assessment. Exposure is generally considered only after, or at the same time as, hazard assessment.
In animal-free risk assessment, also called next-generation risk assessment, exposure is considered from the beginning and used to either make early safety determinations, or to inform the design of testing strategies tailored to create the information needed for risk assessment. Leading with exposure is particularly important for consumer products that have a high expected consumer exposure. The assessment itself is performed in stages.
Computational tools are used in the initial chemical characterization and in potential identification of similar chemicals that can be used to help identify existing safety information. Any new information on biological activity or internal exposure that is needed is generated using nonanimal assessment methods. Finally, results of the biological activity are examined to identify a lowest-effect level. This is then compared with measured or predicted internal concentrations to generate a margin of exposure, which is used to conclude the risk for a given scenario.
Principles and a detailed framework for carrying out a Next Generation Risk Assessment have been developed via partnerships between regulators and industry — development of the framework also involved academics through the former European seventh framework program project, Safety Evaluation Ultimately Replacing Animal Testing. The AFSA program builds on these principles to cover the entire risk-assessment process in eight technical modules, together with an overview of the global regulatory landscape covering cosmetics and chemicals.
1: Following an introductory session on animal-free safety assessment, the program begins with problem formulation, including collecting, collating, and reviewing existing information, initial hypothesis generation and early decision making.
2: The consumer exposure module covers habits and practices, the data and where to find it, and different types of exposure modelling covering the main exposure routes: skin, oral and respiratory.
3: The module on in silico tools covers the variety of different types of computational tools, the data, mathematics and thought processes used to build them; and what they can be used for. This module also covers the use of in silico tools in identification of similar chemicals, and read-across.
4: A module on exposure-based waiving covers how it is applied for three routes of exposure- oral, dermal and inhalation.
5: A separate module covers history of safe use for complex extracts such as botanicals.
6: A module on internal exposure -including absorption, distribution, metabolism, and excretion –covers the types of models used and what data and thinking goes into physiologically-based kinetic modelling as well as in vitro-to-in vivo extrapolation.
7: The module on in vitro data synthesis covers the types of tools used to generate bioactivity data and how the data can be combined to inform hazard identification and characterization.
8: And there’s a final module on integrating all of the information into a risk assessment with case examples for a wide range of decisions, from acute local, endpoint-specific decisions such a skin and eye irritation and skin sensitization, to more comprehensive risk assessment for repeat dose, systemic exposures.
9. Also included is a module describing the global regulatory landscape covering cosmetics and chemicals.
Our intention with this course is to, at least partially, fill the needs of regulators, the regulated community, contractors, consultants and others who are less familiar or comfortable with the use of nonanimal information in safety decisions, and to help secure a future where these methods are a mainstay in a more effective and efficient chemical safety paradigm. We look forward to wide participation.