Systemic Safety

To understand the safety of ingredients if they are absorbed into the body (systemic safety), we do not use an animal study to generate data. Our first question is ‘Can our ingredient cause any sort of biological activity in consumers at the levels they will be exposed to?’. This ‘protection not prediction’ approach is based on the hypothesis that if there is no biological activity, there can be no harm to our consumers.

Making robust decisions on systemic safety without animal data is especially challenging. We have several research projects that are enabling us to address key questions in this complex field and we have been able to build a toolbox of non-animal safety assessment methods. We have developed confidence in the coverage provided by this toolbox, and in investigating when and how we might use higher-tier in vitro tools, such as tissue cultures or micro-physiological systems, to answer specific safety assessment questions.

Exposure

As with any toxicological safety assessment, our next-generation risk assessments (NGRAs) for systemic effects rely on having a good understanding of exposure (how people use our products, how much of an ingredient is absorbed during normal use of our products, and its fate in the body). Important tools we use include in vitro dermal penetration experiments and physiologically based kinetic (PBK) modelling. We have collaborations with leading experts in exposure science, and along with our internal research projects, we are investigating how the metabolism of an ingredient can impact safety assessment.

Bioactivity

It is important we ensure the approach we use is tiered and does not require the generation of any new animal data. Our starting point is maximising the use of appropriate^* existing data on an ingredient, and we then use in silico predictions to guide the development of our safety assessments. In vitro methods are used to generate data that can be modelled to define points of departure (PoDs). The in vitro methods that we use include high throughput transcriptomics, in vitro pharmacological profiling, and a cell stress panel we developed with one of our partners, Cyprotex. These tools have been selected to provide us with wide biological coverage to ensure we consider the different modes of action that could potentially cause adverse effects on consumers.