Safe-by-design: toxicological safety evaluation of CHAMPION polymers and building blocks

In the CHAMPION project, an innovative, non-animal testing strategy is used to rapidly evaluate toxicological safety issues of CHAMPION candidates at a very early stage in the development. This ensures that safety is built into the design of CHAMPION’s materials, and prevents regrettable substitutions.

Many conventional polymers are produced from chemicals with known toxicity issues. CHAMPION’s mission is to ensure that any new materials being developed will have a better overall toxicity profile compared to those currently used, from starting materials through intermediates to the final materials. To accomplish this, an innovative testing strategy has been designed to select candidates with a favourable toxicological profile using high-throughput in vitro safety screening methods.

The testing strategy encompasses a panel of human cell-based CALUX® assays. This panel can be used to rapidly evaluate major types of toxicity relevant for regulatory risk assessment and consumer confidence. Individual assays and combinations thereof have been proven to be highly predictive of chemical toxicities (e.g. endocrine and reproductive toxicity, cytotoxicity, acute toxicity and genotoxicity, Figure 1). The resulting CALUX activity profile can be used for early-stage hazard identification and risk assessment, and provide important information to assist in candidate prioritisation and safe design.

Figure 1 – The general principle of risk assessment using the CALUX assay panel (left panel adapted from: Hanahan, D., and R. A. Weinberg. 2011. 'Hallmarks of cancer: the next generation', Cell, 144: 646-74)

So far, 85 different CHAMPION samples have been analysed using this innovative testing strategy, including monomers, intermediates, polymers, polyesters, industrial samples, reference and validation compounds.

A small selection of the results is shown in Figure 2. The monomers activate no or very few assays (black box), indicating that they are not able to activate the associated receptors or cellular pathways, which are associated with toxicity. The unsaturated polyesters, on the other hand, activate various assays at micromolar concentrations (green box); this is most likely caused by their reactive C=C bonds. This hypothesis is supported by the fact that after the Aza-Michael addition, the reactivity disappeared almost completely (red box).

Figure 2 – The CALUX results for a selection of CHAMPION candidates. Numbers are lowest effect concentrations in LOG(M). Grey = no activity observed.

The testing completed to date, gives no indication that any of the candidates should be ‘flagged’ or discontinued based on their toxicity profile. Following this successful use of the innovative testing strategy, further samples will be tested in the next part of the project.