Toxys and Unilever to explore and develop new approach methods (NAMs) for cellular stress
Toxys and Unilever have signed a collaboration to explore New Approach Methodologies (NAMs) that can be used to provide insight into cellular stress, a key mode of action for consideration in Next Generation Risk Assessment (NGRA) without animal testing. This collaboration will include comparing existing methods, validating the ToxProfiler assay with a collection of reference compounds, and expanding its applicability to coverage of mitochondrial toxicity, a common mode of action responsible for cellular stress and organ toxicity.
Chemical safety and ToxProfiler
In vitro chemical safety assessment often relies on simple and general cytotoxicity endpoint measurements. These results fall short of revealing underlying mechanisms of toxicity and therefore, fail to adequately predict toxicity in humans. NAMs that provide insight into underlying cellular stress mechanisms are hence highly desirable and several assays have been developed and applied in recent years in several NGRA case studies. Comprised by a unique collection of genetically engineered cell lines, ToxProfiler not only reports on activation of different cell stress pathways, but also does this by differentiating between primary and secondary responses in a dose dependent manner.
Mitochondrial toxicity assessment
ToxProfiler MAX (Mitochondrial toxicity Assessment Xtension) offers provisions for mitochondrial toxicity through the Glu/Gal switch approach: test compound exposure is performed in either high glucose or galactose medium. Since the latter induces cells to rely only on mitochondria for metabolism, the difference between the toxic dose of the compound in these two conditions inform on the mechanism of action.
Overview of ToxProfiler MAX reporters and representative confocal images.
The current collaboration aims not only to validate this protocol, but also to explore possibilities to improve mitochondrial toxicity detection further, using additional reporter genes, morphological stains or functional assays.
NGRA framework by Unilever
NGRA is an exposure-led, hypothesis-driven risk assessment approach that incorporates one or more NAMs to ensure that chemical exposures do not cause harm. Unilever strives to make safety decisions without data generated in animal studies and uses a variety of non-animal approaches from QSARs and ‘traditional’ in vitro approaches to Next Generation Risk Assessment (NGRA) informed through innovative NAMs like cellular stress assays. Unilever and Toxys have a productive relationship, with an existing collaboration running to develop and validate the ReproTracker assay developed by Toxys.
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