This month Cyprotex have jointly published a new research article with Unilever entitled ‘Identifying and Characterizing Stress Pathways of Concern for Consumer Safety in Next-Generation Risk Assessment’.
Consumer safety is required for any food or cosmetic product. Next generation risk assessment (NGRA) is an exposure led, hypothesis driven approach which integrates in vitro, in silico and in chemico approaches for chemical safety assessment. Developing suitable high-throughput assays for different toxicity outcomes continues to be a challenge within NGRA. The paper details the work undertaken to develop a cellular stress panel which together with other methodologies, can be used to identify potential chemical liabilities when conducting non-animal safety assessments.
The cellular stress panel, described in the article, is composed of 36 biomarkers representing mitochondrial toxicity, cell stress pathways and cellular health, measured primarily using high content imaging. Response profiles were generated for 13 compounds at exposures consistent with typical use-case scenarios to assess the panel. Of the compounds selected, some have previously shown to cause detrimental effects in some exposed individuals as well as toxicological effects associated with cellular stress. The remaining compounds were selected as they are not associated with adverse effects due to cellular stress at human relevant exposures. For each compound, concentration response data were generated for each biomarker at three timepoints.
One of the key strengths presented in this work is the use of a novel modelling approach, which probabilistically quantifies the uncertainties associated with the data analysis; a key principle of NGRA. Using this approach, compounds were ranked into ‘low’ and ‘high’ risk chemical exposure categories.
The paper presents initial validation of the cellular stress panel, illustrating its use alongside other cellular assays and in silico methodologies as a powerful approach towards non-animal safety testing.
To download the paper, click here.
For enquiries regarding the cell stress panel, click here.