Investigations into the biological activity of avobenzone as part of a Next Generation Risk Assessment

There were no structural analogues for AVB, therefore a read-across safety assessment was not possible. To confirm the MoA for AVB in the safety assessment, potential functional analogues (PFAs) were identified using ToxCast and literature data, whereby AVB showed activity at 17 µM in the “TOX21_MMP_ratio down” assay, suggesting mitochondrial depolarisation is a target mechanism.

Chemicals with the same potential bioactivity were 2-, 3- and 4-hydroxybenzophenone (HDBP), kaempferol and myricetin. To compare bioactivities, transcriptional profiles of AVB and PFAs were generated and used for connectivity map (CMap) analysis. AVB was also tested in an adapted pharmacology profiling panel (APPP). 100 µM AVB and myricetin both elicit transcriptional profiles consistent with a non-specific MoA, namely mitochondrial dysfunction, hypoxic stress and apoptosis.