Ascorbic acid specifically reduces the misclassification of nonirritating reactive chemicals in the OptiSafe™ macromolecular eye irritation test

Expansion of the application domain of a macromolecular ocular irritation test (OptiSafe™)

“…Opti-Safe ™ (“Optimized for Safety”) is a shelf-stable in chemico test method that consists of a proprietary macromolecular test matrix that is used to quantify the potential of an unknown test material to cause eye irritation or eye damage. Damage to macromolecules results in the loss of cell viability, and the extent of measured macromolecular damage is used to predict the toxicity of the material being tested ( Lebrun, 2018 ; 2021 ; Lebrun et al, 2021a , 2021b ; Lebrun et al, 2022 ; Choksi et al, 2020 ; Lebrun et al, 2019 , 2021a , 2021b , 2022a , 2022b ).…”

“…The score is then applied to a prediction model to classify the material tested. For a detailed description, see Lebrun et al, 2022a .…”

“…We then studied the overpredicted chemicals ( Lebrun et al, 2021a ) and found that chemicals associated with reactive oxygen species (ROS) chemistry were commonly overpredicted ( Lebrun et al, 2021b , 2022a ). Based on the hypothesis that naturally occurring antioxidants in tears can deactivate ROS prior to eye damage, we then tested a range of tear antioxidants and identified that ascorbic acid reduces the OptiSafe FP rate ( Lebrun et al, 2021b , 2022a ) and then compared results for the same chemicals with and without ascorbic acid ( Lebrun et al, 2022b ). We then updated the prediction model, the OS physiochemical handling procedures (PCHPs) and also comprehensively determined the impact of adding an antioxidant to the OS test matrix ( Lebrun et al, 2021b , 2022a ).…”

“…Based on the hypothesis that naturally occurring antioxidants in tears can deactivate ROS prior to eye damage, we then tested a range of tear antioxidants and identified that ascorbic acid reduces the OptiSafe FP rate ( Lebrun et al, 2021b , 2022a ) and then compared results for the same chemicals with and without ascorbic acid ( Lebrun et al, 2022b ). We then updated the prediction model, the OS physiochemical handling procedures (PCHPs) and also comprehensively determined the impact of adding an antioxidant to the OS test matrix ( Lebrun et al, 2021b , 2022a ). All prior OS-coded validation study chemicals were then retested ( Lebrun et al, 2022a ).…”

“…We then updated the prediction model, the OS physiochemical handling procedures (PCHPs) and also comprehensively determined the impact of adding an antioxidant to the OS test matrix ( Lebrun et al, 2021b , 2022a ). All prior OS-coded validation study chemicals were then retested ( Lebrun et al, 2022a ). These chemicals included the prior coded validation chemicals described above ( Choksi et al, 2020 ; Lebrun et al, 2021a ).…”