Further optimisation of a macromolecular ocular irritation test (OptiSafe^TM)

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

“…The OS macromolecular test was conducted as previously described ( Choksi et al, 2020 ; Lebrun et al, 2021a , 2022b ) and is briefly described below.…”

“…The OS test is packaged as a complete kit (Lebrun Labs LLC, Anaheim, CA), which includes the OS “Active Agent” (AA) macromolecular reagent formulation (see Lebrun et al, 2022a for a description). As described in prior publications ( Lebrun et al, 2021b , 2022a , 2022b ), samples were initially evaluated using a set of Physiochemical Handling Procedure (PCHP) pretests (see Lebrun et al, 2022a ). Specific physiochemical properties (solubility, buffering capacity, and foaming) of the material to be tested are measured during the pretest step.…”

“…Specific physiochemical properties (solubility, buffering capacity, and foaming) of the material to be tested are measured during the pretest step. Based on these physiochemical properties, there are specific changes in the protocol that improve sensitivity and accuracy ( Lebrun et al, 2021b , 2022a , 2022b ). For substances with significant pH buffering, the buffering power was further evaluated, and the protocol was adjusted to match; testing of insoluble materials does not use membrane discs and surfactants are diluted.…”

“…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 ).…”

“…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 ).…”