Strategy Combining Nonanimal Methods for Ocular Toxicity Evaluation.

Area of Science:

• Toxicology
• Ocular Safety Assessment
• In Vitro Methods

Background:

• The traditional Draize rabbit eye test for ocular toxicity is criticized for technical limitations, ethical concerns, and lack of validation.
• Increasing pressure to reduce animal testing has driven the development of non-animal testing alternatives.
• Regulatory bodies like the UN GHS rely on these tests for classifying chemical eye damage/irritation.

Purpose of the Study:

• To describe detailed protocols for non-animal eye irritation testing.
• To present integrated testing strategies (ITS) for regulatory classification of ocular toxicity.
• To propose modifications for differentiating serious eye damage from reversible irritation.

Main Methods:

• Utilized cell-based assays (Short Time Exposure - STE, OECD No. 491/2017).
• Employed a vascularized membrane model (Hen's Egg Test-Chorioallantoic Membrane - HET-CAM).
• Applied corneal tissue models (Bovine Corneal Opacity and Permeability - BCOP, OECD No. 437/2017) with suggested histomorphometric evaluation.

Main Results:

• These non-animal methods can be applied using top-down or bottom-up approaches for classification and labelling (C&L).
• The BCOP method, with added histomorphometric evaluation, can distinguish between UN GHS Cat. 1 (serious eye damage) and Cat. 2 (eye irritation).

Conclusions:

• Integrated testing strategies (ITS) combining multiple non-animal methods provide reliable alternatives to animal testing for ocular toxicity.
• These validated in vitro methods are crucial for accurate classification and labelling of chemicals regarding eye damage and irritation.
• The proposed modifications enhance the BCOP assay's utility in regulatory risk assessment for eye safety.