Predictive performance of the Vitrigel-eye irritancy test method using 118 chemicals
Hiroyuki Yamaguchi1,2, Hajime Kojima3, Toshiaki Takezawa1
1Division of Animal Sciences, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki, Japan.
Journal of Applied Toxicology : JAT
|October 17, 2015
Summary
The novel Vitrigel-eye irritancy test (EIT) method accurately predicts eye irritation potential using a human corneal epithelium model. Adjusting for acidic chemicals significantly improved its predictive performance for safer chemical development.
Area of Science:
- Toxicology
- Ocular toxicology
- In vitro testing
Background:
- Traditional eye irritancy tests pose ethical concerns and can be time-consuming.
- There is a need for reliable in vitro methods to assess chemical eye irritation potential.
- The Vitrigel-eye irritancy test (EIT) was developed as a novel alternative.
Purpose of the Study:
- To evaluate the predictive performance of the Vitrigel-EIT method for eye irritancy.
- To compare Vitrigel-EIT results with the Globally Harmonized System (GHS) classification.
- To investigate potential improvements in the Vitrigel-EIT method's accuracy.
Main Methods:
- A human corneal epithelium (HCE) model was constructed on a collagen vitrigel membrane.
- Transepithelial electrical resistance (TER) was measured over 3 minutes after chemical exposure.
- 118 chemicals were tested, and results were analyzed against GHS classifications and EPA data.
Main Results:
- The Vitrigel-EIT method achieved 80.5% accuracy, 90.1% sensitivity, and 65.9% specificity.
- Excluding chemicals with pH ≤ 5 improved accuracy to 84.4%, sensitivity to 96.8%, and specificity to 67.4%.
- False positives showed evidence of tight junction disruption (ZO-1 and MUC1 loss), indicating potential irritancy.
Conclusions:
- The Vitrigel-EIT method demonstrates excellent predictive performance for widespread eye irritancy, including mild irritants.
- Adjusting for acidic compounds enhances the method's reliability.
- This in vitro test offers a promising approach for developing safer commodity chemicals.
