Abstract
Highly invasive animal based test procedures for risk assessment such as the Draize eye test are under increasing criticism due to poor transferability for the human organism and animal-welfare concerns. However, besides all efforts, the Draize eye test is still not completely replaced by alternative animal-free methods. To develop an in vitro test to identify all categories of eye irritation, we combined organotypic cornea models based on primary human cells with an electrical readout system that measures the impedance of the test models. First, we showed that employing a primary human cornea epithelial cell based model is advantageous in native marker expression to the primary human epidermal keratinocytes derived models. Secondly, by employing a non-destructive measuring system based on impedance spectroscopy, we could increase the sensitivity of the test system. Thereby, all globally harmonized systems categories of eye irritation could be identified by repeated measurements over a period of 7 days. Based on a novel prediction model we achieved an accuracy of 78% with a reproducibility of 88.9% to determine all three categories of eye irritation in one single test. This could pave the way according to the 3R principle to replace the Draize eye test.
Highlights
Invasive animal based test procedures for risk assessment such as the Draize eye test are under increasing criticism due to poor transferability for the human organism and animal-welfare concerns
An in vitro procedure employing a reconstructed human cornea-like epithelium (RhCE) based on epidermal keratinocytes was accepted as OECD test guideline 4929
Human epithelial cells from skin are employed to create tissue models for eye irritation according to the OECD test guideline 492
Summary
Invasive animal based test procedures for risk assessment such as the Draize eye test are under increasing criticism due to poor transferability for the human organism and animal-welfare concerns. To develop an in vitro test to identify all categories of eye irritation, we combined organotypic cornea models based on primary human cells with an electrical readout system that measures the impedance of the test models. Based on a novel prediction model we achieved an accuracy of 78% with a reproducibility of 88.9% to determine all three categories of eye irritation in one single test This could pave the way according to the 3R principle to replace the Draize eye test. No single test method can completely replace the Draize eye test and category 2 substances causing reversible effects cannot be detected by the available test methods OECD TG 437,438,460,491 and 492. A cornea epithelial model based on human corneal cells should be employed that mimics the histological morphology and the molecular network of native human cornea in comparison to the state of the art skin derived models
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