Testing ocular irritancy in vitro with the silicon microphysiometer

Area of Science:

• Toxicology
• Biotechnology
• Materials Science

Background:

• Ocular irritancy testing traditionally relies on animal models, raising ethical and efficiency concerns.
• Developing reliable in vitro alternatives is crucial for modern safety assessments.
• The light-addressable potentiometric sensor offers a novel approach to non-invasive cellular analysis.

Purpose of the Study:

• To evaluate the silicon microphysiometer as an in vitro alternative for assessing ocular irritancy potential.
• To correlate the instrument's measurements with established in vivo rabbit eye test data.
• To explore the potential of multiple endpoints for comprehensive ocular safety evaluations.

Main Methods:

• Utilized a silicon microphysiometer employing a light-addressable potentiometric sensor.
• Measured cell metabolism by quantifying acid metabolite production from human epidermal keratinocytes.
• Tested 17 liquid materials, including soaps, detergents, and shampoos, comparing results to historical in vivo rabbit eye test data.

Main Results:

• Demonstrated a strong positive correlation (r = 0.86, P < 0.0001) between in vivo irritancy and the concentration causing a 50% decrease in cell acidification rate (MRD(50)).
• Observed potential for additional endpoints, such as cell recovery and metabolic rate changes at sub-inhibitory concentrations.
• Confirmed the non-invasive nature of the microphysiometer, allowing for assessment of cellular response and recovery.

Conclusions:

• The silicon microphysiometer shows significant potential as a reliable and ethical in vitro alternative for ocular safety testing.
• The system's ease of use, strong in vivo-in vitro correlation, and multiple endpoints support its adoption.
• Further research into additional endpoints may enhance its utility in ocular safety assessments.