IN VITRO ASSASY TO PREDICT PHOTOTOXICITY OF CHEMICALS: (II) YEAST GROWTH INHIBITION ASSASY AND BATTERY SYSTEM WITH PHOTOHEMOLYSIS ASSAY

MARIKO SUGIYAMA, HIROSHI ITAGAKI AND SHINOBU KATO
Shiseido Safety & Analytical Research Center, 1050 Nippa-cho, Kohoku-ku, Yokohama, Japan, 223

Regular article AATEX 2(4):193-202

Abstract
The yeast growth inhibition assay, which is based on photodynamic reactions of compounds with cells organelles or DNA, was validated as possible alternative to animal testing to predict phototoxicity of chemicals after optimization of various factors. The data for 24 chemicals (8 fragrances, 5 UV absorbers, 4 drugs, 4 antimicrobials and 3 dyes) were compared with in vivo phototoxicity test results in guinea pigs. The sensitivity, specificity, positive predictive value, negative predictive value and equivalence of the in vitro test were 89%, 80%, 73%, 92% and 81%, respectively. Three chemicals were identified as false positive compounds, and one was identified as a false negative in the yeast growth inhibition assay. Although an excellent correlation was obtained between in vivo studies and yeast growth inhibition assay, a false negative result was still observed, so the combination of the photohemolysis test, which we have already reported, and the yeast test was used as a battery system. The battery system had a sensitivity of 100%, a specificity of 67%, a positive predictive value of 64%, a negative predictive value of 100% and an equivalence of 77%. Because of the sensitivity of 100%, this battery system, which is composed of two methods based on different mechanisms, is considered to be useful as a screening tool for predicting phototoxic potential of new chemicals, as an animal test alternative.

Key words: in vitro test, yeast growth inhibition, phototoxicity, battery system.


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