Phototoxic evaluation of agrochemicals by a newly developed in vitro UVB-induced phototoxicity test using human embryonic stem cell- or induced pluripotent stem cell-derived retinal pigment epithelial cells.

Currently, no suitable method is available for detecting substances with phototoxic potential in the ultraviolet B (UVB) range. Assessments of UVB-induced phototoxicity are required by the European Food Safety Authority, particularly for substances that mainly absorb in the UVB range (UVB absorbers). Therefore, we developed a novel UVB-induced phototoxicity test using human embryonic stem cell (hESC)-/human induced pluripotential stem cell (hiPSC)-derived retinal pigment epithelial cells (RPEs). UVB irradiation did not significantly affect the viability of RPEs, suggesting their resistance to UVB-induced damage. RPEs were then exposed to four phototoxic substances that are UVB absorbers and five non-phototoxic substances, followed by UVB irradiation. Results consistent with in vivo tests were obtained for all nine substances, indicating that the developed method assessed UVB absorbers more accurately than current methods (OECD TG 432 and TG 495). This suggests that the new method can be useful for the phototoxicity evaluation of UVB absorbers. Next, agrochemicals (etoxazole, tolclofos-methyl, esfenvalerate, mandestrobin, and flumioxazin) that showed negative results in the OECD TG 432 test using UVA and visible light irradiation, but are UVB absorbers, were tested. All yielded negative results, indicating that these agrochemicals have no phototoxic potential even in the UVB range.