SPECTROSCOPIC STUDIES OF CUTANEOUS PHOTOSENSITIZING AGENTS‐XIII. _pH DEPENDENCE OF THE PHOTOCHEMISTRY OF PHOTO ALLERGENS BITHIONOL AND FENTICHLOR: AN ELECTRON spIN RESONANCE STUDY OF THE FREE RADICAL PHOTOPRODUCTS

Abstract

The photoallergens bithionol (BT) and fentichlor (FT) generated free radical photoproducts upon UV photolysis which were observable by direct electron spin resonance (ESR). Both the yield and the type of free radical photoproducts were affected by pH, and to some extent, concentration of oxygen and concentrations of the photosensitizers. At pH 8.5, bithionol (0.9 mM) generated a semiquinone type free radical (BI) via a mechanism which probably involves substitution of the 4‐chlorine by hydroxyl to form the corresponding hydroquinone followed by oxidation. The photolysis of 4‐chlorophenol, 4‐chlorocatechol and 2,2'‐methylene‐bis(4‐chlorophenol) also generated the corresponding semiquinone radicals, suggesting that this mechanism is shared by other 4‐chlorophenols. At pH 8.5, only photoproduct BI was observed during the irradiation of BT; FT related photoproducts were not observed at this pH. However, at higher pH values (pH 10.7 or pH 12), FT photoproducts were also observed in addition to BI upon prolonged irradiation. Moreover, the yield of BI increased drastically at higher pH. Oxygen did not play any role at pH 10.7, although it enhanced the yield of BI at pH 8.5. At pH 8.5, irradiated fentichlor generated, in roughly equal amounts, a semiquinone radical (Fla) and an unidentified species which contained two inequivalent protons (FII). At higher pH values (pH 10.7 and pH 12), at least four species were observed. All of the species are believed to be semiquinone radicals and two have been unambiguously identified. The yield of FI increased by a factor of 50 as the pH was increased from 8.5 to 12. Oxygen played only a minor role at pH 10.7 and above. However, at pH 8.5, it also enhanced the yield of FI.

False-negative chemicals in ESR-based photosafety test (ESR-PT) and their significance for photosafety evaluations: examples of bithionol, fenticlor and cilnidipine

“…2 (C), (D)). Although an origin of characteristic single peak signal with a g-value of 2.0048 could not be identified at present, bithionol and fenticlor are known to generate dehalogenated free radicals upon UV irradiation and to yield secondary free radical photoproducts, such as phenoxyl or semiquinone radicals (Li and Chignell, 1989). Accordingly, the observed signal was considered to have resulted from an interaction between 4-hydroxy-TEMP and dehalogenated free radicals or their secondary products generated from these chemicals, since almost no signal was detected without 4-hydroxy-TEMP (data not shown).…”