A predictive mouse ear-swelling model for investigating topical phototoxicity

Abstract

Predictive models should be used to determine the phototoxic potential of consumer products intended for topical exposure and outdoor use. To determine the potential of a compound to elicit a phototoxic reaction, a mouse ear-swelling model, which uses a xenon arc ultraviolet (UV) solar simulator as the radiation source, was used. The UV solar simulator delivered UV radiation from 290 to 400 nm (UVB + UVA) or from 320 to 400 nm (UVA) when appropriate filters were used. With this model, the phototoxic potential of nine known phototoxins and three negative test materials was successfully demonstrated. Based on the time of onset of the phototoxic response following test material application and irradiation, both immediate (20–30 min) and delayed-type (48–96 hr) phototoxic responses were demonstrated using this model with anthracene and 8-methoxypsoralen, respectively. The optimal time for irradiation after application of 8-methoxypsoralen to the ears was 30–60 min. Irradiation of ears immediately after treatment with 8-methoxypsoralen or 6 hr after application resulted in little or no phototoxic response. The phototoxic response to 8-methoxypsoralen was dependent upon the UVA dose and, when tested at a constant UVA dose, the response was concentration dependent. To obtain an optimal phototoxic response to 7-methoxycoumarin, both UVB and UVA radiation were required. These results show that the mouse ear-swelling model, which is quantifiable and more objective than models based on subjective evaluation of skin changes, is an excellent model for investigative and predictive phototoxicity testing.