Cutaneous Phototoxicity: Clinical Observations versus Histopathological Findings.

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Determination of test material-induced cutaneous phototoxicity for risk assessment has traditionally been based on visually observed skin reactions such as erythema, edema, and flaking. Because of its role in determining a toxic effect, the use of histopathological evaluation in this determination arises from time to time. However, there is little published information regarding the time course and types of histopathologic changes in the skin after test material-induced phototoxic insult nor any regulatory requirement or precedent for its use. This work evaluated both the visual and histopathological time course of the phototoxic response of the skin of the Long-Evans rat after oral administration of the phototoxins sparfloxacin and 8-methoxypsoralen (MOP) followed by a single exposure to solar-simulated ultraviolet radiation. Both sparfloxacin and 8-MOP elicited visual cutaneous reactions and microscopic changes consistent with a phototoxic response. The visually observed cutaneous time course and elicited histopathologic changes differed in response and extent for each phototoxin, but in both instances, microscopic evaluation did not alter the determination of a phototoxic response based on visual observations. These results indicate that, though histopathologic evaluations may have value for investigating mechanisms of phototoxicity, histopathologic evaluation of the skin is not warranted for determination of phototoxic potential in safety assessment intended for regulatory submission.