Drug Products and Photocarcinogenesis

Most safety tests are designed to determine whether an agent, such as a drug or chemical, will adversely affect some normal physiological component or process. In contrast, most photobiological safety tests seek to determine whether a chemical can amplify the known noxious effects of an external agent, ultraviolet radiation (UVR). Tests for phototoxicity, for example, determine whether suberythemal doses of radiation will produce acute damage in the presence of the test agent: such tests are always preceded by a determination that the agent alone does not produce such damage. It is understood that higher doses of UVR (or, in some cases, different radiation spectra) are capable of producing erythema in the absence of the test agent, but for testing purposes the effects of low doses of UVR are regarded as the “normal” state against which toxic effects are to be evaluated. Tests for photoallergic properties may go even further in altering the reference “normal” state, by imposing various forms of trauma at either initiation or elicitation stages. The justification for introducing external trauma in a photobiological safety test is the assumption that some exposure to environmental UVR is virtually inevitable; thus an agent which can intensify trauma induced by UVR is capable of intensifying a “normal” and expected biological response.