Photoirritation potential

The 3T3 NRU Assay a Validated Test for the Assessment of a Photoirritation Potential... 

The phototoxicity test 3T3 NRU was proposed in 1994 and is so far the only in vitro method that has been validated by European regulatory authorities for predicting the photoirritant potential of substances [5,40,41]. In this test, the mouse fibroblasts cell line Balb/c 3T3 is exposed to simulated solar UV (or, more frequently, solar UVA) in the presence of the test compound after an incubation of 1 h in the dark. Evaluation of cytotoxicity is performed 24h post-exposure using the neutral red uptake (NRU) method. N RU permits to distinguish live and dead cells, since intact cells retain this dye (detailed method in INVITOX protocol 78). The validation was performed with substances selected on the basis of their in vivo photoirritant or phototoxic properties. Some of these structures are shown in Table 19.1. 

Physicochemical analysis has evaluated the particular chemical properties of test substances, which have been identified as key structural components contributing to penetration, irritation, or sensitization. Absence of absorption in the ultraviolet (UV) range also has been used to suggest lack of photoirritant potential. Physicochemical tests are rapid, cost-effective, easily standardized, and transferable to outside laboratories. 

An important method using fungi is Daniels test for phototoxicity, which utilizes the yeast Candida albicans as the test organism. A 1988 study compared favorably the results of this test with the results of photo-patch testing in volunteers for samples from six furocoumarin-containing plants. Many test materials which produce an erythemic response in the photoirritant test are not analyzed as positive in this test. A new test method, Solatex-pi, has demonstrated capability to predict the potential for photoirritation of materials in this class as well as that of other well-known photoirritants. Solatex-pi utilizes the two compartment physicochemical model of Skintex to predict the interactive effects of specific chemicals and UV radiation. Solatex-pi is being validated by Frame and the BGA (Zebet) as an in vitro test to predict photoirritants. 

This raises concerns over the photoirritancy, photosensitization, and photomutagenicity potential of sunscreens, especially that significant amounts of these photodegradation products may be absorbed through skin... 

When drugs are identified as photoirritants, the FDA recommends that the risk communication include a warning to avoid sun exposure. In the absence of human data, a drug shown to be a photoirritant in nonclinical studies could be indicated as potentially causing photosensitivity. When adequate human data addressing photoirritation are available, they would be included in the description of the product and would supplant animal data. 

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