Modern Approaches to Assessment of the Photo-toxicity (Photoirritation) Potential of Substances and Formulations by Using Tiered Testing Strategy Combining Analytical and In Vitro Test Systems

The goal of photo-safety testing is to detect the adverse effects of substances and products inthe presence of light. This type of testing is relevant for products that enter the skin via dermalpenetration or systemic circulation. Photo-toxicity testing is required only for substancesthat sufficiently absorb UV-light in the wavelength range 290]700nm and where local and/orsystemic exposure is foreseen. Studies on the extent of photo-stability, structure]activity relationships(SARs), and the generation of reactive oxygen species (ROS) after irradiation by UVand visible light, can provide additional indicators that substance or formulation may triggerphoto-toxicity. However, the biological effect and bioavailability also need to be examined. Forphoto-toxicity testing, a thoroughly validated in vitro method, the 3T3 Neutral Red uptakephoto-toxicity assay (3T3 NRU PT assay), is validated and accepted internationally. Thisassay provides indication that a substance might cause photo-toxicity/photo-allergy or otherphoto-induced effect. While highly sensitive, this assay does not provide information on thebioavailability/accumulation of the substance in the skin or eyes. Therefore, more-advanced invitro 3D tissue constructs are suggested as second tier tests, to exclude possible false positivesfrom 3T3 NRU PT assays. Protocols have been developed for both systemic and dermal exposures.These advanced 3D models can be also used for the assessment of photo-potency andnon-phototoxic doses of a phototoxin, whereby a product (e.g. a pharmaceutical) can be stillused in human therapy after careful considerations of other possible side effects. The use ofthe testing strategy described above may significantly minimise risk of photo-toxicity effects,while still permitting the use of substances that would be excluded from further use by a singletest. This testing strategy is applicable to pharmaceuticals, as well as consumer products/cosmetics, and helps to distinguish the possible hazards from the real risks.