Phototoxicity and skin damage: A review of adverse effects of some furocoumarins found in natural extracts

• Published in: Food and chemical toxicology Vol. 200; p. 115332
• Main Authors: Irizar, Amaia, Boislève, Fanny, Gautier, Françoise, Nash, J Frank, Pfuhler, Stefan, Ritacco, Gretchen, Vey, Matthias, Wolf, Nicolas, Cadby, Peter A.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2025
• Subjects: 5-MOP; 8-MOP; Animals; bergapten; Biological Products - chemistry; Biological Products - toxicity; Cosmetics; Dermatitis, Phototoxic - etiology; DNA; Furocoumarin; Furocoumarins - chemistry; Furocoumarins - toxicity; Humans; irradiation; methoxsalen; Natural; Photocarcinogenicity; Photoirritation; Phototoxicity; Plant Extracts - chemistry; Psoralen; PUVA; Skin - drug effects; Skin - radiation effects; sunscreens; therapeutics; ultraviolet radiation; Ultraviolet Rays - adverse effects; UVA; Furocoumarin; UVA; Psoralen; 8-MOP; PUVA; 5-MOP; Phototoxicity; Photocarcinogenicity; Cosmetics; Photoirritation; Natural
• ISSN: 0278-6915; 1873-6351; 1873-6351
• DOI: 10.1016/j.fct.2025.115332

The phototoxicological effects of furocoumarins have been extensively studied. In association with UVA, some of these natural constituents of botanical isolates used in cosmetics, can be photoirritant, photogenotoxic and/or photocarcinogenic. Importantly, not all furocoumarins share the same degree of potency and some are inactive. The more potent furocoumarins, 8-methoxypsoralen and 5-methoxypsoralen, have been subject to extensive mechanistic studies. The formation of adducts with DNA has been widely studied but other contributary mechanisms have also been proposed. The phototoxicological effects, ranging from photoirritation to photocarcinogenicity, are dependent on the dermal dose of furocoumarin and the fluence (dose) of filtered, artificial UVA light. This is particularly evident from photocarcinogenicity studies in animals and from the effect of sequential irradiation sessions in patients receiving Psoralen-UVA (PUVA) therapy. A currently enforced limit of 1 ppm for sun bronzing and sunscreen products for which prolonged intentional exposure to UVA is likely, and 5 ppm total furocoumarin concentration in other cosmetic products, e.g., facial cosmetics, that are likely to be only exposed to adventitious and intermittent UVA irradiation, provides a suitably protective threshold when compared to the UV exposure that has been used in studies on animals and in treating PUVA patients. •Furocoumarins, particularly 8-methoxypsoralen and 5-methoxypsoralen, which are constituents of natural extracts, exhibit photoirritant and photogenotoxic/photocarcinogenic properties following exposure to long wavelength UVA.•Phototoxic effects are dose/concentration-dependent, influenced by dermal penetration of furocoumarins and also by the irradiance/fluence of UVA light.•Mechanistic studies emphasise DNA adduct formation as a primary pre-molecular initiating event, with additional contributory mechanisms proposed.•Cumulative phototoxicity has been demonstrated through animal studies and PUVA therapy in humans, highlighting risks of repeated exposure to the furocoumarin coupled with repeated UVA exposure.•UV exposure itself can lead to similar effects. The anticipated accumulated exposure to UVA through sunlight experienced by a consumer of cosmetic products is far lower than the filtered UVA irradiation dose utilised in human and animal studies.•Regulatory limits of 1 ppm for sunscreens for which prolonged intentional exposure to UVA is foreseen and 5 ppm for other leave-on cosmetics should effectively mitigate the phototoxic risks associated with these botanical constituents.