Phototoxicity, also called photoirritation, is a chemically induced skin irritation, requiring light, that does not involve the immune system.[1] It is a type of photosensitivity.[1][2]
The skin response resembles an exaggerated sunburn. The involved chemical may enter into the skin by topical administration or it may reach the skin via systemic circulation following ingestion or parenteral administration. The chemical needs to be "photoactive," which means that when it absorbs light, the absorbed energy produces molecular changes that cause toxicity. Many synthetic compounds, including drug substances like tetracyclines or fluoroquinolones, are known to cause these effects. Surface contact with some such chemicals causes photodermatitis; many plants cause phytophotodermatitis. Light-induced toxicity is a common phenomenon in humans; however, it also occurs in other animals.
Contents
1Scientific background
2Photosafety evaluation
2.1Physico-chemical properties
2.2In vitro test systems
2.3During drug development
3See also
4References
5External links
Scientific background
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A phototoxic substance is a chemical compound which becomes toxic when exposed to light.
Some medicines: tetracycline antibiotics, sulfonamides, amiodarone, quinolones, psoralen
Many cold pressed citrus essential oils such as bergamot oil[3]
Some plant juices: parsley, lime, and Heracleum mantegazzianum
Phototoxicity is a quantum chemical phenomenon. Phototoxins are molecules with a conjugated system, often an aromatic system. They have a low-lying excited state that can be reached by excitation with visible light photons. This state can undergo intersystem crossing with neighboring molecules in tissue, converting them to toxic free radicals. These rapidly attack nearby molecules, killing cells. A typical radical is singlet oxygen, produced from regular triplet oxygen. Because free radicals are highly reactive, the damage is limited to the body part illuminated.
Photosafety evaluation
Physico-chemical properties
In vitro test systems
3T3 Neutral Red Phototoxicity Test – An in vitro toxicological assessment test used to determine the cytotoxic and photo(cyto)toxicity effect of a test article to murine fibroblasts in the presence or absence of UVA light.
"The 3T3 Neutral Red Uptake Phototoxicity Assay (3T3 NRU PT) can be utilized to identify the phototoxic effect of a test substance induced by the combination of test substance and light and is based on the comparison of the cytotoxic effect of a test substance when tested after the exposure and in the absence of exposure to a non-cytotoxic dose of UVA/vis light. Cytotoxicity is expressed as a concentration-dependent reduction of the uptake of the vital dye - Neutral Red.
Substances that are phototoxic in vivo after systemic application and distribution to the skin, as well as compounds that could act as phototoxicants after topical application to the skin can be identified by the test. The reliability and relevance of the 3T3 NRU PT have been evaluated and has been shown to be predictive when compared with acute phototoxicity effects in vivo in animals and humans." Taken with permission from [1]
During drug development
Several health authorities have issued related guidance documents, which need to be considered for drug development:
ICH (International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use)
M3(R2) "Guidance on Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals"[4]
S9 "Nonclinical Evaluation for Anticancer Pharmaceuticals"[5]
S10 "Photosafety Evaluation"[5]
EMA (European Medicines Agency)
"Note for Guidance on Photosafety Testing" (revision on-hold)[6]
"Question & Answers on the Note for Guidance on Photosafety Testing"[6]
FDA (U.S. Food and Drug Administration)
MHLW/PMDA (Japanese Ministry of Health, Labour and Welfare / Pharmaceuticals and Medical Devices Agency)
See also
Photodynamic therapy
References
^ abAnderson, D.M.; Keith, J.; Novac, P.; Elliott, M.A., eds. (1994). Dorland's Illustrated Medical Dictionary (28th ed.). W. B. Saunders Company. ISBN 0721655777.
^JH Epstein (1999). "Phototoxicity and photoallergy". Seminars in Cutaneous Medicine and Surgery. 18 (4): 274–284. PMID 10604793.
^"Bergamot oil". Drugs.com. 2018. Retrieved 5 December 2018.
Impact of TiO2 nanoparticles on freshwater bacteria from three Swedish lakes.
Farkas J1, Peter H2, Ciesielski TM3, Thomas KV4, Sommaruga R2, Salvenmoser W5, Weyhenmeyer GA6, Tranvik LJ6, Jenssen BM3.
The Science of the total environment.Sci Total Environ.2015 Dec 1;535:85-93. doi: 10.1016/j.scitotenv.2015.03.043. Epub 2015 Mar 23.
Due to the rapidly rising production and usage of nano-enabled products, aquatic environments are increasingly exposed to engineered nanoparticles (ENPs), causing concerns about their potential negative effects. In this study we assessed the effects of uncoated titanium dioxide nanoparticles (TiO2NP
Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv für klinische und experimentelle Ophthalmologie.Graefes Arch Clin Exp Ophthalmol.2015 Sep;253(9):1529-35. doi: 10.1007/s00417-015-3036-9. Epub 2015 May 10.
PURPOSE: Conventional chandelier-endoilluminators used for pars-plana vitrectomy consist of a light-emitting tip attached to an optical fibre. The tip requires introduction into the ocular space through an incision. To achieve complete illumination of the intraocular space, the introduction of more
Kinetic Evaluation of Determinant Factors for Cellular Accumulation of Protoporphyrin IX Induced by External 5-Aminolevulinic Acid for Photodynamic Cancer Therapy.
Nakanishi T1, Ogawa T1, Yanagihara C1, Tamai I1.
Journal of pharmaceutical sciences.J Pharm Sci.2015 Sep;104(9):3092-100. doi: 10.1002/jps.24462. Epub 2015 May 8.
Five-aminolevulinic acid (ALA) is a prodrug to generate phototoxic protoporphyrin IX (PPIX) for photodynamic cancer therapy. It remains unclear how PPIX accumulates in cancer cells; therefore, we aimed to clarify determinant factors by assessing ALA uptake, PPIX biosynthesis, conversion of PPIX to h
Journal of environmental dermatology and cutaneous allergology = / the Japanese Society for Dermatoallergology and Contact Dermatitis 7(3), 177-186, 2013-07-31
Phototoxicity is a chemically induced skin irritation requiring light (photoirritation or photosensitivity). The skin response resembles an exaggerated sunburn. The involved chemical may enter into the skin by topical administration or it may ...
Phototoxicity - these essential oils become toxic when exposed to direct sunlight. These oils are fine in candles, but shouldn't be used in any sort of application where the essential oil will stay on your skin and be exposed to the sun.