Phototoxicity
| Phototoxicity | |
|---|---|
| Other names | Photoirritation |
 | |
| Effect of thecommon rueon skin in hot weather. | |
| Specialty | Dermatology |
Phototoxicity,also calledphotoirritation,is a chemically induced skin irritation, requiring light, that does not involve theimmune system.[1]It is a type ofphotosensitivity.[1][2]
The skin response resembles an exaggeratedsunburn.The involved chemical may enter into the skin bytopical administration,or it may reach the skin viasystemic circulationfollowingingestionor 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 liketetracyclinesorfluoroquinolones,are known to cause these effects. Surface contact with some such chemicals causesphotodermatitis,and many plants causephytophotodermatitis.Light-induced toxicity is a common phenomenon inhumans;however, it also occurs in other animals.
Scientific background
[edit] | This sectionneeds additional citations forverification.(December 2018) |
A phototoxic substance is achemical compoundwhich becomes toxic when exposed to light.
- Somemedicines:tetracycline antibiotics,sulfonamides,amiodarone,quinolones,psoralen
- Many cold pressedcitrusessential oilssuch asbergamot oil[3]
- Some plant juices:parsley,lime,andHeracleum mantegazzianum
- Porphyrins,a class of natural molecules occurring in the body and accumulating in patients with certaingenetic disordersin the building chain of the red blood dyeheme:porphyria
Phototoxicity is a quantum chemical phenomenon. Phototoxins are molecules with aconjugated system,often anaromatic system.They have a low-lyingexcited statethat can be reached by excitation with visible light photons. This state can undergointersystem crossingwith neighboring molecules in tissue, converting them to toxicfree radicals.These rapidly attack nearby molecules, killing cells. A typical radical issinglet oxygen,produced from regulartriplet oxygen.Because free radicals are highly reactive, the damage is limited to the body part illuminated.
Photosafety evaluation
[edit]Physico-chemical properties
[edit]In vitrotest systems
[edit]3T3 Neutral Red Phototoxicity Test – Anin vitrotoxicologicalassessment test used to determine thecytotoxicityand photo(cyto)toxicity effect of atest articleto murinefibroblastsin the presence or absence ofUVA 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. The test compares thecytotoxiceffect of a test substance when tested after the exposure, then tested 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 phototoxicin vivoafter 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 the test 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
[edit]Several health authorities have issued related guidance documents, which need to be considered fordrug development:
- ICH(International Conference on Harmonisation of TechnicalRequirements for Registration of Pharmaceuticals for Human Use)
- EMA(European Medicines Agency)
- FDA(U.S. Food and Drug Administration)
- MHLW/PMDA(Japanese Ministry of Health, Labour and Welfare/Pharmaceuticals and Medical Devices Agency)
Phototoxicity in light microscopy
[edit]When performingmicroscopyon live samples, one needs to be aware that too high light dose can damage or kill the specimens and lead to experimental artefacts. This is particularly important inconfocalandsuper-resolutionmicroscopy.[7][8]
See also
[edit]References
[edit]- ^abAnderson, D.M.; Keith, J.; Novac, P.; Elliott, M.A., eds. (1994).Dorland's Illustrated Medical Dictionary(28th ed.). W. B. Saunders Company.ISBN0721655777.
- ^JH Epstein (1999). "Phototoxicity and photoallergy".Seminars in Cutaneous Medicine and Surgery.18(4): 274–284.doi:10.1016/s1085-5629(99)80026-1.PMID10604793.
- ^"Bergamot oil".Drugs.com. 2018.Retrieved5 December2018.
- ^"Multidisciplinary Guidelines".ICH.Retrieved2013-08-06.
- ^ab"Safety Guidelines".ICH.Retrieved2013-08-06.
- ^ab"European Medicines Agency - Non-clinical: Toxicology".Ema.europa.eu. 2010-06-24. Archived fromthe originalon 2013-01-19.Retrieved2013-08-06.
- ^Icha, Jaroslav; Weber, Michael; Waters, Jennifer C.;Norden, Caren(2017)."Phototoxicity in live fluorescence microscopy, and how to avoid it".BioEssays.39(8): 1700003.doi:10.1002/bies.201700003.hdl:21.11116/0000-0002-8C94-9.ISSN1521-1878.PMID28749075.S2CID19974817.
- ^Laissue, P. Philippe; Alghamdi, Rana A.; Tomancak, Pavel; Reynaud, Emmanuel G.; Shroff, Hari (July 2017)."Assessing phototoxicity in live fluorescence imaging".Nature Methods.14(7): 657–661.doi:10.1038/nmeth.4344.hdl:21.11116/0000-0002-8B80-0.ISSN1548-7105.PMID28661494.S2CID6844352.