Phototoxic
Encyclopedia
Phototoxicity is a chemically induced skin irritation requiring light (photoirritation). 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. In any case, the chemical needs to be "photoactive", which means it is able to absorb photons and, subsequently, to turn the absorbed energy into photoreactivity. Light-induced toxicity is a common phenomenon in man, however, it might occur also in animals. Some plants such as the Giant Hogweed
contain natural compounds (e.g. furocoumarins) that can lead to edemas and lesions of the skin after being touched in sun light. Many synthetic compounds, including drug substances like tetracyclines or fluoroquinolones, are known to cause similar effects.
Giant Hogweed
Heracleum mantegazzianum, commonly known as giant hogweed, cartwheel-flower, wild parsnip, wild rhubarb, giant cow parsnip, or giant cow parsley, is a plant in the family Apiaceae. It typically grows to heights of , sometimes reaching...
contain natural compounds (e.g. furocoumarins) that can lead to edemas and lesions of the skin after being touched in sun light. Many synthetic compounds, including drug substances like tetracyclines or fluoroquinolones, are known to cause similar effects.
Scientific background
A phototoxic substance is a chemical compound which becomes toxic when exposed to light.- Some medicines: tetracycline antibioticsTetracycline antibioticsTetracyclines are a group of broad-spectrum antibiotics whose general usefulness has been reduced with the onset of bacterial resistance. Despite this, they remain the treatment of choice for some specific indications....
, sulfonamides, amiodaroneAmiodaroneAmiodarone is an antiarrhythmic agent used for various types of tachyarrhythmias , both ventricular and supraventricular arrhythmias. Discovered in 1961, it was not approved for use in the United States until 1985...
, quinolones - Many cold pressed citrus essential oils such as bergamotBergamot orangeCitrus bergamia, the Bergamot orange, is a fragrant fruit the size of an orange, with a yellow colour similar to a lemon. Genetic research into the ancestral origins of extant citrus cultivars recently matched the bergamot as a likely hybrid of Citrus limetta and Citrus aurantium...
oil - Some plant juices: parsleyParsleyParsley is a species of Petroselinum in the family Apiaceae, native to the central Mediterranean region , naturalized elsewhere in Europe, and widely cultivated as an herb, a spice and a vegetable.- Description :Garden parsley is a bright green hairless biennial herbaceous plant in temperate...
and Giant hogweedGiant HogweedHeracleum mantegazzianum, commonly known as giant hogweed, cartwheel-flower, wild parsnip, wild rhubarb, giant cow parsnip, or giant cow parsley, is a plant in the family Apiaceae. It typically grows to heights of , sometimes reaching... - Others: psoralenPsoralenPsoralen is the parent compound in a family of natural products known as furocoumarins. It is structurally related to coumarin by the addition of a fused furan ring, and may be considered as a derivative of umbelliferone...
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 RedNeutral redNeutral Red is a eurhodin dye used for staining in histology. It stains lysosomes red. It is used as a general stain in histology, as a counterstain in combination with other dyes, and for many staining methods. Together with Janus Green B, it is used to stain embryonal tissues and supravital...
.
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 http://3t3nru.mbresearchlabs.com/background.htm
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"
- S9 "Nonclinical Evaluation for Anticancer Pharmaceuticals"
- S10 "Photosafety Evaluation"
- EMA (European Medicines Agency)
- "Note for Guidance on Photosafety Testing" (revision on-hold)
- "Question & Answers on the Note for Guidance on Photosafety Testing"
- FDA (U.S. Food and Drug Administration)
- MHLW/PMDA (Japanese Ministry of Health, Labour and Welfare / Pharmaceuticals and Medical Devices Agency)