Phototoxicity

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 humans, 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.

Scientific background

A phototoxic substance is a chemical compound which becomes toxic when exposed to light.

• Some medicines: tetracycline antibiotics, sulfonamides, amiodarone, quinolones
• Many cold pressed citrus essential oils such as bergamot oil
• Some plant juices: parsley and Giant hogweed
• Others: psoralen

Photosafety evaluation

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]

in vivo test systems

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Clinical phototoxicity trials

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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)

See also

• Photodynamic therapy
• Singlet oxygen
• Fluorescence microscopy

External links

• In Vitro Phototoxicity Test
• ICCVAM 3T3 Neutral Red Phototoxicity Testing Page
• 3T3 NRU Phototoxicity Test