Phototoxicity, also called photoirritation, is a chemically induced skin irritation, requiring light, that does not involve the
immune system
The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
.
It is a type of
photosensitivity Photosensitivity is the amount to which an object reacts upon receiving photons, especially visible light. In medicine, the term is principally used for abnormal reactions of the skin, and two types are distinguished, photoallergy and phototoxicit ...
.
[
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
The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, t ...
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
Tetracyclines are a group of broad-spectrum antibiotic compounds that have a common basic structure and are either isolated directly from several species of ''Streptomyces'' bacteria or produced semi-synthetically from those isolated compounds. T ...
or fluoroquinolone
A quinolone antibiotic is a member of a large group of broad-spectrum bacteriocidals that share a bicyclic core structure related to the substance 4-quinolone. They are used in human and veterinary medicine to treat bacterial infections, as wel ...
s, are known to cause these effects. Surface contact with some such chemicals causes photodermatitis
Photodermatitis, sometimes referred to as sun poisoning or photoallergy, is a form of allergic contact dermatitis in which the allergen must be activated by light to sensitize the allergic response, and to cause a rash or other systemic effects o ...
; many plants cause phytophotodermatitis. Light-induced toxicity is a common phenomenon in humans" \n\n\n\n\nThe robots exclusion standard, also known as the robots exclusion protocol or simply robots.txt, is a standard used by websites to indicate to visiting web crawlers and other web robots which portions of the site they are allowed to visi ...
; however, it also occurs in other animals.
Scientific background
A phototoxic substance is a chemical compound which becomes toxic when exposed to light.
* Some medicines
A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the medical field and re ...
: tetracycline antibiotics
Tetracyclines are a group of broad-spectrum antibiotic compounds that have a common basic structure and are either isolated directly from several species of ''Streptomyces'' bacteria or produced semi-synthetically from those isolated compounds. T ...
, sulfonamides
In organic chemistry, the sulfonamide functional group (also spelled sulphonamide) is an organosulfur group with the structure . It consists of a sulfonyl group () connected to an amine group (). Relatively speaking this group is unreactive. ...
, amiodarone
Amiodarone is an antiarrhythmic medication used to treat and prevent a number of types of cardiac dysrhythmias. This includes ventricular tachycardia (VT), ventricular fibrillation (VF), and wide complex tachycardia, as well as atrial fibril ...
, quinolones
Quinolone may refer to:
* 2-Quinolone
* 4-Quinolone
4-Quinolone is an organic compound derived from quinoline. It and 2-quinolone are the two most important parent (meaning simplified) quinolones. 4-Quinolone exists in equilibrium with a mino ...
, psoralen
Psoralen (also called psoralene) is the parent compound in a family of naturally occurring organic compounds known as the linear furanocoumarins. It is structurally related to coumarin by the addition of a fused furan ring, and may be considered ...
* Many cold pressed citrus essential oils
An essential oil is a concentrated hydrophobic liquid containing volatile (easily evaporated at normal temperatures) chemical compounds from plants. Essential oils are also known as volatile oils, ethereal oils, aetheroleum, or simply as the o ...
such as bergamot oilparsley
Parsley, or garden parsley (''Petroselinum crispum'') is a species of flowering plant in the family Apiaceae that is native to the central and eastern Mediterranean region (Sardinia, Lebanon, Israel, Cyprus, Turkey, southern Italy, Greece, ...
, lime, and '' Heracleum mantegazzianum''
* Porphyrins, a class of natural molecules occurring in the body and accumulating in patients with certain genetic defects in the building chain of the red blood dye heme: ''porphyria
Porphyria is a group of liver disorders in which substances called porphyrins build up in the body, negatively affecting the skin or nervous system. The types that affect the nervous system are also known as acute porphyria, as symptoms are ...
''
Phototoxicity is a quantum chemical phenomenon. Phototoxins are molecules with a conjugated system
In theoretical chemistry, a conjugated system is a system of connected p-orbitals with delocalized electrons in a molecule, which in general lowers the overall energy of the molecule and increases stability. It is conventionally represented ...
, often an aromatic system. They have a low-lying excited state
In quantum mechanics, an excited state of a system (such as an atom, molecule or nucleus) is any quantum state of the system that has a higher energy than the ground state (that is, more energy than the absolute minimum). Excitation refers to ...
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 radical
A daughter category of ''Ageing'', this category deals only with the biological aspects of ageing.
Ageing
Ailments of unknown cause
Biogerontology
Biological processes
Causes of death
Cellular processes
Gerontology
Life extension
Metabo ...
s. These rapidly attack nearby molecules, killing cells. A typical radical is singlet oxygen
Singlet oxygen, systematically named dioxygen(singlet) and dioxidene, is a gaseous inorganic chemical with the formula O=O (also written as or ), which is in a quantum state where all electrons are spin paired. It is kinetically unstable at ambi ...
, produced from regular triplet oxygen
Triplet oxygen, 3O2, refers to the ''S'' = 1 electronic ground state of molecular oxygen (dioxygen). It is the most stable and common allotrope of oxygen. Molecules of triplet oxygen contain two unpaired electrons, making triplet oxygen an unus ...
. 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
Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are an immune cell or some types of venom, e.g. from the puff adder (''Bitis arietans'') or brown recluse spider (''Loxosceles reclusa'').
Cell physiology
Treating c ...
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 fro
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"
Phototoxicity in light microscopy
When performing microscopy on 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 in confocal In geometry, confocal means having the same foci: confocal conic sections.
* For an optical cavity consisting of two mirrors, confocal means that they share their foci. If they are identical mirrors, their radius of curvature, ''R''mirror, equals ' ...
and superresolution
Super-resolution imaging (SR) is a class of techniques that enhance (increase) the resolution of an imaging system. In optical SR the diffraction limit of systems is transcended, while in geometrical SR the resolution of digital imaging sensors i ...
microscopy.
See also
* Photodynamic therapy
References
External links
In Vitro Phototoxicity Test
3T3 NRU Phototoxicity Test
{{Authority control
Toxicology