Phototoxicity

Key takeaways

Phototoxicity belongs to science; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Phototoxicity to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Phototoxicity from memory before moving on to harder problems.

Reference excerpt

Phototoxicity is a chemically induced skin irritation, requiring light, that does not involve the immune system. It is a type of photosensitivity. 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, and many plants cause phytophotodermatitis. Light-induced toxicity is a common phenomenon in humans; however, it also occurs in other animals.

Mechanism

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 Some plant juices: parsley, lime, and hogweeds (Heracleum mantegazzianum, Heracleum sosnowskyi, Heracleum persicum) Porphyrins, a class of natural molecules occurring in the body and accumulating in patients with certain genetic disorders in the building chain of the red blood dye heme: porphyria 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 (OECD TG 432) – An in vitro toxicological assessment test used to determine the cytotoxicity 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. The test compares the cytotoxic effect 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 (315-400 nm). 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 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] This test has a sensitivity of 97.3%, a specificity of 86.7% and an accuracy of 94.2% (n=52) in the prediction of phototoxicity compared to human test results. This test is not suitable for UVB-activated compounds or those requiring metabolism. Highly colored or insoluble compounds may be outside of the applicability domain of this test.

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)

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 and super-resolution microscopy.

See also Photodynamic therapy Photoprotection Photosensitivity

References

External links In Vitro Phototoxicity Test 3T3 NRU Phototoxicity Test

Illustrations

Worked examples

Example 1 — a first encounter with Phototoxicity

Start with the simplest possible case. Write down what Phototoxicity claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In science, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Phototoxicity before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Phototoxicity ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Phototoxicity

In research: Phototoxicity appears in science research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Phototoxicity in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Phototoxicity is common in secondary-school and first-year university syllabi. It links to neighbouring topics Toxicology, so understanding it makes those chapters shorter.
In everyday life: Look for Phototoxicity outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

How to study Phototoxicity in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Phototoxicity means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Phototoxicity out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Phototoxicity in simple terms?

Phototoxicity is a chemically induced skin irritation, requiring light, that does not involve the immune system. It is a type of photosensitivity.

Why does Phototoxicity matter?

Because it connects several science ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Phototoxicity?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Phototoxicity.