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Phototoxicity of bergamot oil assessed by in vitro techniques in combination with human patch tests.Toxicology in Vitro : An International... Oct 2007The aim of this study was to clarify the differences in the phototoxicity of bergamot oil obtained from four different suppliers. Spectral and chemical analyses were...
The aim of this study was to clarify the differences in the phototoxicity of bergamot oil obtained from four different suppliers. Spectral and chemical analyses were performed to identify presence of photoactive compounds in the test samples. The phototoxicity was assessed in vitro by the 3T3 NRU phototoxicity test (PT) and subsequently in a phototoxicity test on reconstructed human skin model (H3D PT). Confirmatory photopatch tests in a group of volunteers were performed using the first non-phototoxic concentration determined in the H3D PT. The spectral and chemical analyses revealed, that two samples of bergamot oil exhibited a potential for photoactivation. These oils were subsequently classified as phototoxic in the 3T3 NRU PT, however, only on the basis of borderline results and depending on the solvent used. H3D PT revealed clear classifications, correlating well with the findings of spectral and chemical analysis. The test was, however, not yet capable of precise prediction of safe, non-phototoxic concentrations. Additional endpoints, e.g. interleukin determination might be employed to increase the sensitivity of the test. Although the study showed the usefulness of the tiered testing strategy, currently, the extrapolation of in vitro results to human situation may be performed only to a limited extent.
Topics: Adult; Animals; BALB 3T3 Cells; Dermatitis, Phototoxic; Female; Humans; Mice; Middle Aged; Neutral Red; Patch Tests; Plant Oils; Skin; Solvents; Toxicity Tests; Ultraviolet Rays
PubMed: 17669618
DOI: 10.1016/j.tiv.2007.05.016 -
Clinical Pharmacy Aug 1993Characteristics and diagnosis of photosensitivity are discussed, and drugs available in the United States that cause photosensitivity are identified. In phototoxic... (Review)
Review
Characteristics and diagnosis of photosensitivity are discussed, and drugs available in the United States that cause photosensitivity are identified. In phototoxic reactions, the drug absorbs energy from ultraviolet A (UVA) light and releases it into the skin, causing cellular damage. In photoallergic reactions, light may cause a structural change in a drug so that it acts as a hapten, possibly by binding to proteins in the skin. Once a hapten-protein complex is formed, Langerhans' cells residing in the epidermis can present the antigen to immunocompetent cells, causing hypersensitivity. Phototoxicity is much more common than photoallergy. Drugs that can cause phototoxic reactions include amiodarone, quinolones, and tetracyclines. Drugs that have been associated with photoallergic reactions include thiazides and benzocaine. Pharmacists should be aware of drugs that can cause photosensitivity and should counsel patients taking these drugs to avoid excessive exposure to sunlight.
Topics: Chronic Disease; Dermatitis, Photoallergic; Dermatitis, Phototoxic; Humans; Photosensitivity Disorders
PubMed: 8222522
DOI: No ID Found -
The Journal of Toxicological Sciences Feb 2005Ketoprofen has been reported to have such side effects as photosensitive dermatitis in humans (The Ministry of Health, Labour and Welfare, 2001). In the present study,...
Ketoprofen has been reported to have such side effects as photosensitive dermatitis in humans (The Ministry of Health, Labour and Welfare, 2001). In the present study, as part of a safety evaluation of Miltax, an application drug containing ketoprofen, phototoxicity of Miltax was examined in guinea pigs. In the present skin phototoxicity study, Miltax was applied for 12 hr. Ultraviolet (UV) rays were irradiated to examine whether or not Miltax elicited skin reaction. Two kinds of UV-A plus UV-B dual irradiation and UV-A single irradiation were used for the elicitation. With UV-A plus UV-B dual irradiation on the Miltax application site, no skin reaction was observed at UV irradiation side in any animals, in contrast to the case of the positive control article, 8-methoxypsoralen (8-MOP). Similar results were obtained with UV-A single irradiation. From these results, Miltax that contained ketoprofen did not show any skin phototoxicity in the guinea pig.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Body Weight; Dermatitis, Phototoxic; Dose-Response Relationship, Drug; Erythema; Guinea Pigs; Ketoprofen; Male
PubMed: 15800399
DOI: 10.2131/jts.30.19 -
Toxicology in Vitro : An International... Feb 2008A gram negative bacteria Escherichia coli (Dh5alpha strain) was developed as an alternate test system of phototoxicity. Eight drugs (antibiotics) and cosmetic products...
A gram negative bacteria Escherichia coli (Dh5alpha strain) was developed as an alternate test system of phototoxicity. Eight drugs (antibiotics) and cosmetic products (eight face creams) were examined for their phototoxicity using this test system. Five known phototoxic compounds were used to validate the test system. UVA-radiation induced phototoxicity of these compounds was tested by agar gel diffusion assay. Decrease in colony forming units (CFU) was taken as an end point of phototoxicity. The phototoxic compounds and antibiotics produced significant reduction in CFU (p<0.001) at 80 microg/ml concentrations under exposure to UVA-radiation (5.4-10.8 J/cm(2)). One face cream was found phototoxic and produced significant decrease in CFU of E. coli at 1.0mg/ml concentration under UVA exposure (10.8 J/cm(2)). The minimum effective concentration of tetracycline and dose of UVA-radiation were also determined by observing growth inhibition of E. coli through disc diffusion assay. The observations suggested that E. coli can be used as an alternative test system for phototoxicity evaluation of chemicals. A battery of test systems is required to conclude the toxic/phototoxic potential of a chemical agent. In view of the speed, easiness, sensitivity and low cost, E. coli is introduced as one of the alternate test system for phototoxicity studies in safety evaluation of various chemical ingredients or formulations used in cosmetics and drugs.
Topics: Animal Testing Alternatives; Anti-Bacterial Agents; Colony Count, Microbial; Cosmetics; Dermatitis, Phototoxic; Escherichia coli; Microbial Sensitivity Tests; Toxicity Tests; Ultraviolet Rays
PubMed: 17919881
DOI: 10.1016/j.tiv.2007.08.009 -
Methods in Molecular Biology (Clifton,... 1995
Topics: 3T3 Cells; Animals; Cells, Cultured; Dermatitis, Phototoxic; Epidermal Cells; Humans; Mice; Tetrazolium Salts; Toxicity Tests
PubMed: 7550651
DOI: 10.1385/0-89603-282-5:219 -
The Journal of Toxicological Sciences 2023The interaction between sunlight and drugs can lead to phototoxicity in patients who have received such drugs. Phototoxicity assessment is a regulatory requirement...
The interaction between sunlight and drugs can lead to phototoxicity in patients who have received such drugs. Phototoxicity assessment is a regulatory requirement globally and one of the main toxicity screening steps in the early stages of drug discovery. An in silico-in vitro approach has been utilized mainly for toxicology assessments at these stages. Although several quantitative structure-activity relationship (QSAR) models for phototoxicity have been developed, in silico technology to evaluate phototoxicity has not been well established. In this study, we attempted to develop an artificial intelligence (AI) model to predict the in vitro Neutral Red Uptake Phototoxicity Test results from a chemical structure and its derived information. To accomplish this, we utilized an open-source software library, kMoL. kMoL employs a graph convolutional neural networks (GCN) approach, which allows it to learn the data for the specified chemical structure. kMoL also utilizes the integrated gradient (IG) method, enabling it to visually display the substructures contributing to any positive results. To construct this AI model, we used only the chemical structure as a basis, then added the descriptors and the HOMO-LUMO gap, which was obtained from quantum chemical calculations. As a result, the assortment of chemical structures and the HOMO-LUMO gap produced an AI model with high discrimination performance, and an F1 score of 0.857. Additionally, our AI model could visualize the substructures involved in phototoxicity using the IG method. Our AI model can be applied as a toxicity screening method and could enhance productivity in drug development.
Topics: Humans; Artificial Intelligence; Neural Networks, Computer; Dermatitis, Phototoxic; Drug Development; Drug Discovery
PubMed: 37121739
DOI: 10.2131/jts.48.243 -
Expert Review of Anti-infective Therapy 2015Voriconazole's antifungal spectrum, oral bioavailability, and proven efficacy in treatment of invasive mycoses have led to its widespread off-label use for antifungal... (Review)
Review
Voriconazole's antifungal spectrum, oral bioavailability, and proven efficacy in treatment of invasive mycoses have led to its widespread off-label use for antifungal prophylaxis. There is an increasing recognition that long-term voriconazole use is associated with accelerated sun-induced skin changes that include acute phototoxicity reactions, photoaging, actinic keratosis and esp. among immunocompromised patients, skin cancers. The mechanisms underlying these dermatologic adverse events are not clearly understood. Population-risks of long-term voriconazole use need to be prospectively investigated. This review aims to provide an in-depth assessment of published literature and highlight salient findings from retrospective studies and case series. A broad practical guideline for assessment and management of these patients is provided.
Topics: Animals; Antifungal Agents; Dermatitis, Phototoxic; Humans; Skin Neoplasms; Voriconazole
PubMed: 26488688
DOI: 10.1586/14787210.2015.1102053 -
Nordisk Medicin Dec 1998As phototoxic and photoallergic reactions have been recognised as unwanted skin manifestations caused by any of several hundred substances, drugs and chemicals, it is...
As phototoxic and photoallergic reactions have been recognised as unwanted skin manifestations caused by any of several hundred substances, drugs and chemicals, it is essential to determine the potential photo-sensitising properties of such substances before they are introduced in clinical therapy or made available on the market, in order to avoid such reactions. In cases of phototoxic reactions, the patient presents with skin changes resembling sunburn, sometimes accompanied by blistering, whereas in cases of photoallergic reactions the skin changes are similar to those of allergic contact dermatitis. The two most important aids to clinical investigation are determination of the erythema treshold, or the minimal erythema dose, and photopatch testing. The article reviews the basic mechanisms of photosensitisation, outlining the most important differences between phototoxic and photoallergic reactions, summarises the most frequent photosensitisers, and presents the diagnostic procedures, including the tests used in experimental phototoxicity.
Topics: Dermatitis, Photoallergic; Dermatitis, Phototoxic; Humans
PubMed: 9894409
DOI: No ID Found -
Actas Dermo-sifiliograficas May 2014Thiazides are widely used diuretics that first became available in the 1950s. The first reports of photosensitivity reactions to thiazides were published shortly after... (Review)
Review
Thiazides are widely used diuretics that first became available in the 1950s. The first reports of photosensitivity reactions to thiazides were published shortly after the introduction of these drugs, but few cases have been described since. We review all the cases of photosensitivity due to thiazides published up to December 2011. We found 62 cases, 33 in women and 29 in men. The most common presentation was eczematous lesions in a photodistributed pattern, and the most common causative agent was hydrochlorothiazide. The results of photobiological studies were published in only some of the cases reviewed. In most cases, phototesting revealed an abnormal response to UV-A alone or to both UV-A and UV-B. In some cases, the results of phototesting were normal and only photopatch testing yielded abnormal results. Diagnosis of photosensitivity due to thiazides requires a high degree of suspicion. Ideally, diagnosis should be confirmed by a photobiological study.
Topics: Dermatitis, Phototoxic; Female; Humans; Male; Thiazides
PubMed: 23664250
DOI: 10.1016/j.ad.2013.01.010 -
Clinics in Dermatology 2016Drug-induced photosensitivity refers to the development of cutaneous disease due to the interaction between a given chemical agent and sunlight. Photosensitivity... (Review)
Review
Drug-induced photosensitivity refers to the development of cutaneous disease due to the interaction between a given chemical agent and sunlight. Photosensitivity reactions can be classified as phototoxic or photoallergic. Sometimes, there is an overlap between these two patterns, making their distinction particularly difficult for the clinician. We review the drugs that have been implicated as photosensitizers, the involved mechanism, and their clinical presentations. The main topical agents that cause contact photosensitivity are the nonsteroidal antiinflammatory drugs, whereas the main systemic drugs inducing photosensitivity are antimicrobials, nonsteroidal antiinflammatory agents, and cardiovascular drugs. Drug-induced photosensitivity remains a common clinical problem and is often underdiagnosed.
Topics: Administration, Cutaneous; Administration, Oral; Anti-Arrhythmia Agents; Anti-Infective Agents; Anti-Inflammatory Agents, Non-Steroidal; Antihypertensive Agents; Antineoplastic Agents; Dermatitis, Photoallergic; Dermatitis, Phototoxic; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Psychotropic Drugs
PubMed: 27638435
DOI: 10.1016/j.clindermatol.2016.05.006