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Study of the photostability of 18 sunscreens in creams by measuring the SPF in vitro

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The target of this research was to evaluate the photostability of various sunscreen agents incorporated into an O/W emulsion. The concept of photostability is very important in the field of solar protection. The effectiveness of the anti-solar products is quantified using a universal indicator: the sun protection factor (SPF). This number which can be found on packaging can be given in two different ways: by methods in vivo (Colipa method) and in vitro. It is this last method which was adopted for this study. According to selected filter UVB (currently directive 76/768/EEC modified authorized 18 filters UVB), we can obtain more or less effective creams. We chose the irradiation of sun lotions formulated using the authorized filters, used with their maximum amount of employment, in a Suntest, with an irradiance of 650 W/m(2) throughout variable time. With interval of regular time, one carries out a measurement of SPF in order to establish for each filter the kinetics SPF=f(time). An indicator of stability (t(90)) is then given. In this way, we could classify the filters by order of increasing photostability.
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... The irradiation conditions corresponded to global solar spectral irradiance at sea level measured in accordance with CIE. [30,31] In vitro SPF of the sunscreen creams was determined before and after irradiation by the formula [29][30][31]: ...
... The irradiation conditions corresponded to global solar spectral irradiance at sea level measured in accordance with CIE. [30,31] In vitro SPF of the sunscreen creams was determined before and after irradiation by the formula [29][30][31]: ...
Article
Objective Pickering emulsions are increasingly used in the pharmaceutical and cosmetic fields, especially for topical applications, since these systems require solid particles as emulsifiers instead of surfactants which are known to cause skin irritation. The solid inorganic nanoparticles (TiO2 and ZnO) used as UV filters in sunscreen formulations may also stabilize emulsion droplets, so that the utility of surfactants may be questioned. Surfactant‐free sunscreen emulsions solely stabilized by such nanoparticles (NPs) have been studied. Methods The ability of these NPs to stabilize o/w emulsions containing a ‘model’ oil phase, the C12‐C15 alkylbenzoate, has been assessed. ZnO and hydrophilic silica‐coated TiO2 NPs widely used in sunscreen products were used together with their mixtures. The emulsification efficiency, the control of droplet size and the stability of o/w Pickering emulsions solely stabilized by NPs were investigated. A ZnO/TiO2 NPs mixture characterized by a theoretical SPF of 45 was finally used as unique emulsifiers to develop a surfactant‐free sunscreen emulsion. Results Stable Pickering emulsions containing 10 up to 60 wt% of C12‐C15 alkyl benzoate were formulated with 2 wt% ZnO in the aqueous phase. The droplet size was controlled by the solid NPs content with respect to oil and the emulsification process. Hydrophilic TiO2 NPs did not allow the stabilization of emulsions. The substitution of TiO2 for ZnO up to 60–70 wt% in a 20/80 o/w emulsion was successfully performed. Finally, a ZnO/TiO2 NP mixture was tested as unique emulsifier system for the formulation of a sunscreen cream. Despite a lower viscosity, the obtained Pickering emulsion was stable and exhibited a photoprotective effect similar to the corresponding surfactant‐based sunscreen cream with an in vitro SPF of about 45. Conclusion Surfactant‐free Pickering emulsions can be stabilized by the UV‐filter nanoparticles for the manufacture of sunscreen products.
... A bulk of the UVB (290 to 320 nm) is absorbed through the epidermis of skin, however UVA (320-400 nm) reaches into the dermal layer as well as in systemic circulation, tissues and generates reactive oxygen species (ROS). [26] The ROS influence lipid peroxidation in biological membranes leading to dermatitis, melanoma, inflammations, ageing and other serious skin complications [26][27]. RJPBCS 9(4) Page No. 1453 ...
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In this study, Myrica esculenta extract along with Coenzyme Q10 was entrapped in nano-structured lipid carriers (NLCs), incorporated into gel base to obtain ME nano-cosmeceutical gel and tested for anti-aging potential. Furthermore the methanolic extract (ME) with high antioxidant activity and Coenzyme Q10 were selected for loading in the stable NLCs. Then their characterization, stability study and in-vivo photo-protective study was carried out followed by the determination for skin irritation using albino wistar rat. The results demonstrated that the Coenzyme Q10 ME-NLCs showed good physical stability at 28 days after preparation. The optimized formulation F5 (G0) of Coenzyme Q10 ME-NLCs containing gel exhibited best release with no skin irritation in albino wistar rat. The antiaging parameters evaluated by UVA-UVB induced photo-protective potential and were significantly (p<0.05) with statistically optimized best formulation F5 (G0) Q10-ME NLC gel. The developed nano-cosmeceutical topical gel of Q10 ME extract from this study could be regarded as the effective anti-aging formulation.
... Thus, improvement of OMC photostability was achieved by means of encapsulation of OMC into lipid nanoparticles; however, the percentage of OMC remaining was lower than 90 . Generally, sunscreen is considered photostable when the percentage of UV sunscreen remaining is higher than 90 after exposure to light 40 . Similar findings were also reported for OMC and avobenzone encapsulated in NLC 11 . ...
Article
This study aimed to evaluate the effect of solid lipid and oil structures on the physicochemical properties, kinetic release, photostability, and photoprotection of nanostructured lipid carriers (NLC) containing octyl methoxycinnamate (OMC). OMC was used as a model compound since it is an effective sunscreen agent and is widely used in sunscreen products; however, it is unstable after ultraviolet radiation (UVR) exposure. OMC-loaded NLC were prepared from different solid lipids (cetyl palmitate (CP) or tristearin) and oils (caprylic/capric triglyceride, isopropyl myristate or isononyl isononanoate) at a 4:1 ratio. After production, the particle size (z-ave) and polydispersity index (PDI) of OMC-loaded NLC ranged from 190 to 260 nm and were lower than 0.25, respectively, and the zeta potential (ZP) values were higher than |50 mV|. The Fourier transform infrared (FTIR) spectroscopy results indicated no interaction among the components. Data obtained from differential scanning calorimetry (DSC) and X-ray diffraction showed that the incorporation of oil into solid lipids disturbed the crystallinity of the lipid matrix, depending on the structure of the oil molecule. OMC loaded in tristearin-based NLC (OMC-tristearin-NLC) showed higher release of OMC than OMC loaded in CP-based NLC (OMC-CP-NLC). For photostability properties, OMC-CP-NLC prepared from isononyl isononanoate showed the highest stability owing to the less-ordered structure, providing space for accommodation of OMC, whereas the percentage of OMC remaining in tristearin-based NLC was comparable. Therefore, the degree of protection was dependent on the type of solid lipid and oil. As a result, branched-chain fatty acids provided a higher degree of disturbance than linear-chain fatty acid.
Article
Résumé Les produits de protection solaire (PPS) composés de filtres chimiques et/ou de filtres minéraux occupent aujourd’hui une place importante en photoprotection. Ils ont été à l’origine de larges polémiques, dont certaines ne sont pas éteintes, sur leur efficacité réelle en prévention primaire des cancers cutanés (CC), ainsi que sur leurs risques sanitaire et écologique potentiels. Les filtres chimiques agissent en absorbant le rayonnement lumineux ; on distingue les filtres UVB purs et les filtres larges dont le spectre d’absorption s’étend à l’UVA. Les filtres minéraux diffractent ou réfléchissent le rayonnement ; les deux principaux sont le dioxyde de titane (TiO2) et l’oxyde de zinc (ZnO) ; pour des contingences cosmétiques la taille de leurs particules a été réduite aux nanoparticules. Un PPS doit répondre à des qualités de rémanence, de substantivité et de photostabilité. Deux types de méthodes sont proposés pour l’évaluation des coefficients de protection (CP) des PPS : des méthodes in vivo sur volontaires sains, et des méthodes in vitro utilisant des substrats variés et basés sur la spectrométrie. Le sun protective factor (SPF) in vivo est le CP UVB universellement admis ; pour le CP UVA, la méthode in vivo de la persistent pigment darkening (PPD), bien que non consensuelle, reste à ce jour la plus utilisée en Europe. La mesure de la longueur d’onde critique (Lc) a un intérêt majeur pour définir l’étendue de la protection dans les UVA longs les plus délétères. Les filtres chimiques sont connus pour être à l’origine de réactions locales ; un risque particulier pour l’octocrylène a été évoqué ces dernières années. Récemment, le débat s’est surtout centré sur le risque de perturbations endocriniennes (effet mimant l’estradiol après administration orale à très forte dose chez le rat) pouvant être induites par certains (mais pas les autres !) filtres chimiques, essentiellement le 4-méthylbenzylidène camphre et les benzophénones. Le risque humain paraît peu pertinent dans des conditions normales d’usage de PPS ; le risque environnemental de certains filtres, s’il était avéré, relèverait probablement de leur présence dans bien d’autres produits que les PPS. Les filtres minéraux, souvent prônés chez l’enfant, soulèvent la question du risque des nanoparticules. En tout état, dans le cadre du « Plan d’action national sur la fertilité » et d’une évaluation du risque des nanoparticules, l’Afssaps/ANSM a donné les recommandations adéquates concernant l’incorporation de ces filtres, chimiques et minéraux, dans les produits cosmétiques et le bon usage des PPS. Enfin, les données actuelles ne laissent pas à penser que les PPS puissent avoir un effet délétère en inhibant les effets bénéfiques du soleil, en particulier la synthèse de vitamine D. Les PPS ont démontré, sous couvert d’une utilisation correcte, une efficacité protectrice contre la plupart des effets délétères du soleil à condition d’être conçus en respectant le cahier des charges parfaitement identifié dans les recommandations européennes de 2006. En particulier, les études épidémiologiques démontrent leur efficacité dans la prévention primaire de tous les CC qu’il s’agisse des expositions environnementales ou intentionnelles, et des PPS de protection moyenne suffisent pour cela. Les risques plus que spéculatifs ne doivent certainement pas conduire à dissuader de les utiliser.
Chapter
Skin aging is the result of programmed senescence and prolonged environmental injury to skin. Human skin is continuously exposed to environmental influences and is therefore subjected to both intrinsic as well as extrinsic aging processes. Aged skin is characterized by loss of skin tone and resilience, increased roughness and dryness, irregular pigmentation, sunburn, accelerated skin aging, wrinkles and several malignant skin cancers. The plant secondary metabolites have been exploited for their potential activities like anti-aging, anti-wrinkle, antioxidant, anti-inflammatory, wound healing, skin whitening, anti-cancer, etc. Several scientific validations on natural products derived from traditional system of medicine have been developed in this context. Recent trends in anti-aging research projected the use of natural products derived from ancient era after scientific validation. Therefore, an attempt has been made through this chapter to highlight on skin aging pathways and natural bioactive molecules for management of skin aging.
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The analysis of the permeation kinetics of new UV filter formulations is of great importance since the kinetic parameters are related to the effectiveness of the product over time. The dynamics of this process can be evaluated by means of the calculation of the permeation kinetic constants, which can be obtained from the respective permeation profiles. This paper is aimed at improving the analytical performance of permeation assays using an on-line automatic system with spectrometric detection avoiding the chromatographic procedure and the usually manual sampling steps required using the traditional Franz diffusion cell. Then, the kinetics of permeation of octyl p-methoxycinnamate loaded in different microemulsions through a synthetic membrane (polyamide) was analysed at real time by UV-Vis and fluorescence spectroscopies. The spectral data were obtained at regular intervals of time (5 min) during 60 min, and the concentration of the permeated UV-filter was at each time calculated using univariate linear calibration. The interference caused by the presence of basil essential oil (oily phase) in some microemulsion samples was overcome using synchronous fluorescence spectroscopy (Δλ = 60 nm) and partial least squares. In all cases, the permeation profiles were obtained (first-order kinetics) and the respective permeation kinetic constants were calculated. The validation of the proposed method was assessed by gas chromatographic-mass spectroscopy and non-significant differences for the obtained permeation kinetic constants were found between methods (p = 0.05). Additionally, a commercial sample was analysed with the proposed methods and the results were validated by high performance liquid chromatography technique.
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Homosalate (HMS) is a salicylate molecule that is commonly included within commercial sunscreen formulations to provide protection from the adverse effects of ultraviolet (UV) radiation exposure. In the present work, the mechanisms by which HMS provides UV photoprotection are unravelled, using a multi-pronged approach involving a combination of time-resolved ultrafast laser spectroscopy in the gas-phase and in solution, laser-induced fluorescence, steady-state absorption spectroscopy, and computational methods. The unique combination of these techniques allow us to show that the enol tautomer of HMS undergoes ultrafast excited state intramolecular proton transfer (ESIPT) upon photoexcitation in the UVB (290–320 nm) region; once in the keto tautomer, the excess energy is predominantly dissipated non-radiatively. Sharp transitions are observed in the LIF spectrum at close-to-origin excitation energies, which points towards the potential presence of a second conformer that does not undergo ESIPT. These studies demonstrate that, overall, HMS exhibits mostly favourable photophysical characteristics of a UV filter for inclusion in sunscreen formulations.
Article
Riassunto I prodotti di protezione solare (PPS) composti da filtri chimici e/o filtri minerali occupano, oggi, un posto importante nella fotoprotezione. Sono stati all’origine di ampie polemiche, alcune delle quali non sono ancora cessate, sulla loro reale efficacia nella prevenzione primaria dei carcinomi cutanei (CC), nonché sui loro potenziali rischi sanitari ed ecologici. I filtri chimici agiscono assorbendo le radiazioni luminose; distinguiamo i filtri UVB puri e i filtri larghi, il cui spettro di assorbimento si estende ai raggi UVA. I filtri minerali diffraggono o riflettono le radiazioni; i due principali sono il biossido di titanio (TiO2) e l’ossido di zinco (ZnO); per contingenze cosmetiche la dimensione delle loro particelle è stata ridotta a nanoparticelle. Un PPS deve rispondere alle qualità di persistenza, sostantività e fotostabilità. Vengono proposti due tipi di metodi per la valutazione dei coefficienti di protezione (CP) dei PPS: metodi in vivo su volontari sani e metodi in vitro, che utilizzano vari substrati e basati sulla spettrometria. Il sun protective factor (SPF) in vivo è il CP UVB universalmente accettato; per il CP UVA, il metodo in vivo del persistent pigment darkening (PPD), anche se non consensuale, rimane ancora oggi il più utilizzato in Europa. La misurazione della lunghezza d’onda critica (Lc) ha un grande interesse nel definire l’entità della protezione negli UVA lunghi più deleteri. I filtri chimici sono una nota causa di reazioni locali; è stato menzionato, negli ultimi anni, un rischio particolare per l’octocrilene. Recentemente, il dibattito si è concentrato principalmente sul rischio di perturbazione endocrina (effetto che imita l’estradiolo dopo somministrazione orale a dosi molto elevate nei ratti), che può essere indotto da alcuni (ma non da altri!) filtri chimici, principalmente il 4-metilbenzilidene canfora e i benzofenoni. Il rischio negli umani sembra irrilevante nelle normali condizioni d’uso dei PPS; il rischio ambientale di alcuni filtri, se dimostrato, sarebbe probabilmente dovuto alla loro presenza in molti altri prodotti, oltre ai PPS. I filtri minerali, spesso esaltati nei bambini, sollevano la questione del rischio di nanoparticelle. In ogni caso, nell’ambito del “Piano d’azione nazionale sulla fertilità” e di una valutazione del rischio delle nanoparticelle, l’Afssaps/ANSM ha fornito le raccomandazioni adeguate relative all’incorporazione di questi filtri, chimici e minerali, nei prodotti cosmetici e all’uso corretto dei PPS. Infine, i dati attuali non suggeriscono che i PPS possano avere un effetto dannoso inibendo gli effetti benefici del sole, in particolare la sintesi di vitamina D. I PPS hanno dimostrato, a condizione di un uso corretto, un’efficacia protettiva contro la maggior parte degli effetti deleteri del sole, purché siano progettati in conformità con le caratteristiche specifiche perfettamente identificate nelle raccomandazioni europee del 2006. In particolare, gli studi epidemiologici dimostrano la loro efficacia nella prevenzione primaria di tutti i CC, siano essi dovuti a esposizioni ambientali o intenzionali, e alcuni PPS di protezione media sono sufficienti a questo scopo. I rischi più che speculativi non devono certamente scoraggiare il loro utilizzo.
Article
Background: Sunscreen products aim to help protect the skin against UV radiation and consequently reduce the risk of early skin ageing and skin cancer. However, it is well known that some sunscreen ingredients are not photostable, but this usually refers to irradiation with UV light. Moreover, it has to be mentioned that a relative cumulative erythema effectiveness compliant light source is used for the in vivo sun protection factor (SPF) testing. Here, UV simulators equipped with a xenon arc lamp use filters such as WG320 and UG11 (thickness 1 mm) to minimize infrared (IR) radiation and wavelength below 300 nm. However, under practical conditions, the sunscreen product is not only exposed to UVA/B light, but also to visible light (VIS) and IR light. In fact, the spectrum of solar radiation is composed of approximately 7% UV, 39% VIS and 54% IR. Aims: To investigate the influence of short-wave and long-wave radiation on the photostability of sunscreens. Methods: Irradiation was performed with the Suntest CPS+ that is considered to closely imitate solar radiation. The filter UG11 (thickness 1 mm), which absorbs much of the VIS and IR light, and the glass filter WG320 (thickness 2 mm), which effectively absorbs radiation of wavelengths less than 300 nm, were used in the Suntest CPS+ both individually and in combination and were inserted between the light source and the samples. The following transmission measurements were carried out with Labsphere's UV-2000s device. Here, the effectiveness (percentage change of SPF before irradiation to SPF after irradiation) as a measure of the photostability was calculated. Results: As expected after total solar spectrum irradiation, the effectiveness in all tested sunscreens is lower compared to relative cumulative erythema effectiveness light used for in vitro testing of SPF. In the reference sunscreen formula S2 as well as in the two different sunscreen products, especially long-wave radiation (>400 nm) had an effect on photostability, whereas short-wave radiation had only a minor impact. In contrast, in the BASF sun care gel line only short-wave radiation below 300 nm had an effect on photostability, and blocking VIS and IR light had no effect at all. Conclusion: Based on these data, we can conclude that short waves and/or VIS + IR light have an influence on the photostability of sunscreens.
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We present a novel approach to preparing non-toxic sunscreen active ingredients by electron irradiation of poly(methyl methacrylate) (PMMA) and polystyrene (PS) nanoparticles (NPs). Electron irradiation modifies the molecular structure of the polymers, generating conjugated aliphatic carbon–carbon double bonds in PMMA and conjugated aromatic rings in PS. The conjugation length increases as the electron fluence increases, leading to hyperchromic and bathochromic shifts in the UV-vis absorption spectra of the irradiated polymer NPs. Consequently, the irradiated polymer NPs become capable of UV absorption and the UV-absorbing properties are improved with increasing electron fluence. The UV-screening performance of the electron-irradiated polymer NPs are found to be superior to those of commercially available sunscreen ingredients. In addition, in vitro cytotoxicity and phototoxicity test results show that the irradiated polymer NPs exhibit excellent biocompatibility.
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Two chemical sun filters that are ingredients in sunscreen products have been tested for their dark toxicity and possible toxicity to mouse cells after UV irradiation. Increased toxicity as a result of breakdown of a UVB filter, octyl methoxycinnamate, was observed. UV radiation absorbed by the pure chemical sunscreen may lead to breakdown to more reactive chemical compounds than the unexposed sunscreen filter. The UVA filter included in our tests, butyl methoxydibenzoylmethane, was also toxic in the dark, however, it was the more photostable of the two and no additional significant toxicity was induced by UV irradiation. It can be concluded that the two sun filters are toxic to cells in the dark, but the biological role of this dark toxicity in the skin is not clear. Unstable sun filters may be broken down by UV to form photoproducts that are potentially toxic.
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The photodegradation of 4-aminobenzoic acid, 2-ethylhexyl N,N-dimethyl 4-aminobenzoate (Escalol 507) and 1-glyceryl 4-aminobenzoate (Escalol 106), resulting from irradiation by sun lamps, was examined by UV spectroscopy. 2-ethylhexyl N,N-dimethyl 4-aminobenzoate showed the longest half-life, indicating the highest photostability.
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There are considerable data to suggest that protection from solar ultraviolet (UV) radiation will reduce the risk of acute and chronic skin damage in humans. Whereas the sun protection factor (SPF) provides an index of protection against erythemally effective solar UV, largely confined to the UVB (290-320 nm) and short-wavelength UVA (320-340 nm) region, there is currently no agreed-upon method to measure broad-spectrum protection against long-wavelength UVA (340-400 nm). The objective of these studies was to assess the potential of in vitro UV substrate spectrophotometry and subsequent calculation of the "critical wavelength" value as a measure of broad-spectrum UV protection and as a routine, practical procedure for classification of sunscreen products. The spectral absorption of 59 commercially available sunscreen products and multiple experimental formulas with one or more UV filters was measured. Sunscreen product, 1 mg/cm(2), was applied to a hydrated synthetic collagen substrate, preirradiated with a solar simulator, and then subjected to UV substrate spectrophotometry. Multiple determinations from 5 independent samples per product were used to calculate the critical wavelength value, defined as the wavelength at which the integral of the spectral absorbance curve reached 90% of the integral from 290 to 400 nm. We found that a recognized long-wave UVA active ingredient such as titanium dioxide, zinc oxide, or avobenzone is a necessary but insufficient product requirement for achieving the highest proposed broad-spectrum classification, that is, critical wavelength of 370 nm or more. Although SPF and critical wavelength are largely independent of each other, UVA absorbance must increase commensurate with SPF to maintain the same critical wavelength value. Substrate spectrophotometry and the calculation of critical wavelength can readily account for sunscreen photostability by UV preirradiation. Finally, there is also a strong positive relationship between critical wavelength and a currently available in vivo measure of UVA protection. Determination of critical wavelength by means of UV substrate spectrophotometry provides a rapid, inexpensive, and reliable measure of broad-spectrum protection, which is largely independent of SPF, yet ensures long-wavelength UVA protection commensurate with SPF. The procedure provides a routine, sensitive means of differentiating and classifying sunscreen products and, importantly, obviates the need to subject volunteers to acute exposures of high-dose, nonterrestrial UV, the health risks of which are still poorly understood.
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It is now well documented that chronic UVA exposure induces damage to human skin. Therefore, modern sunscreens should not only provide protection from both UVB and UVA radiation but also maintain this protection during the entire period of exposure to the sun. UVA filters, however, are rare and not sufficiently photostable. We investigated the effect of the introduction of a new UV filter, bis-ethylhexyloxyphenol methoxyphenyl triazine (Tinosorb S), in oil in water sunscreen formulations on the photostability of butyl methoxydibenzoylmethane (Avobenzone [AVB]) after irradiation with an optically filtered Xenon arc source (UV irradiance adjusted at 1 mean effective dose [MED]/min). With spectrophotometrical methods to assess the sun protection factor (SPF) and UVA ratio and chromatographical methods to determine the amount of UV filters recovered after irradiation we showed that Tinosorb S prevented the photodegradation of AVB in a concentration-dependent way, leading to a sustained SPF and UVA ratio even after irradiation with doses of up to 30 MED. Since AVB was shown to destabilize ethylhexyl methoxycinnamate (EHM) we tested the effect of Tinosorb S in sunscreens containing this UV filter combination. Here too Tinosorb S showed photoprotective properties toward both UV filters. Thus, Tinosorb S can be used successfully to improve the photostability and efficiency of sunscreens containing AVB and EHM.
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Allergic contact sensitization to 'para amino' compounds is frequent and the spectrum of cross-reactivity between members of this chemical group is variable. A retrospective analysis of clinical patch test data obtained with a special test series in the centres of the Information Network of Departments of Dermatology (IVDK) between 1995 and 1999. In the 638 patients tested with the above test panel positive reactions were observed most often to p-aminoazobenzene (16.2%), p-phenylenediamine (14.1%), p-toluylenediamine (10.0%), followed by 4,4'-diaminodiphenylmethane (8.5%), Disperse Orange 3 (8.4%) and p-aminophenol (3.1%). Among the 544 patients tested with p-phenylenediamine and all seven additional 'para amino' compounds, concordance between reactions varied greatly. The stronger the positive test reaction to p-phenylenediamine, p-toluylenediamine or p-aminoazobenzene, the more frequently additional positive reactions to the other compounds were observed. A screening employing several 'para amino' compounds is necessary to describe the individual spectrum of allergic contact sensitization, as there is no reliable marker substance. Further research should aim at (i) establishing the mechanism of cross-reactivity to 'para amino' compounds and (ii) identifying exposures in the environment.
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We studied 28 patients with fixed drug eruption (FDE) caused by sulfonamide antibiotics to investigate cross-reactivity between sulfonamide derivatives and p-amino compounds and to explore the usefulness of patch testing, as an alternative to controlled oral challenge testing (COCT), in diagnosis within this clinical area. COCT with sulfamethoxazole (SMX), sulfadiazine (SDZ), sulfamethizole (SMZ), furosemide (FU), procaine (PRO) and glipizide (GPZ) was performed. Patch testing (PT) with SMX and SDZ was carried out. In all patients, the diagnosis of FDE was confirmed by positive COCT and allergy to trimethoprim ruled out by COCT. 42.8 and 31.8% of the SMX-induced FDE patients reacted to SMZ and SDZ, respectively. All patients (n = 28) tolerated FU, PRO and GPZ. COCT performed with the 3 sulfonamide antibiotics in 12 patients was positive in 2 subjects with the 3 drugs, in 2 patients only with SMX and SMZ and in the remaining 8, SMX was the only causative drug. PT was positive in 5 of 25 patients positive on COCT. The probability of obtaining a positive PT was higher among patients who had a residual lesion than that among those who lacked this. Cross-reactivity between different sulfonamide antibiotics is thus variable, being most likely between SMX and SMZ. We have found no cross-reactivity between sulfonamide antibiotics and other sulfonamide derivatives or p-amino drugs in FDE. PT is a useful tool in the diagnosis of FDE, especially if there are residual lesions, because it avoided the need for COCT in 20% of patients.