Phototoxic plant burns: report of a case and review of topical wound treatment in children.

Acute photodermatitis provoked by skin contact with giant hogweed (Heracleum mantegazzianum) and exposure to ultraviolet radiation is a rare cause of phytophotodermatitis in children. We report the case of a 10-year-old girl with extensive photodermatitis after contact with giant hogweed and prolonged exposure to sunlight. The lesions involved 10% of the body surface area, mainly the lower extremities. After initial application of topical steroids to the skin erythema, the topical approach was changed due to extensive bullae. Debridement and temporary wound closure with an adequate dressing was undertaken. This is the first case report of application of Suprathel (PolyMedics Innovations, Denkendorf, Germany) on a phytophototoxic burn-like wound with a favorable outcome.

Assessing phytophotodermatitis: boy with erythema and blisters on both hands.

Phytophotodermatitis (PPD) is a phototoxic reaction which occurs when the skin comes in contact with a photosensitizer and is subsequently exposed to radiation. PPD is often seen in people handling furocoumarin-containing products, such as agricultural workers, bartenders, florists, and gardeners. It may also be seen in beachgoers, athletes, and children. The pattern of the lesions usually resembles streaks; the hands and mouth are most commonly affected due to eating and handling of the offending furocoumarin-containing agents.

Environmental effects on cellular photosensitization: correlation of phototoxicity mechanism with transient absorption spectroscopy measurements.

Little is directly known about the influence of the local environment experienced by a photosensitizer in a biological system on its photophysics and photochemistry. In this paper, we have addressed this issue by correlating mechanistic studies using laser flash photolysis with cellular phototoxicity data, obtained under the same experimental conditions. In particular, we have focused on the interaction between local concentrations of photosensitizer (deuteroporphyrin) and oxygen in determining the mechanism of phototoxicity in L1210 cells. In cells, as well as in models such as liposomes and red blood cell ghosts, hypochromicity and a reduction in fluorescence and intersystem crossing yields are observed on increasing the photosensitizer concentration between 0.5 and 20 microM, which illustrates the onset of a self-association. In aerated cellular preparations, the phototoxicity is predominantly type II (singlet oxygen) for all concentrations studied but an oxygen-independent mechanism occurs at the higher concentrations in deaerated samples. These observations are readily explained by consideration of triplet state kinetics as a function of oxygen and photosensitizer concentrations in cells. The rate constant for quenching of the photosensitizer triplet state by oxygen in cells was measured as 6.6 x 10(8) M-1 s-1 and by photosensitizer ground state as approximately 10(6) M-1 s-1 (in terms of local concentration). The latter reaction gave rise to a long-lived species that is presumably responsible for the oxygen-independent phototoxicity observed at the higher photosensitizer concentrations used. This self-quenching of the triplet state is postulated to arise from electron transfer resulting in radical ion formation. Under conditions where no self-quenching contributes, the phototoxicity measured as a function of oxygen concentration correlates well with a model based on the determined kinetic parameters, thus, unambiguously proving the intermediacy of singlet oxygen. These effects should be borne in mind when interpreting phototoxicity mechanisms from in vitro cell studies. The excellent correlation achieved between laser flash photolysis data and measured phototoxicity gives credence to the direct use of photophysical techniques to elucidate photochemical mechanisms in biological media.

Dual role of melanins and melanin precursors as photoprotective and phototoxic agents: inhibition of ultraviolet radiation-induced lipid peroxidation.

Ultraviolet radiation (UVR) is one of the risk factors for skin cancer and the main inducer of melanin pigmentation, the major protective mechanism of mammalian skin against radiation damage. The melanin pigments, eumelanin and pheomelanin, are likely to be important in protection against UVR, but their precursors are generally considered as phototoxic. The available data suggest DNA damage as the mechanism of phototoxicity. However, the effect of melanin precursors on membrane damage through lipid peroxidation, another important and probably more relevant (from the point-of-view of the melanosomal confinement of these molecules) mechanism of phototoxicity, not known. As a model system for UVR-melanin-membrane interactions, we irradiated liposomes in the presence of eumelanin, pheomelanin and two of their major precursors, 5,6-dihydroxyindole (DHI) and 5-S-cysteinyldopa (SCD). The presence of the two melanin precursors substantially reduced the formation of lipid peroxidation products resulting from UVR exposure. The antioxidant activity of the melanin precursors was diminished under strong prooxidant conditions (presence of Fe3+). These results suggest that melanin precursors may have an important role in the protection of skin against the harmful effects of UVR including photocarcinogenesis.

Analysis for the potential of polystyrene and TiO2 nanoparticles to induce skin irritation, phototoxicity, and sensitization.

The human skin equivalent model (HSEM) is well known as an attractive alternative model for evaluation of dermal toxicity. However, only limited data are available on the usefulness of a HSEM for nanotoxicity testing. This study was designed to investigate cutaneous toxicity of polystyrene and TiO2 nanoparticles using cultured keratinocytes, a HSEM, and an animal model. In addition, we also evaluated the skin sensitization potential of nanoparticles using a local lymph node assay with incorporation of BrdU. Findings from the present study indicate that polystyrene and TiO2 nanoparticles do not induce phototoxicity, acute cutaneous irritation, or skin sensitization. Results from evaluation of the HSEMs correspond well with those from animal models. Our findings suggest that the HSEM might be a useful alternative model for evaluation of dermal nanotoxicity.

Analytical studies on photochemical behavior of phototoxic substances; effect of detergent additives on singlet oxygen generation.

PURPOSE: Monitoring of reactive oxygen species (ROS) generation from photoirradiated compounds would be effective for the prediction of the phototoxic potential. The aim of this investigation was to clarify the possible role of biomimetic vehicle systems on the photochemical properties of phototoxic compounds, focusing on the singlet oxygen generation. MATERIALS AND METHODS: Nine phototoxic and one non-phototoxic compounds (200 microM), dissolved in Tween 20, sodium laurate, or sodium dodecyl sulfate (SDS) micellar solution, were exposed to UVA/B light (250 W/m2), and singlet oxygen generation was monitored by RNO bleaching methodology. Photochemical properties of photosensitizers were also evaluated by UV measurement, and the interaction of photosensitizers with surfactant micelles was assessed by Z-potential and NMR spectroscopic analyses. RESULTS: All phototoxic compounds tended to generate singlet oxygen under light exposure in the all micellar solutions tested. There appeared to be some differences in photoreactivity of both cationic and anionic photosensitizers among the micelles tested, whereas ROS data on anthracene, dissolved in three micellar solutions, were found to be quite similar. Photosensitizers exhibited no significant changes in UV spectral patterns among the dissolving micellar solutions. Addition of cationic photosensitizer at the final concentration of 100 microM into 100 mM SDS solution resulted in the 20 mV increase of zeta potential and transition of NMR spectral pattern, which would reflect the electrostatic interaction with anionic micelles. CONCLUSION: Based on the data obtained, the photoreactivity of photosensitizing molecules, especially cationic and anionic photosensitizers, strongly depends on the physicochemical properties of the microenvironment.

Final report on the safety assessment of Mentha Piperita (Peppermint) Oil, Mentha Piperita (Peppermint) Leaf Extract, Mentha Piperita (Peppermint) Leaf, and Mentha Piperita (Peppermint) Leaf Water.

Mentha Piperita (Peppermint) Oil, Mentha Piperita (Peppermint) Leaf Extract, Mentha Piperita (Peppermint) Leaf, Mentha Piperita (Peppermint) Leaf Water are obtained from the Mentha piperita plant. The oil is currently used in cosmetic formulations as a fragrance component, but previously had been also described as a denaturant. The extract and leaves are described as biological additives, but only the extract is reported to be used. Peppermint Water is described as a flavoring agent or fragrance component, but is not currently in use. Peppermint Oil is used at a concentration of < or = 3% in rinse-off formulations and < or = 0.2% in leave-on formulations. Peppermint Oil is composed primarily of menthol and menthone. Other possible constituents include pulegone, menthofuran, and limone. Most of the safety test data concern Peppermint Oil. The oil is considered to present the "worst case scenario" because of its many constituents, so data on the oil were considered relevant to the entire group of ingredients. Peppermint Oil was minimally toxic in acute oral studies. Short-term and sub-chronic oral studies reported cystlike lesions in the cerebellum in rats that were given doses of Peppermint Oil containing pulegone, pulegone alone, or large amounts (>200 mg/kg/day) of menthone. Pulegone is also a recognized hepatotoxin. Repeated intradermal dosing with Peppermint Oil produced moderate and severe reactions in rabbits, although Peppermint Oil did not appear to be phototoxic. Peppermint Oil was negative in the Ames test and a mouse lymphoma mutagenesis assay but gave equivocal results in a Chinese hamster fibroblast cell chromosome aberration assay. In a carcinogenicity study of toothpaste and its components, no apparent differences were noted between mice treated with Peppermint Oil and those treated with the toothpaste base. Isolated clinical cases of irritation and/or sensitization to Peppermint Oil and/or its constituents have been reported, but Peppermint Oil (8%) was not a sensitizer when tested using a maximization protocol. It was expected that dermal absorption of Peppermint Oil would be rapid, following that of menthol, a major component, but in no case would be greater than absorption through the gastrointestinal tract. Because of the toxicity of pulegone, the safe concentration of this constituent was limited to < or = 1%. This concentration was achievable both by controlling the time of harvest and processing technique. There is evidence that menthol can enhance penetration of other agents. Formulators were cautioned that this enhanced penetration can affect the use of other ingredients whose safety assessment was based on their lack of absorption. With the limitation that the concentration of pulegone in these ingredients should not exceed 1%, it was concluded that Mentha Piperita (Peppermint) Oil, Mentha Piperita (Peppermint) Extract, Mentha Piperita (Peppermint) Leaves, Mentha Piperita (Peppermint) Water are safe as used in cosmetic formulations.

Comparison of the in vivo efficiency of photofrin II-, mTHPC-, mTHPC-PEG- and mTHPCnPEG-mediated PDT in a human xenografted head and neck carcinoma.

BACKGROUND AND OBJECTIVE: One of the approaches to enhance the selectivity and efficiency of photodynamic therapy (PDT) was the conjugation of the photosensitizer meta-tetrahydroxyphenylchlorin (mTHPC) to the water-soluble polymer polyethylene glycol (PEG). Several studies have demonstrated that mTHPC-PEG has a higher selectivity and a longer circulating half-life than free mTHPC, whereas no in vivo effect of this benefit could be seen. STUDY DESIGN/MATERIALS AND METHODS: In a model of RAG-2-mice bearing a human oral squamous cell carcinoma xenograft (XF 354), the in vivo efficiency assessed as growth retardation or remission caused by Photofrin II and free mTHPC was compared with mTHPC coupled in two different ways to polyethylene glycol (PEG). One hundred and fourty-nine female RAG-2-mice were randomised into one control group and 13 therapy groups. Treatment parameters were adapted from those routinely applied in animal studies. RESULTS: Photofrin II-mediated PDT and mTHPC-mediated PDT were both in vivo highly effective, whereas mTHPC induced less scars. The in vivo results after mTHPC-PEG-mediated PDT were disappointing, whereas the effectiveness of mTHPCnPEG-mediated PDT, a newly coupled macromolecular photosensitizer, were promising. CONCLUSIONS: These results demonstrated the impact of the method of linkage between the photoactive agent mTHPC and polyethylene glycol (PEG) upon the in vivo effectiveness. mTHPC and mTHPCnPEG are promising photosensitizers for the future, especially for the cosmetic treatment needs of head and neck surgery.

Use of dermal equivalent and skin equivalent models for identifying phototoxic compounds in vitro.

Phototoxicity inducing in vivo photoirritation, a reversible inflammatory reaction of the skin after chemical contact and UVA radiation exposure, is increasingly observed as a side effect associated with the use of both cosmetics and systemic drugs. In order to systematically screen for the phototoxic potential of new compounds, we propose two three-dimensional models suitable for in vitro testing: a dermal equivalent (DE) and a skin equivalent (SE) model. The DE model includes a collagen-glycosaminoglycans-chitosan porous matrix populated by normal human fibroblasts. The SE model is made by seeding normal human keratinocytes onto the DE, leading to a fully differentiated epidermis. The objectives of this pilot study are: 1) to compare the deleterious effects of UVA radiation on the two models and 2) to evaluate to what extent the in vitro results can predict the in vivo phototoxicity caused by well-known photoirritant compounds, included in the COLIPA validation phototoxicity reference chemical list. Dilutions of thiourea, sulisobenzone, promethazine, chlorpromazine and tetracycline were applied (20 microliters) onto DEs and SEs (n = 6) and incubated for 1 h (or 15 h) at 37 degrees C. Irradiated samples received 3 J/cm2 UVA. The 24 h post-irradiation residual cellular viability was measured using the MTT test on treated and untreated tissues and IL-1 alpha release measurement in collected SE culture media. A concordance in terms of photoirritant/non-photoirritant was obtained between the in vivo data and the in vitro results, suggesting that the DE and the SE models could be integrated, after a complete validation study, into a protocol for in vitro testing of the photoirritant potential of new molecules.

Photodynamic therapy with mTHPC and polyethylene glycol-derived mTHPC: a comparative study on human tumour xenografts.

The photosensitizing properties of m-tetrahydroxyphenylchlorin (mTHPC) and polyethylene glycol-derivatized mTHPC (pegylated mTHPC) were compared in nude mice bearing human malignant mesothelioma, squamous cell carcinoma and adenocarcinoma xenografts. Laser light (20 J/cm2) at 652 nm was delivered to the tumour (surface irradiance) and to an equal-sized area of the hind leg of the animals after i.p. administration of 0.1 mg/kg body weight mTHPC and an equimolar dose of pegylated mTHPC, respectively. The extent of tumour necrosis and normal tissue injury was assessed by histology. Both mTHPC and pegylated mTHPC catalyse photosensitized necrosis in mesothelioma xenografts at drug-light intervals of 1-4 days. The onset of action of pegylated mTHPC seemed slower but significantly exceeds that of mTHPC by days 3 and 4 with the greatest difference being noted at day 4. Pegylated mTHPC also induced significantly larger photonecrosis than mTHPC in squamous cell xenografts but not in adenocarcinoma at day 4, where mTHPC showed greatest activity. The degree of necrosis induced by pegylated mTHPC was the same for all three xenografts. mTHPC led to necrosis of skin and underlying muscle at a drug-light interval of 1 day but minor histological changes only at drug-light intervals from 2-4 days. In contrast, pegylated mTHPC did not result in histologically detectable changes in normal tissues under the same treatment conditions at any drug-light interval assessed. In this study, pegylated mTHPC had advantages as a photosensitizer compared to mTHPC. Tissue concentrations of mTHPC and pegylated mTHPC were measured by high-performance liquid chromatography in non-irradiated animals 4 days after administration. There was no significant difference in tumour uptake between the two sensitizers in mesothelioma, adenocarcinoma and squamous cell carcinoma xenografts. Tissue concentration measurements were of limited use for predicting photosensitization in this model.