• Toxicological Research
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• v.31 no.2
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• pp.97-104
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• 2015

The skin exposure to solar irradiation and photoreactive xenobiotics may produce abnormal skin reaction, phototoxicity. Phototoxicity is an acute light-induced response, which occurs when photoreacive chemicals are activated by solar lights and transformed into products cytotoxic against the skin cells. Multifarious symptoms of phototoxicity are identified, skin irritation, erythema, pruritis, and edema that are similar to those of the exaggerated sunburn. Diverse organic chemicals, especially drugs, are known to induce phototoxicity, which is probably from the common possession of UV-absorbing benzene or heterocyclic rings in their molecular structures. Both UVB (290~320 nm) and UVA (320~400 nm) are responsible for the manifestation of phototoxicity. Absorption of photons and absorbed energy (hv) by photoactive chemicals results in molecular changes or generates reactive oxygen species and depending on the way how endogenous molecules are affected by phototoxicants, mechanisms of phototoxcity is categorized into two modes of action: Direct when unstable species from excited state directly react with the endogenous molecules, and indirect when endogeneous molecules react with secondary photoproducts. In order to identify phototoxic potential of a chemical, various test methods have been introduced. Focus is given to animal alternative test methods, i.e., in vitro, and in chemico assays as well as in vivo. 3T3 neutral red uptake assay, erythrocyte photohemolysis test, and phototoxicity test using human 3-dimensional (3D) epidermis model are examples of in vitro assays. In chemico methods evaluate the generation of reactive oxygen species or DNA strand break activity employing plasmid for chemicals, or drugs with phototoxic potential.

• Environmental Analysis Health and Toxicology
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• v.17 no.3
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• pp.253-259
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• 2002

The phototoxicity inhibitory activity of 15 natural products having antiinflammatory effect was screened by three in vitro methods: yeast growth inhibition test with Candida albicans, RBC photohemolysis and MTT assay. We induced phototoxic reaction by irradiating UVA (365 nm) on chlorpromazine (CPZ) that has been widely documented as phototoxic agent in clinical and experimental studies and then observed the effects of the natural products after treating them with CPZ. In yeast growth inhibition test, X. stramonium showed the inhibitory effect on the UVA phototoxicity and E. officinalis, Yeast, P. suffruticosa showed phototoxicity inhibitory effect in that their ％ hemolysis compared with control were 36.14${\pm}$ 2.69, 42.82${\pm}$1.35, 36.41${\pm}$0.48 on UVA. In MTT assay, all tested natural products increased cell viability compared with the control.

• YAKHAK HOEJI
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• v.60 no.2
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• pp.53-57
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• 2016

This study was performed to examine the skin phototoxicity of purified bee venom (Apis mellifera L.) collected using bee venom collector. To confirm whether the gel containing purified bee venom (BV gel) causes photototoxicity when used for the skin medicinal products, phototoxicity testing was conducted using guinea pig models. The BV gel (0.1 ml/site) was administered transdermally to guinea pigs. 8-MOP was used to introduce positive control response. After administration, the guinea pigs were irradiated with UVA ($15J/cm^2$) with doses based on standard phototoxicity study guidelines. In the weight measurement and clinical observation, BV gel groups didn't show any significant changes compared with control group. BV gel groups did not show any symptoms such as erythema and edema formation of skin. This study demonstrated that BV gel has promising potential external treatment for topical uses that do not induce significant levels of skin phototoxicity.

• Environmental Analysis Health and Toxicology
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• v.15 no.1_2
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• pp.13-18
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• 2000

A few in vitro methods were developed to compare the result on the phototoxicity of phenothiazines. By the MTT assay, the Candida test, and the RBC photohemolysis, the phototoxicities of UVA and UVB irradiation were measured. This paper presents the comparisons of methods which are effective to measure the phototoxicities of the chemicals causing phototoxicity and photoallergy. The tested chemicals of phenothiazines include Chlorpromazine, Promethazine, Perphenazine, Chlorprothixene, Trifluoperazine and Thioridazine. Each chemical represented variable results according to the test methods. MTT assay shows the most sensitive method.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.13 no.1
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• pp.1-6
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• 1987

We have confirmed the phototoxicity of orange flower absolute, studied the phototoxic ingredient and developed a method to eliminate it. To confirm the phototoxicity, we tested French orange flower absolute, Moroccan absolute and Egyptian absolute with Hartley strain guinea Pig under UV irradiation ranging from 320400 nm supplied with fluorescent lamps. Using a combination of isolation techniques including HPLC and IR, we were able to confirm that the phototoxic agent was bergapten. The development of a non-phototoxic orange flower absolute using ion exchange chromatography is described.

• Biomolecules & Therapeutics
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• v.10 no.4
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• pp.274-280
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• 2002

The fluoroquinolones have been reported to cause, although at low frequency, severe phototoxicity which is due to singlet oxygen produced by ultraviolet-A (UVA; 320-400 nm) exposure. The objective of this study was to evaluate the phototoxicity based on plasma and tissue concentrations of commonly prescribed fluoroquinolones; lomefloxacin (LFLX), enoxacin (ENX), ofloxacin (OFLX), and ciprofloxacin (CPFX). The phototoxic potentials were investigated by measuring increments in ear thickness, 24 hrs after these fluoroquinolones were orally administered to Balb/c mice, which they were exposed to UVA 17.5 J/$\textrm{cm}^2$ for 2 hrs following drug administration. The fifty percent ear thickness increment-inducing doses ($ETID_{50}$), determined by single ascending dosing of each fluoroquinolone to mice, were calculated to be 50(LMFX), 250(ENX), 770(OFLX), 1100(CPFX) mg/kg. Post the administration of ETID$_{50}$, drug concentrations in plasma and ear tissue were measured at specified times and phototoxicities were quantified. Both peak plasma ($\mu\textrm{g}$/ml) and ear tissue ($\mu\textrm{g}$/g) concentrations were summarized as follows; 7.3/1.4 for LMFX, 15.0/1.6 for ENX, 90.1/18.4 for OFLX and 87.2/3.7 for CPFX. The degree of photo toxicity was more relevant to plasma concentrations than tissue concentrations. In order to assess the effect of irradiation time after drug administration on phototoxicity, the 2 hr UVA irradiation was given at 0, 1, 2, 3, and 5 hr after administering $ETID_{50}$, respectively and photo toxicities were evaluated. The shorter inteval between dosing and UVA exposure was, the higher risk of phototoxicity was produced.d.

• Toxicological Research
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• v.18 no.3
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• pp.227-232
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• 2002

In order to find out the appropriate in vitro method for high correlation with in vivo, we com-pared the sensitivities of phototoxicity (PT) in vitro method between in human keratinocytes, HaCaT cells and in 3T3 fibroblast cells derived from Balb/c mice. Both cells were exposed to six known phototoxic chemicals : promethazine, neutral red, chlortetracycline, amiodarone, bithionol, 8-methoxypsoralen, or non-phototoxic chemical, ALS (ammonium laureth sulfate) and then irradiated with 5 J/$cm^2$ of UVA. Cell viability ($IC_{50}$ ) was measured by neutral red uptake (NRU) assay. The ratio of $IC_{50}$ value of chemicals in the presence and absence of UVA was determined by the cut-off value. The phototoxic potential of test chemicals in NRU assay was determined by measuring the photoirriation factor (PIF) with a cut-off value of 5. In both 3T3 and HaCaT cells, all known phototoxic chemicals were positive (over 5 of PIF value), except that bithionol was found to be non-phototoxic to HaCaT cells, and ALS, non-phototoxic chemical was negative. These results suggest that Balb/c 3T3 cell was more sensitive than HaCaT cell to predict phototoxicity potential.

• Archives of Pharmacal Research
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• v.22 no.2
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• pp.143-150
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• 1999

melatonin (MLT), N-acetyl-5-methoxytryptamine, is mainly secreted by the pineal gland. The ultraviolet (UV), infrared (IR) and 1H-NMR spectra of irradiated and non-irradiated MLT were measured, and phototoxicity tests of MLT, anthracence (positive control) and sodium lauryl sulfate (SLS, negative control) were performed. The methods employed include both in vitro test such as MTS assay using the human fibroblast cell and yeast growth inhibition assay using Candida albicans and in vivo method using the skin of guinea pig. UV absorption spectra and 1H-NMR spectra of MLT were changed by UVA (365 nm, 15 J/$\textrm{cm}^2$), but IR spectra of MLT were not changed. The fifty percent inhibitory concentration (IC50) ratio (UV-/UV+) of MLT was 10. The inhibition zone of irradiated-paper disks treated with MLT was not observed. According to the results of histophathological examination, no pathologic lesion was observed in the non-irradiated group, but slight degeneration of keratinocytes in the epidermis, homorrhage and vasodilation in dermis were observed in the irradiated group. These results indicated that the molecular structure of MLT is altered by UVA to unidentified photoproducts and a moderate phototoxicity of MLT is predicted.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.35 no.3
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• pp.193-202
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• 2009

This study was done to assess an alternative method as a replacement of in vivo phototoxicity test. The human fibroblasts were exposed to several phototoxic chemicals (promethazine, chlorpromazine chlortetracycline, 8-methoxypsoralen, neutral red, bithionol) and non-phototoxic materials (cinnamic aldehyde, p-aminobenzoic acid, sodium lauryl sulfate, L-cysteine). The cell viability was measured by neutral red uptake (NRU) assay. The results of the NRU phototoxicity (PT) assay showed a close agreement with in vivo test except bithionol. We also have tested the cosmetic ingredients including $Medimin^{(R)}$ A, $Medimin^{(R)}$ D, $LG^{(R)}$ 106W, $Phytoclear^{(R)}$ EL-1, Carex humilis L. extract, Canna indica L. extract, Salvia miltiorrhira Bunge extract, $Parsol^{(R)}$ MCX and $Parsol^{(R)}$ 1789. Most materials except Salvia miltiorrhira Bunge extract did not show any phototoxicity.

• Journal of Food Hygiene and Safety
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• v.17 no.4
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• pp.188-192
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• 2002

The phototoxicity inhibitory activity of 15 natural products having antiinflammatory effect was screened by three in vitro methods : yeast growth inhibition test with Candida albicans, RBC photohemolysis and MTT assay. We induced phototoxic reaction by irradiating UVB (312 nm) on chlorpromazine (CPZ) that has been widely documented as phototoxic agent in clinical and experimental studies and then observed the effects of the natural products after treating them with CPZ. In yeast growth Inhibition test, P. persica and E. officinalis showed the inhibitory effect on the UVB phototoxicity and E. officinalis, yeast, P. suffruticosa showed phototoxicity inhibitory effect in that their ％ hemolysis compared with control were 45.76 $\pm$ 0.91, 34.42$\pm$1.01, 35.30 $\pm$4.76 on UVB. In MTT assay, all tested natural products increased cell viability compared with the contort.