rhododendrol and Hypopigmentation

Individuals who used skin-whitening cosmetics (quasi-drugs) containing 2% rhododendrol-containing agents, developed leukoderma at a higher frequency than those who have used other skin-whitening cosmetics. The Rhododenol Research Team (RD-Team) was formed and commissioned by Kanebo Cosmetics Inc. to conduct research in treatments of rhododendrol-induced leukoderma (RDL), to evaluate effective treatment options from a medical standpoint, and provide information to a wide range of people. In this study, we evaluated the efficacy of various treatments for RDL from a medical perspective, based on the information published in the literature as original or review articles. We searched the PubMed (international) and the Igaku Chuo Zasshi (ICHUSHI) (Japanese) databases using the keywords "Rhododenol" and "rhododendrol", for articles published between July 2013 and November 2020. We discuss the main clinical findings and treatments (topical, oral, phototherapy, and surgical) of this condition based on the literature review. We found that ultraviolet light therapy is the most effective treatment for RDL. We have also summarized reports of the efficacy of oral vitamin D3 in RDL. A topical prostaglandin derivative has been reported in a new study to be effective. We have provided guidance for patients using self-tanning and skin-whitening agents to improve their quality of life. Finally, we have highlighted the importance of providing patients with information on contact dermatitis and instructing them to discontinue product use immediately if they develop any symptoms of contact dermatitis while using skin-whitening agents.

Topics: Butanols; Humans; Hypopigmentation; Melanocytes; Quality of Life

A small proportion of individuals utilizing cosmetics containing rhododendrol developed leukoderma with various pathological conditions, in some cases indistinguishable from vitiligo. In this review, we investigate and evaluate the major considerations for developing rhododendrol-induced leukoderma based on data from original or review articles published in the literature to provide a wide range of information regarding the pathophysiology, mechanisms, risk evaluation, and possible mechanism-based treatments. We compile and discuss the latest information, including data related to the cytotoxicity of rhododendrol, cytoprotective functions, and involvement of the immune system, and consider the possibility of novel treatments based on the differences between individual patients and on the mechanism underlying the onset of the condition. Understanding the pathophysiology of rhododendrol-induced leukoderma helps not only elucidate the mechanisms of non-segmental vitiligo onset and progression, but also suggests prevention and treatment.

Topics: Butanols; Humans; Hypopigmentation; Melanocytes; Vitiligo

Topics: Animals; Butanols; Humans; Hypopigmentation; Melanocytes; Monophenol Monooxygenase; Reactive Oxygen Species; Skin Lightening Preparations; Ultraviolet Rays

Recently, an unexpected outbreak of patients with leukoderma occurred in Japan with the use of brightening/lightening cosmetics containing rhododendrol (RD). Patients developed leukoderma mostly on the skin sites repeatedly applied with RD, but some patients also had vitiligo-like lesions on the non-applied sites. RD is a tyrosinase-competitive inhibiting substance, thereby serving as an inhibitor of melanin synthesis. Upon inhibition of tyrosinase, RD is converted to new products such as tyrosinase-catalyzed hydroxyl-metabolite, which damage melanocytes. The melanocyte cell lysates seem to induce T-cell response. The frequencies of CD8+ T cells in both lesional skin and peripheral blood are significantly higher in the RD leukoderma as well as non-segmental vitiligo patients than in normal controls. In HLA-A*02:01 positive cases, circulating Melan-A-specific cytotoxic T cells can be detected at a high frequency. It is thus suggested that RD-induced leukoderma is induced by not only cytolysis of melanocytes but also subsequent immune reactions toward melanocytes.

Topics: Butanols; CD8-Positive T-Lymphocytes; Cosmetics; Humans; Hypopigmentation; Melanocytes; Monophenol Monooxygenase

Rhododendrol (RD), 4-(4-hydroxyphenyl)-2-butanol, inhibits melanin synthesis and had been used in skin-whitening cosmetic products until 2013. However, some individuals developed leukoderma on the skin where RD had been applied and have suffered from refractory depigmentation even after discontinuing RD application. Bimatoprost is a prostaglandin F2α analog and is often used for eyelash growth for cosmetic reasons as well as in the treatment of glaucoma. It was reported that bimatoprost induced skin pigmentation in addition to iris pigmentation as adverse effects. Therefore, we conducted an open-label single-center pilot study to evaluate the effectiveness of bimatoprost on refractory RD-induced leukoderma. Eleven Japanese female patients with skin type III who developed leukoderma on the exact or slightly extended area of skin where RD had been applied and gained a halt of enlargement of leukoderma or repigmentation on a part of the affected skin after discontinuation of RD were enrolled. Bimatoprost 0.03% solution was applied on the leukoderma once daily for 3 months, and then the frequency of application was increased to twice daily for the subsequent 3 months. Ten patients completed the 6-month course of bimatoprost application. In four patients, bimatoprost application brought slight improvement in RD-induced refractory leukoderma by dermatologists' evaluation. Because the number of enrolled patients was limited, further larger studies are necessary to better assess the effectiveness of bimatoprost in inducing repigmentation in patients with RD-induced refractory leukoderma.

Topics: Administration, Cutaneous; Adult; Aged; Bimatoprost; Butanols; Drug Resistance; Female; Humans; Hypopigmentation; Japan; Melanocytes; Middle Aged; Pilot Projects; Skin; Skin Lightening Preparations; Skin Pigmentation; Treatment Outcome

Oxidative metabolism of rhododendrol (RD), a skin-whitening ingredient, by tyrosinase has caused leukoderma in a certain population of Japanese consumers. Toxic RD metabolites and reactive oxygen species are proposed causes for the melanocyte death. However, the mechanism by which reactive oxygen species are produced during RD metabolism remains elusive. Some phenolic compounds are known to act as suicide substrates for tyrosinase, resulting in release of a copper atom and hydrogen peroxide during its inactivation. We hypothesized that RD may be a suicide substrate for tyrosinase and that the released copper atom may be responsible for the melanocyte death through hydroxyl radical production. In line with this hypothesis, human melanocytes incubated with RD showed an irreversible decrease in tyrosinase activity and underwent cell death. A copper chelator, d-penicillamine, markedly suppressed the RD-dependent cell death without significantly affecting the tyrosinase activity. Peroxide levels in RD-treated cells were not affected by d-penicillamine. Given the unique enzymatic properties of tyrosinase, we conclude that RD acted as a suicide substrate and resulted in release of a copper atom and hydrogen peroxide, which would collectively impair melanocyte viability. These observations further imply that copper chelation may alleviate chemical leukoderma caused by other compounds.

Topics: Chelating Agents; Copper; Humans; Hydrogen Peroxide; Hypopigmentation; Melanocytes; Monophenol Monooxygenase; Penicillamine; Reactive Oxygen Species

Topics: Animals; Butanols; Cholecalciferol; Hypopigmentation; Mice

The tyrosinase inhibitor rhododendrol (RD), used as a skin whitening agent, reportedly has the potential to induce leukoderma.. Although an immune response toward melanocytes was demonstrated to be involved in leukoderma, the molecular mechanism is not fully understood.. We hypothesized that if RD is a pro-hapten and tyrosinase-oxidized RD metabolites are melanocyte-specific sensitizers, the sensitizing process could be reproduced by the human cell line activation test (h-CLAT) cocultured with melanocytes (h-CLATw/M) composed of human DC THP-1 cells and melanoma SK-MEL-37 cells. Cell surface expression, ROS generation and ATP release, mRNA expression, and the effects of several inhibitors were examined.. When RD was added to the h-CLATw/M, the expression of cell-surface CD86 and IL-12 mRNA was greatly enhanced in THP-1 cells compared with those in the h-CLAT. The rapid death of melanoma cells was induced, with ROS generation and ATP release subsequently being greatly enhanced, resulting in the cooperative upregulation of CD86 and IL-12. Consistent with those observations, an ROS inhibitor, ATP receptor P2X7 antagonist, or PERK inhibitor antagonized the upregulation. CD86 upregulation was similarly observed with another leukoderma-inducible tyrosinase inhibitor, raspberry ketone, but not with the leukoderma noninducible skin-whitening agents ascorbic acid and tranexamic acid.. RD is a pro-hapten sensitizer dependent on tyrosinase that induces ROS generation and ATP release from melanocytes for CD86 and IL-12 upregulation in DCs, possibly leading to the generation of tyrosinase-specific cytotoxic T lymphocytes. The coculture system h-CLATw/M may be useful for predicting the sensitizing potential to induce leukoderma.

Topics: Adenosine Triphosphate; B7-2 Antigen; Butanols; Coculture Techniques; Humans; Hypopigmentation; Interleukin-12; Melanocytes; Melanoma; Monophenol Monooxygenase; Reactive Oxygen Species; Skin Lightening Preparations; THP-1 Cells; Up-Regulation

Idiopathic leukoderma is a skin disorder characterized by patchy loss of skin pigmentation due to melanocyte dysfunction or deficiency. Rhododendrol (RD) was approved as a cosmetic ingredient in Japan in 2008. However, it was shown to induce leukoderma in approximately 20,000 customers. The prediction of cytotoxicity, especially to melanocytes in vivo, is required to avoid such adverse effects. Since the use of higher vertebrates is prohibited for medicinal and toxicological assays, we used zebrafish, whose melanocytes were regulated by mechanisms similar to mammals. Zebrafish larvae were treated with RD in breeding water for 3 days, which caused body lightening accompanied by a decrease in the number of melanophores. Interestingly, black particles were found at the bottom of culture dishes, suggesting that the melanophores peeled off from the body. In addition, RT-PCR analysis suggested that the mRNA levels of melanophore-specific genes were significantly low. An increase in the production of reactive oxygen species was found in larvae treated with RD. The treatments of the fish with other phenol compounds, which have been reported to cause leukoderma, also induced depigmentation and melanophore loss. These results suggest that zebrafish larvae could be used for the evaluation of leukoderma caused by chemicals, including RD.

Topics: Animals; Butanols; Disease Models, Animal; Hypopigmentation; Zebrafish

Topics: Butanols; Dihydroxyacetone; Humans; Hypopigmentation; Quality of Life

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Autoantibodies; Butanols; Child, Preschool; Female; Humans; Hypopigmentation; Male; Middle Aged; Skin Lightening Preparations; Vitiligo; Young Adult

Topics: Administration, Cutaneous; Adult; Bimatoprost; Butanols; Cosmetics; Dermatologic Agents; Drug Administration Schedule; Female; Humans; Hypopigmentation; Skin Pigmentation; Treatment Outcome

Chemical leukoderma is a patchy hypopigmentation in the skin. Phenol derivatives such as raspberry ketone have been reported to cause the development of occupationally induced leukoderma. Recently, 2% (w/w) rhododenol, a reduced form of raspberry ketone used in a skin-lightning agent, also caused the development of leukoderma in >16,000 users, about 2% of all users, in Asian countries including Japan. However, a method for assessing the risk of leukoderma caused by 2% rhododenol has not been established despite the fact that the development of leukoderma caused by 30% rhododenol was previously shown in animal experiments. Establishment of a novel technique for risk assessment of leukoderma in humans caused by external treatment with chemicals is needed to prevent a possible future chemical disaster. This study demonstrated that external treatment with 2% rhododenol and the same concentration of raspberry ketone caused the development of leukoderma in murine tail skin without exception with significant decreases in the amount of melanin and number of melanocytes in the epidermis. Thus, a novel in vivo technique that can assess the risk of leukoderma caused by 2% rhododenol was developed. The unique technique using tail skin has the potential to prevent chemical leukoderma in the future.

Topics: Animals; Butanols; Butanones; Epidermal Cells; Epidermis; Humans; Hypersensitivity; Hypopigmentation; Melanins; Melanocytes; Mice; Skin; Toxicity Tests

4-(4-Hydroxyphenyl)-2-butanol (rhododendrol, RD), a skin-whitening agent, was reported to cause skin depigmentation in some users, which is attributed to its cytotoxicity to melanocyte. It was reported that cytotoxicity to melanocyte is possibly mediated by oxidative stress in a tyrosinase activity-dependent manner. We examined the effect of UV radiation (UVR) on RD-induced melanocyte cytotoxicity as an additional aggravating factor. UVR enhanced RD-induced cytotoxicity in normal human epidermal melanocytes (NHEMs) via the induction of endoplasmic reticulum (ER) stress. Increased generation of intracellular reactive oxygen species (ROS) was detected. Pretreatment with N-acetyl cysteine (NAC), antioxidant and precursor of glutathione significantly attenuated ER stress-induced cytotoxicity in NHEMs treated with RD and UVR. Increase in cysteinyl-RD-catechol and RD-pheomelanin in NHEMs treated with RD and UVR suggested that, after UVR excitation, RD or RD metabolites are potent ROS-generating substances and that the tendency to produce RD-pheomelanin during melanogenesis amplifies ROS generation in melanocytes. Our results help to elucidate the development mechanisms of RD-induced leukoderma and provide information for innovation of safe skin-whitening compounds.

Topics: Acetylcysteine; Antioxidants; Apoptosis; Butanols; Caspase Inhibitors; Cell Survival; Cells, Cultured; Endoplasmic Reticulum Stress; Humans; Hypopigmentation; Melanins; Melanocytes; Oxidative Stress; Reactive Oxygen Species; Skin Lightening Preparations; Ultraviolet Rays

Rhododendrol (4-(4-hydroxyphenyl)-2-butanol) has been used as a lightening/whitening cosmetic but was recently reported to induce leukoderma. Although rhododendrol has been shown to be transformed by tyrosinase to hydroxyl-rhododendrol, which is cytotoxic to melanocytes, its detailed mechanism of action including the involvement of reactive oxygen species is not clearly understood.. To confirm the relationship of hydroxyl radical generation to melanocyte cytotoxicity induced by rhododendrol, this study was performed.. An electron spin resonance method with a highly sensitive detection system was utilized to monitor hydroxyl radicals generated from two distinct normal human epidermal melanocyte lines with different levels of tyrosinase activity after the addition of various amounts of rhododendrol. Cytotoxicity of rhododendrol was analyzed by AlamarBlue assay under the same condition.. Hydroxyl radicals were generated depending on the amounts of rhododendrol and/or tyrosinase. After the correlation between hydroxyl radical generation with melanocyte viability was confirmed, an inhibitor of oxidative stress, N-acetyl cysteine, was shown to dramatically diminish rhododendrol-induced generation of hydroxyl radicals and melanocyte cytotoxicity by increasing glutathione levels. In contrast, buthionine sulfoximine, which depletes glutathione, augmented both of those parameters.. Suppressing oxidative stress would prevent and/or mitigate some phenol derivative-induced leukoderma by avoiding hydroxyl radical-initiated melanocyte cytotoxicity.

Topics: Antioxidants; Butanols; Cell Line; Cell Survival; Humans; Hydroxyl Radical; Hypopigmentation; Melanocytes; Monophenol Monooxygenase; Oxidative Stress; Skin; Skin Lightening Preparations; Skin Pigmentation

Topics: Adult; Aged; Butanols; Cosmetics; Drug Eruptions; Female; Humans; Hypopigmentation; Japan; Middle Aged; Skin Lightening Preparations; Stem Cells

Rhododendrol, a phenolic compound contained in lightening/whitening cosmetics, can bind and inhibit tyrosinase and was reported to induce leukoderma in Japan. Only 2% of the cosmetics users are affected, and tacrolimus is effective in treatment of the condition.. To test the hypothesis that the disease is an autoimmune disorder.. Short-term T-cell lines were established using peripheral blood mononuclear cells from 8 patients with human melanoma-associated and tyrosinase-derived synthetic peptides. The effects of rhododendrol on melanoma immunization were also examined.. Seven out of 8 patients were positive for HLA-DR4. Both class I- and class II-restricted and tyrosinase peptide-specific T-cell responses were observed. Immunization of mice with rhododendrol-treated and irradiated B16 melanoma cells successfully delayed the growth of melanoma cells in vivo.. Rhododendrol-induced leukoderma is an autoimmune disorder, with rhododendrol as an environmental factor and HLA-DR4 as a genetic factor. Rhododendrol might be effective in treating melanomas.

Topics: Animals; Butanols; Cell Culture Techniques; Disease Models, Animal; Female; Humans; Hypopigmentation; Immunity, Cellular; Immunotherapy; Melanoma; Mice; Mice, Inbred C57BL; Monophenol Monooxygenase; T-Lymphocytes

Many users in Japan of skin brightening/lightening cosmetics containing rhododendrol (RD) have developed leucoderma. Leucoderma appears on skin areas repeatedly treated with RD-containing cosmetics. RD-induced leucoderma (RDIL) presents different degrees of well-defined hypopigmentation. It is crucial to determine the degree of hypopigmentation to differentiate RDIL from vitiligo vulgaris (VV).. To quantitatively evaluate hypopigmentation of RDIL lesions and the recovery of pigmentation, and to compare the hypopigmentation with VV and normal skin.. Sixteen cases of RDIL, nine cases of VV and 15 healthy controls were examined using a novel multispectral camera (MSC) that can simultaneously obtain the reflection intensity at 10-nm wavelength intervals from 400 to 760 nm of the photographed area. ∆Absorbance was calculated by subtracting the log of reflection intensity of the target area from that of a white reflection standard.. Most RDIL lesions showed lower ∆Absorbance than healthy skin and higher ∆Absorbance than VV lesions between 400 and 550 nm. Statistical comparison of the maximum ∆Absorbance from 420 to 460 nm (Max∆Absorbance) for VV, RDIL and control skin showed that the Max∆Absorbance of RDIL was significantly higher than that of VV and lower than that of control skin. The comparison of ∆Absorbance of the same sites in RDIL lesions between the initial visit and 6 months later showed significant improvement after 6 months.. These studies demonstrated quantitative changes in RDIL and its recovery phase and suggested the utility of a MSC in obtaining objective colour information of skin disorders.

Topics: Adult; Aged; Butanols; Case-Control Studies; Diagnosis, Differential; Female; Humans; Hypopigmentation; Japan; Middle Aged; Skin Lightening Preparations; Spectrophotometry; Vitiligo

Rhododendrol is a phenolic compound that shows a tyrosinase-dependent toxicity for melanocytes and occasionally induces a vitiligo-like skin depigmentation. The post-tyrosinase mechanisms determining melanocyte death or survival, however, are far from clear. Here, we find that rhododendrol treatment leads to a reduction in the levels of cellular glutathione but also induces a cellular antioxidant response that eventually increases glutathione levels. We further find that rhododendrol toxicity is enhanced when glutathione levels are experimentally reduced and alleviated when glutathione levels are increased. Hence, it appears that the size of the preexisting glutathione pool along with the capacity to supply glutathione via the antioxidant response determines whether melanocytes survive or die after rhododendrol exposure. It is conceivable, therefore, that rhododendrol-induced leukoderma depends on the capacity to maintain appropriate glutathione levels and that enhancement of glutathione levels may preserve a patient's melanocytes and potentially help in repigmentation.

Topics: Butanols; Cell Survival; Cells, Cultured; Glutathione; Humans; Hypopigmentation; Melanocytes; Protective Agents

Topics: Adolescent; Adult; Aged; Butanols; Cellular Senescence; Cosmetics; Female; Humans; Hypopigmentation; Imaging, Three-Dimensional; Male; Middle Aged; Nevus; Quality of Life; Vitiligo; Young Adult

Because some users develop depigmentation after the use of melanogenesis-inhibiting products containing the quasi-drug ingredient Rhododenol, Japanese Dermatological Association (JDA) established a Special Committee on the Safety of Cosmetics Containing Rhododenol on July 17, 2013 and management guide for dermatologists has been updated on the website in order to delineate the diagnostic criteria for Rhododenol-induced leukoderma and provides a broad guide for standard treatment based on current knowledge. This guide is produced on the basis of the guide (version 7) updated on June 20, 2014 in the website. Rhododenol-induced leukoderma refers to depigmentation of varying severity that develops after the use of cosmetics containing Rhododenol, mainly at the site of use. In most cases, repigmentation of part or all the affected area is evident after discontinuation. Histopathologically cellular infiltration around the hair follicles and melanophages are present in most cases. The number of melanocytes in the lesion is declined but not totally absent in most cases. Rhododenol itself is a good substrate for tyrosinase, resulting in the formation of Rhododenol metabolites (e.g., Rhododenol quinone). Melanocytes are damaged by Rhododenol metabolites during the subsequent metabolic process. The continued use of cosmetics containing Rhododenol thus induces tyrosinase activity-dependent cytotoxicity in melanocytes in the epidermis at application sites, resulting in decreasing the amount of melanin produced by melanocytes; the addition of some other factor to this process is believed to subsequently cause the decrease or disappearance of melanocytes themselves from the epidermis.

Topics: Butanols; Cosmetics; Drug Eruptions; Humans; Hypopigmentation; Skin Lightening Preparations

As reported in the mass media on July 2013, numerous consumers who had used the cosmetic ingredient containing rhododendrol (4-(4-hydroxyphenyl)-2-butanol, Trade name; rhododenol), which is a melanin inhibitor isolated from Acer nikoense Maxim, released from Kanebo Cosmetics Inc. (Tokyo, Japan) noticed leukoderma patches on their face, neck and hands. We have experienced 32 cases that developed leukoderma after using such cosmetics so far and skin biopsy samples in some cases were obtained from both leukoderma and pigmented lesions. A histopathological analysis for skin lesions obtained from such patients notably showed basal hypo-pigmentation, melanin incontinence, and remaining melanocytes in most patients which is not relevant in vitiligo vulgaris. Subsequently, we comprehensively carried out immunohistochemical analyses of immune-competent cells infiltration to assess the effect of the cellular immune response to inducible hypopigmentation. Furthermore, detailed morphological observations performed by electron-microscopy notably showed the presence of melanocytes with only a small number of melanosomes, dermal fibroblasts containing melanosome globules and melanophages whereas no damage associated with melanosome transfer and the basal layer apparatus. These findings provide a cue to diagnose as rhododenol-induced leukoderma differentiate from vitiligo vulgaris and for rhododendrol to induce local immunity in addition to melanocyte damage.

Topics: Butanols; CD4-CD8 Ratio; Cosmetics; Fibroblasts; Humans; Hypopigmentation; MART-1 Antigen; Melanocytes; Microphthalmia-Associated Transcription Factor; Skin; T-Lymphocytes, Regulatory

Topics: Autophagy; Butanols; Cell Survival; Cells, Cultured; Humans; Hypopigmentation; Lysosomes; Melanins; Melanocytes; Melanosomes; Signal Transduction

Topics: Butanols; Cosmetics; Genotype; HLA-A24 Antigen; Humans; Hypopigmentation; MART-1 Antigen; Melanocytes; Monophenol Monooxygenase; T-Lymphocytes, Cytotoxic

Topics: Butanols; CD8-Positive T-Lymphocytes; Chemokine CCL17; Chemokine CCL22; Cosmetics; Humans; Hypopigmentation; Lymphocyte Count; Receptors, CCR4; Skin; Vitiligo

Topics: Biphenyl Compounds; Butanols; Dermatitis, Allergic Contact; Female; Humans; Hypopigmentation; Middle Aged; Phenols; Skin Lightening Preparations

Rhododendrol, an inhibitor of melanin synthesis developed for lightening/whitening cosmetics, was recently reported to induce a depigmentary disorder principally at the sites of repeated chemical contact. Rhododendrol competitively inhibited mushroom tyrosinase and served as a good substrate, while it also showed cytotoxicity against cultured human melanocytes at high concentrations sufficient for inhibiting tyrosinase. The cytotoxicity was abolished by phenylthiourea, a chelator of the copper ions at the active site, and by specific knockdown of tyrosinase with siRNA. Hence, the cytotoxicity appeared to be triggered by the enzymatic conversion of rhododendrol to active product(s). No reactive oxygen species were detected in the treated melanocytes, but up-regulation of the CCAAT-enhancer-binding protein homologous protein gene responsible for apoptosis and/or autophagy and caspase-3 activation were found to be tyrosinase dependent. These results suggest that a tyrosinase-dependent accumulation of ER stress and/or activation of the apoptotic pathway may contribute to the melanocyte cytotoxicity.

Topics: Agaricales; Apoptosis; Butanols; Caspase 3; Catalytic Domain; Cell Survival; Cells, Cultured; Chelating Agents; Copper; Endoplasmic Reticulum Stress; Enhancer Elements, Genetic; Enzyme-Linked Immunosorbent Assay; Gene Expression Profiling; Gene Expression Regulation; Humans; Hypopigmentation; Inhibitory Concentration 50; Interleukin-8; Melanocytes; Monophenol Monooxygenase; Phenylthiourea; Pigmentation; Reactive Oxygen Species; RNA, Small Interfering; Skin Lightening Preparations; Up-Regulation; Vitiligo

Tyrosinase, the rate-limiting enzyme required for melanin production, has been targeted to develop active brightening/lightening materials for skin products. Unexpected depigmentation of the skin characterized with the diverse symptoms was reported in some subjects who used a tyrosinase-competitive inhibiting quasi-drug, rhododendrol.. To investigate the mechanism underlying the depigmentation caused by rhododendrol-containing cosmetics, this study was performed.. The mechanism above was examined using more than dozen of melanocytes derived from donors of different ethnic backgrounds. The RNAi technology was utilized to confirm the effect of tyrosinase to induce the cytotoxicity of rhododendrol and liquid chromatography-tandem mass spectrometry was introduced to detect rhododendrol and its metabolites in the presence of tyrosinase.. Melanocyte damage was related to tyrosinase activity at a certain threshold. Treatment with a tyrosinase-specific siRNA was shown to dramatically rescue the rhododendrol-induced melanocyte impairment. Hydroxyl-rhododendrol was detected only in melanocytes with higher tyrosinase activity. When an equivalent amount of hydroxyl-rhododendrol was administered, cell viability was almost equally suppressed even in melanocytes with lower tyrosinase activity.. The generation of a tyrosinase-catalyzed hydroxyl-metabolite is one of the causes for the diminishment of the melanocyte viability by rhododendrol.

Topics: Bleaching Agents; Butanols; Cell Survival; Humans; Hypopigmentation; Melanins; Melanocytes; Monophenol Monooxygenase; RNA, Small Interfering; Skin; Skin Pigmentation