Quantification of Arbutin and its degradation products, hydroquinone and p-Benzoquinone, in hyperpigmentation topical formulation: Effect of extraction procedure and interference assessment.

The utilization of Hydroquinone (HQ) in over-the-counter skincare items is subject to restrictions. Consequently, Arbutin (AR) serves as a reliable alternative for addressing hyperpigmentation in non-prescription topical formulations. Nevertheless, AR undergoes decomposition into HQ and p-Benzoquinone (BZ) when exposed to temperature stress, ultraviolet light, or dilution in an acidic environment, all of which can induce skin toxicity. The intention of this paper is to investigate the effect of extraction procedure on the conversion of AR to HQ and or BZ and to evaluate kinetics of AR hydrolysis to HQ. Meanwhile this study aims to evaluate AR and BZ interference with the United States Pharmacopoeia (USP) identification and assessment method for HQ Hydrolytic stress during extraction conditions underwent optimization through systematic screening tests. Subsequent assessment of the residual drug and its degradation products were achieved by HPLC method. The resulting data were meticulously fitted to various kinetic models. To analyze the potential interference of AR in HQ measurement using USP method, the standard concentrations of AR and HQ were analyzed through UV-VIS spectrophotometry. For enhanced certainty, a validated HPLC method analysis was also conducted. Notably, the acid hydrolysis of AR exhibited independence from its initial concentration. So, the hydrolytic degradation of AR exhibited a Zero-order kinetic profile. Furthermore, the proven interference of AR in the UV-VIS spectrophotometry method was identified within the context of the USP method. This study successfully utilized an adopted HPLC method for the concurrent quantification of AR, HQ, and BZ. The potential interference of AR in the UV-VIS spectrophotometric assay for HQ may lead to false results especially for regulatory purposes.

Avaliação da rotulagem de cosméticos clareadores de pele comercializados em Juazeiro, Bahia, Brasil / Evaluation of the labeling of skin lightening cosmetics marketed in Juazeiro, Bahia, Brazil

A hiperpigmentação da pele, principalmente na região facial, resulta em um incômodo estético que afeta a qualidade de vida do indivíduo, levando a busca por produtos clareadores. Este estudo avaliou a conformidade dos rótulos de cosméticos comercializados como "produtos clareadores de pele", bem como a existência de substâncias clareadoras proibidas neste tipo de produto. Foi realizada uma análise transversal descritiva qualitativa no período de abril a maio de 2022, em busca por cosméticos comercializados em estabelecimentos farmacêuticos e lojas de produtos cosméticos localizadas no município de Juazeiro/BA. Foram selecionados 18 produtos e os desvios de rotulagem identificados com base na legislação utilizada vigente à época do estudo, foram: ausência de informações sobre advertências/restrições de uso e número de registro incompleto, equivalente a 16,7% (n = 3) das amostras. A hidroquinona, proibida nesse tipo de produto, foi encontrada em um cosmético (5,5%). Embora a maioria das amostras analisadas esteja em conformidade com as exigências legais, os resultados evidenciam descumprimentos, indicando a necessidade de uma fiscalização mais rigorosa a fim de evitar possíveis danos à saúde do usuário.

Skin hyperpigmentation, particularly in the facial region, can be an aesthetic nuisance that affects an individual's quality of life, leading them to seek out whitening products. This study evaluated the compliance of cosmetics labels marketed as "skin lightening products", and assessed the presence of whitening substances prohibited in this type of product. A qualitative, descriptive, cross-sectional analysis was conducted between April and May 2022 in Juazeiro, Bahia, Brazil, focusing on cosmetics sold in pharmaceutical establishments and cosmetic product stores. Eighteen products were selected, and labeling deviations identified based on the legislation in force at the time of the study. These included a lack of information on warnings/use restrictions and incomplete registration numbers, affecting 16.7% (n = 3) of the samples. Hydroquinone, prohibited in this type of product by the legislation, was detected in one cosmetic (5.5%). Although most of the analyzed samples comply with legal requirements, the observed non-compliance highlights the need for more stringent inspection to prevent potential harm to user's health.

Skin lightening products' violations in Europe: An analysis of the rapid alert system for dangerous non-food products 2005-2018.

BACKGROUND: Skin lightening products containing dangerous levels of chemicals pose a serious health concern for consumers. However, to date, the extent of these products in Europe has not been extensively studied. The aim of this study was to determine whether harmful skin lightening products are available for sale in Europe and what violations exist regarding their composition. MATERIALS AND METHODS: We queried the Rapex database, which is the Rapid Alert System for dangerous non-food products among 31 European countries, to identify skin lightening cosmetics reported between 2005 and 2018, and presented a detailed summary of these notifications. RESULTS: In the years 2005-2018, of all violations regarding cosmetics, 26.3% concerned skin lightening products. In the database, 266 reports on skin lightening products were identified. Most of the notifications came from Germany (17.29%), France (17.29%), Portugal (15.41%), and the United Kingdom (11.65%). The majority of the registered products originated from non-European countries, mainly the Côte d'Ivoire (29.70%). The major reason for the violation was the content of hydroquinone, mercury, or clobetasol propionate. CONCLUSIONS: Hazardous skin lightening products that are not in line with European cosmetics legislation are available on the European market. Most of the products are imported. The main risk associated with these products is the content of hydroquinone, mercury, and clobetasol propionate. It is important to bear in mind that this study focuses on the Rapex system and other sources of information may exist. Based on our findings, a more comprehensive evaluation by international authorities is justified.

Skin depigmenting action of silkworm (Bombyx mori L.) droppings in zebrafish.

The excrement of silkworms (Bombyx mori L.), referred to here as silkworm droppings (SDs), is used as a traditional drug in eastern medicine to treat skin diseases such as urticaria and atopy. However, the depigmentation effects of SDs have not previously been evaluated. We focused on the depigmentation effect of a methanol extract of SDs and isolated components of the extract using a zebrafish model system. (+)-Dehydrovomifoliol (M-1), (6R,7E,9R)-9-hydroxy-4,7-megastigmadien-3-one (M-2), (3S,5R,8R)-3,5-dihydroxymegastigma-6,7-dien-9-one (M-3), roseoside (M-4), and citroside A (M-5) were isolated from only SDs extract (SDE), and chemical structures were identified through spectroscopic methods. Toxicity of SDE was evaluated by assessing its effect on the viability of human fibroblast cells and the hatching rate of zebrafish embryos. In addition, the depigmentation ability of SDE and isolated constituents was evaluated using a zebrafish model. Binary threshold, histograms, and the size of the black spots on the dorsal region of zebrafish larvae were analyzed using image analysis tools. Finally, SDE is a non-toxic material and has a dose-dependent depigmentation effect in zebrafish larvae. Moreover, various doses of compounds isolated from SDE, namely, M-1 to M-5, had a depigmentation effect. In particular, M-5 inhibited melanin synthesis in melanocytes stimulated by α-melanocyte stimulating hormone (α-MSH). Together, our results suggest that SDs can be used for depigmentation purposes in health and/or cosmetic applications.

Mercury contamination in facial skin lightening creams and its health risks to user.

This study aims to determine concentrations of mercury in facial skin lightening cream according to different price categories (category I:

Development and validation of an ultraviolet-visible spectrophotometric method for determination of phenylethyl resorcinol in new topical nanoemulsions.

OBJECTIVE: To develop a rapid, simple and efficient ultraviolet-visible (UV-vis) spectrophotometric method for the quantification of phenylethyl resorcinol (PR), a potent skin-lightening agent, incorporated into new topical nanoemulsions, and to validate this method according to International Commission for Harmonization (ICH) guidelines. METHODS: UV-vis spectrophotometric method for quantification of PR in new topical nanoemulsions was developed and validated in terms of specificity, linearity, sensitivity, precision and accuracy. The method was applied to determine PR content (extraction recoveries) in the nanoemulsions and entrapment efficiencies. RESULTS: The calibration curve for PR was linear in the range of 10-60 µg mL-1 , with a determination coefficient (r2 ) which is higher than 0.999. The limit of detection (LOD) and limit of quantitation (LOQ) were 1.55 and 4.69 µg mL-1 , respectively. The method was shown to be specific, precise [intraday, interday and reproducibility levels relative standard deviation < 3%] and accurate (between 91.90 ± 1.28% and 104.73 ± 0.60%). The extraction recoveries of PR in nanoemulsions were 97.07%, 96.64% and 103.54% at concentrations of 3, 6 and 9 mg mL-1 , respectively. The entrapment efficiencies were nearly 100%, which agrees with the oil core location of PR in nanoemulsions. CONCLUSION: This developed method was confirmed to be rapid, simple, cost-effective, specific, precise, accurate and suitable for determination of PR content in nanoemulsions and entrapment efficiencies.

Mercury, hydroquinone and clobetasol propionate in skin lightening products in West Africa and Canada.

Skin lightening products are types of cosmetics (creams, gels, lotions and soaps) applied voluntarily on skin. Several of these products contain a variety of active ingredients that are highly toxic. Among those toxic agents, the present study focuses on mercury, hydroquinone, and clobetasol propionate. Out of the 93 lightening soaps and 98 creams purchased in large city markets in sub-Saharan West Africa and in small ethnic shops in Canada, 68-84% of all creams and 7.5-65% of all soaps exceeded regulatory guidelines for at least one active ingredient when considering different regulations. Mercury was found in high concentrations mainly in soaps, while hydroquinone and clobetasol propionate concentrations exceeded US FDA standards in some creams for all countries included in our study. Concentrations of the three compounds declared on labels of soaps and creams usually did not correspond to concentrations actually measured, particularly for mercury and hydroquinone. Overall, our results indicate that most studied skin-lightening products are potentially toxic and that product labels are frequently inaccurate with respect to the presence of toxic agents.

Potential health consequences of applying mercury-containing skin-lightening creams during pregnancy and lactation periods.

Many studies have highlighted the widespread use of skin-lightening creams containing mercury by women during and after pregnancy to remove dark spots. Women, especially pregnant and lactating mothers using these products are at risk of mercury poisoning because sometimes it has no clinical symptoms, particularly during early exposure. Studies have shown that prenatal and postnatal mercury exposure can cause permanent neurological damage in children. Furthermore, mercury can cause women infertility and birth defects. Even though several studies have examined the reproductive and/or developmental consequences of gestational and lactational mercury exposure from fish consumption and/or dental amalgam, no studies have assessed the possible effects of the long-term use of mercury-containing skin-lightening products by women of childbearing age on their pregnancy outcome and children's health. This commentary aims to collate information on the popular use of mercury-containing skin-lightening creams and sheds the light to the readers about the limitations of the available data on its impact during a prenatal and/or postnatal period. There is an urgent need to assess the adverse health effects of applying these products during pregnancy or lactation on child growth and development through birth cohort studies. Until data from these studies are available, women should be advised not to use topical skin-lightening creams during pregnancy and lactation.

Opinion of the Scientific Committee on Consumer safety (SCCS)--Opinion on the safety of the use of α-arbutin in cosmetic products.

CONCLUSION OF THE OPINION: The SCCS considers the use of α-Arbutin safe for consumers in cosmetic products in a concentration up to 2% in face creams and up to 0.5% in body lotions. A potential combined use of α-Arbutin and other hydroquinone releasing substances in cosmetic products has not been evaluated in this Opinion.

Safety evaluation of metal exposure from commonly used moisturizing and skin-lightening creams in Nigeria.

The concentrations of ten metals (Cd, Pb, Ni, Cr, Cu, Co, Fe, Mn, Zn and Al) were measured in some commonly used moisturizing and skin-lightening creams in Nigeria with a view to providing information on the risk of exposure to metals from the use of these products. The metal concentrations in these products were measured by atomic absorption spectrometry after acid digestion of the samples. The measured concentrations of metals in the skin moisturizing creams ranged from <0.15 to 6.3 µg/g Cd, <0.02 to 17.5 µg/g Cu, 2.25 to 6.25 µg/g Cr, <0.25 to 124.3 µg/g Al, 0.2 to 7.3 µg/g Pb, <0.03 to 10.7 µg/g Ni, 17.3 to 372.0 µg/g Zn, <0.02 to 1.0 µg/g Co, 17.75 to 28.8 µg/g Mn, <0.1 to 89.8 µg/g Fe while the concentrations of metals in the skin-lightening products ranged from <0.15 to 16.5 µg/g Cd, <0.02 to 10.0 µg/g Cu, 4.25 to 8.0 µg/g Cr, <0.25 to 128.0 µg/g Al, 0.5 to 4.5 µg/g Pb, <0.03 to 1.65 µg/g Ni, 24.7 to 267.5 µg/g Zn, <0.02 to 2.5 µg/g for Co, 19.3 to 31.8 µg/g Mn, 9.5 to 211.63 µg/g Fe. In a significant number (>93%) of the samples investigated the concentrations of Pb, Cd, Ni and Co were below the specified limit, or the maximal limit for impurities in colour additives in cosmetics for external use. However, Cr was found at concentrations above the allergenic limit of 1 µg/g. The results also showed that skin-lightening creams contained higher concentrations of the studied metals than the moisturizing creams, except for Ni, which indicates that persons who uses skin-lightening creams in preference to moisturizing ones, are exposed to higher concentrations of metals.

Phenolic composition, antioxidant, anti-wrinkles and tyrosinase inhibitory activities of cocoa pod extract.

BACKGROUND: Cocoa pod is an outer part of cocoa fruits being discarded during cocoa bean processing. Authors found out that data on its usage in literature as cosmetic materials was not recorded in vast. In this study, cocoa pod extract was investigated for its potential as a cosmetic ingredient. METHODS: Cocoa pod extract (CPE) composition was accomplished using UHPLC. The antioxidant capacity were measured using scavenging assay of 1,2-diphenyl-2-picrylhydrazyl (DPPH), ß-carotene bleaching assay (BCB) and ferric reducing antioxidant power (FRAP). Inhibiting effect on skin degradation enzymes was carried out using elastase and collagenase assays. The skin whitening effect of CPE was determined based on mushroom tyrosinase assay and sun screening effect (UV-absorbance at 200-400 nm wavelength). RESULTS: LC-MS/MS data showed the presence of carboxylic acid, phenolic acid, fatty acid, flavonoids (flavonol and flavones), stilbenoids and terpenoids in CPE. Results for antioxidant activity exhibited that CPE possessed good antioxidant activity, based on the mechanism of the assays compared with ascorbic acid (AA) and standardized pine bark extract (PBE); DPPH: AA > CPE > PBE; FRAP: PBE > CPE > AA; and BCB: BHT > CPE > PBE. Cocoa pod extract showed better action against elastase and collagenase enzymes in comparison with PBE and AA. Higher inhibition towards tyrosinase enzyme was exhibited by CPE than kojic acid and AA, although lower than PBE. CPE induced proliferation when tested on human fibroblast cell at low concentration. CPE also exhibited a potential as UVB sunscreen despite its low performance as a UVA sunscreen agent. CONCLUSIONS: Therefore, the CPE has high potential as a cosmetic ingredient due to its anti-wrinkle, skin whitening, and sunscreen effects.

Characterization of suspected illegal skin whitening cosmetics.

An important group of suspected illegal cosmetics consists of skin bleaching products, which are usually applied to the skin of the face, hands and décolleté for local depigmentation of hyper pigmented regions or more importantly, for a generalized reduction of the skin tone. These cosmetic products are suspected to contain illegal active substances that may provoke as well local as systemic toxic effects, being the reason for their banning from the EU market. In that respect, illegal and restricted substances in cosmetics, known to have bleaching properties, are in particular hydroquinone, tretinoin and corticosteroids. From a legislative point of view, all cosmetic products containing a prohibited whitening agent are illegal and must be taken off the EU market. A newly developed screening method using ultra high performance liquid chromatography-time off flight-mass spectrometry allows routine analysis of suspected products. 163 suspected skin whitening cosmetics, collected by Belgian inspectors at high risk sites such as airports and so-called ethnic cosmetic shops, were analyzed and 59% were classified as illegal. The whitening agents mostly detected were clobetasol propionate and hydroquinone, which represent a serious health risk when repeatedly and abundantly applied to the skin.

Spectrometric analysis of mercury content in 549 skin-lightening products: is mercury toxicity a hidden global health hazard?

BACKGROUND: Cosmetic skin lightening is practiced worldwide. Mercury is a well-documented melanotoxin added to some lightening products. However, mercury can cause many dermatologic, renal, and neurologic problems. The Food and Drug Administration limits the amount of mercury in cosmetic products to trace amounts, 1 ppm. OBJECTIVE: The objective of this study was to quantitatively evaluate a large international sample of lightening products for mercury content, focusing on products available to US consumers either online or in stores. METHODS: A total of 549 skin-lightening products, manufactured in 32 countries, were purchased online in the United States, Taiwan, and Japan and in stores in the United States, China, Taiwan, Thailand, Japan, and Sri Lanka. Cosmetics were screened for mercury content above 200 ppm using a low-cost portable x-ray fluorescence spectrometer. RESULTS: Of the 549 tested products, 6.0% (n = 33) contained mercury above 1000 ppm. In all, 45% of mercury-containing samples contained mercury in excess of 10,000 ppm. Of lightening products purchased in the United States, 3.3% were found to contain mercury in excess of 1000 ppm. LIMITATIONS: Our study did not evaluate creams for other melanosuppressive ingredients. Only 1 sample of each product was tested. CONCLUSION: Our study confirms the national and global presence of mercury in skin-lightening products.

Public health department response to mercury poisoning: the importance of biomarkers and risks and benefits analysis for chelation therapy.

Chelation therapy is often used to treat mercury poisoning. Public health personnel are often asked about mercury toxicity and its treatment. This paper provides a public health department response to use of a mercury-containing cosmetic in Minnesota, a perspective on two unpublished cases of chelation treatment for postulated mercury toxicity, and comments on the use of a nonsystemic treatment for removal of mercury following the Iraqi seed coat poisoning incident. Physicians should evaluate sources of exposure, biomarkers, and risks and benefits before recommending chelation therapy for their patients. Potential risks to chelation therapy and its little understood subtle or latent effects are areas of public health concern.