Dermatite de contato à metilisotiazolinona ­ estamos atentos a essa epidemia? / Contact dermatitis due to methylisothiazolinone ­ are we aware of this epidemic?

Metilclorotiazolinona e metilisotiazolinona (MCI/MI) são os ingredientes ativos no Kathon CG®, um conservante de cosméticos no mercado desde os anos 80. Eles aparecem numa mistura de conservantes na proporção de 3:1. Metilisotiazolinona (MI) isolada tinha sido aprovada como conservante desde 2005, uma vez que foi considerada menos sensibilizante comparado à porção clorada. Entretanto, ela tem sido usada numa concentração muito maior para ser efetiva, e isso tem causado a atual epidemia de alergia a essa substância. O objetivo dessa revisão foi examinar o atual surto de casos de alergia de contato a metilisotiazolinona (MI) no mundo, um fenômeno que tem sido observado em vários países, inclusive no Brasil. As fontes de dados incluíram os principais artigos originais e revisões indexadas nos bancos de dados PubMed, MEDLINE, LILACS e SciELO que foram publicadas nos últimos anos. Os resultados mostram elevado grau de positividade de testes de contato tanto à associação MCI/MI quanto à MI isolada, e significativo aumento da prevalência de alergia a esta substância nos últimos anos. Em conclusão, alertamos que devemos estar atentos a esse importante conservante. Salientamos que a associação MCI/MI nos testes pode não diagnosticar casos de alergia à MI. Apesar dessa substância isolada não se encontrar na bateria padrão brasileira, a pesquisa de sua sensibilidade é fundamental.

Methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI) are the active ingredients in Kathon CG®, a cosmetic preservative available in the market since the 80s. MCI and MI are mixed in a ratio 3:1. MI alone was approved for use as a preservative in 2005, as it was considered a less sensitizing agent compared to chlorine. However, it has been used at a much higher concentration to be effective and this has caused the current epidemic of allergy to this substance. This review aimed to examine the current outbreak of cases of contact allergy to MI observed in several countries, including Brazil. Data sources were major original articles and reviews indexed in PubMed, MEDLINE, LILACS and SciELO databases and published in recent years. The results showed a high rate of positive tests for allergy both to MCI/MI combination and to MI alone, as well as a significant increase in the prevalence of allergy to this substance in recent years. In conclusion, this common preservative requires attention. Importantly, MCI/MI combination tests may not diagnose cases of allergy to MI alone. Although this substance is not found alone in the Brazilian standard battery, research on its sensitivity is essential.

Eye irritation tests of polyhexamethylene guanidine phosphate (PHMG) and chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) using a tissue model of reconstructed human cornea-like epithelium

Disinfectants including polyhexamethylene guanidine phosphate (PHMG) and mixtures of chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) have been widely used in Korea to prevent microbial growth in the humidifier water, which triggered an outbreak of serious respiratory diseases. In addition to the respiratory syndrome, disease-related symptoms including liver toxicity, asthma, and skin allergies were also found after extensive survey of people exposed to the humidifier disinfectants (HDs). In this study, eye irritation tests were performed based on the Organization for economic co-operation and development (OECD) test guidelines 492 using EpiOcular™ which is a tissue model of reconstructed human cornea-like epithelium. As results, the raw materials of PHMG (26% as active ingredient) and CMIT/MIT (1.5% as active ingredient) were classified under UN globally harmonized system of classification and labeling of chemical (GHS) category 1 or category 2. However, aqueous dilutions of raw materials such as market products of HDs that contain 0.13% of PHMG and 0.03% of CMIT/MIT or further dilutions of the market products for humidifier that contain 0.0013% of PHMG and 0.0003% of CMIT/MIT were classified under any category, which suggested absence of eye irritation at the test concentration.

Eye irritation tests of polyhexamethylene guanidine phosphate (PHMG) and chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) using a tissue model of reconstructed human cornea-like epithelium

Disinfectants including polyhexamethylene guanidine phosphate (PHMG) and mixtures of chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) have been widely used in Korea to prevent microbial growth in the humidifier water, which triggered an outbreak of serious respiratory diseases. In addition to the respiratory syndrome, disease-related symptoms including liver toxicity, asthma, and skin allergies were also found after extensive survey of people exposed to the humidifier disinfectants (HDs). In this study, eye irritation tests were performed based on the Organization for economic co-operation and development (OECD) test guidelines 492 using EpiOcular™ which is a tissue model of reconstructed human cornea-like epithelium. As results, the raw materials of PHMG (26% as active ingredient) and CMIT/MIT (1.5% as active ingredient) were classified under UN globally harmonized system of classification and labeling of chemical (GHS) category 1 or category 2. However, aqueous dilutions of raw materials such as market products of HDs that contain 0.13% of PHMG and 0.03% of CMIT/MIT or further dilutions of the market products for humidifier that contain 0.0013% of PHMG and 0.0003% of CMIT/MIT were classified under any category, which suggested absence of eye irritation at the test concentration.

Major concerns regarding lung injury and related health conditions caused by the use of humidifier disinfectant

A total of 221 patients were evaluated to be humidifier disinfectant associated with lung injury (HDLI) through two rounds of programs through April 2015. The humidifier disinfectant (HD) brands most often associated with HDLI were found to be Oxy (n=151, 68 %) and Cefu (n=26, 17 %). Polyhexamethylene guanidine used for disinfectant for four types of HD brands including Oxy was found to be associated with the highest number of HDLI cases (n=188). Further programs are operating to identify various health effects including lung injury which may be associated with the use of HD. Not only national agencies, but also pertinent environmental health societies should cooperate in the necessary investigations so that this tragedy can be properly addressed and future incidents concerning chemicals and chemical-containing products can be prevented.

Determination of Methylisothiazolinone and Chloro-methylisothiazolinone in Cosmetics by High Performance Liquid Chromatography / 环境与健康杂志

Objective To develop a high performance liquid chromatography method for the determination of methylisothiazolinones and chloro-methylisothiazolinoe in cosmetics. Methods The cosmetic samples were extracted with methanol. The analytes were separated with the mobile phase of V(Methanol)∶V(Water)= 25∶75 at the flow rate of 1.0 ml/min and detected at the wavelength of 276 nm. Results The linear range of the method was 0.05-100 mg/ml for methylisothiazolinone and 0.0125-25 mg/ml for chloro-methylisothiazolinoe. The limit of detection of methylisothiazolinone and chloro-methylisothiazolinoe were 0.08 and 0.2 ?g respectively. The recovery rates were 84.5%-93.9% with the RSD of 2.5%-9.4% (n=6) for methylisothiazolinone and 88.3%-92.9% with the RSD of 2.9%-5.8% (n=6) for chloro-methylisothiazolinoe. Conclusion The method is simple,rapid,accurate and is suitable for the determination of methylisothiazolinone and chloro-methylisothiazolinoe in cosmetics.