Methylisothiazolinone: The Common Cosmetic Ingredient Linked to Contact Allergy

Introduction

Methylisothiazolinone is used as a preservative in both industrial products and cosmetics. The first cases of allergic contact dermatitis (ACD) caused by methylisothiazolinone as an occupational disease were described in 2004 and 2006 (1, 2), and in 2010 the first cases related to the use of methylisothiazolinone in cosmetic products were confirmed (3).

Historical overview

Methylisothiazolinone in combination with methylchloroisothiazolinone (in a ratio of 1:3) has been used in various products since the beginning of the 1980s. It is one of the most common preservatives used in cosmetics and industrial products (4, 5). Due to its frequent use, this substance is one of the most common allergens among preservatives causing ACD (6–8). Clinical studies with humans and animals have shown that methylchloroisothiazolinone and methylisothiazolinone can cause contact allergy, although methylchloroisothiazolinone is a stronger allergen than methylisothiazolinone (9, 10). Currently, in the European Union, the maximum allowed concentration of methylchloroisothiazolinone and methylisothiazolinone in cosmetics is 0.0015%. Methylisothiazolinone started to be used as a separate preservative in industry in 2000, and since 2005 its use has been allowed in cosmetic products and household goods. According to the European Scientific Committee on Consumer Safety and the Cosmetic Ingredient Review in the United States, the safe concentration of methylisothiazolinone in cosmetics is 0.01% (11, 12). Until then, the maximum permitted concentration of methylisothiazolinone in cosmetics was 0.00037% (in combination with methylchloroisothiazolinone) – so since 2005, the concentration of methylisothiazolinone in cosmetic products has increased by more than 25 times. A study by Rohm and Haas found that the non-sensitizing concentration of methylisothiazolinone is up to 0.06% (12).

ACD caused by Methylisothiazolinone

The first reports in Europe of contact allergy to methylchloroisothiazolinone/methylisothiazolinone appeared in 1980, but cases of sensitization to these substances, especially to methylisothiazolinone, are increasing. ACD most commonly occurs in women on the forearms or face. Facial dermatitis usually appears in patches or affects only the eyelids, despite the use of cosmetics on the entire face. Atypical morphologies of ACD have also been described, such as those resembling seborrheic dermatitis, photodermatitis, erythema multiforme, or pseudolymphoma. Methylchloroisothiazolinone/methylisothiazolinone found in wet wipes can cause intertriginous or buttock dermatitis. Other unexpected sources of methylchloroisothiazolinone/methylisothiazolinone can be carpet shampoos and fabric softeners. Several cases have been described in which methylchloroisothiazolinone/methylisothiazolinone found in indoor paints caused airborne dermatitis (3, 13, 14). The dermatitis disappeared when the walls were treated with sodium bisulfite, which inactivated methylchloroisothiazolinone/methylisothiazolinone, or when the concentration of these allergens in indoor air was no longer measurable after 25 days. Many cases of ACD are known in which concentrated methylchloroisothiazolinone/methylisothiazolinone fluid came into contact with various parts of the skin. Sensitization to methylchloroisothiazolinone/methylisothiazolinone can develop after a chemical burn and manifest as ACD. The first cases of allergy solely to methylisothiazolinone were described in 2004 by Isaksson et al. (1) and in 2006 by Thyssen et al. (2). Patients were diagnosed with an occupational disease – ACD caused by methylisothiazolinone after contact with wallpaper adhesives and paints. In 2010, the first cases related to the use of methylisothiazolinone in cosmetics were reported (3). Of the seven described patients, six developed perianal dermatitis after using wet toilet paper, and one patient developed eyelid dermatitis from makeup remover.

Methylisothiazolinone in products

Methylisothiazolinone is used in various cosmetic products – hair care products (shampoos, conditioners, hairspray), various creams, oils, soaps, bath products, makeup products (mascara, makeup remover, face powder), hair dyes, nail care products, deodorants, shaving products, as well as products for babies. Methylisothiazolinone is most widely used in rinse-off cosmetic products (15), and one of the most common sources of exposure to it is wet wipes. Increasing use of methylisothiazolinone in cosmetics has also been observed. For example, in the United States, the use of methylisothiazolinone as a preservative almost doubled from 2007 to 2010. In the workplace, exposure to methylisothiazolinone occurs when using paints, adhesives, varnishes, glazes, and other industrial products. Painters are the most common group to suffer from occupational ACD due to methylisothiazolinone – they account for almost 50% of occupational ACD cases (15). Methylisothiazolinone can be found in household products such as dishwashing liquids, soaps, laundry detergents, stain removers, fabric softeners, glass cleaners, and other cleaning products.

Prevalence of ACD caused by Methylisothiazolinone

In Europe, the prevalence of contact allergy to methylisothiazolinone fluctuates between 1.4% and 1.54%, as determined in three clinical studies. In a study conducted in Denmark between 2006 and 2010, methylisothiazolinone was ranked as the fourth most common allergen among preservatives. One of the first studies showing an increasing prevalence of allergy to methylisothiazolinone was conducted in Finland between 2006 and 2008. It was found that in 2006, 0.9% of patients were allergic to methylisothiazolinone, while in 2008, this figure rose to 1.8%. Subsequently, a drastic increase in sensitization to methylisothiazolinone has been observed in other countries, leading to discussion of an epidemic of contact allergy to this preservative. Cosmetics Europe recommends that its members do not use methylisothiazolinone in leave-on products and use only 0.0015% in rinse-off products.

Situation in Lithuania

A study conducted in 2014 revealed that methylisothiazolinone and methylchloroisothiazolinone/methylisothiazolinone are the most commonly used preservatives in cosmetics manufactured in Lithuania. Methylchloroisothiazolinone/methylisothiazolinone were declared in 20 (48%) of the tested cosmetic products, while methylisothiazolinone was found in 7 (16.8%) products, six of which were creams. Cases of allergy to methylisothiazolinone and methylchloroisothiazolinone are also increasing in Lithuania. Sensitization to methylchloroisothiazolinone/methylisothiazolinone was observed in 1.9% of individuals with dermatitis in studies conducted between 2005 and 2006, which increased to 10.3% during the period 2010–2012. Allergic contact dermatitis to methylisothiazolinone was detected in 14.3% of patients, and allergic contact dermatitis to methylchloroisothiazolinone/methylisothiazolinone in 10.9% of patients, in patch tests conducted at the Allergy and Immunology Diagnostic and Treatment Day Hospital of Vilnius University Hospital Santariškės Clinics between 2014 and 2016.

Clinical Case

A 32-year-old patient presented with recurrent armpit dermatitis. The dermatitis was particularly severe in the axillary fold and almost absent in the hairy area. Patch tests with the European baseline series of contact allergens and the antiperspirant used by the patient (manufactured by Garnier) showed positive reactions to both methylisothiazolinone and methylchloroisothiazolinone/methylisothiazolinone, as well as to the antiperspirant itself, which contained methylisothiazolinone. The patient was informed about where these preservatives could still be found. It turned out that they were also present in the shower gel and shampoo she used. After changing her body care products, the dermatitis did not recur.

Summary

Methylisothiazolinone and methylchloroisothiazolinone are strong allergens for humans. Unfortunately, they can still be found in cosmetic products, including those intended for children's skincare. The European Commission is considering the possibility of banning or significantly reducing the allowed concentration limit of these preservatives. Some manufacturers voluntarily refrain from using them, but there is still a high probability of encountering these allergens in everyday life. Source: "Internistas" No. 5, 2016.