Sensitization

Technical Summary:

Short chain alkyl-methacrylate esters (MMA, EMA, nBMA, iBMA and 2-EHMA) are high production volume chemicals and have been reviewed extensively under EU and OECD Existing Chemicals Risk Assessment programs. MMA has been the subject of an EU Risk Assessment (2002) and OECD review (2007). EMA, nBMA, iBMA and 2-EHMA underwent review as a category in the OECD SIAR program (2009). Data on MAA, the common metabolite, has also been reviewed in the EU Risk Assessment (2002).

Drawing from the OECD SIAR (Summary Initial Assessment Report) on short chain alkyl-methacrylate esters and including information on MMA from the EU and OECD reviews we can conclude the following:

All short chain alkyl-methacrylate esters (MMA, EMA, nBMA, iBMA and 2-EHMA) appear to give equivocal results in adjuvant studies in guinea pigs and, on balance, they may be regarded as weak contact sensitizers. Short chain alkyl-methacrylate esters have been reported to cross react with other methacrylate esters, but not with acrylate esters.

Methacrylate esters are generally regarded by dermatologists as skin sensitizing and consequently EMA and n-BMA are often included in dermatological patch tests when exposure to (meth)acrylates is suspected. Despite this, very few cases of confirmed contact allergy to EMA or BMA esters have been reported in the literature appearing to confirm that the contact sensitizing potential of these esters is low. As in animals, methacrylate esters can cross-react with other methacrylates but not with acrylates in humans.

Considerably more human data are available on the more widely used ester, MMA. The EU and OECD risk assessment on MMA extensively reviewed the available human information and concluded "There have been numerous reports on skin sensitization in certain occupational environments, where frequent and prolonged unprotected skin contact with monomer containing preparations was common practice. In the literature cases of sensitization of patients with implanted acrylic bone cement, of patients with hearing aids and of persons using synthetic fingernails have been reported."

Since the EU and OECD reviews Betts et al., published a paper on the potency of MMA to induce contact allergy in the Local Lymph Node Assay (LLNA) and reviewed prevalence data for published clinical studies on contact allergy due to MMA in humans (i.e. Rustemeyer T and Frosch P J, 1996 (also as Peiler et al., 1996); Schnuch and Geier, 1994 and Kiec-Swierczynska, 1996). Based upon the low potency of MMA to induce allergy in the LLNA assay and in observing that there was a positive bias to inclusion of sensitized individuals in the test cohort used in these studies, thereby overstating actual prevalence, Betts concluded that MMA "has only a relatively weak potential to cause the acquisition of skin sensitization" (Betts et al., 2006).

Methacrylic acid, the common hydrolysis product for these methacrylate esters, is not a contact allergen (ECETOC, 1996; OECD 2002).

References:

Betts C, Dearman RJ, Heylings JR, Kimber I and Basketter DA: Skin sensitization potency of methyl methacrylate in the local lymph node assay: comparisons with guinea-pig data and human experience. Contact Dermatitis Volume 55 Issue 3, Pages 140 - 147.

Kiec-Swierczynska, M.: Occupational allergic contact dermatitis due to acrylates in Lodz. Contact Dermatitis 34(6) 419-422 (1996).

Peiler D, Rustemeyer T, Frosch P J. Dermatitis in dental technicians - irritation and allergy. Gemeinschaftstagung der DKG, des IVDK unde der ABD der DKG, p93 (1996).

Rustemeyer T, Frosch P J. Occupational skin diseases in dental laboratory technicians - 1) clinical picture and causative factors. Contact Dermatitis 34 125-133 (1996).