摘要：

Author(s): Ana Giménez-Arnau 1 Keywords : acrylates; allergy; contact dermatitis; contact urticaria; dimethylfumarate; fumaric acid; irritant; sensitization An epidemic of contact allergy to dimethylfumarate (DMFu) was experienced in Europe (2008-2009). This human health hazard was identified through the individual daily practice of physicians. Active contact dermatitis networks and a multidisciplinary approach to the problem allowed the identification of the responsible allergen and the source of exposure. As a result of fast, active and accurate communication, global measures were taken to avoid the risk. No specific environmental hazard has been associated with DMFu until now. Nevertheless, because DMFu has been demonstrated to be a human health hazard inducing dermatitis, a Registration, Evaluation, Authorisation and Restriction of Chemicals restriction dossier has been created to make the Commission Decision of March 17th 2009 (EU Decision 2009/251/EC) permanent, requiring Member States to ensure that products containing the biocide dimethylfumarate are not placed in or made available on the market. This article will provide an update on different aspects related to the epidemic of allergy induced by DMFu in Europe. DMFu's chemical and biological properties, as well as its pharmaceutical and industrial uses, are reviewed. The European DMFu epidemic positions this biocide as a real human health hazard that needs a global approach in order to avoid its use. DMFu chemistry The chemical formula of fumaric acid (FA) is HO 2 CCH=CHCO 2 H. This white crystalline compound is the E-isomer of the two isomeric unsaturated dicarboxylic acids, the other being the Z-isomer, maleic acid (MA) containing cis-carboxylic groups. It shows a fruit-like taste. The salts and esters of fumaric acid are known as fumarates (Table 1) [1,2] . DMFu's chemical properties are summarized in Box 1. Because of its vapor pressure, DMFu can be considered to be a volatile organic compound (VOC). Indeed, a substance is considered to be a VOC if its boiling point is between 50 and 100°°C and 240 and 260°°C (International Organization for Standardization [2005]). DMFu is hydrolyzed to monomethyl fumarate (MMF) in an alkaline environment (pH 8), but not in an acidic environment (pH 1). Its volatile nature gives DMFu the capacity to impregnate the surrounding objects. Despite its volatile nature, DMFu has been detected in textiles for long periods of time, even after repeated washing. DMFu biology & applications Fumaric acid is found in fumitory ( Fumaria officialis ), bolete mushrooms (specifically Boletus fomentarius var. pseudo-igniarius ), lichen and Iceland moss. It is an intermediate in the citric acid cycle used by cells to produce energy in the form of ATP from food. It is also a byproduct of the urea cycle. Human skin naturally produces FA when exposed to sunlight. Fumaric acid has used as a food acidulate since 1946 because it is considered to be nontoxic. It is generally applied as a substitute for tartaric acid and occasionally in place of citric acid, at a rate of 1.36 g of citric acid to every 0.91 g of FA for the same taste. It is also used...

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