Methyldibromo glutaronitrile: clinical experience and exposure-based risk assessment CLAUS ZACHARIAE 1 ,SURESH RASTOGI 2 ,CHARLOTTE DEVANTIER 3,4 ,TORKIL MENNE ´ 1 AND JEANNE DUUS JOHANSEN 4 1 Department of Dermatology, Gentofte Hospital, University of Copenhagen, Copenhagen, 2 Department of Atmospheric Environment, National Environmental Research Institute, Roskilde, 3 Department of Dermatology, Odense University Hospital, Odense, 4 National Allergy Research Centre, Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark In the year 2000, the level of methyldibromo glutaronitrile (MDGN) allergy in dermatology clinics in Europe exceeded the level of allergies to all other preservatives, with a prevalence of 35%. In the present study, cases of primary sensitization and elicitation to MDGN due to cosmetic products were collected over an 8-month period at the Department of Dermatology, Gentofte University Hospital. The aim was to identify the products related to hand eczema, assess exposure to MDGN in these products and relate the findings to results from a newly developed updated risk assessment model for contact allergy. Out of 24 patients with a positive patch test to MDGN, 17 patients with hand eczema were identified. In 11 of these patients, cosmetic products used in relation to the onset of the disease were shown to contain MDGN (65%). In 8 of these 11 cases, primary sensitization was probable, 5 due to hand/body lotions and 3 due to lotions and/or liquid hand soap. Chemical analysis of 12 products showed that lotions contained 149–390 ppm of MDGN, liquid hand soap 144–399ppm,arinsingcream293ppmandshampoos78–79ppm.Theshampooexposurewasnotof certain relevance to the eczema. Applying the newly developed updated risk assessment model showed that the concentrations of MDGN in lotions of 149–390 ppm exceeded the calculated maximum acceptable exposure level for MDGN, which would be expected to lead to sensitization in consumers using such products, as seen in the current study. The present cases and updated exposure-based risk assessment process add to the evidence and need for re-defining safe-use concentrations of MDGN in cosmetic products. Keywords: contact allergy; exposure assessment; hand eczema; methyldibromo glutaronitrile; risk assessment. # Blackwell Munksgaard, 2003. Accepted for publication 25 February 2003 Methyldibromo glutaronitrile (MDGN) has been a recognized contact allergen since 1983 (1). A worker exposed to glue preserved with MDGN developed allergic contact dermatitis on the hands and fore- arms.TheEUScientificCommitteeonCosmetology approved MDGN in 1986 for use in cosmetic pro- ducts at a maximum concentration of 01%, based on The European Cosmetic Toiletry and Perfumery Association (COLIPA) dossiers submitted in 1981 and 1984 (2). The dossiers contained information about an irritancy study performed in rabbits and a negative human repeated insult patch test study. Since then, accumulating evidence from animal studies and clinical observations has demon- strated that MDGN is a potent and clinically significant allergen (3–13). This, however, has not led to any change in the COLIPA dossiers. The problems arising from such insufficient and outdated risk assessment were presented in a letter to the EU Commission in 2001. In this letter, the European Environmental and Contact Dermatitis Research Group provided data for 10 years of monitoring of contact allergy to preser- vatives in Europe, showing a rapidly increasing level of contact allergy to MDGN in recent years (13). In 1998–2000, the level of MDGN allergy in dermatology clinics exceeded the level of allergies to all other preservatives, with a prevalence of 35% in the year 2000 (13). The aim of the present study was to collect cases of primary sensitization and elicitation to MDGN due to cosmetic products and relate these Contact Dermatitis 2003: 48: 150–154 Copyright # Blackwell Munksgaard 2003 Printed in Denmark. All rights reserved CONTACT DERMATITIS ISSN 0105-1873