title: Methyldibromoglutaronitrile: skin sensitization and quantitative risk assessment.
abstract: Preservatives can be a frequent cause of allergic contact dermatitis (ACD). A quantitative risk assessment (QRA) method for identifying safe exposure levels has been suggested as a more effective tool for this purpose. This work assesses the validity of QRA by its retrospective application to the sensitizing preservative methyldibromoglutaronitrile (MDGN), which has recently been associated with unacceptable exposure levels in consumer products. Using a recently published QRA analysis of 4 preservatives in 5 consumer product types, the accuracy of the predictions for MDGN was assessed in light of what is known clinically about the nature and incidence of ACD to this material. Based on a local lymph node assay (LLNA) EC3 value (concentration of test chemical required to provoke a 3-fold increase in lymph node cell proliferation) of 0.9% in a weight-of-evidence approach to the identification of thresholds for the induction of skin sensitization, it can be determined that the acceptable levels of exposure to MDGN in a range of products range from as little as 25 ppm to in excess of 10,000 ppm. Thus, proactive use of QRA, used conservatively and in combination with expert judgment, would have limited the problem of ACD to this new preservative that is known to have caused problems on the consumer market.
authors.affiliation: DABMEB Consultancy Ltd., Sharnbrook, Bedfordshire, UK. david.basketter@ukonline.co.uk
authors.forename: David A
authors.initials: DA
authors.lastname: Basketter
mesh_terms: D000485:Allergens / Q000633:toxicity*; D000818:Animals; D003257:Consumer Product Safety; D003358:Cosmetics / Q000633:toxicity*; D017449:Dermatitis, Allergic Contact / Q000209:etiology* / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D006801:Humans; D023441:Local Lymph Node Assay; D009570:Nitriles / Q000633:toxicity*; D011310:Preservatives, Pharmaceutical / Q000633:toxicity*; D015203:Reproducibility of Results; D018570:Risk Assessment; D012867:Skin / Q000187:drug effects*; D012882:Skin Tests
chemical_list: D000485:Allergens; D003358:Cosmetics; D009570:Nitriles; D011310:Preservatives, Pharmaceutical; C039411:1,2-dibromo-2,4-dicyanobutane