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Notes: The objective of the study was to investigate, using the Repeated Open Application Test (ROAT), two key parameters of exposure – allergen concentration (dose/unit area) and time in terms of the elicitation capacity of methylchloroisothiazolinone and methylisothiazolinone (MCI/MI) in MCI/MI-sensitised individuals and to explore the inter-relationship between these two key factors. The study was designed as a double-blind, placebo-controlled, dose-response ROAT preceded by a Diagnostic Patch Test (DPT). 79 patients with a known MCI/M allergy were contacted, 29 were diagnostically patch tested and 25 had their allergy confirmed. 25 MCI/M-allergic subjects and 10 healthy non-allergic control subjects were challenged with 2 ppm of MCI/MI/unit area of skin for 4 weeks. After a wash out period of at least 4 weeks the subjects were challenged with 7.5 ppm of MCI/MI/unit area of skin for 4 weeks. A ROAT with 2 drops of solution twice a day was conducted on the volar aspect of the left and right forearms on a 3 × 3 cm area resulting in dose/unit area of MCI/MI of 0.025 mg/cm2 and 0.095 mg/cm2 for 2 ppm and 7,5 ppm MCI/MI respectively. The elicitation capacity of MCI/MI in MCI/MI sensitive patients is dependent on the exposure dose/unit area and time The results of this study will be a useful addition to the risk assessment information available for MCI/MI. The risk assessment for the use of MCI/MI in rinse off consumer products is unaffected by the results of this study.

Notes: For new chemicals introduced into the workplace or marketplace, and which come into contact with the skin, it is necessary, to conduct a thorough skin safety testing and risk assessment program to be certain that the exposures will be well tolerated. One vital risk assessment process involves the determination of allergic skin reactions, referred to as skin sensitization, the clinical manifestation of which is allergic contact dermatitis. The process by which low molecular weight chemicals induce and elicit skin sensitization is dependent on many factors including the ability of the chemical to penetrate the skin, react with protein, and trigger a cell-mediated immune response. Based on our chemical, cellular and molecular understanding of allergic contact dermatitis, it is possible to carry out a quantitative risk assessment. It has been well known for years that chemical allergens display dose-response characteristics regardless of whether the sensitization is induced in an experimental system or in humans. Moreover, it is well known that the critical exposure determinant for evaluating skin sensitization risk is dose per unit area of skin exposed. The skin sensitization testing and risk assessment process for new ingredients and consumer products generally follows a step-wise approach that may involve structure-activity evaluations, analytical assessments, preclinical skin sensitization testing (e.g., the mouse local lymph node assay), confirmatory clinical testing (e.g., the human repeat insult patch test), and benchmarking of resulting data against similar ingredients and product types. Essential elements for conducting a sound risk assessment involve the development of an understanding of the sensitization potential of the contact allergen and the likely dose, nature, extent and duration of exposure. With an understanding of the exposure and potency of the chemical one can assess whether the chemical, under the specific conditions of exposure, ould pose an acceptable or unacceptable risk of induction of skin sensitization. As with any test method or risk assessment approach, it is critical to understand the strengths and limitations so that one can conduct the best assessment possible and assure the skin safety of the chemical under evaluation.