sodium-dodecyl-sulfate and 1-2-dibromo-2-4-dicyanobutane

The first step in regulatory evaluation of substances involves the identification of their intrinsic hazards, including the potential for skin sensitization. This is, quite properly, entirely different from assessment of the risks to human health, which might arise from incorporation of substances in products. EU guidance on regulations concerning the classification of skin sensitizers suggests a range of sources of information be deployed in the hazard identification process. These include chemical structure, predictive animal tests, and various types of human data. Where the information is clear-cut, then uncertainties rarely arise. However, for some materials, discordant information arises, perhaps because the substance is on the borderline of test sensitivity and classification (sensitizing materials of insufficient potency do not classified according to the EU scheme), due to conflicting results in predictive tests or for other reasons. In this study, we review data on a number of substances where a classification decision is complicated by such discordances and seek to use these examples to demonstrate how best to make a weight of evidence decision on whether a substance should, or should not, be classified as a skin sensitizer.

Topics: Allergens; Animals; Benzalkonium Compounds; Betaine; Cyclohexenes; Dermatitis, Allergic Contact; False Negative Reactions; False Positive Reactions; Humans; Limonene; Nitriles; Parabens; Preservatives, Pharmaceutical; Sodium Dodecyl Sulfate; Solvents; Sulfanilic Acids; Surface-Active Agents; Terpenes

The present study was undertaken to evaluate the combined effect of the preservative methyldibromo glutaronitrile (MDBGN) and sodium lauryl sulfate (SLS) on the elicitation response of allergic contact dermatitis. 20 volunteers with contact allergy to MDBGN were patch tested with 5 concentrations (10, 50, 100, 500 and 1000 p.p.m.) of MDBGN alone and in combination with 0.25% SLS on the upper arms for 24 h. Skin reactions were evaluated by clinical scoring, and data were evaluated by logistic dose-response models. Additionally, evaluation of skin reactions was performed by measurement of transepidermal water loss (TEWL) and skin colour. Measurements were obtained at baseline and at D3 and D7. As evaluated by clinical assessment, allergic reactions to MDBGN were elicited at lower concentrations when applied in combination with SLS than when applied alone. The response was augmented by a factor of 6.4. An increased response to combined exposure to SLS and MDBGN as compared with MDBGN alone was confirmed by TEWL and colour measurements. Effects of exposure time and concentration of the detergent are discussed. In conclusion, an augmented response was found after concurrent application of MDBGN and SLS. The response was augmented by a factor of 6.4, with confidence limits of 2.8-14.6 (P < 0.0001). This result is important in relation to the determination of threshold values and the risk assessment of contact allergens in consumer and industrial products, where allergens are often present in combination with surfactants.

Topics: Allergens; Colorimetry; Dermatitis, Allergic Contact; Detergents; Dose-Response Relationship, Drug; Female; Humans; Logistic Models; Male; Nitriles; Patch Tests; Preservatives, Pharmaceutical; Sodium Dodecyl Sulfate; Time Factors