Final report on the safety assessment of Stearamide DIBA-Stearate.

Stearamide DIBA-Stearate is a substituted dihydroxyisobutylamine (DIBA) that functions in cosmetic formulations as an opacifying agent, a surfactant-foam booster, and a viscosity increasing agent. Stearamide DIBA-Stearate was reportedly used in four cosmetic formulations, at concentrations of 1% to 3%. Few data on this ingredient were available. Data on related ingredients, including Dibutyl Adipate, Diisopropyl Adipate, Stearamide DEA, and Stearamide MEA, were considered in the assessment of safety. A formulation containing 1.3% Stearamide DIBA-Stearate (further diluted to 4% of the formulation) was mildly irritating but nonsensitizing in an repeated-insult patch test (RIPT). The same dilution was noncomedogenic. At a concentration of 20%, Dibutyl Adipate had an oral LD50 of 2 g/kg. Subchronic dermal exposure of rabbits (1.0 ml/kg/day) caused a reduction in weight gain that was not observed at a dose of 0.5 ml/kg/day. In studies using rabbits, undiluted Dibutyl Adipate caused mild to moderate skin irritation and minimal ocular irritation. When pregnant rats were treated intraperitoneally with approximately 1.75 ml/kg Dibutyl Adipate during gestation, the incidence of fetal gross abnormalities was increased. No effect was observed at smaller doses. Diisopropyl Adipate had low acute oral and percutaneous toxicity, and was only a very mild ocular irritant. In skin irritation studies using rabbits, 5.0% to 100% Diisopropyl Adipate caused minimal to mild irritation; these results were also seen in clinical testing with only moderate cumulative irritation, and no sensitization or photosensitization. A formulation containing 5.27% Stearamide MEA was not toxic to rats when applied topically daily for 13 weeks. In studies using rabbits, Stearamide DEA (35% to 40%) was not a skin or ocular irritant, and Stearamide MEA (5.27%) was not an ocular irritant. At 17%, Stearamide MEA was not irritating to the skin, but caused minimal to moderate irritation to the eyes of rabbits. Stearamide MEA (5.27%) did not cause sensitization during a clinical study. It was not possible, however, to determine the relevance of these data on related ingredients. Therefore, it was concluded that the available data are insufficient. Additional data needs are (1) method of manufacture; (2) chemical characterization, including impurities; (3) dermal absorption; if significantly absorbed, then a 28-day dermal toxicity study and a reproductive and developmental toxicity study may be needed; (4) two genotoxicity assays, at least one in a mammalian system; if positive, then a 2-year dermal carcinogenesis study using National Toxicology Program (NTP) methods may be needed; (5) ultraviolet (UV) absorption data; if significant absorption occurs in the UVA or UVB range, photosensitization data are needed. Absent these data, it was concluded that the available data are insufficient to support the safety of Stearamide DIBA-Stearate as used in cosmetic products.

Occupational contact dermatitis to propacetamol. Allergological and chemical investigations in two new cases.

BACKGROUND AND OBJECTIVE: In 2 new cases of occupational contact dermatitis due to a recently described allergen (propacetamol), a prodrug which is a soluble diethylglycidyl ester of paracetamol, an allergological investigation was performed to elucidate the nature of the allergen involved in the propacetamol contact sensitivity. OBSERVATIONS: Two nurses with eczema of the hands and face had positive patch tests to Pro-Dafalgan. Every day the nurses prepared injections of Pro-Dafalgan (propacetamol dissolved in sodium citrate). The sensitization was due to propacetamol and not to the solvent. To elucidate which part of propacetamol was responsible for the sensitization, the 2 nurses were patch-tested with diethylamine, paracetamol (diluted in different vehicles) and some of their chemical analogues and potential impurities which were all negative. CONCLUSIONS: Propacetamol induces airborne contact dermatitis with no evidence of sensitization to paracetamol or diethylglycine, possibly because of either the presence of unknown impurities and/or an antigenic structure related to the covalent bond of the prodrug.

[Threshold of contact allergy to stearamidoethyl diethylamine in guinea pigs].

The cationic surfactant, stearamidoethyl diethylamine (SD) is an emulsifier used in topical medications and cosmetics. It has been reported to cause allergic contact dermatitis. This report concerns a study of the sensitizing capacity of SD in guinea pigs, using the modified maximization method (8) and closed epicutaneous test (10); the induction concentration was 10% in petrolatum. By the modified maximization method, 8 of 20 (40%) of the guinea pigs were sensitized to 1% SD, mean response 1.9; and 6 (30%) to 0.5% SD, mean response 1.4. In closed epicutaneous tests, 3 of 20 (15%) guinea pigs also showed reactions to 1%, and 2 of 20 (10%) to 0.5% SD. The results from modified maximization test showed that SD is a moderate sensitizer, as the sensitizing rate is in the range of 26-50% (below 26% is classified as "mild", and above 50% is "strong"). Even with a less sensitive closed epicutaneous test, its sensitivity could also be detected. From a risk-benefit point of view, no substantial risk for cosmetic chemicals intended for extensive use on normal and diseased skin will be accepted. Drugs may be acceptable, in spite of their sensitizing potential, because of their inherent benefit. As such, this surfactant may be only suitable in prescription drugs. Allergic contact dermatitis is rarely reported from cationic surfactants. Lack of suspicion of these not-necessarily-innocent chemicals has been partially responsible. The potential widespread use of emulsifiers with sensitizing capacity warrants further surveillance, as does the possibility of cross reaction between various emulsifiers.