Final Report on the Amended Safety Assessment of Diisopropyl Dimer Dilinoleate,Dicetearyl Dimer Dilinoleate,Diisostearyl Dimer Dilinoleate,Dioctyl Dimer Dilinoleate,Dioctyldodecyl Dimer Dilinoleate,and Ditridecyl Dimer Dilinoleate

Abstract

Diisopropyl Dimer Dilinoleate, Dicetearyl Dimer Dilinoleate, Diisostearyl Dimer Dilinoleate, Dioctyl Dimer Dilinoleate, Dioctyldodecyl Dimer Dilinoleate, and Ditridecyl Dimer Dilinoleate are diesters of their respective alcohols and dilinoleic acid. They function as skin-conditioning agents in a variety of cosmetic products at concentrations around 10%, but may be used at concentrations up to 53% in lipsticks. These ingredients do not absorb radiation in the ultraviolet (UV) UVA or UVB range and the only impurities expected are <0.5% dilinoleic acid, <0.1% isopropyl alcohol or <1% isostearyl alcohol, and/or small amounts of dilinoleic acid and cetearyl alcohol or octyldodecanol, depending on which diester is used. The potential skin penetration of these ingredients was evaluated using an estimate of the octanol/water partition coefficient (logP of 17.7) based on the structure of Diisopropyl Dimer Dilinoleate. This is consistent with the insolubility of these ingredients in water. Safety test data on dilinoleic acid (no adverse effects) were considered relevant because dilinoleic acid is a component of these diesters and a likely breakdown product. The acute oral and dermal LD50 values for rats of Diisopropyl, Diisostearyl, and Dioctyldodecyl Dimer Dilinoleate were >5.0 g/kg. In a subchronic feeding study, macrophage aggregation was seen in the mesenteric lymph node at the lowest dose level (0.1% in the diet). These ingredients did not produce skin or ocular irritation in animal tests, nor were they comedogenic. Ames testing, clastogenesis in human lymphocytes in culture, and L5178Y mouse lymphoma cell forward mutations were all negative, indicating no dilinoleic acid genotoxicity. No carcinogenicity or reproductive/developmental toxicity data were available; however, structural alerts that would suggest a mutagenic or carcinogenic risk are absent. Significant reproductive/developmental toxicity or other systemic toxicity is not expected with these ingredients because they remain on the skin surface. In clinical studies, cosmetic formulations containing these ingredients did not produce skin irritation or sensitization, although one report of sensitization to dilinoleic acid appeared in the case literature. The Panel did note that the concentration of use of Diisopropyl Dimer Dilinoleate was reportedly as high as 53% in lipsticks, but that the highest concentration tested for irritation/sensitization is 27%. Given the size of these molecules, their relative insolubility in water, their lipophilic nature, and the absence of any significant case reports of allergic reactions, a use concentration of 53% is not likely to be associated with any adverse effects. Accordingly, these diesters were considered safe as used in cosmetic products.