Final Report of the Cosmetic ingredient Review Expert Panel on the Safety Assessment of Poiyisobutene and Hydrogenated Polyisobytene as Used In Cosmetics

摘要

Poiyisobutene and Hydrogenated Poiyisobutene are homopolymers of isobutene. These ingredients are produced in a wide range of molecular weights. Polybutene is a chemically related cosmetic ingredient previously determined to be safe as used in cosmetic products. Poiyisobutene is used in cosmetic products as a binder, film former, and nonaqueous viscosity-increasing agent. Hydrogenated Poiyisobutene functions as a skin-conditioning agent-emollient and nonaqueous viscosity-increasing agent with a wide range of uses in cosmetic formulations. The estimated octanol water partition coefficient for Hydrogenated Poiyisobutene and Polybutene is log K_(ow) of 13.27 and the estimated water solubility was 5.6 X 10~(-3) ng/L for Hydrogenated Poiyisobutene and Polybutene. Acute oral toxicity testing demonstrated no effects other than lethargy in one rat study. The oral LD50 was >5.0 g/kg in rats. No short-term or subchronic animal toxicity data were available. A 2-year chronic oral toxicity study of Polybutene revealed no gross or microscopic pathological changes, and no changes in body weights or food consumption, hematological results, urology, or tumor formation that could be correlated with Polybutene ingestion, except that in the 20,000 ppm group, three out of six males that died between weeks 17 and 24 exhibited hematuria. In a 2-year chronic oral toxicity study of Polybutene in Beagle dogs, no abnormalities in body weight, food consumption, survival, behavioral patterns, hematology, blood chemistry, urinalysis, liver function, gross and histopathologic examinations, or organ weights and ratios were reported. In a three-generation reproductive study in Charles River albino rats that ingested Polybutene, none of the animals in successive generations differed from controls with regard to weight gain, litter size, the number of stillborn, and the number of viable pups during lactation. The survival, body weights, and reactions of test animals were comparable to those of controls. Neither Poiyisobutene nor Hydrogenated Poiyisobutene were ocular irritants, nor were they dermal irritants or sensitizers. Poiyisobutene was not comedogenk in a rabbit ear study. Poiyisobutene did not induce transformation in the Syrian hamster embryo (SHE) cell transformation assay, but did enhance 3-methylcholanthrene-induced transformation of C3H/10T1/2 cells. In a carcinogenic-ity study in mice, Polyisobutene was not carcinogenic, nor did it promote the carcinogenicity of 7,12-dimethylbenz(alpha)anthracene. Clinical patch tests uncovered no evidence of dermal irritation and repeat-insult patch tests with a product containing 4% Hydrogenated Poiyisobutene or 1.44% Hydrogenated Poiyisobutenefound no reactions greater than slight erythema. These products also were not phototoxic or photoallergenic. The product containing 4% Hydrogenated Poiyisobutene was not an ocular irritant in a clinical test. The Cosmetic Ingredient Review (CIR) Expert Panel recognized that there are data gaps regarding use and concentration of these ingredients. However, the overall information available on the types of products in which these ingredients are used and at what concentrations indicate a pattern of use, which was considered by the Expert Panel in assessing safety. Although there is an absence of dermal absorption data for Poiyisobutene and Hydrogenated Poiyisobutene, the available octanol water partition coefficient data and the low solubility in water suggest very slow absorption, so additional data are not needed. Gastrointestinal absorption is also not a major concern due to the low solubility of these chemicals. Although one in vitro study did report that Poiyisobutene did promote cellular transformation, a mouse study did not find evidence of tumor promotion. Because lifetime exposure studies using rats and dogs exposed to Polybutene failed to demonstrate any carcinogenic or tumor promotion effect, and a three-generation reproductive/developmental toxicity study