Final Report on the Safety Assessment of Methoxyisopropanol and Methoxyisopropyl Acetate as Used in Cosmetics

Abstract

Methoxyisopropanol and Methoxyisopropyl Acetate, commonly known as propylene glycol monomethyl ether (PGME) and propylene glycol monomethyl ether acetate (PGMEA), respectively, have fragrance, solvent, and viscosity-decreasing functions in cosmetics, although only Methoxyisopropanol is in current use at concentrations ranging from 4% to 35%. Methoxyisopropanol is easily absorbed into the bloodstream upon inhalation or ingestion. The acetate ester is readily metabolized to Methoxyisopropanol in the body, which is excreted unchanged in the expired breath or in the urine as free or conjugated Methoxyisopropanol, or as the primary metabolite propylene glycol. In acute oral toxicity studies, the LD(50) values of Methoxyisopropanol were 4.6 to 9.2 g/kg in rats, with similar low acute toxicity in other animal species. Inhalation exposures of rats, mice, and rabbits to 3000 ppm Methoxyisopropanol for 6 h per day for 9 days to 13 weeks produced increased relative liver weights, signs of central nervous system (CNS) depression, and in some cases, elevated serum alkaline phosphatase, alanine aminotransferase, or hepatocellular hypertrophy, but the kidneys were unaffected. The no observed adverse effect level (NOAEL) for 13-week inhalation exposures to Methoxyisopropanol was 1000 ppm in rats and rabbits. In a 90-day dermal exposure study using rabbits, 10 ml/kg undiluted Methoxyisopropanol produced narcosis and increased kidney weights and the NOAEL was 7.0 ml/kg. Chronic (2-year) daily inhalation exposures of rats and mice to 3000 ppm Methoxyisopropanol produced signs of liver toxicity (rats and mice) and some evidence of renal toxicity in rats. The only observation at 1000 ppm was dark foci of the liver in male rats. For female rats and male and female mice, the NOAEL of this chronic inhalation study was 1000 ppm Methoxyisopropanol. Methoxyisopropanol and Methoxyisopropyl Acetate were found to be nonirritating to slightly irritating and non-sensitizing in rabbit and guinea pig skin. Repeated applications of undiluted Methoxyisopropanol to the eyes of rabbits produced transient slight to moderate irritation. Pregnant rats exposed to 200 or 600 ppm Methoxyisopropanol by inhalation on gestation days 6 to 17 had no effects on maternal health or normal fetal development. Adult male rats exposed to these concentrations had no effects on the reproductive organs. Pregnant rats and rabbits exposed to 500 to 3000 ppm Methoxyisopropanol by inhalation during gestation had no significant embryotoxic or fetotoxic effects, althougth CNS depression and reduced body weight gain were observed in the 3000 ppm group. In a two-generation inhalation study using rats, continuous inhalation of 3000 ppm Methoxyisopropanol produced CNS depression, prolonged estrous cycles, reduced fertility indices, reduced pup weights and pup survival, and delayed sexual development, with a NOAEL for reproductive and developmental effects of 1000 ppm. In a continuous breeding protocol using mice, 2.0% Methoxyisopropanol in drinking water produced reduced growth, r...

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