4 Final Report on the Safety Assessment of Phenethyl Alcohol

Abstract

Phenethyl Alcohol (PEA) is an aromatic alcohol that is used as a fragrance and an antimicrobial preservative in cosmetic formulations. PEA is metabolized to phenyl-acetic acid in mammals. In humans, it is excreted in urine as the conjugate phenylacetylglutamine. The acute oral LD50s of PEA to rats ranged from 2.5 to 3.1 ml/kg, and for mice and guinea pigs was 0.8 to 1.5 g/kg and 0.4 to 0.8 g/kg, respectively. The dermal LD50s for rabbits and guinea pigs were 0.8 g/kg and 5 g/kg, respectively. PEA was slightly to moderately irritating to the skin of rabbits and guinea pigs and was not a guinea pig sensitizer. PEA, in concentrations of 1 % or greater, was irritating to the eyes of rabbits. PEA was neither an irritant nor a sensitizer in human studies. PEA was not mutagenic in the Ames test or in an Escherichia coli DNA-polymerase-deficient assay system. PEA did inhibit the repair of radiation-induced breaks in the DNA of E. coli. PEA did not increase the number of sister chromatid exchanges in human lymphocytes. Maternal exposure to PEA, microencapsulated in the feed, at concentrations of 1000, 3000, and 10,000 ppm had no effect on embryo-fetal loss, or embryo-fetal development and morphology. There was an increased incidence of incomplete ossification in the 10,000 ppm PEA group litters. Doses of 0.14, 0.43, and 1.40 ml/kg of PEA were applied to the skin of pregnant rats. Maternal toxicity was marked at the highest dose, Morphological abnormalities in fetuses in the 1.40 ml/kg PEA group were observed. The number of fetuses with moderate degrees of reduced ossification and with cervical rib(s) was significantly greater in the 0.43 ml/kg PEA group than in the controls. The incidence of structural changes was slightly greater in 0.14 ml/kg PEA-treated rats than in control rats. Dermal doses of 0.07,0.14,0.28,0.43, and 0.70 ml/kg/day PEA to pregnant rats significantly increased cervical ribs in the 0.70 ml/kg/day group litters. The highest no observed adverse effect level (NOAEL) was 0.43 ml/kg/day for cervical rib malformation (teratogenic effect). The dermal applied teratogenicity NOAEL of 0.43 ml/kg/day was used to estimate a safe use level of 1.0% PEA in cosmetic products.