Final report on the amended safety assessment of Propyl Gallate

Int J Toxicol. 2007:26 Suppl 3:89-118. doi: 10.1080/10915810701663176.

Abstract

Propyl Gallate is the n-propyl ester of gallic acid (3,4,5-trihydroxybenzoic acid). It is soluble in ethanol, ethyl ether, oil, lard, and aqueous solutions of polyethylene glycol (PEG) ethers of cetyl alcohol, but only slightly soluble in water. Propyl Gallate currently is used as an antioxidant in a reported 167 cosmetic products at maximum concentrations of 0.1%. Propyl Gallate is a generally recognized as safe (GRAS) antioxidant to protect fats, oils, and fat-containing food from rancidity that results from the formation of peroxides. Data on dermal absorption are not available, but Propyl Gallate is absorbed when ingested, then methylated, conjugated, and excreted in the urine. The biological activity of Propyl Gallate is consistent with its free-radical scavenging ability, with effects that include antimicrobial activity, enzyme inhibition, inhibition of biosynthetic processes, inhibition of the formation of nitrosamines, anesthesia, inhibition of neuromuscular response to chemicals, ionizing/ultraviolet (UV) radiation protection, chemoprotection, antimutagenesis, anticarcinogenesis and antitumorigenesis, antiteratogenesis, and anticariogenesis. Animal toxicity studies indicate that Propyl Gallate was slightly toxic when ingested, but no systemic effects were noted with dermal application. Propyl Gallate is a strong sensitizer when tested intradermally, less sensitizing when tested topically, and nonsensitizing topically at 0.1% in one study. In a second study, Propyl Gallate (15 mg dissolved in 8 ml vehicle) was sensitizing to guinea pigs. Acute eye irritation tests conducted on nine cosmetic formulations, each containing less than 1% Propyl Gallate, were negative. A phototoxicity study conducted on a cosmetic formulation containing 0.003% Propyl Gallate determined that the product was not phototoxic to guinea pigs. In one study, female rats fed 0.5 g Propyl Gallate had substantially increased fetal resorption rates when compared to controls, but in four other studies, Propyl Gallate at doses up to 2.04 g/kg was nonteratogenic in rats, rabbits, mice, and hamsters. In clinical cumulative irritancy tests, Propyl Gallate was nonirritating at concentrations up to 10%. Patch tests at concentrations less than 1% yielded positive elicitation responses. Repeat-insult patch tests using cosmetic formulations with 0.003% Propyl Gallate produced no irritation or sensitization. Propyl Gallate at a concentration of 10% in alcohol was nonphototoxic in 25 subjects. Cosmetic formulations, each containing 0.003% Propyl Gallate, produced no signs of photosensitization or phototoxicity in a total of 371 subjects. Although Propyl Gallate is not a skin irritant in clinical tests, the available data demonstrate that it is a skin sensitizer and that it may be a sensitizer at lower concentrations than originally thought, i.e., at concentrations less than 1%. In actual practice, cosmetic formulations contain Propyl Gallate at concentrations up to 0.1% and usage has increased over the past 20 years. In spite of the increased exposure associated with increased use, it is the clinical experience of the Panel that the use of Propyl Gallate in cosmetics has not resulted in sensitization reactions. Therefore, the Panel believes that a concentration limitation of 0.1% in cosmetics is necessary (given the evidence of sensitization at concentrations less than 1%) and sufficient (given that current products are not producing adverse reactions).

Publication types

  • Review

MeSH terms

  • Animals
  • Antioxidants / toxicity*
  • Consumer Product Safety
  • Cosmetics / toxicity*
  • Humans
  • Propyl Gallate / toxicity*
  • Toxicity Tests

Substances

  • Antioxidants
  • Cosmetics
  • Propyl Gallate