Final Report on the Safety Assessment of Glutaral

Abstract

The dialdehyde Glutaral (also commonly called glutaraldehyde) is used in a wide variety of cosmetics as a preservative. In vitro dermal penetration studies of Glutaral indicate low penetration through animal skin and even less through human skin. The oral LD50 of Glutaral for rats ranged from 66 mg/kg up to 733 mg/kg. A 28-day dermal toxicity study of Glutaral produced skin irritation and slight effects on weight and blood chemistry with concentrations as low as 50 mg/kg/day. Animal skin irritation was dose-dependant, with a no-effect concentration of 1%. Ocular exposure to Glutaral caused severe irritation in rabbits at concentrations 1%, with a no-effect level of 0.1%. Glutaral was not embryotoxic, fetotoxic, or teratogenic at concentrations that did not cause severe maternal toxicity. The no observable adverse effects level for reproduction toxicity was > 1,000 ppm. Bacterial mutagenesis tests produced mixed results, as would be expected for a preservative. In most mammalian system mutagenesis tests, Glutaral was not genotoxic. In a 2-year drinking water study in rats, there was an increase in large granular lymphocytic leukemia (LGLL), but only in females administered 50–1,000 ppm Glutaral. The response was not dose dependent. Clinical studies report some evidence of dermal irritation and sensitization, but no photosensitization. Occupational data and animal studies indicate that inhalation of Glutaral can cause respiratory irritation, in addition to skin effects. Evaluation of the increased incidence of LGLL in the 2-year drinking water study indicated that the incidence was within the historical control levels for this spontaneously occurring neoplasm. These data, however, were not considered sufficient to base a finding of safety of Glutaral in products intended for prolonged use. It was concluded that a 2-year dermal carcinogenicity study following National Toxicology Program (NTP) procedures was needed to complete the safety assessment of Glutaral for use in leave-on products. For rinse-off products, it was concluded that the ocular and dermal irritancy of Glutaral could be substantially avoided if the concentration did not exceed 0.5% and exposure was only brief and discontinuous. Because it can cause respiratory irritation, it was concluded that Glutaral should not be used in aerosolized cosmetic products.