Amended Final Report on the Safety Assessment of Nonoxynol-1, -2, -3, -4, -5, -6, -7, and -81

Abstract

Nonoxynol-1, -2, -3, -4, -5, -6, -7, and -8 (low molecular weight Nonoxynols) are ethoxylated alkylphenols used in cosmetic formulations as surfactants-emulsifying agents, principally in hair dyes and colors. The safety of Nonoxynols were assessed previously (Elder, R. L., ed. 1983. Final report on the safety assessment of Nonoxynol-2, -4, -8, -9, -10, -12, -14, -15, -30, -40, and -50. J. Am. Coll. Toxicol. 2:35–60). This report amends the conclusion on Nonoxynol-2, -4, and -8 reached in that report. There was no significant skin penetration using cadaver skin in which Nonoxynols-2, -4, and -9 were applied in conditions simulating leave-on or rinse-off applications. Under both conditions, the total skin penetration of Nonoxynol-2, -4, and -9 was less than 1% over a 48-hour period. Results of acute oral toxicity studies indicated that these low molecular weight Nonoxynols were at most slightly toxic. Nonoxynol-5 and -6 produce severe ocular irritation in test animals. They also produce skin irritation in test animals, but are not sensitizers. Due to the severity of ocular irritation reactions in animals, avoiding the use of products containing low molecular weight Nonoxynols in the area surrounding the eyes was discussed. The no-adverse-effect level in reproductive and developmental toxicity tests in which Nonoxynol-9 was delivered orally or intravaginally was higher than any possible exposure from cosmetic products. There was no evidence for genotoxicity or carcinogenicity. Ethylene oxide residues, although present in small amounts in several preparations, were not considered sufficient to present a carcinogenesis risk. The report discusses the need to ensure that the use of cosmetic products containing Nonoxynols should not result in ethylene oxide exposures above 0.1 mg/day. Unreacted nonylphenol may be present in low molecular weight Nonoxynols, but levels appear to be <500 ppm. The report discusses the need for cosmetic product formulators to exercise care so that any Nonylphenol in finished products is not found in toxic amounts. Clinical studies using Nonoxynol-9 showed irritation of the vaginal mucosa, along with increased epithelial disruption. A 2% solution of Nonoxynol-8.3 and -9 was sensitizing in dermatitis patients. A repeat insult patch test in normal volunteers using Nonoxynol-2 at a concentration of 5 % showed no evidence of allergic contact dermatitis, but there were reactions at 10%. Based on the available animal and clinical data, Nonoxynols-1 through -8 are safe as used in rinse-off products and safe for use in leave-on products at concentrations no greater than 5%.