Final report on the safety assessment of pentasodium pentetate and pentetic acid as used in cosmetics.

Pentasodium Pentetate and Pentetic Acid function as chelating agents in cosmetics. Pentasodium Pentetate is readily soluble in water, but the corresponding free acid is not. Pentasodium Pentetate is used in almost 400 cosmetic products over a wide range of product categories, although it is mostly used in hair dyes and colors at use concentrations of 0.1% to 1.0%. Pentetic Acid is used in 150 cosmetic products, mostly in hair dyes and colors. Chelating agents are used in cosmetics to remove calcium and magnesium cations, which impede foaming and cleansing performance and which can cause a haze in clear liquids. The acute oral LD(50) of Pentasodium Pentetate in rats was > 5 g/kg. The acute dermal LD(50) of Pentapotassium Pentetate using rats was reported to be > 2 g/kg. The intraperitonal LD(50) of Pentetic Acid was reported to be 585 mg/kg. Short-term studies of the calcium and sodium salts of Pentetic Acid in male mice demonstrated no dose-related toxicity over the dose range of 10, 100, and 250 mg/kg. In a 4-week dermal toxicity study, daily topical application of 0.05% Pentasodium Pentetate to shaved and abraded rabbit skin produced moderate erythema after the first week and throughout the study, but no systemic toxicity. Pentasodium Pentetate or Pentapotassium Pentetate applied to intact albino rabbit skin were not irritating. A 40% solution of Pentapotassium Pentetate was not sensitizing in a guinea pig maximization test. The no observed adverse effect level (NOAEL) for rats given 40% Pentapotassium Pentetate by oral gavage was reported to be 83 mg/kg day(-1). Subchronic inhalation evaluation of a bath freshener containing 0.05% or 0.09% Pentasodium Pentetate using albino rats determined that there was no cumulative systemic toxicity attributable to the ingredient at either concentration. The no observed effect level (NOEL) for maternal toxicity in pregnant rats was 400 mg/kg body weight and for fetal toxicity was 100 mg/kg body weight. Another reproductive toxicity study evaluated Pentetic Acid-Zn with and without sodium chloride in pregnant C57/B1 Dougherty mice. No toxicity was found without added sodium chloride. Pentapotassium Pentetate was not mutagenic in an Ames test, with or without metabolic activation. The same material tested in Chinese hamster ovary cells was not clastogenic. Calcium Pentetate at 1.351 microg/ml produced a statistically significant increase in the number of sister-chromatid exchanges. Pentasodium Pentetate is nonirritating to moderately irritating, but not a sensitizer in clinical tests. A human comedogenicity (acne promotion) test using Pentasodium Pentetate found no effect. Although data are lacking on the dermal penetration of these two ingredients, other chelating agents such as EDTA do not penetrate the skin, so it is likely that Pentasodium Pentetate and Pentetic Acid also would not penetrate. The high water solubility of Pentasodium Pentetate and the low water solubility of Pentetic Acid also support that their dermal penetration will be low. Other chelating agents, including EDTA and its salts, have been determined to be safe in the current practices of use in cosmetics. Meta-, Tri-, and Hexametaphosphate salts are chelating agents determined to be safe in the current practices of use in cosmetics. Metasilicate salts were found to be safe as chelating agents in cosmetics when formulated to avoid irritation. Overall, these data were considered sufficient to support the safety of Pentesodium Pentetate and Pentetic Acid as used in cosmetics.