Amended final report of the safety assessment of Drometrizole as used in cosmetics.

Drometrizole is used in cosmetics as an ultraviolet (UV) light absorber and stabilizer. In an earlier safety assessment, the available data were found insufficient to support the safety of this ingredient, but new data have been provided and assessed. In voluntary industry reports to the Food and Drug Administration, this ingredient is reported to be used in noncoloring hair care products, and in an industry use concentration survey, uses in nail care products at 0.07% were reported. Drometrizole has absorbance maxima at 243, 298, and 340 nm. Drometrizole is used widely as a UV absorber and stabilizer in plastics, polyesters, celluloses, acrylates, dyes, rubber, synthetic and natural fibers, waxes, detergent solutions, and orthodontic adhesives. It is similarly used in agricultural products and insecticides. Drometrizole is approved as an indirect food additive for use as an antioxidant and/or stabilizer in polymers. Short-term studies using rats reported liver weight increases, increases in the activities of enzymes aminopyrine N-demethylase, and UDP glucuronosyl transferase, but no significant effects were noted in the activities of acid hydrolases or in hepatocyte organelles. Although Drometrizole is insoluble in water and soluble in a wide range of organic solvents, a distribution and elimination study using rats indicated that some Drometrizole was absorbed, then metabolized and excreted in the urine. Drometrizole and products containing Drometrizole were nontoxic in acute oral, inhalation, and dermal studies using animals. No increase in mortality or local and/or systemic toxicity were observed in a 13-week oral toxicity study using dogs; the no observed effect level (NOEL) was 31.75 mg/kg day(- 1) for males and 34.6 mg/kg day(-1) for females. In a 2-year feeding study using rats, a NOEL of 47 to 58 mg/kg day(- 1) was reported. Developmental studies of Drometrizole in rats and mice found no teratogenic effects and a NOEL of 1000 mg/kg day(- 1) was reported. Drometrizole was not genotoxic in Ames tests, a mouse bone marrow micronucleus test, or somatic mutation assays observing interphase nuclei and chromosomal aberrations using Chinese hamsters. There was no evidence of dominant lethal effects in studies using mice or rats. Drometrizole at a 1% concentration was minimally to moderately irritating to rabbit eyes, if followed by rinsing, but mildly to severely irritating in unrinsed eyes. A nail product containing 0.03% Drometrizole, however, was nonirritating to unrinsed rabbit eyes. A nail polish containing 1.0% Drometrizole was nonirritating to rabbit skin and Drometrizole was negative for sensitization in two Magnusson-Kligman maximization tests in guinea pigs. In clinical tests, Drometrizole at 1% was nonirritating in a single-insult patch test. No irritation or eczematous reactions were observed in 300 patients (with or without dermatosis) treated with daily applications of Drometrizole for 8 weeks. In a 3-year clinical therapeutic trial conducted to evaluate the effectiveness of two UV absorbing preparations containing up to 5% Drometrizole, two hypersensitivity reactions were observed during 445 applications. Although there are case reports in which Drometrizole was considered the sensitizing agent, clinical tests of cosmetic products containing 0.03% to 1.0% Drometrizole produced no irritation, sensitization, photosensitization, or phototoxicity in a total of 436 subjects. The Cosmetic Ingredient Review (CIR) Expert Panel assumes that Drometrizole is used in both noncoloring hair care and nail care products at low concentrations. The available safety test data do not suggest any adverse effects associated with exposure to Drometrizole. This toxicologic profile, coupled with the low concentration of use and the unlikely dermal penetration of a chemical that is insoluble in water, support the conclusion that Drometrizole can be safely used in cosmetics.