Final Report on the Safety Assessment of p-Aminophenol, rn-Aminophenol, and o-Aminophenol p-Aminophenol (PAP), rn-Aminophenol (MAP), and o-Aminophenol (OAP) are used in permanent (oxidative) hair dyes at concentrations from 0.1 to 5%.In vivo and in vitro skin absorption studies indicated that 11 % of the dermally applied I4C-PAP was detected in the excreta, viscera, and skin of the test animals. The oral LDSos of PAP, MAP, and OAP in rats ranged from 600 to 1300 mg/kg. Topical application of PAP at concentrations up to 8.00 g/kg to the skin of New Zealand white (NZW) rabbits produced no skin irritation and no mortality. PAP, MAP, and OAP were irritating t o eyes of NZW rabbits at a concentration of 2.5%. MAP at 3% was nonsensitizing in guinea pigs; PAP at 2 % sensitized 9 of 10 guinea pigs. Neither PAP nor MAP produced photosensitization in guinea pigs. No treatment-related toxicity was found in three separate four-generation chronic dermal toxicity and reproduction studies of hair dye formulations containing the three Aminophenols. Additional studies on the pure ingredients were also nonteratogenic; embryotoxicity was reported.A range of results was obtained from studies assessing the mutagenic activity of the Aminophenols. PAP tested positive in six of eight mutagenicity tests. MAP and OAP gave positive results in two of eight and five of seven mutagenicity tests, respectively. Oxidative hair dye formulations containing PAP, MAP, and OAP did not produce gross or microscopic alterations or have carcinogenic effects after chronic topical application to mice. Feeding of OAP-HCI and PAP to rats at a dose of 8 mmol/kg produced neither hepatic cirrhosis nor neoplastic lesions. A 3% solution of MAP in an aqueous vehicle was neither a significant irritant nor sensitizer in t w o clinical studies. A variety of epidemiological studies have not indicated that occupational exposure to, and personal use of, hair dyes containing the Aminophenols presented a carcinogenic risk. A discussion of the significance of the mutagenic data in the safety assessment and the potential for human effects is presented. On the basis of the available animal and clinical data presented in this report it is concluded that p-, m-, and o-Aminophenols are safe as cosmetic ingredients in the present practices of use and concentrations. 279 at Bobst Library, New York University on May 16, 2015 ijt.sagepub.com Downloaded from 280 COSMETIC INGREDIENT REVIEW
CH EM1 STRYara-, meta-, and ortho-Aminophenols are the three possible isomers of a di-P substituted aminohydroxybenzene, with the empirical formula CsH,NO and molecular weight 109.1 2. These Aminophenols can be manufactured by the reduction of their corresponding isomeric nitrophenols.'') Cosmetic MAP is "an off-white to gray-green solid" available as a 98% pure material. It is soluble in 40 parts of cold water and freely soluble in hot water, alcohol, and ether. Manufactured by the reduction of rn-nitrophenol, cosmetic MAP contains no more than 0.02°/0 ash, 150 ppm iron, and trace amounts of water...
