Aminomethyl propanol and aminomethyl propanediol are substituted aliphatic alcohols that function as pH adjusters in cosmetic products at concentrations less than 10%; additionally, aminomethyl propanediol is a fragrance. Extensive oral toxicity data are reviewed, with fewer inhalation toxicity data. Dermal toxicity data are presented that demonstrate, for example, that a mascara with 1.92% aminomethyl propanediol does not cause dermal irritation or allergic contact sensitization, suggesting that the maximum reported use concentration of 2% in mascara would be safe. Although these ingredients are primary amines that are not substrates for N-nitrosation, they may contain secondary amines as impurities in finished products that may undergo N-nitrosation. These ingredients should not be included in cosmetic formulations containing N-nitrosating agents. The Cosmetic Ingredient Review Expert Panel concludes that aminomethyl propanol and aminomethyl propanediol are safe as cosmetic ingredients in the practices of use and concentrations as described in this safety assessment.
1. Elder RL. Final report on the safety assesment of aminomethyl-propanol and aminomethylpropanediol.J Am Coll Toxicol.1990;9:203–228.
2.
2. Elder RL. Final report on the safety assesment of diisopropanolamine, triisopropanolamine, isopropanalomine, and mixed isopro-panalomine.JACT.1987;6:53–76.
4. Gottschalk TE, McEwen GN Jr. International Cosmetic Ingredient Doctionary and Handbook. 11th ed.Washington, DC: Cosmetic, Toiletry, and Fragrance Association; 2006.
5.
5. Kroschwitz J. Kirk-Othmer Encyclopedia of Chemical Technology. 4th ed.New York, NY: John Wiley; 1999.
6.
6. Grasselli JC. Atlas of Spectral Data and Physical Constants for Organic compounds. Cleveland, Ohio: CRC Press; 1975.
7.
7. Estrin NF, Haynes CR, Whelan JM. CTFA Specifications/ Spectra. Washington, DC: Cosmetic, Toiletry, and Fragrance Association; 1982.
8.
8. Champion MH, Quast JF. Gas-liquid chromotagraphic identification and determination of alkanomalamines, 1: application to aerosol hair sprays.J Assoc Offic Anal Chem.1971;54:1175–1178.
9.
9. Angus Chemical Company. Information about impurities in aminomethyl propanol and aminomethyl propanediol. 2007. Unpublished data submitted by CTFA.
10.
10. International Minerals and Chemical Corporation (IMCC). Technical data sheet: the aminohydroxy compounds, NP Series. 1987. Unpublished data submitted by CTFA.
11.
11. Food and Drug Administration (FDA). Frequency of use of cosmetic ingredients. FDA database. 2007. Washington, DC: 2.F-06-18753. Submitted by FDA in response to FOI request F-06-18753.
12.
12. CTFA. Current use concentration: aminomethyl propanol and aminomethyl propanediol. 2007. Submission of unpublished data.
13.
13. CTFA. Aminomethylpropanol, aminomethylpropanediol: summary of unpublished safety data. 1981. Submission of unpublished data.
14.
14. Ministry of Health, Labor and Welfare (MHLW). MHW Ordinance 331, Appendix 1. List of ingredients that cosmetics shall not contain. Ministry of Health, Labor and Welfare, Pharmaceutical and Medical Safety Bureau, Inspection and Guidance Division, 2-2, 1-chome, Kasumigaseki, Chiyoda-ku, Tokyo 100-8045, Japan.
15.
15. Ministry of Health, Labor and Welfare. MHW Ordinance 331, Appendices 2-4. Restricted lists 2-2, 1 chome, Kasumigaseki, Chiyoda-ku, Tokyo 100-8045, Japan. 2005.
16.
16. European Union. 1976, Council Directive 1976/768/EEC of 27 July 1976 on the Approximation of the Laws of the Member States Relating to Cosmetic Products, as amended through Commission Directive 2003/83/EC. 2005. http://europa.eu.int/eur-lex/ lex/LexUriServ/site/en/consleg/1976/L/01976L0768-20050913-en. pdf. Accessed July 11, 2006.
17.
17. Jensen PA, O'Brien D. Industrial Hygiene. New York, NY: John Wiley; 1993.
18.
18. Bower D. Unpublished information on hair spray particle sizes provided at the September 9, 1999 CIR Expert Panel meeting. Washington, DC.
19.
19. Johnsen M. A. The influence of particle size.Spray Technology and Marketing.November 2004:24–27.
20.
20. O'Neil MJ. The Merck Index. 14th ed.Whitehouse Station, NJ: Merk; 2006.
21.
21. Reichmann KW, Petersen RV. Temperature studies with nonaqu-eous emulsions.J Pharm Sci.1973;62:1850–1856.
22.
22. Bennett ED. Andersen FA, Tavana C. Antimicrobial properties of butanolamines and propanolamines in metal working fluids.J Gen Appl Microbiol.1979;25:63–69.
23.
23. Code of Federal Regulations. Revised as of April 1, 2006. Title 21 Part 175.105. Indirect food additives: adhesives and components of coatings.
24.
24. Musial W, Kubis A. Preliminary evaluation of interactions between selected alcoholamines and model skin sebum components.Chem Pharm Bull.2006;54:1076–1081.
25.
25. Russell PJ, Greene ST, Mulford DJ. The effect of 2-amino-2-methylpropanol on rat-liver mitochondria.Biochim Biophys Acta.1965;98:445–453.
26.
26. Hume JW, Mulford DJ, Russell PJ. Effect of 3-amino-propanol on choline deficiency in rats.Proc Soc Exp Biol Med.1965;118:430–433.
27.
27. Yue KT, Mulford DJ, Russell PJ. Metabolism of 2-amino-methylpropanol in young rats.Arch Biochem Biophys.1970;136:47–53.
28.
28. Power C. Acute oral toxicity of P-1826 (AMP) in the rat (summary). Pharmacology Laboratories. Unpublished data submitted by Dow Chemical Company. 1973.
29.
29. CTFA. Acute oral toxicity study in albino rats of a hair spray containing 0.25% AMP. Study 77395-1. 1977. Unpublished data submitted by CTFA.
30.
30. CTFA. Acute oral toxicity study in albino rats of ahair spray containing 0.58% AMP. Study 77395-1. 1977. Unpublished data submitted by CTFA.
31.
31. CTFA. Acute oral toxicity in albino rats of a hair spray containing 0.59% AMP. Study 78391. 1979. Unpublished data submitted by CTFA.
32.
32. CTFA. Acute oral toxicity study in albino rats of cosmetic formulations containing 0.58, 0.59. and 0.58% AMP. Study 78435. 1979. Unpublished data submitted by CTFA.
33.
33. Bio-Test Laboratories. Results of acute oral toxicity study: aerosol spray containing AMPD. 1969. Unpublished data submitted by CTFA.
34.
34. Schafer E. W, Bowles W. A. Acute oral toxicity and repellency of chemicals to house and deer mice.Arch Environ Contam Toxicol.1985;14:111–129. Unpublished data submitted by CTFA.
35.
35. CTFA. Summary of toxicological data for AMP and AMPD. 1987.
36.
36. CTFA. Acute inhalation toxicity study in albino rats of a hair spray containing 0.59% AMP. Study 78391. 1979. Unpublished data submitted by CTFA.
37.
37. CTFA. Acute inhalation toxicity study of three cosmetic formulations containing AMP. Study 78435. 1979. Unpublished data submitted by CTFA.
38.
38. CTFA. Modified FHSA inhalation test-albino rats. Study 6003. 1980. Unpublished data submitted by CTFA.
39.
39. Detwiler-Okabayashi KA, Schaper MM. Respiratory effects of a synthetic metalworking fluid and its components. Arch. Toxicol.70(3-4):195–201.
40.
40. CTFA. Acute inhalation toxicity (FHSA) in rats of a hair spray containing 0.50% AMPD. Study A 3622. 1980. Unpublished data submitted by CTFA.
41.
41. Parekh C. Dermal toxicity of P-1826 (AMP) International Minerals and Chemical Corp. Unpublished data submitted by Dow Chemical Company. 1980.
42.
42. International Research and Development Corporation (IRDC). 1976. Eight week tolerance study in mice. Document no. 000231-000241. Submitted by FDA in response to FOI request no. F86-38214. 10 pages.
43.
43. IRDC. 1976. Eight week tolerance in rats. Document no. 000243-000255. Submitted by FDA in response to FOI request no. F86-38214. 12 pages.
44.
44. IRDC. 1976. Twenty eight day dietary range finding study in dogs. Document no. 000209-000229. Submitted by FDA in response to FOI request no. F86-38214. 21 pages.
45.
45. CTFA. Subacute inhalation toxicity study in albino rats of a hair spray containing 0.58% of AMP. Study 77395-1. 1977. Unpublished data submitted by CTFA.
46.
46. Albany Medical College. A 90-day safety evaluation study of 2-amino-2-methyl-1-propanol (AMP) in rats. Document 000257-000397. 1977. Submitted by FDA in response to FOI request no. F86-38214. 16 pages.
47.
47. Litton Bionetics, Inc. 1976. Mutagenicity evaluation of P-1826 (Lot 6C29-9B) final report. Document no. 000620-000628. Submitted by FDA in response to FOI request no. F86-38214. 8 pages.
48.
48. Parekh C. A three month in diet toxicity study of 2-amino-2-methyl-1-propanol in dogs. Report PLR-175. International Minerals and Chemical Corp. 1981. Unpublished data submitted by CTFA.
49.
49. Hazelton Laboratories. 90-day inhalation toxicity study of pump spray formulations in cynimolgus monkeys. Project 223-103. 1977. Unpublished data submitted by CTFA.
50.
50. CTFA. Subacute inhalation toxicity study in cynomolgus monkeys of a hair spray containing 0.21% AMP. Study A-6020. 1980. Submission of unpublished data.
51.
51. CTFA. Thirteen week subchronic inhalation toxicity study in albino rats. Project code 0161. 1981. Submission of unpublished data.
52.
52. CTFA. Thriteen week subacute inhalation toxicity study in the albino rat and golden hamster. N. B. Ref. SAI 75-2. 1975. Submission of unpublished data.
53.
53. Griffin T. B. A one-year oral toxicity study of AMP in dogs (summary). Coulston Research Inc. Unpublished data submitted by Dow Chemical Company. 1990.
54.
54. Cosmetic, Toiletry, and Fragrance Association (CTFA). Primary skin irritation study in rabbits. Test S6/114. 1974. Submission of unpublished data.
55.
55. CTFA. Acute primary skin irritation-albino rabbits. Study 6003. 1979. Submission of unpublished data.
56.
56. CTFA. Primary dermal irritation in rabbits of a hair spray containing 0.25% of AMP. Study 7779. 1977. Submission of unpublished data.
57.
57. CTFA. Primary dermal irritation in rabbits of a hair spray containing 0.58% AMP. Study 77395-1. 1977. Submission of unpublished data.
58.
58. CTFA. Primary dermal irritation in rabbits of a hair spray containing 0.59% AMP. Study 78435. 1979. Submission of unpublished data.
59.
59. CTFA. Primary dermal irritation in rabbits of cosmetic formulations containing 0.58, 0.59, and 0.58% AMP. Study 78435. 1979. Submission of unpublished data.
60.
60. CTFA. Primary skin irritation in rabbits of a formulation containing 0.22% AMP-95. Test 515-051. 1984. Submission of unpublished data.
61.
61. CTFA. Primary irritancy in rabbits of a foam hair groom containing 0.715% AMPD. Study A-2063. 1980. Submission of unpublished data.
62.
62. CTFA. Prmary irritancy in rabbits of a hair spray containing 0.50% AMPD. Study A-3665. 1980. Submission of unpublished data.
63.
63. International Minerals & Chemical Corporation (IMCC). Intradermal sensitization potential of AMP. Report PLR-265/AMR-103. 1982. Unpublished data submitted by CTFA.
64.
64. IMCC. Topical sensitization potential of AMP (P-1826). 1982. Unpublished data submitted by CTFA.
65.
65. Buehler E. V. Delayed contact hypersensitivity in the guinea pig.Arch Dermatol.1965;91:171–175.
66.
66. Power C. AMP Regular and AMP 95-eye irritation tests-rabbits (summary). Commercial Solvents Corp. Unpublished data submitted by Dow Chemical Company. 1975.
67.
67. CTFA. Ocular irritation in rabbits of a hair spray containing 0.25% AMP/ Study 7779. 1977. Submission of unpublished data.
68.
68. CTFA. Ocular irritation in rabbits of a hair spray containing 0.58% AMP. Study 77395-1. 1977. Submission of unpublished data.
69.
69. CTFA. Acute opthamalic irritancy-albino rabbits: Sprayed eyes. Study 6003. 1979. Submission of unpublished data.
70.
70. CTFA. Ocular irritation in rabbits of a hair spray containing 0.59% AMP. Study 78391. 1979. Submission of unpublished data.
71.
71. CTFA. Eye irritation potential of a cosmetic formulation containing 0.22% AMP-95. Test E56-216. 1984. Submission of unpublished data.
72.
72. MB Research Laboratories. Bovine corneal opacity and permeability test (BCOP). Project MB 05-13741.09. 2005. Unpublished data submitted by CTFA.
73.
73. CTFA. Acute eye irritancy in rabbits of a hair spray containing 0.40% AMPD. Study A-1421. 1980. Submission of unpublished data.
74.
74. CTFA. Acute eye irritancy of a foam hair groom containing 0.715% AMPD. Study A-2063. 1980. Submission of unpublished data.
75.
75. Carney EW, Quast JF, Zablotny C. L. 2-Methyl-2-aminopropanol hydrcloride: a reproduction/developmental toxicity screening test in CD rats. Toxicology & Environmental Research and Consulting. Unpublished data submitted by Dow Chemical Company. 2005.
76.
76. Carney EW, Thorsrud B. AMP: dermal development toxicity study in CRL:CD(SD) rats. Toxicology & Environmental Research and Consulting. Unpublished data submitted by Dow Chemical Company. 2006.
77.
77. Litton Bionetics, Inc. Mutagenicity evaluation of P-1826 (Lot 6C29-9B)(AMP). 1976.
78.
78. Wagner VO, Bonvillain AJ. Salmonella/Escherichia coli plate incorporation mutagenicity assay with a confirmatory assay (summary). Microbiological Associates, Inc. Unpublished data submitted by Dow Chemical Company. 1996.
79.
79. RCC NOTOX. Mutagenic activity of 2-amino, 2-methyl, 1,3-propanediol in the Ames Salmonella/microsome test. RCC NOTOX study ref. 1173/ES395. 1988. Unpublished data submitted by CTFA.
80.
80. San RHC, Clarke JJ. In vitro mammalian cell gene mutation test with an independent repeat assay (summary). Microbiological Associates, Inc. Unpublished data submitted by Dow Chemical Company. 1997.
81.
81. Gudi R. Mammalian erythrocyte micronucleus test (Summary). MA Bio Services, Inc. Unpublished data submited by Dow Chemical Company. 1998.
82.
82. CTFA. Skin irritation potential (human patch test) of a product containig 0.22% AMP-95. Test 5549-26. 1984. Submission of unpublished data.
83.
83. CTFA. Primary irritancy in humans of a hair spray containing 0.40% AMPD. Study G-245. 1980. Submission of unpublished data.
84.
84. CTFA. Allergic contact sensitization test. Test 355-85. 1985. Submission of unpublished data.
85.
85. TKL Research, Inc. Repeated insult patch study of a leave-in hair gel containing 3.8% aminomethyl propanol. 2000. Unpublished data submitted by CTFA.
86.
86. AMA Laboratories, Inc. 100 human subject repeat insult patch skin irritation/sesitization evaluation (semiocclusive patch). 2000. Unpublished data submitted by CTFA.
87.
87. Harrison Research Laboratories, Inc. Final report: repeated insult patch test. HRL panel 04-104. 2004. Unpublished data submitted by CTFA.
88.
88. Consumer Product Testing Co. Repeated insult patch test. Experiment C05-0646.01. 2005. Unpublished data submitted by CTFA.
89.
89. Harrison Research Laboratories, Inc. Final report: repeated insult patch test on a dyeless hair dye base containing 7% aminomethyl propanol. HRL panel 06-121. 2006. Unpublished data submitted by CTFA.
90.
90. Consumer Product Testing Co. Repeated Insult Patch Test. Experiment C05-1214.02. 2006. Unpublished data submitted by CTFA.
91.
91. Food and Drug Research Laboratories. Evaluation of dermal effects of a cosmetic formulation containing 0.073% AMPD: Repeated insult patch test. 1972. Unpublished data submitted by CTFA.
92.
92. Hill Top Research, Inc. Modified repeated insult patch test of a cosmetic formulation containing 0.50% AMPD. 1973. Unpublished data submitted by CTFA.
93.
93. Consumer Product Testing Co. Repeated insult patch test. Experiment C01-0066.02. 2001. Unpublished data submitted by CTFA.
94.
94. Cipolla C, Belisario A, and Sassi C. Airborne contact dermatitis from 2-amino-2-methyl-1-propanol in a cosmetic company.Arh Hig Rada Toksikol.1997;48:205–209.
95.
95. Gottschalk TE, McEwen GN Jr. International Cosmetic Ingredient Dictionary and Handbook. 11th ed.2006. Washington, DC: Cosmetic, Toiletry, and Fragrance Association.
96.
96. Lewis R. J. Hawley's Condensed Chemical Dictionary. 13th ed.New York, NY: John Wiley; 1997.
97.
97. Lewis R. J. Sax's Dangerous Properties of Industrial Materials. 10th ed.New York, NY: John Wiley; 2000.
