Download safety assessment of LAO and more Study Guides, Projects, Research Materials science in PDF only on Docsity!
Journal of the American College of Toxicology 13(3):231-245, Raven Press, Ltd., New York
Final Report on the Safety Assessment of
Lauramine Oxide and Stearamine Oxide
Summary: Lauramine Oxide and Stearamine Oxide are aliphatic tertiary amine oxides that are used mostly in hair care products as foam builders and stabi- lizers, viscosity enhancers, emollients, conditioners, emulsifiers, antistatic agents, and wetting agents. Both compounds are susceptible to nitrosation and can form nitrosamines in the presence of nitrosating agents. In rats, up to 40% of Lauramine Oxide applied to the skin was absorbed. In two human volun- teers, 92% of the dose applied to the skin was recovered from the skin. The oral LD,, in rats for a formulation containing 0.3% Lauramine Oxide was estimated to be >20 &g. At a concentration of 30%, Lauramine Oxide produced severe dermal reactions in rabbits, but at 0.3% only slight to moderate erythema with slight edema, fissuring, and slight to moderate epithelial desquamation were found. Stearamine Oxide applied to rabbit skin at 5% did not cause irritation. Both ingredients caused mild, transient ocular irritation in rabbits. Clinical data showed dermal exposure to 3.7% Lauramine Oxide to be a mild initant, with a slight potential for mild cumulative skin initation at concentrations as low as 2%. At 0.3%, Lauramine Oxide was not a sensitizer in clinical studies. Lau- ramine Oxide was nonmutagenic in the Ames assay, but was mutagenic after nitrosation. Lauramine Oxide at 0.1% in drinking water was not carcinogenic in rats, but at 0.1% with 0.2% sodium nitrate did increase the incidence of liver neoplasms. Based on this animal data, neither ingredient should contain N-ni- trow compounds nor be used in formulationscontaining nitrosating agents. On the basis of the available animal and clinical data, it is concluded that Lau- ramine Oxide and Stearamine Oxide are safe as cosmetic ingredients for rinse- off products, but that the concentration in Lauramine Oxide leave-on prod- ucts should be limited to 3.7% and that of Stearamine Oxide limited to 5%. Key Words: Safety assessment-Lauramine Oxide-Stearamine Oxide.
Lauramine Oxide and Stearamine Oxide are aliphatic tertiary amine oxides that are used in cosmetics as foam builders and stabilizers, viscosity enhancers, emol- lients, conditioners, emulsifiers, antistatic agents, and wetting agents.
CHEMISTRY Definition and Structure Lauramine Oxide is the aliphatic tertiary amine oxide that generally conforms to the structure (Estrin et al., 1982; Klein, 1981):
CH
I
I
CH3(CHJ11 - N + 0
CH,
232 COSMETIC INGREDIENT REVIEW
Synonyms for Lauramine Oxide (CAS No. 1643-20-5) are: N,N-dimethyl-1-
dodecanamine-N-oxide; 1-dodecanamine, N, N-dimethyl-, N-oxide; lauryl di- methyl amine oxide; dodecylamine, N, N-dimethyl, N-oxide; dimethyldodecy- lamine N-oxide; dodecyldimethylamine oxide; lauryldimethylamine oxide; and ammonyx LO (Estrin et al., 1982; Sweet, 1987). Stearamine Oxide is an aliphatic tertiary amine oxide with the following struc- ture (Estrin et al., 1982; Klein, 1981):
CH I
I CH
CH3(CH2)17-N --* 0
Other names for Stearamine Oxide (CAS No. 257 1-88-2)include: N,N-dimethyl-
1-octadecanamine-N-oxide; 1-octadecanamine, N,N-dimethyl-, N-oxide; stearyl
dimethylamine oxide; and ammonyx SO (Estrin et al., 1982; Sweet, 1987).
Properties
Lauramine Oxide is a clear, pale-yellow liquid that is typically 3040% active, and Stearamine Oxide is a pearly white paste that is formulated to be 25% active (Hunting, 1983). The physical properties of Lauramine Oxide and Stearamine Oxide are shown in Table 1. Both Lauramine Oxide and Stearamine Oxide are polar amine oxides that un- dergo hydrogen bonding. The dipole moment for the N-O bond is 4.38. Lauramine Oxide and Stearamine Oxide are hygroscopic and do not dry easily. Both com- pounds are stable in detergent formulations, and do not show any oxidizing prop- erties. However, Lauramine Oxide and Stearamine Oxide are susceptible to ni- trosation (Swern, 1979; Hunting, 1983). Studies of Lauramine Oxide and Stearamine Oxide indicate that these compounds have the potential to form car- cinogenic nitrosamines when ingested with nitrate (Lijinsky, 1982; Lijinsky et al., 1981). Lauramine Oxide and Stearamine Oxide have either nonionic or cationic prop-
TABLE 1. Chemical and physical properties Lauramine Oxide Stearamine Oxide References Molecular weight 229.46 313 Sweet (1987); Density 0.947 Smith (1987) Viscosity 60°C, 48 Smith (1987) pK, (1% solution) 3.6 Smith (1987) Solubility Water Ethanol, acetone; will Hunting (1983); disperse in water Smith (1987) Pour point (“C) 50 Smith (1987) Gel point (“C) 59 Smith (1987)
Smith (1987) (at 65°C (g/ml)) 10% aqueous (cp)
J Am Coll Toxicol, Vol. 13, No.3, 1994
234 COSMETIC INGREDIENT REVIEW
TABLE 2. Nitrosamine levels in Lauramine Oxide" Description NDMA (ppb) NAlkylMA Total (ppb) Lot 128: Sample A Sample B Lot 65: Sample A Lot 44: Sample A Sample B Detection limit
210 119 294 38 1 373 20
250 138 128 ND ND 80
460 257 422 381 373
NDMA, nitrosodimethylamine; NAlkylMA, nitrosoalkylmethylamine. a No data on nitrosamines in Stearamine Oxide are currently available.
sifiers, antistatic agents, and wetting agents (Klein, 1981 ; Nikitakis, 1988; Smith et al., 1987). The product formulation data submitted to the Food and Drug Administration (FDA) in 1992 reported that Lauramine Oxide and Stearamine Oxide were used in a total of nine and 37 cosmetic product formulations, respectively (Tables 3 and 4) (FDA, 1992). Concentration of use values are no longer reported to the FDA by the cosmetic industry (Federal Register, 1992). However, product formulation data submitted to the FDA in 1989 stated that Lauramine Oxide was used at concentrations < 1% in hair rinses, tonics, dressings, and other hair grooming aids, and at up to 10% in shampoos (FDA, 1989). Data submitted in 1984 indicated that Stearamine Oxide was used at up to 10% in hair conditioners and shampoos, and up to 5% in hair rinses and other skin care preparations (FDA, 1984).
International Lauramine Oxide and Stearamine Oxide solutions are approved for use in cos- metic products in Japan (Nikko Chemicals Co., Ltd., 1990).
Noncosmetic Use Lauramine Oxide and Stearamine Oxide are used as light duty liquid detergents, and oil sequestering agents in industry (Smith et al., 1987; Oyewo, 1986; Thorhaug and Marcus, 1987).
BIOLOGY
Absorption, Metabolism, Excretion, and Distribution
Two groups of four male and one group of four female Sprague-Dawley rats were given 100 mg/kg of [methyl-14C]LauramineOxide (specific activity 1.3 mCi/
g) or [l-d~decyl-'~C]Lauramine Oxide (specific activity 1 mCi/g) orally in a met-
abolic study. There were no significant differences in metabolism or distribution of the compounds between male and female rats. Approximately 75% of the total radioactivity was excreted within 24 h of oral administration. The rats eliminated 71 and 53% of the administered dose of [methyl-14C]LauramineOxide and [l- d~decyl-'~C]LauramineOxide, respectively, in their urine, 13 and 23% as 14C02, and 12 and 9% in their feces. Over two-thirds of the radioactivity expired as 14C
J Am CONToxicol. Vol. 13, No. 3, 1994
LA URAMINE OXIDEISTEARAMINE OXIDE 235
TABLE 3. Cosmetic product formulation data for Lauramine Oxide (FDA, 1992)" Total no. of (^) Total no. of Product category formulations in category formulations containing ingredient Hair rinses (noncolonng) 83 3 Hair shampoos (noncolonng) 953 3 Tonics, dressings, and other hair grooming aids 548 3 1992 totals 9 a CIR requests that the cosmetic industry provide current formulation data on each product cate- gory.
appeared within 12 h after administration of either dose. The largest concentration of radioactivity in the tissue was found in the liver. Radioactivity was also found in the kidneys, intestine, lungs, spleen, heart, pancreas, bone marrow, leg mus- cles, testes, ovaries, and whole blood (Rice, 1977). Aqueous [methyl-'4C]Lauramine Oxide (10 mg containing 1.3 mCi/g) was ap- plied to the skin of four Sprague-Dawley rats to test metabolism and absorption
of the compound. Over 72 h, 14.2% of the total radioactivity was found in the
urine, 2.5% in the CO,, and 1.8% in the feces. Radioactivity was detected in the liver, kidneys, testes, blood, and expired CO, (Rice, 1977). In a similar study, aqueous [meth~l-'~C]Lauramine Oxide (10 mg containing 13 pCi radioactivity) was applied to the skin of four rats. Approximately 40% of the total radioactivity was absorbed through the skin. Fourteen percent of the radio- activity was excreted in the urine, 2.5% was recovered as I4CO2,and 1.8% was eliminated in the feces (Drotman, 1977). Four Sprague-Dawley rats were given intraperitoneal injections of 22 mg [meth- yl-14C]LauramineOxidekg (specific activity 1.3 mCi/g). Sixty-seven percent of the total radioactivity was eliminated in the urine, 8% was expired as I4CO2,and 6% was eliminated in the feces within 24 h. The distribution of radioactivity was essentially the same as that seen in rats given oral doses of Lauramine Oxide. The conclusion was that "... microbial metabolism by gastrointestinal flora does not play a major role in the absorption and excretion of [Lauramine Oxide] in rats" (Rice, 1977).
Oral administration of a solution containing 50 mg [l-d~decyl-'~C]Lauramine
Oxide (100 pCi of 14C)to two humans resulted in excretion patterns of radioac-
TABLE 4. Cosmetic product formulation data for Stearamine Oxide (FDA, 1992)" Total no. of (^) Total no. of Product category formulations in category formulations containing ingredient Hair conditioners 666 18 Hair rinses (noncolonng) 83 5 Hair shampoos (noncolonng) 953 9 Other skin care preparations 848 5 1992 totals 37 ~ CIR requests that the cosmetic industry provide current formulation data on each product cate- gory.
J A m Coll Toxicol, Vol. 13, No. 3, 1994
LAURAMINE OXIDEISTEARAMINE OXIDE 237
SpragueDawley-derived rats were exposed for 4 h to this aerosol at a concen-
tration of 5.3 mg/L. The Equivalent Aerodynamic Diameter of the aerosol was 3. pm with a geometric standard deviation of 1.91. The animals were observed during the exposure and two times daily for 14 days, and body weights were recorded before exposure and on days 1 , 3 , 7 , and I4 postexposure. At necropsy, the major organs in the abdominal and thoracic cavities were weighed and ob- served. No deaths occurred during the study and all the rats appeared normal. A slight drop in body weight was observed in the males on day 1, but weight was gained normally for the remainder of the study. The weight gain in the females was normal. The organ weights were all within the anticipated normal control ranges for both sexes. No exposure-related pharmacotoxic signs were evident in any of the organs. The 4-h LDSofor this aerosol was greater than 5.3 mg/L nominal (International Research and Development Corporation, 1990a). The potential for this same formulation to produce upper airway irritation in mice was also studied. Liquid droplet aerosols at concentrations of 0.2, 1.0, and 5.2 mg/L were tested on three groups of four male Swiss-Webster mice. Only the heads of the mice were exposed to the aerosol. The average respiratory rate was monitored using plethysmography 5 min before, 10 min during, and 10 min after each exposure, and the percentage change in respiratory rate was calculated. A decrease in respiratory rate was considered a response to upper airway irritation. A transient decrease was observed in the respiratory rate of the 1.0 mg/L exposed group, but this was not considered significant because no signs of irri- tation were seen at greater exposure concentrations. The groups treated with 1 .O mg/L and 5.2 mg/L had a 6% decrease in their average respiratory rates. How- ever, these decreases were not attributed to upper airway imtation because the respiratory rates were even lower during the postexposure recovery period. No decrease in respiratory rate was observed in the 0.2 mg/L exposed mice (Inter- national Research and Development Corporation, 199Ob).
Subchronic Dermal Toxicity
New Zealand White rabbits were used to assess the cutaneous and systemic toxicity of a formulation containing 0.3% active Lauramine Oxide. The abraded skin of five female and five male rabbits was exposed to the formulation five times a week for 4 weeks. The dosage was 2 ml/kg/day. A control group of five female and five male rabbits was exposed to distilled water. All animals survived to
termination. No significant differences in mean body weights, body weight
changes, clinical observations, mean absolute organ weights, or organ-to-body weight ratio between the treated and control groups were observed. Lauramine Oxide caused slight to moderate erythema in female rabbits, and both male and female rabbits had slight edema, atonia, and fissuring, and slight to moderate desquamation. Histologically, both groups had a high incidence of subacute in- flammation in the treated skin. The lesions were described as “... minimal infiltrations of lymphocytes with a few neutrophils and plasma cells in the super- ficial dermis.” Two cases of epidermal acanthosis, one case of crusting, and one
J Am Coll Toxicol, Vol. 13, No. 3, 1994
238 COSMETIC INGREDIENT REVIEW
case of superficial dermal hemorrhage were also observed (Hazelton Laboratories America, Inc., 1990).
Dermal Irritation
The primary dermal irritation potential of three formulations, each containing 30% Lauramine Oxide, was evaluated using New Zealand White rabbits. Three
male and three female rabbits had 0.5 ml of each formulation applied under oc-
clusive patches to separate sites on their clipped backs for 24 h. The sites were rinsed after patch removal and were scored for erythema, eschar, and edema at the time of removal and 48 h later. The primary dermal indices (maximum possible score: 8) were 7.0, 7.2, and 7.6. Moderate to severe erythema and edema, two cases of necrosis, and one case of necrosis and fissuring with bleeding were observed at the 24-h grading period. At the 72-h reading, there was severe ery- thema and edema, eschar, fissuring with bleeding, and necrosis and/or thickened skin (Ricerca, Inc., 1988). The dermal imtation potential of Stearamine Oxide was conducted on albino rabbits in accordance with the Code of Federal Regulations 21, Part 191.1 (g) (2), 191.11. Patches of 5% active Stearamine Oxide (0.5 ml) were applied to the intact and abraded skin of six rabbits for 24 h. The application sites were graded at the
time of removal and 48 h later. No signs of irritation were observed at any time
during the study (Leberco Laboratories, 1973). Like et al. (1975) reported that Stearamine Oxide (5% active) was not a primary irritant when tested using the methods of Draize (1959).
Ocular Irritation The ocular irritation potential of formulations containing 0.3% active Lau- ramine Oxide was evaluated by instilling 10 p 1 into the conjunctival sac of New Zealand White rabbits. The eyes of some rabbits were rinsed with distilled water. Irritation was scored according to the method of Draize (1959)(maximum possible score: 110). Slight irritation of the conjunctivae was observed in all unrinsed eyes and in two of three rinsed eyes at the 24-h grading period. The maximum average score was 2.0 for the animals with unrinsed eyes, and 1.3 for those whose eyes were rinsed. All eyes were clear after 48 h (Springborn Life Sciences, Inc., 1987). In other studies using Lauramine Oxide, no imtation was observed. The max- imum average score was 0 for both the rinsed and unrinsed eyes (Oak Ridge Research Institute, 1989b; Hazelton Laboratories America, Inc., 1986). Stearamine Oxide was tested for ocular imtation according to the methods of Draize (1959). A 5% active sample of Stearamine Oxide (pH 7.5, dose 0.1 ml) was instilled into the conjunctival sac of three albino rabbits. The eyes were examined 24, 48, and 76 h after instillation. Minimal eye irritation was reported. At the 24-h grading period, two of the rabbits had redness of the conjunctiva, and one of these also had chemosis. The average eye irritation score was 2.67. No imtation was seen after 24 h (Industrial Biology Laboratories, Inc., 1963). Like et al. (1975) reported that Stearamine Oxide (5% active) was not an ocular irritant when tested using the methods of Draize (1959).
J A m Coll Toxicol, Vol. 13, No. 3 , 1994
240 COSMETIC INGREDIENT REVIEW
Lauramine Oxide with sodium nitrite in the drinking water of male rats “... results in the formation of at least one carcinogenic nitrosamine which is respon- sible for the increased incidence of liver neoplasms.”
The carcinogenicity of the nitrosation products of Lauramine Oxide (ni-
trosodimethylamine, N-nitroso-N-methyldodecylamine and N-nitroso-N-
methyltetradecylamine) has been documented in studies by The National Re- search Council, Committee on Nitrite and Alternative Curing Agents in Food (1981); Ketkar et al. (1981); Lijinsky et al. (1981); Cardy and Lijinsky (1980); Althoff and Lijinsky (1977); Lijinsky and Taylor (1975); and Magee and Barnes (1956).
CLINICAL ASSESSMENT OF SAFETY Dermal Irritation
The irritancy of Lauramine Oxide was tested using ten volunteer subjects. Each
subject was patch tested with a 3.7% aqueous solution of Lauramine Oxide. Five
of the tested individuals had mild irritation 48 h after exposure. These subjects were exposed a second time in an open test, and no irritation occurred (Muston et al., 1977). The cumulative irritancy potential of Lauramine Oxide was also tested. Ten subjects had 1.0, 2.0, 3.0, 4.0, and 5.0% Lauramine Oxide applied to their backs on Monday, Wednesday, and Friday for 48 h. A total of three consecutive appli- cations was made. The sites were scored at the time of each patch removal. Scoring was based upon a standardized interpretation system for ten panelists’ irritation scores for 21 days, which was modified to account for three applications rather than 21. Scores were determined by totalling the three observation scores for each site. The maximum possible score was 90. The authors classified 1.0% Lauramine Oxide as having no cumulative irritation with a score of 4.5. At con- centrations of 2.0, 3.0,4.0, and 5.0%, Lauramine Oxide had cumulative irritation scores of 10.5, 11.5, 15.0, and 24.0, respectively, which were considered evidence of a slight potential for very mild cumulative irritation (In Vitro Alternatives, IRC., 1992a).
Dermal Sensitization
A formulation containing 0.3% active Lauramine Oxide was diluted to a 50% (w/v) solution with distilled water and was tested for allergic contact sensitization potential using repeated occlusive patch application procedures. Patches with 0. ml of the diluted formula were applied every Monday, Wednesday, and Friday for
3 weeks to the lateral surface of the upper arm.The 101 participants removed the
patches 24 h after application, and the patch sites were graded before the appli- cation of the new patch. The challenge patches were applied -17 days after the last induction application, and the sites were graded 48 and 96 h after patch removal. Twenty-four of the participants had reactions during the induction phase of the test. Of these, 14 had single reactions, seven had two reactions, one had four
J Am Coll Toxicol, Vol. 13, No. 3, 1994
LA URAMINE OXIDEISTEARAMINE OXIDE 241
reactions, and two had six reactions. All of the reactions during the induction phase were described as Grade 1, very mild erythematous responses. In addition, two of these participants had barely perceptible reactions at the original patch sites during the challenge phase (one during the 48-h grading, and the other at both the 48- and 96-h grading periods). The formulation containing Lauramine Oxide did not cause sensitization (Harris Laboratories, Inc., 1987). Using the same methodology with 84 volunteers, another formulation contain- ing 0.3% active Lauramine Oxide was diluted to a 50% aqueous (wlv) solution and was tested for its skin sensitization potential. Slight irritation was observed in nine individuals during the induction phase. During the challenge phase, four partici- pants had slight erythema (one at the original patch site, and three on the alternate site) at the 48-h grading period, and only one individual had mild irritation at the original site during the 96-h grading period (CTFA, 1986). Standard repeat insult patch methodology also was used to study another cos- metic formulation containing 0.3% active Lauramine Oxide. Occlusive patches containing 0.3 ml of a 10% (w/v) solution of this formulation with distilled water were applied to the skin of 107 individuals for 24 h. During the challenge phase, four individuals had mild erythema, and one had both erythema and mild edema. This latter individual was rechallenged at both the original and alternate sites. Patches of distilled water and 0.5% sodium lauryl sulfate were also applied at these sites to serve as negative and positive controls, respectively. All the patches were applied for 24 h and the sites were scored 48 and 96 h after application. The subject had mild erythema at the original and alternate patch sites treated with the experimental sample, and at the alternate site of the positive control sample at the 48-h grading period. All signs of irritation disappeared by 96 h. Consequently, no evidence of delayed contact hypersensitivity to this formulation was observed (Hill Top Research, Inc., 1989). In a similar study, 141 subjects were tested with 1.5% Lauramine Oxide during the first six induction exposures, and with 0.75% Lauramine Oxide for the last three induction exposures and for the challenge exposure. The concentration of Lauramine Oxide was reduced because several of the participants had mild irri- tation. The application sites were scored (on a scale of G3) 48 and 96 h after the challenge exposure. At the 48-h reading period, 46 individuals received scores of 0.5, 12 received scores of 1, and two received scores of 2. At the 96-h reading, six individuals had scores of 0.5. According to the authors, these scores were the same as those observed during induction, and were indicative of primary and cumulative irritation rather than a delayed reaction. Lauramine Oxide was not considered a sensitizer under these test conditions (In Vitro Alternatives, Inc., 1992b).
SUMMARY Lauramine Oxide and Stearamine Oxide are used in cosmetics as foam builders and stabilizers, viscosity enhancers, emollients, conditioners, emulsifiers, anti- static agents, and wetting agents. Lauramine Oxide was reported to contain up to 460 ppb of carcinogenic N-nitrosamines. Data regarding the contamination of Stearamine Oxide with such impurities were not available.
J Am Coil Toxicol. Vol. 13, NO. 3, 1994
LA URAMINE OXIDEISTEARAMINE OXIDE 243
safe as cosmetic ingredients for rinse-off products under present conditions of
use. For use in leave-on products, the Expert Panel concludes that Lauramine Oxide should be limited to 3.7% and Stearamine Oxide to 5%.
Acknowledgment: Susan N. J. Pang, Scientific Analyst and Writer, prepared this report.
REFERENCES
Althoff J, Lijinsky W. (1977) UMary bladder neoplasms in Syrian hamsters after administration of N-nitroso-N-methyl-N-dodecylamine. Z Krebsforsch 90:227-3 I. Ames BN, McCann J, Yamasaki E. (1975) Methods for detecting carcinogens and mutagens with the Salmonellalmammalian-microsome mutagenicity test. M u m Res 3 1 :347-64. Andrews AW, Thibault LH, Lijinsky W. (1978) The relationship between mutagenicity and carcino- genicity of some nitrosamines. Mutarion Res 51:3 1%26. Andrews AW, Lijinsky W, Snyder SW. (1984) Mutagenicity of amine drugs and their products of nitrosation. Muiat Res 135:105-8. Cardy RH, Lijinsky W. (1980) Comparison of the carcinogenic effects of five nitrosamines in guinea pigs. Cancer Res 403187944. Challis BC, Fine DH, Goff EU, Hoffman GA, Shuker DEG. (1982) Amine nitrosation and nitrosation by gaseous nitrogen dioxide. In: Bartsch H, Oneil IK, Castegnaro M, Okada M, eds. N-nitroso compounds: occurrence and biological effecis. Lyon, France: International Agency for Research on Cancer. 11-20. [IARC Scientific Publication No. 41.1 [Secondary reference from NRC (1983)l. Cosmetic, Toiletry, and Fragrance Association (CTFA). (1986) Submission of unpublished data by CTFA. Human sensitization test of mousse VT formula without propellant. Study no. 8609-4.; Devinsky F. (1985) Amine oxides. X. Non-aromatic amine oxides: physico-chemical properties and some characteristic reactions. Acta Fac Pharm Univ. Comenianae 39: 173-96. Draize JH. (1959) Dermal toxicity. In: Staff of the Division of Pharmacology of the Federal Food and Drug Administration, eds. Appraisal of the safefy of chemicals in foods, drugs and cosmetics. Austin, TX: Association of Food and Drug Officials of the United States, 6 5 9. Drotman RB. (1977) Metabolism of cutaneously applied surfactants. Proc. Third Conf. Cutaneous Toxicity, Washington, DC, May 1618,1976. In: Curaneous Toxicity. Drill VA, Lazar P, eds. New York: Academic Press, 95-109. Estrin NF, Crosley PA, Haynes CR, eds. (1982) CTFA cosmetic ingredient diciionary, 3rd ed. Wash- ington, D.C.: Cosmetic, Toiletry and Fragrance Assoc., Inc., 153, 301. Federal Register. (January 28, 1992). Modification in voluntary filing of cosmetic product ingredient and cosmetic raw material composition statements. Final rule. 57:3128-30. Food and Drug Administration. (1984) Cosmetic product formulation data: ingredients used in each product category. Washington, DC. Food and Drug Administration. (1989) Cosmetic product formulation data: ingredients used in each product category. Washington, DC. Food and Drug Administration. (1992) Frequency of use data. Washington, DC. Harris Laboratories, Inc. (1987) Submission of unpublished data by CTFA. Human sensitization test [of a formulation containing 0.3% Lauramine Oxide]. Project no. 10821.; Hazelton Laboratories America, Inc. (1985) Submission of unpublished data by CTFA. Up and down procedure for estimating acute oral toxicity (LD50) in rats of G0955.01 [foam formulation con- taining 0.3% Lauramine Oxide] and G0932.01 [liquid formulation containing 0.3% Lauramine Oxide]. Sample no. 60803842.* Hazelton Laboratories America, Inc. (1986) Submission of unpublished data by CTFA. Rabbit eye irritation (Low volume procedure) of G0955.01 [foam formulation containing 0.3% Lauramine Oxide] and G0932.01 [liquid formulation containing 0.3% Lauramine Oxide]. Sample no. 60803843.; Hazelton Laboratories America, Inc. (1990) Submission of unpublished data by CTFA. 28-day sub- chronic percutaneous toxicity study in rabbits with (32926.02 [formulation containing 0.3% Lau- ramine Oxide]. Study no. 297-570.; Hecht S S , Momson JB, Wenninger JA. (1982) N-nitroso-N-methyldodecylamine and N-nitroso-N- methyltetradecylamine in hair-care products. Food Chem Toxicol 20: 165-9.
J Am Coll Toxicol, Vol. 13. No. 3, 1994
244 COSMETIC INGREDIENT REVIEW
Hill Top Research, Inc. (1989) Unpublished data submitted by CTFA. Human repeated insult patch test [of a formulation containing 0.3% Lauramine Oxide]. Report no. 89-0043-73D.* Hunting AL. (1983) Encyclopedia of shampoo ingredients. Cranford, N.J.: Micelle Press, 138-9, 268-9, 376. Industrial Biology Laboratories, Inc. (1963) Unpublished data submitted by CTFA. Rabbit eye i m - tation study [of 5% Stearamine Oxide].* Inoue K, Sunakawa T, Takayama. (1980) Studies of in vitro cell transformation and mutagenicity by surfactants and other compounds. Food Cosmet Toxicol. 18:28%96. International Research and Development Corporation. (1990a) Submission of unpublished data by CTFA. Acute inhalation toxicity in rats [from a formulation containing 0.3% Lauramine Oxide]. Study no. 191-1447.* International Research and Development Corporation. (199Ob) Submission of unpublished data by CTFA. Evaluation of the upper airway irritation potential of a test material [0.3% Lauramine Oxide]. Study no. 191-1448.* In Vitro Alternatives, Inc. (1992a) Submission of unpublished data by CTFA. Human cumulative irritation. Three patch application test.* In Vitro Alternatives, Inc. (1992b) Submission of unpublished data by CTFA. Human repeated insult patch test.* Ketkar MB, Althoff J, Lijinsky W. (1981) The carcinogenic effect of nitrosomethyldodecylamine in European hamsters. Cancer Lerr 13:165-8. Klein K. (1981) Amine oxides in cosmetic formulations. Drug Cosmet Ind 129 (JuIy):38, 40, 42. Leberco Laboratories. (1973) Unpublished data submitted by CTFA. [Dermal imtation study of 5% active Lauramine Oxide].* Leberco Testing Inc. (1985) Unpublished data submitted by CTFA. [Acute oral toxicity study of a 20% dilution of Lauramine Oxidel.* Lijinsky W, Taylor HW. (1975) Induction of urinary bladder tumors in rats by administration of nitrosomethyldodecylamine. Cancer Res 35:958-61. Lijinsky W, Saavedra JE, Reuber MD. (1981) Induction of carcinogenesis in Fischer rats by methyl- alkylnitrosamines. Cancer Res 41: 1288-92. Lijinsky W. (1982) Carcinogenesis by exposure to nitrites and amines. In: Magee PN, ed. Banbury Report, Vol. 12. Nitrosamines and human cancer; Meeting X V l. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory 257-70. Lijinsky W. (1984) Induction of tumors in rats by feeding nitrosatable amines together with sodium nitrite. Food Chem Toxicol22:715-20. Like B, Somentino R, Petrocci A. (1975) Utility of amine oxides in oiI/water cosmetic systems. J Soc Cosmet Chem 26:155-68. Magee PN, Barnes JM. (1956) The production of malignant primary hepatic tumours in the rat by feeding dimethylnitrosamine. Br J Cancer 10: 114-22. Muston HL, Boss JM, Summerly R. (1977) Dermatitis from Ammonyx LO, a constituent of a surgical scrub. Contact dermatitis. 3:347-8. National Research Council, Committee on Nitrite and Alternative Curing Agents in Food. (1981) The health effects of nitrate, nitrite, and N-nitroso compounds. Washington, D.C.: National Academy Press. [Secondary reference from NRC, 19831. National Research Council. (1983) An assessment of the health risks of morpholine and diethylami- noethanol. Prepared for the Army Medical Research and Development by the Committee on Toxicology contract DAMD-17-82-C-3028. NTIS No. PB85-122661. Nikitakis J, ed. (1988) CTFA Cosmetic Ingredient Handbook, 1st edition. Washington, D.C.: Cos- metic, Toiletry and Fragrance Assoc., Inc., 246, 397. Nikko Chemicals Co., Ltd. (1990) The newest list of Japanese cosmetic ingredients '89/'90. Tokyo: Nikko Chemicals Co., Ltd. Oak Ridge Research Institute. (1989a) Submission of unpublished data by CTFA. Acute oral toxicity (LD50) [of 0.3% Lauramine Oxide] in rats. Test no. 089-0116.; Oak Ridge Research Institute. (1989b) Submission of unpublished data by CTFA. Rabbit eye imtation (Low volume procedure) [of 0.3% Lauramine Oxide]. Test no. 089-0117.: Oyewo EO. (1986) The acute toxicity of three oil dispersants. Environ Pollut Series A 41:23-31. Rice DP. (1977) The absorption, tissue distribution, and excretion of dodecyldimethylamine oxide (DDAO) in selected animal species and the absorption and excretion of DDAO in man. Toxicol Appl Pharmacol39:377-89. Ricerca, Inc. (1988) Submission of unpublished data from CTFA. Comparative dermal irritation screen
J Am CON Toxicol, Vol. 13, No. 3, 1994
