Final Report on the Safety Assessment of Methyldibromo Glutaronitrile

1996 ◽  
Vol 15 (2) ◽  
pp. 140-165 ◽  
Keyword(s):  
Guinea Pig ◽  
Safety Assessment ◽  
Developmental Toxicity ◽  
Final Report ◽  
Dermal Toxicity ◽  
Thyroid Glands ◽  
Cosmetic Formulations ◽  
Halogen Compound ◽  
Thyroid Hyperplasia ◽  
Mammalian System

The halogen compound Methyldibromo Glutaronitrile is used in a wide variety of cosmetics as a preservative. Concentrations in cosmetic formulations reportedly range from 0.0075 to 0.06%. The oral LD50 in rats is 640 mg/kg. Dogs on a diet of 4,000 ppm Methyldibromo Glutaronitrile for 13 weeks developed thyroid hyperplasia; those on a diet of 167 ppm exhibited no hyperplasia, although the thyroid glands were enlarged. Application of Methyldibromo Glutaronitrile at a level of 4.0 g/kg to the skin of rats for 21 days produced severe irritation. A concentration of 0.025% applied to the skin of rabbits in a 28-day dermal toxicity study resulted in only slight to moderate irritation. No evidence of sensitization was found in guinea pig studies, nor was photosensitization reported in mouse studies. No reproductive or developmental toxicity was noted in two rat studies. Methyldibromo Glutaronitrile was not mutagenic in a series of mammalian system tests. Clinical data using repeat insult patch testing (HRIPT) methods indicated that concentrations as low as 0.025% produced a positive reaction in a few individuals. To limit the possibility that formulations containing this ingredient will lead to sensitization, it was concluded that leave-on formulations should contain 0.025% Methyldibromo Glutaronitrile. Rinse-off formulations, because the duration of exposure is much less, are considered safe as currently used

Final Report on the Safety Assessment of Dimethyl Stearamine

1995 ◽  
Vol 14 (6) ◽  
pp. 428-432
Keyword(s):  
Safety Assessment ◽  
Developmental Toxicity ◽  
Final Report ◽  
Inhalation Toxicity ◽  
Dermal Toxicity ◽  
Ocular Irritation ◽  
Dermal Irritation ◽  
Safety Test ◽  
Mammalian System ◽  
Additional Safety

Dimethyl Stearamine is a tertiary aliphatic amine that is used as an antistatic agent in cosmetics at concentrations up to 5%. Bacterial studies suggest antibacterial action at concentrations as low as 3.6 moles per 106. Mutagenicity testing was negative, even though the ingredient can act as a biocide. Additional safety test data are needed, including concentration of use, impurities, inhalation toxicity (or information on particle size), ocular irritation, dermal irritation and sensitization, and a 28-day dermal toxicity study (possibly followed by absorption, distribution, and metabolism studies). Additionally, if significantly absorbed, reproduction and developmental toxicity (including teratogenicity) data and two genotoxicity assays, one using a mammalian system, are needed. If the mutagenesis data are positive, then a dermal carcinogenesis study may be needed. In the absence of this further information, the available data are insufficient to support the safety of Dimethyl Stearamine in cosmetics.

Final Report on the Safety Assessment of PPG-9, -25, and -40 Diethylmonium Chloride

1999 ◽  
Vol 18 (3_suppl) ◽  
pp. 57-59
Author(s):  
F. Alan Andersen
Keyword(s):  
Additional Data ◽  
Developmental Toxicity ◽  
Dermal Absorption ◽  
Clinical Test ◽  
Final Report ◽  
Test Results ◽  
Dermal Toxicity ◽  
Carcinogenicity Study ◽  
Cosmetic Formulations ◽  
Mammalian System

PPG-9, -25, and -40 Diethyhnonium Chloride are quaternary ammonium salts that function as antistatic agents in cosmetic formulations. Only PPG-9 and -25 Diethylmonium Chloride are reported to be used. Neither animal test data nor clinical test results were available. No data were provided in response to requests of interested parties to supply the needed data. Accordingly, the available data are insufficient to support the safety of these ingredients in cosmetics. The additional data needed include: (1) current concentration of use; (2) dermal absorption using PPG-9 Diethylmonium Chloride; if significantly absorbed, then a 28-day dermal toxicity study will be needed; (3) two genotoxicity assays, at least one in a mammalian system, of PPG-9 Diethyhnonium Chloride; if positive, then a 2-year dermal carcinogenicity study using NTP methods may be needed; (4) human skin sensitization and irritation at concentration of use; and (5) impurities data, especially nitrosamines. Depending on the findings in these studies, additional data such as reproductive and developmental toxicity may be needed.

2 Final Report on the Safety Assessment of Dilauryl Thiodipropionate

1992 ◽  
Vol 11 (1) ◽  
pp. 25-41 ◽  
Keyword(s):  
Guinea Pig ◽  
Safety Assessment ◽  
Lauryl Alcohol ◽  
Final Report ◽  
Cosmetic Products ◽  
Dermal Toxicity ◽  
Safety Test ◽  
Human Volunteers ◽  
Test Concentration ◽  
Rats And Mice

Dilauryl Thiodipropionate (DLTDP) is the diester of lauryl alcohol and 3,3′-thiodipro-pionic acid which is used as an antioxidant and sequestering agent in cosmetics at concentrations up to 1%. When administered orally to rats and mice, DLTDP was slightly toxic and was relatively nontoxic in subchronic oral studies with rats. No irritation was produced by a formulation containing 0.05% DLTDP when tested at 0.0025% on intact and abraded skin. DLTDP was nonmutagenic in four different assay systems. This cosmetic ingredient was not a teratogen or reproductive toxicant in oral studies in mice, rats, hamsters or rabbits. A formulation containing 0.05% DLTDP when tested at 0.05% was not a sensitizer in a guinea pig maximization test. DLTDP, at a concentration of 0.05% in a makeup foundation, was not an irritant, sensitizer, or phototoxin when tested on human volunteers. The maximum reported safety test concentration used in dermal toxicity of DLTDP was 0.05%. The report limits its safety conclusion by concluding that DLTDP is safe for use in cosmetic products at the maximum dermal tested concentration of 0.05%.

Final Report on the Safety Assessment of Isostearamidopropyl Morpholine Lactate

1999 ◽  
Vol 18 (3_suppl) ◽  
pp. 51-56 ◽  
Author(s):  
F. Alan Andersen
Keyword(s):  
Developmental Toxicity ◽  
Metabolic Activation ◽  
Skin Penetration ◽  
Toxicity Study ◽  
Final Report ◽  
Inhalation Toxicity ◽  
Oral Toxicity ◽  
Rabbit Skin ◽  
Cosmetic Formulations ◽  
Mammalian System

Isostearamidopropyl Morpholine Lactate is the lactic acid salt of isostearamidopropyl morpholine used as an antistatic agent in 20 cosmetic formulations, mostly hair preparations. The concentration of use in hair preparations is in the 1-5% range- Isostearamidopropyl Morpholine Lactate was nontoxic in acute oral toxicity studies in rats. Although Morpholine is considered a cutaneous, ocular, and mucous membrane irritant, and a sensitizer, Isostearamidopropyl Morpholine Lactate exhibits none of the sensitization and irritant reactions observed with Morpholine. Isostearamidopropyl Morpholine Lactate was minimally irritating to rabbit eyes, and mildly irritating to intact and abraded rabbit skin. Although sensitization was not seen in clinical tests, some irritancy was noted. Isostearamidopropyl Morpholine Lactate was not mutagenic in the Ames test, with or without metabolic activation, although cell killing was seen at most test concentrations. Although Morpholine is readily nitrosated to form carcinogenic nitrosamines, N-nitroso impurities were not detected in Isostearamidopropyl Morpholine Lactate. Mutagenicity data on Isostearamidopropyl Morpholine Lactate in a mammalian system were not available, nor were data available on skin penetration or toxicity associated with inhalation exposures. Accordingly, the safety of this ingredient in leave-on cosmetic formulations could not be determined. Based on the available data, this ingredient was considered safe for use in rinse-off cosmetic products. Additional data needed for assessing the safety of leave-on uses include: (i) skin penetration; if there is significant skin penetration, then both a 28-day dermal toxicity study to assess general skin and systemic toxicity, and a reproductive and developmental toxicity study are needed; (ii) one genotoxicity study in a mammalian system; if positive, then a 2-year dermal carcinogenesis study using National Toxicology Program (NTP) methods may be needed; and (iii) inhalation toxicity data.

scholarly journals Final Report on the Safety Assessment of Glyceryl Stearate and Glyceryl Stearate/SE

1982 ◽  
Vol 1 (4) ◽  
pp. 169-192 ◽  
Keyword(s):  
Adverse Effects ◽  
Safety Assessment ◽  
Mouse Skin ◽  
Toxicity Tests ◽  
Final Report ◽  
Acute Oral Toxicity ◽  
Dermal Toxicity ◽  
Oral Toxicity ◽  
Patch Tests ◽  
Cosmetic Formulations

Glyceryl Stearate and Glyceryl Stearate/SE are the esterification products of glycerine and stearic acid, and are used in cosmetic formulations as emollients, emulsifiers, and stabilizers. In acute oral toxicity studies in rats, both ingredients were slightly toxic. Glyceryl Stearate in the diet of rats for three consecutive generations had no adverse effects. Five percent Glyceryl Stearate did not promote the carcinogenicity of DMBA in mouse skin. In subchronic and chronic dermal toxicity tests, Glyceryl Stearate was nontoxic to rabbits but did cause moderate irritation. Primary eye irritation studies, at concentrations up to 100%, were mildly irritating or nonirritating to rabbits. Single and Repeated Insult Patch Tests showed both ingredients to be nonsensitizing and nonirritating. Products containing 2% Glyceryl Stearate were nonphototoxic and nonphotoallergenic. On the basis of the available data, it is concluded that Glyceryl Stearate and Glyceryl Stearate/SE are safe for topical application to humans in the present practices of use and concentration.

Final Report on the Safety Assessment of Hexamidine and Hexamidine Diisethionate1

2007 ◽  
Vol 26 (3_suppl) ◽  
pp. 79-88 ◽  
Keyword(s):  
Guinea Pig ◽  
Safety Assessment ◽  
Expert Panel ◽  
Developmental Toxicity ◽  
The Body ◽  
Tissue Type ◽  
Clinical Test ◽  
Final Report ◽  
Contact Sensitivity ◽  
Cosmetic Products

Hexamidine Diisethionate functions as a biocide in cosmetics at concentrations of 0.03% to 0.1% in 38 cosmetic products. Hexamidine functions as a biocide and preservative in cosmetics, but is not in current use in cosmetics, but it is used in over-the-counter (OTC) drug products. Hexamidine was poorly absorbed by human cadaver skin when in water-oil formulations or in a gel that simulated a cosmetic product formulation. Hexamidine Diisethionate was poorly absorbed by the skin of live rats and was not stored in any tissue type. Hexamidine Diisethionate given to rats intravenously was rapidly metabolized to Hexamidine. Excretion was primarily via the feces, with a small amount excreted in the urine. Acute oral LD50 values of Hexamidine Diisethionate were 0.71 to 2.5 g/kg in mice and 0.75 g/kg in rats. Dermal exposure to 4 g/kg Hexamidine Diisethionate in rats or up to 9.4 ml/kg of a 0.1% Hexamidine Diisethionate solution under occlusion in rabbits produced no mortality or other signs of toxicity. The no-observed-effect level (NOEL) for oral subchronic toxicity of Hexamidine Diisethionate in rats was 50 mg/kg/day. No signs of toxicity were observed with 2% Hexamidine Diisethionate in subchronic studies using rabbits. Application of 0.1 ml of 0.11% Hexamidine Diisethionate in aqueous solution to the eyes of rabbits produced transient reactions; 0.05% produced no reactions. Slight erythema was observed with 0.10% Hexamidine Diisethionate applied to the abraded skin of 1/11 albino rabbits. A 40% solution of Hexamidine Diisethionate applied to 10% of the body surface of rats produced slight erythema, slight edema, and scabbing in some animals at varying times after treatment. Hexamidine Diisethionate was not a sensitizer in the guinea pig maximization test or in an intracutaneous guinea pig sensitization test. Hexamidine Diisethionate was not a photosensitizer in albino rabbits. Hexamidine Diisethionate was not mutagenic in a bacterial reverse mutagenicity assay or clastogenic in mammalian cells. Hexamidine Diisethionate at 0.10% did not provoke primary irritation, inflammation, or sensitization in a clinical test of 200 human subjects. One case report of photosensitivity to Hexamidine and one of contact sensitivity to Hexamidine were reported. There were nine case reports of contact sensitivity to Hexamidine Diisethionate. A European safety assessment recommended a limit of 0.1% Hexamidine Diisethionate in leave-on and rinse-off cosmetic products. In considering the available data, the Cosmetic Ingredient Review (CIR) Expert Panel acknowledged the lack of carcinogenicity and reproductive/developmental toxicity data. Because genotoxicity studies were negative, and there were no structural alerts, the Panel concluded that it was unlikely that these ingredientswould be carcinogenic. Because the rate of absorption of Hexamidine and Hexamidine Diisethionate is slow, there is no tissue accumulation, and excretion is rapid and complete, and there was no toxicity in a subchronic study, the Panel concluded that dermal exposures would not likely present a risk of reproductive/ developmental toxicity. The Panel noted that a guinea pig maximization study using Hexamidine Diisethionate produced no dermal reactions and that a clinical test at 0.1% produced no irritation or sensitization. The Panel also expressed concern regarding the possible presence of 1,4-dioxane as an impurity, and stressed that the cosmetic industry should continue to use the necessary purification procedures to remove these impurities from the ingredient before blending into cosmetic formulations. The Panel noted that there are no data for concentration of use for eye makeup and baby products, and was concerned that there should not be unrestricted concentration levels in these product categories. Although there are gaps in knowledge about product use, the overall information available on the types of products in which these ingredients are used and at what concentration indicate a pattern of use. Within this overall pattern of use, the Expert Panel considers all ingredients in this group to be safe at concentrations up to and including 0.1%.

Final Report on the Safety Assessment of Dimethyl Lauramine

1995 ◽  
Vol 14 (3) ◽  
pp. 193-195
Keyword(s):  
Safety Assessment ◽  
Aliphatic Amine ◽  
Safety Data ◽  
Final Report ◽  
Cosmetic Products ◽  
Dermal Toxicity ◽  
Ocular Irritation ◽  
Dermal Irritation ◽  
Cosmetic Formulations ◽  
Genotoxicity Tests

Dimethyl Lauramine is a tertiary aliphatic amine intended for use in cosmetics as an antistatic agent, but no actual uses were reported in 1993. The antimicrobial and fungicidal properties of Dimethyl Lauramine are well documented. Because of a lack of other data, however, the safety of Dimethyl Lauramine for use in cosmetic formulations has not been substantiated. The data needed to make a safety assessment include the basic chemistry (p H, impurities, and UV spectral analysis), 28-day dermal toxicity, ocular irritation, human dermal irritation and sensitization, human photosensitization if the material absorbs in the UVA or UVB region of the spectrum, genotoxicity evaluated in two different assays, and carcinogenicity tests if the genotoxicity tests are positive. It cannot be concluded that this ingredient is safe for use in cosmetic products until these safety data have been obtained and evaluated.

scholarly journals Addendum to the Final Report on the Safety Assessment of PEGs Lanolin to Include PEG-5, -10, -24, -25, -35, -55, -100, and -150 Lanolin; PEG-5, -10, -20, -24, -30, and -70 Hydrogenated Lanolin; PEG-75 Lanolin Oil; and PEG-75 Lanolin Wax1

1999 ◽  
Vol 18 (1_suppl) ◽  
pp. 61-68
Keyword(s):  
Safety Assessment ◽  
Animal Studies ◽  
Developmental Toxicity ◽  
Final Report ◽  
Clinical Safety ◽  
Cosmetic Ingredients ◽  
Cosmetic Formulations ◽  
Hydroxy Esters ◽  
Few Data ◽  
Related Compounds

The safety of selected polyethylene glycols (PEGS) Lanolin polymers was previously reviewed. This review completes the safety assessment of all the PEGs Lanolin polymers and related cosmetic ingredients. PEGs Lanolin are prepared by ethoxylating the hydroxy fatty acids, hydroxy esters, sterols, and alcohols present in whole lanolin. The number of moles of ethylene oxide reacted with each respective lanolin component corresponds to the average polyethylene glycol chain length. PEGs Lanolins, PEGs Hydrogenated Lanolins, PEG Lanolin Oil, and PEG Lanolin Wax are used as emulsifying, soluhilizing, and cleansing agents. PEGs Hydrogenated Lanolins are also hair-conditioning agents and skin-conditioning emollients. Few data on the PEGs Lanolin were available regarding systemic toxicity, mutagenicity, carcinogenicity, and clinical safety. Related compounds including PEGs, Lanolin, and Lanolin Oil have been previously reviewed. Based on clinical data in burn patients, PEGs were mild irritants/sensitizers and there was evidence of nephrotoxicity. No such effects were seen in animal studies on intact skin. Cosmetic manufacturers should continue to adjust product formulations to minimize any untoward effects when products are used on damaged skin. No evidence of phototoxic effects was found in clinical studies. Comedogenic effects have resulted from the use of cosmetic products containing lanolin compounds. No evidence of mutagenicity, carcinogenicity, or reproductive and developmental toxicity was found with these related compounds. Although metabolites of ethylene glycol monoalkyl ethers are reproductive and developmental toxins, it was considered unlikely that the relevant metabolites would be found in or produced from the use of PEGs Cocamine in cosmetic formulations. Based primarily on data from ingredients with related structures, it was concluded that PEG-S, -10, -24, -25, -35, -55, -100, and -150 Lanolin; PEG-S, -10, -20, -24, -30, and -70 Hydrogenated Lanolin; PEG-75 Lanolin Oil; and PEG-75 Lanolin Wax are safe for use in cosmetic formulations under the present practices of use.

Final Report on the Safety Assessment of Laneth-10 Acetate Group

1982 ◽  
Vol 1 (4) ◽  
pp. 1-24 ◽  
Keyword(s):  
Guinea Pig ◽  
Topical Application ◽  
Safety Assessment ◽  
Final Report ◽  
Acute Oral Toxicity ◽  
Cosmetic Products ◽  
Dermal Toxicity ◽  
Oral Toxicity ◽  
Toxicity Studies ◽  
Animal Data

The Laneths are ethoxylated lanolin alcohols that may be acetylated and used in a wide variety of cosmetic products. Acute oral toxicity studies indicate that Laneth-10 Acetate is relatively nontoxic to the rat; acute dermal toxicity studies indicate that it is relatively nontoxic to the guinea pig. Laneth-10 Acetate was found to be a mild, transient irritant to the rabbit's eye. Laneth-10 Acetate was shown to be nonirritating and nonsensitizing to SO subjects. Laneth-16 is slightly toxic when administered orally to the rat. Neither Laneth-16 nor Laneth-25 was a skin irritant or sensitizing agent in 50 subjects. On the basis of the available animal data and limited human experience presented in this report, it is concluded that the Laneths are safe for topical application to humans in the present practices of use and concentration.

Final Report On the Safety Assessment of Sodium Lauraminopropionate and Sodium Lauriminodipropionate

1997 ◽  
Vol 16 (1_suppl) ◽  
pp. 1-9 ◽  
Author(s):  
F. Alan Andersen
Keyword(s):  
Safety Assessment ◽  
Developmental Toxicity ◽  
Safety Data ◽  
Chemical Characterization ◽  
Current Data ◽  
Albino Rats ◽  
Clinical Test ◽  
Final Report ◽  
Dermal Irritation ◽  
Cosmetic Formulations

Sodium Lauraminopropionate and Sodium Lauriminodipropionate are used in a variety of cosmetic formulations as antistatic agents, hair conditioning agents, and surfactants. Current data on concentrations at which these ingredients appear in cosmetic formulations were unavailable. The oral LD50 for Sodium Lauraminopropionate in albino rats was reported to be 8 g/kg. Evidence from limited studies in rabbits suggests that Sodium Lauraminopropionate and Sodium Lauriminodipropionate are both dermal and ocular irritants. No evidence of sensitization was found in guinea pigs with either ingredient. No data were available on the teratogenic, mutagenic, or carcinogenic potential of these ingredients, nor was there any clinical test data available. Because of the lack of data, the safety of Sodium Lauraminopropionate and Sodium Lauriminodipropionate could not be substantiated. The data needed to make a safety assessment include the method of manufacture, chemical characterization (i.e., data on purity / impurities), chemical and physical properties of Sodium Lauraminopropionate, concentration of use in cosmetic formulations, 28-day dermal toxicity, dermal reproductive and developmental toxicity, any available ocular irritation data (no new studies should be undertaken to provide this data), dermal irritation and sensitization at concentration of use, and two different genotoxicity studies (one using a mammalian system). If the latter data are positive, dermal carcinogenesis data using the methods of the National Toxicology Program will be needed. It cannot be concluded the these ingredients are safe for use in cosmetic products until these safety data have been obtained and evaluated.

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