scholarly journals Amended Final Report on the Safety Assessment of Nonoxynol-1, -2, -3, -4, -5, -6, -7, and -81

1999 ◽  
Vol 18 (1_suppl) ◽  
pp. 11-31
Keyword(s):  
Molecular Weight ◽  
Ethylene Oxide ◽  
Safety Assessment ◽  
Skin Penetration ◽  
Toxicity Tests ◽  
Low Molecular Weight ◽  
Vaginal Mucosa ◽  
Final Report ◽  
Cosmetic Products ◽  
Ocular Irritation

Nonoxynol-1, -2, -3, -4, -5, -6, -7, and -8 (low molecular weight Nonoxynols) are ethoxylated alkylphenols used in cosmetic formulations as surfactants-emulsifying agents, principally in hair dyes and colors. The safety of Nonoxynols were assessed previously (Elder, R. L., ed. 1983. Final report on the safety assessment of Nonoxynol-2, -4, -8, -9, -10, -12, -14, -15, -30, -40, and -50. J. Am. Coll. Toxicol. 2:35–60). This report amends the conclusion on Nonoxynol-2, -4, and -8 reached in that report. There was no significant skin penetration using cadaver skin in which Nonoxynols-2, -4, and -9 were applied in conditions simulating leave-on or rinse-off applications. Under both conditions, the total skin penetration of Nonoxynol-2, -4, and -9 was less than 1% over a 48-hour period. Results of acute oral toxicity studies indicated that these low molecular weight Nonoxynols were at most slightly toxic. Nonoxynol-5 and -6 produce severe ocular irritation in test animals. They also produce skin irritation in test animals, but are not sensitizers. Due to the severity of ocular irritation reactions in animals, avoiding the use of products containing low molecular weight Nonoxynols in the area surrounding the eyes was discussed. The no-adverse-effect level in reproductive and developmental toxicity tests in which Nonoxynol-9 was delivered orally or intravaginally was higher than any possible exposure from cosmetic products. There was no evidence for genotoxicity or carcinogenicity. Ethylene oxide residues, although present in small amounts in several preparations, were not considered sufficient to present a carcinogenesis risk. The report discusses the need to ensure that the use of cosmetic products containing Nonoxynols should not result in ethylene oxide exposures above 0.1 mg/day. Unreacted nonylphenol may be present in low molecular weight Nonoxynols, but levels appear to be <500 ppm. The report discusses the need for cosmetic product formulators to exercise care so that any Nonylphenol in finished products is not found in toxic amounts. Clinical studies using Nonoxynol-9 showed irritation of the vaginal mucosa, along with increased epithelial disruption. A 2% solution of Nonoxynol-8.3 and -9 was sensitizing in dermatitis patients. A repeat insult patch test in normal volunteers using Nonoxynol-2 at a concentration of 5 % showed no evidence of allergic contact dermatitis, but there were reactions at 10%. Based on the available animal and clinical data, Nonoxynols-1 through -8 are safe as used in rinse-off products and safe for use in leave-on products at concentrations no greater than 5%.

6: Final Report on the Safety Assessment of Panthenol and Pantothenic Acid

1987 ◽  
Vol 6 (1) ◽  
pp. 139-162 ◽  
Keyword(s):  
Safety Assessment ◽  
Skin Irritation ◽  
Allergic Sensitization ◽  
Pantothenic Acid ◽  
Final Report ◽  
Test Substance ◽  
Cosmetic Products ◽  
Toxicological Effects ◽  
Ocular Irritation ◽  
Low Concentrations

Panthenol is the alcohol analogue of Pantothenic Acid (vitamin B3). The LD50for D-Panthenol administered orally to mice was 15 g/kg. No toxicological effects were associated with the subchronic and/or chronic oral administration of Panthenol to rats. Minimal cutaneous hyperkeratosis was noted in rats in a subchronic dermal study of creams containing 0.2% Panthenol. In ocular irritation studies involving rabbits, concentrations up to 2% produced, at most, slight conjunctival redness and chemosis. Panthenol (100%) and products containing Panthenol (0.5% and 2%) administered to rabbits during skin irritation studies caused reactions ranging from no skin irritation to moderate-to-severe erythema and well-defined edema. Neither teratogenic nor fetotoxic effects were noted in the offspring when rats were fed calcium pantothenate prior to mating and throughout gestation. Skin irritation and sensitization studies of cosmetic products at concentrations up to 0.5% indicated that they were, at most, mild irritants but did not induce allergic sensitization. No test substance-related observations of eye irritation were reported for 23 subjects receiving instillations of products containing 0.1% Panthenol. Mutagenicity and carcinogenicity data were not available for the safety assessment of Panthenol. It is noted that the level of this ingredient required by humans exceeds the amount that could be absorbed from the low concentrations used in cosmetic products. The human metabolic requirement would preclude the likelihood of genotoxicity. It is concluded that Panthenol and Pantothenic Acid are safe as presently used in cosmetics.

Final Report On the Safety Assessment of Benzoxiquine1

1997 ◽  
Vol 16 (1_suppl) ◽  
pp. 117-122
Author(s):  
F. Alan Andersen
Keyword(s):  
Safety Assessment ◽  
Safety Data ◽  
Metabolic Activation ◽  
Final Report ◽  
Cosmetic Products ◽  
Over The Counter ◽  
Drug Products ◽  
Ocular Irritation ◽  
Dermal Irritation ◽  
Mammalian System

Benzoxiquine is described as a biocide for use in cosmetic products. It is currently reported to be used in only one product. In a separate finding, the Food and Drug Administration determined that Benzoxiquine is not generally recognized as safe and effective in over-the-counter topical antifungal drug products. The only data available on the toxicity of Benzoxiquine indicates that it is mutagenic in the Ames test without metabolic activation. Because of the lack of data, the safety of Benzoxiquine could not be substantiated. The data needed to make a safety assessment include purity/impurities, ultraviolet absorption (if there is absorption, then photosensitization data will be needed), 28-day dermal toxicity, dermal teratogenicity, ocular irritation (if already available only), dermal irritation and sensitization, 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 that Benzoxiquine is safe for use in cosmetic products until these safety data have been obtained and evaluated.

2: Final Report on the Safety Assessment of Propylene Carbonate

1987 ◽  
Vol 6 (1) ◽  
pp. 23-51 ◽  
Keyword(s):  
Aqueous Solution ◽  
Dna Repair ◽  
Propylene Carbonate ◽  
Clinical Studies ◽  
Safety Assessment ◽  
Skin Irritation ◽  
Final Report ◽  
Clear Liquid ◽  
Cosmetic Products ◽  
Ocular Irritation

Propylene Carbonate is a nonviscous, clear liquid that is used in cosmetic products at concentrations ranging from 0.1% to 5%. Undiluted Propylene Carbonate produced minimal to moderate ocular irritation and slight erythema in rabbits. The dermal LD50 in rabbits of the undiluted ingredient was >20 ml/kg. Undiluted Propylene Carbonate was nontoxic by inhalation to dogs and guinea pigs in a 21-day study. Propylene Carbonate was negative for mutagenicity in the Ames Assay, and negative for genotoxicity in the Rat He-patocyte Primary Culture/DNA Repair Test. In clinical studies, undiluted Propylene Carbonate caused moderate skin irritation, whereas 5 and 10% Propylene Carbonate in aqueous solution produced no skin irritation or sensitization. Cosmetic products containing up to 20% Propylene Carbonate were essentially nonsensitizing and, at most, moderately irritating to human skin, nonphototoxic, and nonphotosensitizing. It is concluded that Propylene Carbonate is safe as a cosmetic ingredient in the present practices of use and concentration.

Final Report on the Safety Assessment of Pentaerythritol Rosinate

1994 ◽  
Vol 13 (5) ◽  
pp. 395-399 ◽  
Keyword(s):  
Safety Assessment ◽  
Chronic Toxicity ◽  
Historical Data ◽  
Final Report ◽  
Uvb Radiation ◽  
Cosmetic Products ◽  
Ocular Irritation ◽  
Dermal Irritation ◽  
Animal Data ◽  
Rosin Acids

Pentaerythritol Rosinate is the ester of rosin acids derived from Rosin with the polyol, pentaerythritol, used as a skin conditioning and viscosity increasing agent in mascaras. Animal data indicate little evidence of sub-chronic toxicity in feeding studies with Pentaerythritol Rosinate at concentrations up to 5%, or of chronic toxicity in feeding studies with the ingredient at 0.05%. No evidence of carcinogenicity was found in the chronic feeding studies. Historical data indicate that Pentaerythritol Rosinate may be used in cosmetics at concentrations up to 10%. The safety of use of this concentration of Pentaerythritol Rosinate has not been demonstrated. The data needed to evaluate safety include current concentration of use, source and method of manufacture, chemistry (UV spectral analysis, pH, and impurities), ocular irritation, human dermal irritation, sensitization, and photosensitization (only if the ingredient is found to absorb UVA or UVB radiation). It cannot be concluded that this ingredient is safe for use in cosmetic products until the cited data have been obtained and evaluated.

scholarly journals Safety Assessment of Pentaerythrityl Tetra-Di-t-Butyl Hydroxyhydrocinnamate as Used in Cosmetics

2018 ◽  
Vol 37 (3_suppl) ◽  
pp. 80S-89S ◽  
Author(s):  
Wilbur Johnson ◽  
Wilma F. Bergfeld ◽  
Donald V. Belsito ◽  
Ronald A. Hill ◽  
Curtis D. Klaassen ◽  
...  
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Patch Test ◽  
Percutaneous Absorption ◽  
Safety Assessment ◽  
Expert Panel ◽  
Skin Irritation ◽  
Skin Penetration ◽  
Toxicity Data ◽  
Cosmetic Products

Pentaerythrityl tetra-di -t-butyl hydroxyhydrocinnamate functions as an antioxidant in cosmetic products and is used at concentrations up to 0.8%. Given the high molecular weight of this ingredient, skin penetration is not likely. The available toxicity data, together with the low ingredient use concentrations, suggest that systemic toxicity would not be likely if percutaneous absorption were to occur. Additionally, the negative human repeated insult patch test data at a concentration of 0.5% were deemed sufficient for evaluating the skin irritation and sensitization potential of pentaerythrityl tetra-di -t-butyl hydroxyhydrocinnamate over the range of use concentrations in cosmetic products. The Cosmetic Ingredient Review Expert Panel concluded that pentaerythrityl tetra-di -t-butyl hydroxyhydrocinnamate is safe in cosmetics in the present practices of use and concentration described in this safety assessment.

Amended Final Report On the Safety Assessment of Pentaerythrityl Rosinate

1998 ◽  
Vol 17 (4_suppl) ◽  
pp. 83-94
Author(s):  
F.A. Andersen
Keyword(s):  
Chemical Structure ◽  
Safety Assessment ◽  
Additional Data ◽  
Developmental Toxicity ◽  
Toxicity Study ◽  
Final Report ◽  
Cosmetic Products ◽  
Carcinogenicity Study ◽  
Ocular Irritation ◽  
Dermal Irritation

Pentaterythrityl Rosinate (previously called Pentaerythritol Rosinate) is the ester of rosin acids with the polyol pentaerythritol. It is used as a skin conditioning agent-emollient and viscosity increasing agent-nonaqueous in a few cosmetic formulations. In a previous safety assessment, it was concluded that the available data were insufficient to support the safety of this ingredient in cosmetic products. Additional data needed included: concentration of use, source and method of manufacture, chemistry (ultraviolet [UV] spectral analysis, pH, and impurities), ocular irritation, human dermal irritation and sensitization, and photosensitization (only if Pentaerythritol Rosinate absorbs UVA or UVB light). It was also noted that the carcinogenic potential of this ingredient was still of concern because of the low concentration tested in the available carcinogenicity study. Additional data were received. This ingredient is produced by the fractional distillation of crude tall oil to form rosin, which is then esterified with monopentaerythritol. It is typically used at concentrations of 0. 5-10%. It does not significantly absorb in the UVA or UVB portion of the spectrum. Formulations with 10% Pentaerythrityl Rosinate produced only minimal ocular irritation. Likewise tests of formulations with the ingredient at concentations of 7-9.2% resulted in minimal dermal irritation. The ingredient was nonsensitizing in animal maximization tests. Clinical tests of formulations with the ingredient at concentrations of 7-9.6% resulted in neither irritation nor sensitization. No data, however, were provided on possible impurities. Absent information on the actual chemical structure, the lack of information on impurities was considered significant. On further review, a single carcinogenicity study with negative results reported in the earlier safety assessment was considered inadequate. The absence of genotoxicity data was also considered significant. The lack of impurity and chemical structure information also raised a concern about the need for reproductive and developmental toxicity data. On the basis of this further review, it was concluded that the available data are still insufficient to support the safety of this ingredient in cosmetic products. Additional data needed include: (1) two genotoxicity assays, at least one in a mammalian system; if positive, then a 2-year dermal carcinogenicity study using National Toxicology Program (NTP) methods is needed; (2) dermal absorption; if significantly absorbed, then both a 28-day dermal toxicity study and a reproductive and developmental toxicity study may be needed; and (3) chemical properties, including structure and impurities.

Final Report on the Safety Assessment of Octoxynol-1, Octoxynol-3, Octoxynol-5, Octoxynol- 6, Octoxynol-7, Octoxynol-8, Octoxynol-9, Octoxynol-10, Octoxynol-11, Octoxynol-12, Octoxynol-13, Octoxynol-16, Octoxynol-20, Octoxynol-25, Octoxynol-30, Octoxynol-33, Octoxynol-40, Octoxynol-70, Octoxynol-9 Carboxylic Acid, Octoxynol-20 Carboxylic Acid, Potassium Octoxynol-12 Phosphate, Sodium Octoxynol-2 Ethane Sulfonate, Sodium Octoxynol-2 Sulfate, Sodium Octoxynol-6 Sulfate, and Sodium Octoxynol-9 Sulfate1

2004 ◽  
Vol 23 (1_suppl) ◽  
pp. 59-111 ◽  
Keyword(s):  
Elevated Temperature ◽  
Carboxylic Acid ◽  
Ethylene Oxide ◽  
Organic Acids ◽  
Safety Assessment ◽  
Final Report ◽  
Cosmetic Products ◽  
Chain Lengths ◽  
Synthesis Reactions ◽  
Long Chain

Octoxynols are ethoxylated alkylphenols in which the size of the molecule is related to the number of moles of ethylene oxide used in synthesis. Reactions are performed at elevated temperature, under pressure, and in the presence of NaOH. It is possible that the synthesis may leave trace amounts of ethylene oxide, 1,4-dioxane, and unreacted C9 phenols. Octoxynols of various chain lengths as well as octoxynol salts and organic acids function in cosmetics either as surfactants—emulsifying agents, surfactants—cleansing agents, surfactant—solubilizing agents, or surfactants—hydrotropes in a wide variety of cosmetic products at concentrations ranging from 0.0008% to 25%, with most less than 5.0%. The octoxynols are chemically similar to nonoxynols, the safety of which were previously considered. Long-chain nonoxynols (9 and above) were considered safe as used, whereas short-chain nonoxynols (8 and below) were considered safe as used in rinse-off products and safe at concentrations less than 5% in leave-on formulations.

1: Final Report on the Safety Assessment of Sodium Lauryl Sulfoacetate

1987 ◽  
Vol 6 (3) ◽  
pp. 261-277 ◽  
Keyword(s):  
Clinical Studies ◽  
Guinea Pigs ◽  
Safety Assessment ◽  
Sodium Lauryl Sulfate ◽  
Skin Irritation ◽  
Final Report ◽  
Lauryl Sulfate ◽  
Cosmetic Products ◽  
Cosmetic Product ◽  
Ocular Irritation

Sodium Lauryl Sulfoacetate is a detergent used in cosmetic products. A 12% solution of the ingredient was slightly toxic to rats in an acute oral study. No treatment-related effects of significance were noted in rats in a subchronic study at a dose of 75 mg/kg/day. Some effects were observed at 250 and 750 mg/kg/day. Minimal to slight ocular irritation occurred in rabbits when tested with 3.0% Sodium Lauryl Sulfoacetate. A diluted product tested at 1% Sodium Lauryl Sulfate was nonirritating to the genital mucosa of rabbits. No skin irritation, sensitization, or phototoxicity was noted in guinea pigs exposed to a cosmetic product containing 2% Sodium Lauryl Sulfoacetate. Cosmetic products containing up to 16% Sodium Lauryl Sulfoacetate were nonmutagenic in the Ames Salmonella/microsome assay, both with and without activation. In clinical studies, Sodium Lauryl Sulfoacetate was a mild to strong skin irritant but not a sensitizer at concentrations up to 2.0%. The irritant effects are similar to those produced by other detergents, and the severity of the irritation appears to increase directly with concentration. It is concluded that Sodium Lauryl Sulfoacetate is safe for use in cosmetic products in the present practices of use and concentration.

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.

Final Report on the Safety Assessment of Cetyl Lactate and Myristyl Lactate

1990 ◽  
Vol 1 (2) ◽  
pp. 97-107 ◽  
Keyword(s):  
Safety Assessment ◽  
Skin Irritation ◽  
Final Report ◽  
Cosmetic Products ◽  
Rabbit Skin ◽  
Ocular Irritation ◽  
Myristyl Alcohol ◽  
Irritation Test ◽  
Skin Irritation Test ◽  
Available Information

Cetyl Lactate and Myristyl Lactate are the esters of lactic acid and either cetyl or myristyl alcohol. They are used in a wide variety of cosmetic products up to a maximum concentration of 25%. The acute oral LD50 of Cetyl Lactate is estimated from studies with rats to be greater than 20 g/kg. Cetyl Lactate was shown to be minimally irritating to rabbit skin and nonirritating or only slightly irritating to rabbit eyes in Draize irritation tests. At 25%, Cetyl Lactate produced no signs of toxicity or irritation in a 30-day rabbit-skin irritation study. Cetyl Lactate was found to be minimally irritating and nonsensitizing to human skin at concentrations up to 5%. The acute oral LD50 of Myristyl Lactate is estimated from studies with rats to be greater than 20 g/kg. Myristyl Lactate was shown to be minimally irritating in Draize primary skin irritation tests, but one contradictory study concluded that undiluted Myristyl Lactate produced moderate irritation. It produced no signs of ocular irritation in Draize rabbit eye irritation tests. Mild irritation was elicited by a formulation in a modified Draize rabbit skin irritation test. The same formulation was found to be nonirritating and nonsensitizing in a human repeated insult patch study. Based on the available information, it is concluded that Cetyl Lactate and Myristyl Lactate are safe in the present practices of use.

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