Final Report on the Safety Assessment of Butoxyethanol

1996 ◽  
Vol 15 (6) ◽  
pp. 462-526 ◽  
Keyword(s):  
Developmental Toxicity ◽  
Occupational Exposures ◽  
Metabolic Activation ◽  
Petroleum Distillate ◽  
Final Report ◽  
Inhalation Toxicity ◽  
Clinical Tests ◽  
Negative Effects ◽  
Corneal Injury ◽  
Butoxyacetic Acid

Butoxyethanol is an ether alcohol used as a solvent in hair and nail products at concentrations up to 10%. This ingredient is absorbed through the skin, metabolized to butoxyacetic acid, and excreted in urine. Acute inhalation toxicity was related to concentration and duration of exposure; pathological changes occur in the kidneys, liver, and lungs. Butoxyethanol was only slightly toxic in an acute oral study in rats and in a dermal study in rabbits. Butoxyethanol was nephrotoxic in an intravenous study in rats, but not when administered intraperitoneally. No evidence of genotoxicity was seen in a battery of tests with metabolic activation, but positive and negative effects were seen in the absence of metabolic activation. A dermal study of a cosmetic product containing 10% Butoxyethanol was not carcinogenic in rats, whereas a rust-preventive product containing 2.5% Butoxyethanol was carcinogenic (90.9% of the rust preventive was a petroleum distillate). There is some evidence for reproductive and developmental toxicity in oral and inhalation studies involving rats, rabbits, and mice, but no such effects in dermal studies in rats. Clinical tests and reports from occupational exposures indicate Butoxyethanol to be an irritant when inhaled. Butoxyethanol was not a sensitizer or photosensitizer in clinical tests. Undiluted Butoxyethanol is recognized to be a severe ocular irritant, but aqueous concentrations of 15 and 5% produced only moderate and no corneal injury, respectively. In consideration of these data, the Cosmetic Ingredient Review Expert Panel concluded that this ingredient may be used safely in hair and nail cosmetic products at concentrations up to 10%.

Final Report On the Safety Assessment of Iodopropynyl Butylcarbamate (IPBC)

1998 ◽  
Vol 17 (5_suppl) ◽  
pp. 1-37 ◽  
Author(s):  
Rebecca S. Lanigan
Keyword(s):  
Weight Gain ◽  
Animal Studies ◽  
Developmental Toxicity ◽  
Metabolic Activation ◽  
Transient Behavior ◽  
Lung Edema ◽  
Final Report ◽  
Inhalation Toxicity ◽  
Clinical Tests ◽  
Oral Toxicity

Iodopropynyl Butylcarbamate (IPBC) functions as a preservative in a wide variety of cosmetic formulations. Although concentrations as high as 0.1% have been reported, most applications appear to require this preservative at less than 0.0125%. IPBC readily penetrates through the skin. The average acute oral LD50 in rats is 1.47 g/kg. Rats fed IPBC for 4 weeks had increased liver weights and decreased plasma cholinesterase activity, and rats fed IPBC for 13 weeks had transient behavior alteration, increased liver weights, hepatocyte enlargement, stomach lesions, and decreased weight gain. Rats administered IPBC as dusts and liquid aerosols had labored breathing—lung edema, emphysema, and reddened lungs were observed after exposure. Dermal irritation, but no evidence of skin sensitization, was seen in animal studies. At concentrations of 0.5%, IPBC caused iritis and conjunctival irritation in rabbit eyes, but exposure to concentrations up to 0.015% produced only slight conjunctival redness. IPBC was not genotoxic, with or without metabolic activation. No evidence of carcinogenic potential was found in a 104-week chronic oral toxicity study using rats. Reductions in weight gain were observed, along with inflammation of the nonglandular stomach and lesions in the submaxillary salivary gland. In reproductive and developmental toxicity studies using rats and mice, IPBC had no significant effect on fertility, reproductive performance, or on the incidence of fetal malformations. IPBC was found to be mildly irritating, but not sensitizing in clinical testing. At concentrations up to 0.1%, IPBC was not comedogenic in clinical tests. Given the acute inhalation toxicity observed in animals, the potential for mild irritation, and the absence of any data on comedogenicity at concentrations higher than 0.1 % in clinical tests, the Expert Panel concluded that IPBC is safe as a cosmetic ingredient at concentrations ≤0.1 %, but that it should not be used in products intended to be aerosolized.

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.

Final Report on the Safety Assessment of Cetethyl Morpholinium Ethosulfate

2001 ◽  
Vol 20 (3_suppl) ◽  
pp. 99-102 ◽  
Keyword(s):  
Safety Assessment ◽  
Developmental Toxicity ◽  
Quaternary Salt ◽  
Skin Penetration ◽  
Toxicity Study ◽  
Final Report ◽  
Inhalation Toxicity ◽  
Absorption Data ◽  
Dermal Irritation ◽  
Safety Test

Cetethyl Morpholinium Ethosulfate is a quaternary salt used as an antistatic agent and as a surfactant in several hair care products. The concentration at which this ingredient is used is unknown, although data reported in 1984 indicated a maximum concentration of 1%. In an inhalation toxicity study, the approximate lethal concentration of Cetethyl Morpholinium Ethosulfate was 0.403 mg/mm3. This ingredient was shown to be a severe ocular irritant in an animal study. No other safety test data on this ingredient were available. These data were clearly insufficient to support the safety of Cetethyl Morpholinium Ethosulfate in cosmetics. Data available on Morpholine were summarized, but these data themselves were insufficient to support safety. The data needed in order to complete the safety assessment of Cetethyl Morpholinium Ethosulfate include: methods of manufacture and impurities, especially nitrosamines; current concentration of use; 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; two genotoxicity studies, at least one in a mammalian system, if positive, then a 2-year dermal carcinogenisis study using National Toxicology Program (NTP) methods may be needed; ultraviolet (UV) absorption data, if significantly absorbed, then photosensitization data are needed; dermal irritation and sensitization; and ocular toxicity, if available.

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 Octyldodecyl Stearoyl Stearate

2001 ◽  
Vol 20 (3_suppl) ◽  
pp. 51-59 ◽  
Keyword(s):  
Fatty Acids ◽  
Developmental Toxicity ◽  
Chemical Properties ◽  
Metabolic Activation ◽  
Test System ◽  
Dermal Absorption ◽  
Esterification Reaction ◽  
Final Report ◽  
Cosmetic Formulations ◽  
Long Chain

Octyldodecyl Stearoyl Stearate functions as an occlusive skin-conditioning agent and as a nonaqueous viscosity-increasing agent in many cosmetic formulations. Current concentrations of use are between 0.7% and 23%, although historically higher concentrations were used. The chemical is formed by a high-temperature, acid-catalyzed esterification reaction of long-chain alcohols (primarily C-20) and a mixture of primarily C-18 fatty acids. Levels of stearic acid, octyldodecanol, and octylydocecyl hydroxystearate in the final product are 5% or less—no other residual compounds are reported. Only limited safety test data were available on Octyldodecyl Stearoyl Stearate, but previous safety assessments of long-chain alcohols and fatty acids found these precursors to be safe for use in cosmetic formulations. Octyldodecyl Stearoyl Stearate produced no adverse effects in acute exposures in rats. The chemical was mostly nonirritating to animal skin at concentrations ranging from 7.5% to 10%; one study did find moderate irritation in rabbit skin at a concentration of 7.5%. Clinical tests at a concentration of 10.4% confirmed the absence of significant irritation in humans. An ocular toxicity study in rabbits found no toxicity. No evidence of genotoxicity was found in either a mammalian test system or in the Ames test system, with or without metabolic activation. The available data on Octyldodecyl Stearoyl Stearate and the previously considered data on long-chain alcohols and fatty acids, however, did not provide a sufficient basis to make a determination of safety. Additional data needs include (1) chemical properties, including the octanol/water partition coefficient; and (2) if there is significant dermal absorption or if significant quantities of the ingredient may contact mucous membranes or be ingested, then reproductive and developmental toxicity data may be needed. Until such time as these data are received, the available data do not support the safety of Octyldodecyl Stearoyl Stearate as used in cosmetic formulations.

Final Report on the Safety Assessment of Ethoxyethanol and Ethoxyethanol Acetate

2002 ◽  
Vol 21 (1_suppl) ◽  
pp. 9-62 ◽  
Keyword(s):  
Acetic Acid ◽  
Developmental Toxicity ◽  
Sister Chromatid Exchanges ◽  
Kidney Damage ◽  
Final Report ◽  
Inhalation Toxicity ◽  
Oral Toxicity ◽  
Routes Of Administration ◽  
Toxicity Studies ◽  
Mild Anemia

Ethoxyethanol is an ether alcohol described as a solvent and viscosity-decreasing agent for use in cosmetics. Ethoxyethanol Acetate is the ester of Ethoxyethanol and acetic acid described as a solvent for use in cosmetics. Although these ingredients have been used in the past, neither ingredient is in current use. Ethoxyethanol is produced by reacting ethylene oxide with ethyl alcohol. Ethoxyethanol Acetate is produced via an esterification of Ethoxyethanol and acetic acid, acetic acid anhydride, or acetic chloride. Ethoxyethanol is metabolized to ethoxyacetaldehyde, which is further metabolized to ethoxyacetic acid, which is also a metabolite of Ethoxyethanol Acetate. Low to moderate acute inhalation toxicity is seen in animals studies. Acute oral toxicity studies in several species reported kidney damage, including extreme tubular degeneration. Kidney damage was also seen in acute dermal toxicity studies in rats and rabbits. Minor liver and kidney damage was also seen in short-term studies of rats injected subcutaneously with Ethoxyethanol, but was absent in dogs dosed intravenously. Mixed toxicity results were also seen in subchronic tests in mice and rats. Ethoxyethanol and Ethoxyethanol Acetate were mild to moderate eye irritants in rabbits; mild skin irritants in rabbits, and nonsensitizing in guinea pigs. Most genotoxicity tests were negative, but chromosome aberrations and sister-chromatid exchanges were among the positive results seen. Numerous reproductive and developmental toxicity studies, across several species, involving various routes of administration, indicate that Ethoxyethanol and Ethoxyethanol Acetate are reproductive toxicants and teratogens. Mild anemia was reported in individuals exposed occupationally to Ethoxyethanol, which resolved when the chemical was not used. Reproductive effects have been noted in males exposed occupationally to Ethoxyethanol. Although there are insufficient data to determine the potential carcinogenic effects of Ethoxyethanol or Ethoxyethanol Acetate, there is evidence that these chemicals are absorbed across human skin and that they are reproductive and developmental toxicants via dermal exposure. Therefore, these ingredients are unsafe for use in cosmetic formulations.

Final Report on the Safety Assessment of Phloroglucinol

1995 ◽  
Vol 14 (6) ◽  
pp. 468-475 ◽  
Keyword(s):  
Developmental Toxicity ◽  
Skin Irritation ◽  
Metabolic Activation ◽  
Current Data ◽  
Dermal Absorption ◽  
Distribution Data ◽  
Final Report ◽  
Cosmetic Products ◽  
Hair Dyes ◽  
Carcinogenicity Study

The aromatic alcohol Phloroglucinol is used in several hair dyes and colors as an antioxidant and hair colorant. Current data on use concentrations was not available. In rats, Phloroglucinol has an LD50 of 5.2 g/kg. Subcutaneous injections of unrefined 0.05 M and 0.01 M solutions of Phloroglucinol caused positive dermal reactions in guinea pigs at both activation and challenge. At a concentration of 3.0 mg/ml, Phloroglucinol induced Trp+ revertants in Saccharomyces and induced chromosome breaks in CHO cells, with and without metabolic activation. These data are not sufficient to demonstrate the safety of Phloroglucinol. Additional data are needed, including information on purity/impurities; types of cosmetic products in which and the typical concentrations at which the ingredient is used; 28-day dermal toxicity study in animals, and depending on the results, dermal absorption, metabolism, and distribution data may be needed; and, if significantly absorbed, dermal reproduction and developmental toxicity (including teratogenicity) data may be needed; human skin irritation data; data from two different genotoxicity assays (one using a mammalian system); and, if the genotoxicity studies are positive, data from an animal carcinogenicity study done by NTP methods is needed. On the basis of the available data, it cannot be concluded that Phloroglucinol is safe for use in cosmetic products.

scholarly journals Final Report on the Safety Assessment of Polyquaternium-7

1995 ◽  
Vol 14 (6) ◽  
pp. 476-484 ◽  
Keyword(s):  
Aqueous Solution ◽  
Developmental Toxicity ◽  
Dermal Exposure ◽  
Final Report ◽  
Ammonium Compound ◽  
Clinical Tests ◽  
Cosmetic Formulations ◽  
Carcinogenic Effects ◽  
Acrylamide Monomer ◽  
Ocular Exposure

The quaternary ammonium compound Polyquaternium-7 is used as an antistatic agent, film former, and hair fixative in a wide variety of cosmetics. This ingredient is formed by the polymerization of acrylamide with dimethyl dialylammonium chloride; residual acrylamide monomer can be found at levels as high as 10 ppm. An 8% aqueous solution of Polyquaternium-7 is typically supplied and this solution may be used in cosmetic formulations at a concentration as high as 5%. Most uses are at lower concentrations. Rats were fed up to 50,000 ppm of an 8% aqueous solution for 30 days; a decrease in organ weight was noted in the higher exposure groups. Dermal exposure of rats to 2.25 ml/kg per day for 14 weeks was nonirritating to both intact and abraded skin. Dermal exposure of rabbits to an 8% solution produced no irritation, and ocular exposure showed mild irritation that cleared after 24 h. Polyquaternium-7 was not mutagenic in an Ames test. Repeated insult patch test data suggest that 8% Polyquaternium-7 is at best a mild cumulative irritant, but not a sensitizer. Clinical tests with an 8% solution indicated that Polyquaternium-7 is not a photosensitizer. Given its structure, this material is considered not likely to be significantly absorbed in the skin and therefore is unlikely to produce general toxicity, developmental toxicity, or mutagenic/carcinogenic effects under use conditions. The presence of unreacted acrylamide monomer is considered sufficiently low so as to have no toxicologic significance. Based on the available data, it is concluded that Polyquaternium-7 is safe for use in cosmetic formulations.

Final Report On the Safety Assessment of Hc Orange No. 11

1998 ◽  
Vol 17 (4_suppl) ◽  
pp. 21-37 ◽  
Author(s):  
Monice Zondlo Fiume
Keyword(s):  
Expert Panel ◽  
Developmental Toxicity ◽  
Skin Irritation ◽  
Skin Penetration ◽  
Oral Exposure ◽  
Final Report ◽  
Clinical Tests ◽  
Hair Dyes ◽  
Hair Dye ◽  
Carcinogenicity Study

HC Orange No. 1 is used as a colorant in semipermanent hair dyes. The highest concentration reported to be used is 0.15%, but information from manufacturers suggested that higher concentrations may be used in the future. Skin penetration through cadaver skin was 1.28% at 24 hours. In studies using rats, acute oral exposure studies produced little toxicity, and short-term toxicity studies produced reduced body weight and increased liver and kidney weights, relative to controls in animals fed 0.5% HC Orange No. 1. There was no evidence of reproductive or developmental toxicity in rats fed up to 1.25% HC Orange No. 1 or in a multigeneration study using rats in which 0.15% HC Orange No. 1 was painted on the skin. While evidence suggests this ingredient is a mild ocular irritant, no skin irritation, sensitization, or photosensitization was seen in animal or clinical tests. The preponderance of data (four out offive studies) indicate that this ingredient is not genotoxic. Hepatocellular and parathyroid hyperplasia were noted in the dermal carcinogenicity study, but the overall findings were clearly negative. Because the highest concentration tested that produced no significant sensitization in clinical tests was 3%, the Expert Panel concluded that safety could be assured only at levels ≤3%. The Expert Panel recognized that this concentration may be greater than that currently used in hair dye formulations.

Final Report of the Cosmetic Ingredient Review Expert Panel Amended Safety Assessment of Calendula officinalis—Derived Cosmetic Ingredients

2010 ◽  
Vol 29 (6_suppl) ◽  
pp. 221S-243S ◽  
Author(s):  
F. Alan Andersen ◽  
Wilma F. Bergfeld ◽  
Donald V. Belsito ◽  
Ronald A. Hill ◽  
Curtis D. Klaassen ◽  
...  
Keyword(s):  
Safety Assessment ◽  
Seed Oil ◽  
Expert Panel ◽  
Developmental Toxicity ◽  
Final Report ◽  
Repeat Dose ◽  
Clinical Tests ◽  
Calendula Officinalis ◽  
Cosmetic Ingredients ◽  
Dose Oral

Calendula officinalis extract, C officinalis flower, C officinalis flower extract, C officinalis flower oil, and C officinalis seed oil are cosmetic ingredients derived from C officinalis. These ingredients may contain minerals, carbohydrates, lipids, phenolic acids, flavonoids, tannins, coumarins, sterols and steroids, monoterpenes, sesquiterpenes, triterpenes, tocopherols, quinones, amino acids, and resins. These ingredients were not significantly toxic in single-dose oral studies using animals. The absence of reproductive/developmental toxicity was inferred from repeat-dose studies of coriander oil, with a similar composition. Overall, these ingredients were not genotoxic. They also were not irritating, sensitizing, or photosensitizing in animal or clinical tests but may be mild ocular irritants. The Cosmetic Ingredient Review (CIR) Expert Panel concluded that these ingredients are safe for use in cosmetics in the practices of use and concentration given in this amended safety assessment.

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