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 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 Azulene

1999 ◽  
Vol 18 (3_suppl) ◽  
pp. 27-32 ◽  
Author(s):  
F. Alan Andersen
Keyword(s):  
Safety Assessment ◽  
Animal Studies ◽  
Skin Irritation ◽  
Skin Penetration ◽  
Toxicity Study ◽  
Final Report ◽  
Ciliary Activity ◽  
Oral Toxicity ◽  
Wide Range ◽  
Cosmetic Formulations

Azulene is an extract from the volatile oil of several perennial herbs and is detected in tobacco smoke. It functions as a skin conditioning agent in cosmetic formulations, including hair dyes. Azulene is reported to be used in a wide range of cosmetic formulations, but these reported uses are likely to be uses of guaiazulene, a chemically related colorant, because there are currently no suppliers of Azulene to the cosmetics industry. The anti-inflammatory action of Azulene has been demonstrated in several animal studies. Effects at the cellular level are reported to include inhibition of respiration and growth, but no effect on ciliary activity or membrane permeability. Relatively low oral toxicity was seen in acute animal studies. Azulene was not mutagenic in an Ames test, with and without metabolic acfivation. An allergic response to Azulene was noted in one case report. These data were clearly insufficient to support the safety of Azulene in cosmetics. Additional data needed to make a safety assessment include: methods of manufacture and impurities, especially naphthalenes; 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; one genotoxicity study in a mammalian system, if positive, then a 2-year dermal carcinogenesis study using National Toxicology Program methods is needed; skin irritation and sensitization in animals or humans; and ocular toxicity.

scholarly journals Final Report on the Safety Assessment of Di-t-Butylhydroquinone

1996 ◽  
Vol 15 (4) ◽  
pp. 301-310 ◽  
Keyword(s):  
Developmental Toxicity ◽  
Safety Data ◽  
Skin Penetration ◽  
Uv Absorption ◽  
Final Report ◽  
Cosmetic Products ◽  
Dermal Irritation ◽  
Chronic Study ◽  
Mammalian System ◽  
Additional Safety

Di-t-Butylhydroquinone is an antioxidant that may be used in cosmetic products; currently, however, there are no reported uses. Di-t-Butylhydroquinone is approved for use as an indirect food additive. Very little data relevant to assessing the safety of Di-t-Butylhydroquinone in cosmetics are available. In a study in which rats were exposed to 2% Di-t-Butylhy-droquinone in their feed, all died within 2 weeks. Other studies reported results that vary as a function of the base feed used. In a chronic study, rats fed up to 0.2% Di-t-Butylhydroquinone did not exhibit a significant response. Exposure of male Syrian hamsters to 1% Di-t-Butylhydroquinone in the feed resulted in inflammation, hyperkeratosis, hyperplasia, and papillomas in the non-squamous stomach. Animal tests show that Di-t-Butylhydroquinone as low as 10% can cause erythema, but not sensitization. Di-t-Butylhydroquinone does not appear to cause depigmentation. However, additional safety data are needed. Information is needed on the concentration of its use in cosmetics, the presence of impurities, UV absorption, 28-day dermal toxicity, skin penetration, dermal irritation and sensitization, and genotoxicity, (two different assays, one in a mammalian system). Additionally, if there is UV absorption, photosensitization data are needed; if there is significant skin absorption, reproductive and developmental toxicity data may be needed; and if there is positive mutagenicity, a dermal carcinogenicity assay is needed. In the absence of these data, it was concluded that the available data are not sufficient to support the safety of Di-t-Butylhydroquinone in cosmetic products.

4 Final Report on the Safety Assessment of Butyl Stearate, Cetyl Stearate, Isobutyl Stearate, Isocetyl Stearate, Isopropyl Stearate, Myristyl Stearate, and Octyl Stearate

1985 ◽  
Vol 4 (5) ◽  
pp. 107-146 ◽  
Keyword(s):  
Safety Assessment ◽  
Animal Studies ◽  
Health Effect ◽  
Final Report ◽  
Cosmetic Products ◽  
Oral Toxicity ◽  
Potential Health ◽  
Rabbit Skin ◽  
Cosmetic Ingredients ◽  
Cosmetic Formulations

The 7 Stearates described in this report are either oily liquids or waxy solids that are primarily used in cosmetics as skin emollients at concentrations up to 25 percent. The toxicology of the Stearates has been assessed in a number of animal studies. They have low acute oral toxicity and are essentially nonirritating to the rabbit eye when tested at and above use concentration. At cosmetic use concentrations the Stearates are, at most, minimally irritating to rabbit skin. In clinical studies the Stearates and cosmetic products containing them were at most minimally to mildly irritating to the human skin, essentially nonsensitizing, nonphototoxic and nonphotosensitizing. Comedogenicity is a potential health effect that should be considered when the Stearate ingredients are used in cosmetic formulations. On the basis of the information in this report, it is concluded that Butyl, Cetyl, Isobutyl, Isocetyl, Isopropyl, Myristyl, and Octyl Stearate are safe as cosmetic ingredients in the present practices of use.

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.

scholarly journals Final Report on the Safety Assessment of Propylene Glycol (PG) Dicaprylate, PG Dicaprylate/Dicaprate, PG Dicocoate, PG Dipelargonate, PG Isostearate, PG Laurate, PG Myristate, PG Oleate, PG Oleate SE, PG Dioleate, PG Dicaprate, PG Diisostearate, and PG Dilaurate

1999 ◽  
Vol 18 (2_suppl) ◽  
pp. 35-52 ◽  
Author(s):  
Wilbur Johnson
Keyword(s):  
Polyethylene Glycol ◽  
Propylene Glycol ◽  
Skin Irritation ◽  
Skin Penetration ◽  
Final Report ◽  
Limited Data ◽  
Oral Toxicity ◽  
Cosmetic Ingredients ◽  
Cosmetic Formulations ◽  
Safety Assessments

The Propylene Glycol Dicaprylate family of ingredients includes several esters and diesters of Propylene Glycol and fatty acids. These ingredients are used in cosmetic formulations as skin conditioning agents, viscosity increasing agents, and surfactants. Two skin irritation studies (minimal to no irritation) and a comedogenicity study (insignificant comedogen) on Propylene Glycol Dicaprylate/Dicaprate and a skin irritation study (slight) and an acute oral toxicity study (nontoxic) on Propylene Glycol Laurate were available. Available data were also found indicating that Propylene Glycol Dicaprylate/Dicaprate and Propylene Glycol Dipelargonate may enhance the skin penetration of other chemicals. Because of the ability of these Polyethylene Glycol esters and diesters to enhance penetration of other agents, it was recommended that care be taken in using these and other Polyethylene Glycol esters and diesters in cosmetic products. Previous Cosmetic Ingredient Review safety assessments of related ingredients, including Polyethylene Glycol, Polyethylene Glycol Stearate, Coconut Oils and Acids, Isostearic Acid, Lauric Acid, Myristic Acid, Oleic Acid, and Caprylic/Capric Triglyceride, were summarized. Included were mutagenicity, chronic toxicity, and skin irritation and sensitization data. Based in part on the limited data available on the ingredients included in the report, but more so on the previous reviews of chemically similar moieties, it was concluded that Propylene Glycol Dicaprylate, Propylene Glycol Dicaprylate/Dicaprate, Propylene Glycol Dicocoate, Propylene Glycol Dipelargonate, Propylene Glycol Isostearate, Propylene Glycol Laurate, Propylene Glycol Myristate, Propylene Glycol Oleate, Propylene Glycol Oleate SE, Propylene Glycol Dioleate, Propylene Glycol Dicaprate, Propylene Glycol Diisostearate, and Propylene Glycol Dilaurate are safe for use as cosmetic ingredients in the present practices of use.

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.

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 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

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