Final Report On the Safety Assessment of Polyvinylpyrrolidone (PVP)

1998 ◽  
Vol 17 (4_suppl) ◽  
pp. 95-130 ◽  
Author(s):  
Bindu Nair
Keyword(s):  
Molecular Weight ◽  
Animal Studies ◽  
Developmental Toxicity ◽  
Average Molecular Weight ◽  
Skin Irritation ◽  
Lymphoid Hyperplasia ◽  
Final Report ◽  
Ocular Irritation ◽  
Negative Findings ◽  
Gross Lesions

Polyvinylpyrrolidone (PVP) is a linear polymer of 1-vinyl-2-pyrrolidone monomers used as a binder, emulsion stabilizer, film former, hair fixative, and suspending agent-nonsurfactant. The molecular weight of the polymer ranges from 10,000 to 700,000. PVP K-30, with an average molecular weight of 40,000, is typically used in cosmetic formulations. The highest concentration reported to be used is 35%. There was no significant absorption of PVP K-30 given orally to rats, and the acute oral LD50 was >100 g/kg for rats and guinea pigs. Neither toxic effects nor gross lesions were found in rats maintained for two years on a diet containing 10% PVP K-30. Short-term PVP inhalation studies produced mild lymphoid hyperplasia and fibroplasia in rats, but no inflammatory response. In animal studies, no evidence of significant ocular irritation, skin irritation, or skin sensitization was found at PVP-iodine solution concentrations of 10%. While PVP-iodine is not a cosmetic ingredient, these negative findings were considered to support the safety of the PVP component. Undiluted PVP K-30 was not a dermal irritant or sensitizer in clinical tests. No developmental toxicity was seen in vehicle controls where PVP was used as a vehicle for another agent. In certain assay systems, PVP was genotoxic, but was negative in the majority of studies. Orally administered PVP significantly decreased the rate of bladder tumors in mice exposed to bracken fern. Several studies tested the carcinogenicity of subcutaneous implants of particulate PVP in rats, mice, and rabbits. Although the majority of these studies conducted in rats were positive, tumors (sarcomas) were localized to the site of implantation. Based on the available data, it was concluded that PVP is safe as used in cosmetics.

Final Report on the Safety Assessment of Carbomers-934, -910, -934P, -940, -941, and -962

1990 ◽  
Vol 1 (2) ◽  
pp. 109-141 ◽  
Keyword(s):  
Molecular Weight ◽  
Acrylic Acid ◽  
Safety Assessment ◽  
Animal Studies ◽  
Skin Irritation ◽  
Final Report ◽  
Pathological Changes ◽  
Cosmetic Ingredients ◽  
Body Weights ◽  
Available Information

The Carbomers are synthetic, high molecular weight, nonlinear polymers of acrylic acid, cross-linked with a polyalkenyl polyether. The Carbomer polymers are used in cosmetics and emulsifying agents at concentrations up to 50%. Acute oral animal studies showed that Carbomers-910, -934, -934P, -940, and -941 have low toxicities when ingested. Rabbits showed minimal skin irritation and zero to moderate eye irritation when tested with Carbomers-910 and -934. Subchronic feeding of rats and dogs with Carbomer-934 in the diet resulted in lower than normal body weights, but no pathological changes were observed. Dogs chronically fed Carbomer-934P manifested gastrointestinal irritation and marked pigment deposition within Kupffer cells of the liver. Clinical studies with Carbomers showed that these polymers have low potential for skin irritation and sensitization at concentrations up to 100%. Carbomer-934 demonstrated low potential for phototoxicity and photo-contact allergenicity. On the basis of the available information presented and as qualified in the report, it is concluded that the Carbomers are safe as cosmetic ingredients.

scholarly journals Final Report on the Safety Assessment of Triacetin

2003 ◽  
Vol 22 (2_suppl) ◽  
pp. 1-10
Keyword(s):  
Acetic Acid ◽  
Cell Growth ◽  
Expert Panel ◽  
Developmental Toxicity ◽  
Final Report ◽  
Food Ingredient ◽  
Ocular Irritation ◽  
Cosmetic Formulations ◽  
Cell Growth And Proliferation ◽  
Available Information

Triacetin, also known as Glyceryl Triacetate, is reported to function as a cosmetic biocide, plasticizer, and solvent in cosmetic formulations, at concentrations ranging from 0.8% to 4.0%. It is a commonly used carrier for flavors and fragrances. Triacetin was affirmed as a generally recognized as safe (GRAS) human food ingredient by the Food and Drug Administration (FDA). Triacetin was not toxic to animals in acute oral or dermal exposures, nor was it toxic in short-term inhalation or parenteral studies, and subchronic feeding and inhalation studies. Triacetin was, at most, slightly irritating to guinea pig skin. However, in one study, it caused erythema, slight edema, alopecia, and desquamation, and did cause some irritation in rabbit eyes. Triacetin was not sensitizing in guinea pigs. Triacetin was not an irritant or a sensitizer in a clinical maximization study, and only very mild reactions were seen in a Duhring-chamber test using a 50% dilution. In humans, Triacetin reportedly has caused ocular irritation but no injury. Triacetin was not mutagenic. Although there were no available reproductive and developmental toxicity data, Triacetin was quickly metabolized to glycerol and acetic acid and these chemicals were not developmental toxins. Reports of 1,2-glyceryl diesters, which may be present in Triacetin, affecting cell growth and proliferation raised the possibility of hyperplasia and/or tumor promotion. The Cosmetic Ingredient Review (CIR) Expert Panel concluded, however, that the effects of 1,2-glyceryl diesters on cell growth and proliferation require longer ester chains on the glycerin backbone than are present when acetic acid is esterified with glycerin, as in Triacetin. On the basis of the available information, the CIR Expert Panel concluded that Triacetin is safe as used in cosmetic formulations.

8 Final Report on the Safety Assessment of Polyquaternium-11

1983 ◽  
Vol 2 (5) ◽  
pp. 161-178 ◽  
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Skin Irritation ◽  
Low Molecular Weight ◽  
Final Report ◽  
Dermal Toxicity ◽  
Molecular Weight Polymer ◽  
Patch Tests ◽  
Skin Patch ◽  
Available Information

Polyquaternium-11 is a quaternized copolymer of vinylpyrrolidone and di-methylamine ethylmethacrylate, and is used at concentrations up to 50% in a variety of hair care preparations. The acute oral LD50 in test animals of high molecular weight Polyqua-ternium-11 is estimated to be greater than 12.8 g/kg; the LD50 for the low molecular weight polymer is calculated to be 6.2 g/kg. At concentrations of up to 50% in water, the raw ingredient produced no signs of skin or eye irritation. There was no evidence of dermal toxicity in subchronic tests nor in a maximization test for sensitization. In clinical studies, 1 of 19 subjects showed slight skin irritation after a 24-hour single insult skin patch with 9.5% Polyquaternium-11 in water. Repeated insult patch tests at concentrations up to 50% produced no instances of skin sensitization and only isolated instances of transient skin irritation. Clinical photoreactivity studies on both low and high molecular weight polymers showed no evidence of phototoxicity or photoallergenicity. From the available information, it is concluded that Polyquaternium-11 is safe as a cosmetic ingredient in the present practices of use.

4: Final Report on the Safety Assessment of Toluene

1987 ◽  
Vol 6 (1) ◽  
pp. 77-120 ◽  
Keyword(s):  
Human Skin ◽  
Safety Assessment ◽  
Animal Studies ◽  
Skin Irritation ◽  
Final Report ◽  
Cosmetic Products ◽  
Skin Exposure

Toluene has a wide variety of noncosmetic applications. However, the cosmetic use is limited to nail products at concentrations up to 50%. Toluene was practically nontoxic when given orally to rats; acute oral LD50 values ranged from 2.6 g/kg to 7.5 g/kg. Results of animal studies indicated that undiluted Toluene is a skin irritant. No skin irritation or sensitization was observed in subjects treated with cosmetic products containing 31-33% Toluene. No phototoxic or photoallergic reactions were noted in subjects treated with 25% or 30% Toluene. The sole cosmetic use of Toluene is in products intended to be applied directly to the nail; therefore, human skin exposure to this ingredient will be minimal under conditions of cosmetic use. On the basis of the available data and the limited user skin exposure from cosmetic products containing Toluene, it is concluded that this ingredient is safe for cosmetic use at the present practices of use and concentration.

5 Final Report on the Safety Assessment of Propylene Glycol Stearate and Propylene Glycol Stearate Self-Emulsifying

1983 ◽  
Vol 2 (5) ◽  
pp. 101-124 ◽  
Keyword(s):  
Propylene Glycol ◽  
Safety Assessment ◽  
Animal Studies ◽  
Skin Irritation ◽  
Final Report ◽  
Cosmetic Products ◽  
Dermal Toxicity ◽  
Cosmetic Ingredients ◽  
Available Information

Propylene Glycol Stearates (PGS) are a mixture of the mono- and diesters of triple-pressed stearic acid and propylene glycol and are used in a wide variety of cosmetic products. Studies with 14C-labeled PGS show that it is readily metabolized following ingestion. In rats, the acute oral LD50 has been shown to be approximately 25.8 g/kg. The raw ingredient produced no significant dermal toxicity, skin irritation, or eye irritation in acute tests with rabbits. Subchronic animal studies produced no evidence of oral or dermal toxicity. Propylene glycol monostea-rate was negative in in vitro microbial assays for mutagenicity. In clinical studies, PGS produced no significant skin irritation at concentrations up to 55% nor skin sensitization on formulations containing 2.5%. Photo-contact allergenicity tests on product formulations containing 1.5% PGS were negative. From the available information, it is concluded that Propylene Glycol Stearates are safe as cosmetic ingredients in the present practices of use.

Final Report on the Safety Assessment of Oleth-2, -3, -4, -5, -6, -7, -8, -9, -10, -11, -12, -15, -16, -20, -23, -25, -30, -40, -44, and -501

1999 ◽  
Vol 18 (2_suppl) ◽  
pp. 17-24 ◽  
Author(s):  
F. Alan Andersen
Keyword(s):  
Polyethylene Glycol ◽  
Ethylene Oxide ◽  
Animal Studies ◽  
Oleyl Alcohol ◽  
Body Weight Gain ◽  
Developmental Toxicity ◽  
Final Report ◽  
Exposure Group ◽  
Cosmetic Formulations ◽  
Mild Irritant

The Oleth family of ingredients are the polyethylene glycol (PEG) ethers of oleyl alcohol. They are manufactured by the ethoxylation of oleyl alcohol with the number of moles of ethylene oxide corresponding to the average polyethylene glycol chain length desired. Not all of the polymer chain lengths covered in this assessment are currently reported to be used, but all are listed as cosmetic ingredients and may have been used in the past and could be used in the future. Oleths are surfactants used as emulsifying, cleansing, and solubilizing agents in cosmetic formulations. Limited safety test data are available on ingredients in the Oleth family, all consistent with surfactant properties. In feeding studies, Oleth-20 was associated with reduced body weight gain. Hepatic lesions in one exposure group were not found in any other exposure group, but were found in the controls. Oleth-20 and Oleth-10 were found to have moderate ocular irritation potential, and Oleth-10 was considered to be a cumulative skin irritant. Toxicity data, including reproductive and developmental toxicity, carcinogenesis data, and clinical testing data, available from previous safety assessments on Polyethylene Glycol and Oleyl Alcohol, were summarized. The principal finding related to PEGs, based on clinical data in burn patients, is that PEGs were mild irritant/sensitizers and there was evidence of nephrotoxicity. No such effects were seen in animal studies on intact skin. Cosmetic manufacturers should adjust product formulations containing Polyethylene Glycol to minimize any untoward effects when products are used on damaged skin. 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 Oleths in cosmetic formulations. Of concern was the possible presence of 1,4-dioxane and ethylene oxide impurities. The importance of using the necessary purification procedures to remove these impurities was stressed. Based on particle size and cosmetic use considerations, it was not considered that these ingredients, in formulation, are respirable. Based in part on the limited data available on Oleths included in the report and on the previous reviews of Polyethylene Glycol and Oleyl Alcohol, it was concluded that Oleth-2, -3, -4, -5, -6, -7, -8, -9, -10, -11, -12, -15, -16, -20, -23, -25, -30, -40, -44, and -50 are safe 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.

Final Report on the Safety Assessment of Peg-30,-33,-35,-36, ANd-40 Castor Oil and Peg-30 and-40 Hydrogenated Castor Oil

1997 ◽  
Vol 16 (3) ◽  
pp. 269-306 ◽  
Keyword(s):  
Clinical Data ◽  
Castor Oil ◽  
Animal Studies ◽  
Developmental Toxicity ◽  
Final Report ◽  
Carcinogenic Effect ◽  
Intravenous Drugs ◽  
Cosmetic Formulations ◽  
Anaphylactoid Reactions ◽  
Hydrogenated Castor Oil

PEG Castor Oils and PEG Hydrogenated Castor Oils are a family of polyethylene glycol derivatives of castor oil and hydrogenated castor oil that are used in over 500 formulations representing a wide variety of cosmetic products. They are used as skin conditioning agents and as surfactants (emulsifying and or solubilizing agents). The PEG Castor Oils and PEG Hydrogenated Castor Oils include various chain lengths, depending on the quantity of ethylene oxide used in synthesis. Although not all polymer lengths have been studied, it is considered acceptable to extrapolate the results of the few that have been studied to allingredients in the family. Because a principal noncosmetic use of PEG Castor Oils is as solvents for intravenous drugs, clinical data are available that indicate intravenous exposure can result in cardiovascular changes. Results from animal studies indicate very high LD50 values, with some evidence of acute nephrotoxicity in rats but not in rabbits. Short-term studies with intravenous exposure produced some evidence of toxicity in dogs but not in rabbits. Intramusuclar injection produced no toxicity in several species, including dogs. Subchronic oral studies also were negative. No dermal or ocular irritation was observed in studies in rabbits. Irritation was seen during induction, but no sen-sitization was found on challenge in guinea-pig studies using up to 50% PEG-35 Castor Oil; however, thisingredient was found to be a potent adjuvant in guinea pigs and mice. No evidence of developmental toxicity was seen in mice and rat feeding studies. Theseingredients, tested as vehicle controls, produced no mutagenic or carcinogenic effect. Clinical data are generally negative for irritation and sensitization, although some anaphylactoid reactions have been seen in studies of intravenous drugs in which PEG-35 Castor Oil was used as the vehicle. Because the maximum concentration used in animal sensitization studies was 50% for PEG Castor Oils and 100% for PEG Hydrogenated Castor Oils, it was concluded that PEG Castor Oils are safe for use in cosmetic formulations up to a concentration of 50% and that PEG Hydrogenated Castor Oils are safe as used in cosmetic formulations.

Final Report on the Safety Assessment of Acetamide MEA

1993 ◽  
Vol 12 (3) ◽  
pp. 225-236 ◽  
Keyword(s):  
Guinea Pigs ◽  
Safety Assessment ◽  
Skin Irritation ◽  
Nitroso Compounds ◽  
Final Report ◽  
Skin Exposure ◽  
Ocular Irritation ◽  
Cosmetic Formulations ◽  
A Minor ◽  
Primary Irritation

Acetamide MEA is used in cosmetics as a skin conditioning agent-humectant and hair conditioning agent. Oral LD50s of 27 g/kg were reported for Acetamide MEA in rats. No rabbits died following an acute dermal exposure of 20 ml/kg Acetamide MEA. In ocular irritation studies, 70% Acetamide MEA and cosmetic formulations containing 1.3% Acetamide MEA were classified as nonocular irritants in rabbits. Only mild skin irritation occurred following a 24-h skin exposure to undiluted Acetamide MEA. In the maximization test, Acetamide MEA was classified as a nonsensitizer in guinea pigs when tested at a concentration of 5.0%. Neither primary irritation nor sensitization reactions to 7.5% Acetamide MEA were observed in a human repeated insult patch test. Acetamide MEA was not nonmutagenic in the Ames assay. In the presence of nitrosating agents, Acetamide MEA may form N-nitroso compounds; acetamide may be a minor impurity in Acetamide MEA. On the basis of the data presented in this report, it is concluded that Acetamide MEA is safe as a cosmetic ingredient at concentrations not to exceed 7.5% in leave-on products and is safe in the present practice of use in rinse-off products. Cosmetic formulations containing Acetamide MEA should not contain nitrosating agents or significant amounts of free acetamide.

Final Report on the Safety Assessment of Sodium Metaphosphate, Sodium Trimetaphosphate, and Sodium Hexametaphosphate

2001 ◽  
Vol 20 (3_suppl) ◽  
pp. 75-89 ◽  
Keyword(s):  
Developmental Toxicity ◽  
Contact Allergy ◽  
Skin Irritation ◽  
Oral Care ◽  
Sodium Hexametaphosphate ◽  
Calcium Deposition ◽  
Final Report ◽  
Inorganic Polyphosphate ◽  
Sodium Metaphosphate ◽  
Sodium Trimetaphosphate

These inorganic polyphosphate salts all function as chelating agents in cosmetic formulations. In addition, Sodium Metaphosphate functions as an oral care agent, Sodium Trimetaphosphate as a buffering agent, and Sodium Hexametaphosphate as a corrosion inhibitor. Only Sodium Hexametaphosphate is currently reported to be used. Although the typical concentrations historically have been less than 1%, higher concentrations have been used in products such as bath oils, which are diluted during normal use. Sodium Metaphosphate is the general term for any polyphosphate salt with four or more phosphate units. The four-phosphate unit version is cyclic, others are straight chains. The hexametaphosphate is the specific six-chain length form. The trimetaphosphate structure is cyclic. Rats fed 10% Sodium Trimetaphosphate for a month exhibited transient tubular necrosis; rats given 10% Sodium Metaphosphate had retarded growth and those fed 10% Sodium Hexametaphosphate had pale and swollen kidneys. In chronic studies using animals, growth inhibition, increased kidney weights (with calcium deposition and desquamation), bone decalcification, parathyroid hypertrophy and hyperplasia, inorganic phosphaturia, hepatic focal necrosis, and muscle fiber size alterations. Sodium Hexametaphosphate was a severe skin irritant in rabbits, whereas a 0.2% solution was only mildly irritating. A similar pattern was seen with ocular toxicity. These ingredients were not genotoxic in bacterial systems nor were they carcinogenic in rats. No reproductive or developmental toxicity was seen in studies using rats exposed to Sodium Hexametaphosphate or Sodium Trimetaphosphate. In clinical testing, irritation is seen as a function of concentration; concentrations as high as 1% produced no irritation in contact allergy patients. Because of the corrosive nature of Sodium Hexametaphosphate, it was concluded that these ingredients could be used safely if each formulation was prepared to avoid skin irritation; for example, low concentration in a leave-on product or dilution of a higher concentration as part of product usage.

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