2 Final Report on the Safety Assessment of p-Aminophenol, m-Aminophenol, and o-Aminophenol

1988 ◽  
Vol 7 (3) ◽  
pp. 279-333 ◽  
Keyword(s):  
Topical Application ◽  
Guinea Pigs ◽  
Safety Assessment ◽  
Mutagenic Activity ◽  
Skin Irritation ◽  
Final Report ◽  
Hair Dyes ◽  
Hair Dye ◽  
Mutagenicity Tests

p-Aminophenol (PAP), m-Aminophenol (MAP), and o-Aminophenol (OAP) are used in permanent (oxidative) hair dyes at concentrations from 0.1 to 5%. In vivo and in vitro skin absorption studies indicated that 11% of the dermally applied 14C-PAP was detected in the excreta, viscera, and skin of the test animals. The oral LD50s of PAP, MAP, and OAP in rats ranged from 600 to 1300 mg/kg. Topical application of PAP at concentrations up to 8.00 g/kg to the skin of New Zealand white (NZW) rabbits produced no skin irritation and no mortality. PAP, MAP, and OAP were irritating to eyes of NZW rabbits at a concentration of 2.5%. MAP at 3% was nonsensitizing in guinea pigs; PAP at 2% sensitized 9 of 10 guinea pigs. Neither PAP nor MAP produced photosensitization in guinea pigs. No treatment-related toxicity was found in three separate four-generation chronic dermal toxicity and reproduction studies of hair dye formulations containing the three Aminophenols. Additional studies on the pure ingredients were also nonteratogenic; embryotoxicity was reported. A range of results was obtained from studies assessing the mutagenic activity of the Aminophenols. PAP tested positive in six of eight mutagenicity tests. MAP and OAP gave positive results in two of eight and five of seven mutagenicity tests, respectively. Oxidative hair dye formulations containing PAP, MAP, and OAP did not produce gross or microscopic alterations or have carcinogenic effects after chronic topical application to mice. Feeding of OAP-HCl and PAP to rats at a dose of 8 mmol/kg produced neither hepatic cirrhosis nor neoplastic lesions. A 3% solution of MAP in an aqueous vehicle was neither a significant irritant nor sensitizer in two clinical studies. A variety of epidemiological studies have not indicated that occupational exposure to, and personal use of, hair dyes containing the Aminophenols presented a carcinogenic risk. A discussion of the significance of the mutagenic data in the safety assessment and the potential for human effects is presented. On the basis of the available animal and clinical data presented in this report it is concluded that p-, m-, and o-Aminophenols are safe as cosmetic ingredients in the present practices of use and concentrations.

Final Report on the Safety Assessment of Hydroxybenzomorpholine

1991 ◽  
Vol 10 (1) ◽  
pp. 205-213 ◽  
Keyword(s):  
Safety Assessment ◽  
Micronucleus Test ◽  
Coal Tar ◽  
Skin Irritation ◽  
High Dose ◽  
Final Report ◽  
Oral Toxicity ◽  
Hair Dyes ◽  
Hair Dye ◽  
Rabbit Eye

Hydroxybenzomorpholine (HBM) is a heterocyclic compound that is used in cosmetics as a coupler in coal tar hair dyes. No deaths were reported in a subchronic oral toxicity study in rats. Some degenerative changes in the cortical tubules of the kidneys were observed in the mid and high-dose groups. HBM was considered to be practically nonirritating to the rabbit eye and produced only slight skin irritation. HBM was neither a sensitizer nor a photoallergen. HBM was not mutagenic in either the Ames assay or in the mouse micronucleus test. On the basis of the data included in the report, Hydroxybenzomorpholine is considered to be safe as a hair dye ingredient at the current concentrations of use.

scholarly journals 6: Final Report on the Safety Assessment of Disperse Black 9

1986 ◽  
Vol 5 (3) ◽  
pp. 205-223
Keyword(s):  
Acute Toxicity ◽  
Guinea Pigs ◽  
Safety Assessment ◽  
Human Subjects ◽  
Systemic Toxicity ◽  
Final Report ◽  
Hair Dyes ◽  
Hair Dye ◽  
Toxicological Effects ◽  
Reproductive Effects

Disperse Black 9 is a monoazo dye used in hair dyes at a concentration not exceeding 0.4%. In acute toxicity studies, Disperse Black 9 was slightly toxic to practically nontoxic when administered orally and practically nontoxic when administered intraperitoneally. At a concentration of 100% the dye was nonirritating to rabbit eyes and was nonirritating to both the intact and abraded skin of rabbits at concentrations up to 0.38%. Disperse Black 9 at 25% did not produce either irritation or sensitization in guinea pigs. In subchronic oral studies Disperse Black 9 was toxic at 1% but not at 0.1 %. There were no signs of local or systemic toxicity at concentrations up to 0.24% in formulations. In chronic studies, dye containing 0.13% Disperse Black 9 was nontoxic to dogs. A hair dye formulation containing 0.5% Disperse Black 9 produced no significant toxicological effects when applied dermally to mice for 20 months. Disperse Black 9 (0.13% in a dye composite) produced neither teratogenic nor reproductive effects in rats or rabbits. Disperse Black 9 was nonmutagenic in four different assay systems. Disperse Black 9, 0.5% in a hair dye, was not carcinogenic when dermally applied to mice. A 3% suspension of the dye produced no irritation or sensitization in human subjects. On the basis of the available data, it is concluded that Disperse Black 9 is safe for use as a cosmeticingredient.

Final Report on the Safety Assessment of HC Yellow No. 51

2007 ◽  
Vol 26 (2_suppl) ◽  
pp. 113-124
Keyword(s):  
Patch Test ◽  
Safety Assessment ◽  
Coal Tar ◽  
Skin Irritation ◽  
Laboratory Animals ◽  
Test Material ◽  
Oral Exposure ◽  
Final Report ◽  
Hair Dyes ◽  
Hair Dye

HC Yellow No. 5 is a direct hair dye. Hair dyes containing HC Yellow No. 5, as “coal tar” hair dye products, are exempt from the principal adulteration provision and from the color additive provision of the Federal Food, Drug, and Cosmetic Act of 1938 when the label bears a caution statement and “patch test” instructions for determining whether the product causes skin irritation. Preliminary testing on or by individuals should be done using an open patch test that is evaluated at 48 h after application of the test material. Users, therefore, would be able to determine their individual reactions to hair dye products containing HC Yellow No. 5. Absorption of HC Yellow No. 5 is minimal through skin ( < 0.2%). The oral LD50 for rats is 555.56 mg/kg. No significant toxic effects were observed after chronic oral exposure of HD Yellow No. 5 to dogs. Mild dermal irritation, but no dermal sensitization or ocular irritation was observed in laboratory animals. Results of fertility and reproductive performance, teratology, and developmental studies were negative. HC Yellow No. 5 was found to be nonmutagenic and noncytotoxic in standard laboratory assays. A current review of the hair dye epidemiology literature identified that use of direct hair dyes, although not the focus in all investigations, appears to have little evidence of an association with cancer or other adverse events. Based on the available safety test data on HC Yellow No. 5, the Panel determined that this ingredient likely would not have carcinogenic potential as used in hair dyes. The Cosmetic Ingredient Review (CIR) Expert Panel concluded that HC Yellow No. 5 is safe as a hair dye ingredient in the practices of use and concentration as described in this safety assessment.

scholarly journals 5: Final Report on the Safety Assessment of 2-Methylresorcinol and Resorcinol

1986 ◽  
Vol 5 (3) ◽  
pp. 167-203 ◽  
Keyword(s):  
Guinea Pigs ◽  
Safety Assessment ◽  
Human Subjects ◽  
Oral Feeding ◽  
Final Report ◽  
Clinical Testing ◽  
Oral Toxicity ◽  
Hair Dyes ◽  
Hair Dye ◽  
Dermal Application

2-Methylresorcinol and Resorcinol are most frequently used in cosmetic hair dye formulations at concentrations between 1 and 5%. The results of cutaneous and oral feeding studies have indicated that both 2-Methylresorcinol and resorcinol are readily absorbed by rodents and are rapidly eliminated. Acute oral toxicity studies indicate that 2-Methylresorcinol is moderately toxic and Resorcinol is slightly to moderately toxic. Subchronic feeding and dermal studies of bothingredients produced no significant effects. A chronic dermal study was uneventful. Significant skin effects were observed in mice, but not in rabbits, following dermal application of Resorcinol at 5%. A 10% Resorcinol solution was not irritating to guinea pigs. A 2.5% 2-Methylresorcinol solution was classified as a primary irritant in rabbits, but 10% 2-Methylresorcinol was not irritating to guinea pigs. 2-Methylresorcinol was not an ocular irritant at 2.5%, but irritation was produced at 5% concentration in unwashed rabbit eyes. Neither 2-Methylresorcinol at 5% nor Resorcinol at 3% produced sensitization in guinea pigs. 2-Methylresorcinol was not photoallergenic to guinea pigs but was a sensitizer at 10%. Resorcinol was not photoallergenic to guinea pigs but was a sensitizer at 10%. Resorcinol and 2-Methylresorcinol were nonmutagenic in microbial and tissue culture assays for mutagenicity. Topically applied hair dyes containing 2-Methylresorcinol and Resorcinol were negative for carcinogenicity. Resorcinol showed no cocarcinogenic potential when tested on mice and rats. 2-Methylresorcinol at 3% concentration produced no evidence of irritation or sensitization in human subjects. Resorcinol was a mild skin irritant and rare sensitizer in clinical testing, but not when tested on nonclinical groups. On the basis of the available animal and clinical data, it is concluded that 2-Methylresorcinol and Resorcinol are safe as cosmeticingredients in the present practices of use and concentrations.

5 Final Report on the Safety Assessment of 2-Methyl-5-Hydroxyethylaminophenol

1990 ◽  
Vol 9 (2) ◽  
pp. 185-202
Keyword(s):  
Patch Testing ◽  
Safety Assessment ◽  
Human Studies ◽  
Final Report ◽  
Hair Dyes ◽  
Hair Dye

2-Methyl-5-Hydroxyethylaminophenol is used in oxidative hair dyes as a coupler at concentrations ranging from ≤ 0.1 to 5.0%. Only slight absorption was observed in skin studies. The LD50 of the ingredient in mice ranged from 2.5 to 3.84 g/kg. The ingredient was less of an irritant when tested alone than when tested in hair dye formulations. The compound is neither a mutagen nor a teratogen. 2-Methyl-5-Hydroxyethylaminophenol was classified as a nonirritant and weak sensitizer in human studies. Precautionary statements and instructions for patch testing are required on the label when used in oxidative hair dyes. On the basis of the available data included in the report, 2-Methyl-5-Hydroxyethylaminophenol is considered to be safe for use in the present practices of use and concentrations.

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.

6 Final Report on the Safety Assessment of p-Phenylenediamine

1985 ◽  
Vol 4 (3) ◽  
pp. 203-266 ◽  
Keyword(s):  
Safety Assessment ◽  
Animal Species ◽  
Epidemiological Data ◽  
Test System ◽  
Final Report ◽  
Hair Dyes ◽  
Hair Dye ◽  
Animal Data ◽  
Concentration Test ◽  
Animal Toxicity

p-Phenylenediamine is a cosmetic hair dye intermediate used in permanent hair coloring products at concentrations of up to 5 percent (diluted 1:1 with an oxidizing agent prior to application). The extensive animal toxicity test data on p-Phenylenediamine and permanent cosmetic hair dyes containing this compound show that the degree of toxicity varies with concentration, test system and animal species. Animal data support a conclusion that this compound is neither a teratogen nor a carcinogen. Epidemiological data also support that hair dyes containing this ingredient are not carcinogenic. p-Phenylenediamine is a sensitizer and some persons may be sensitized under intended conditions of use. For those persons not sensitized, it is concluded that p-Phenylenediamine is safe as a hair dye ingredient at the current concentrations of use.

Amended Final Report On the Safety Assessment of Pyrocatechol

1997 ◽  
Vol 16 (1_suppl) ◽  
pp. 11-58 ◽  
Author(s):  
F. Alan Andersen
Keyword(s):  
Bone Marrow ◽  
Safety Assessment ◽  
Female Rats ◽  
Tumor Promoter ◽  
Oral Exposure ◽  
Final Report ◽  
Hair Dyes ◽  
Absorption Data ◽  
Male And Female Rats

Pyrocatechol is a phenol used primarily in hair dyes but has one reported use in skin care preparations. When this ingredient was first reviewed it was concluded that Pyrocatechol was safe for use in formulations designed for discontinuous, brief use followed by rinsing from the skin and hair at concentrations of up to 1.0%. This amendment to that report was prepared in order to incorporate the results from several studies, including those reporting immunologic, carcinogenic, and cocarcinogenic effects of Pyrocatechol. In vitro, Pyrocatechol has been shown to affect several immunologic and other properties of murine bone marrow cells, both alone and when combined with hydroquinone. Pyrocatechol, when produced as an hepatic metabolite of benzene, has been reported to concentrate in the bone marrow and to adversely affect hematopoietic precursor cells. These effects are somewhat species specific. In vivo, dermal exposure of mice to Pyrocatechol affects the number and distribution of Langerhans cells at the site of exposure but is not associated with a change in contact sensitivity. Oral exposure of pregnant rats to Pyrocatechol did result in an increase in teratogenic effects. The results of a micromass teratogen test in vitro were also positive. Pyrocatechol was tested in a number of bacterial and mammalian mutagenesis systems. Both negative and positive results were observed. Carcinogenicity studies were conducted in rats and mice. Pyrocatechol was provided in the feed. While adenomatous hyperplasia was noted in both species, adenocarcinomas were seen in male and female rats only. In cocarcinogenesis studies there is a similar pattern of hyperplasia and adenomas of the glandular stomach in the groups exposed to Pyrocatechol alone. When administered with several other carcinogens, Pyrocatechol had a cocarcinogenic effects. Pyrocatechol was not a tumor promoter in dermal studies. Based on these data and the significant potential for skin absorption of Pyrocatechol in leave-on preparations, it was concluded that Pyrocatechol is unsafe for use in leave-on cosmetic formulations. Pyrocatechol used in a rinse-off application such as hair dyes may not present a similar concern if Pyrocatechol is completely and rapidly oxidized. Because no data were available, it was concluded that there are insufficient data to support the safety of this ingredient. The data needed to complete the safety assessment include the extent and rate of oxidation when used in hair dyeing. If not rapidly and completely oxidized, then further chemical characterization of cosmetic grade Pyrocatechol is needed, along with cutaneous absorption data in aqueous and alcohol vehicles and ultraviolet absorption data (if positive, photosensitization studies may be needed).

Final Report on the Safety Assessment of 4-Methoxy-m-Phenylenediamine, 4-Methoxy-m-Phenylenediamine Sulfate, and 4-Methoxy-m-Phenylenediamine-HCl

1992 ◽  
Vol 11 (4) ◽  
pp. 381-422 ◽  
Keyword(s):  
Safety Assessment ◽  
The United States ◽  
Final Report ◽  
Cosmetic Products ◽  
Hair Dyes ◽  
Teratogenic Effects ◽  
Hair Dye ◽  
Tissue Abnormalities ◽  
Rats And Mice ◽  
Dermal Application

The hair dye ingredient 4-Methoxy-m-Phenylenediamine Sulfate (4-MMPDS) prior to 1978 was used extensively used in the United States. Concerns raised because of studies which showed the hair dye to be an animal carcinogen prompted the voluntary reformulation and deletion of 4-MMPD in hair dyes containing this ingredient. No reports were made on the use of this ingredient until 1989 when 17 uses were reported. Assays on volunteers indicate that less than 0.2% of the dye penetrates the scalp and that about 3.9% is absorbed through the skin of the forearm. The dye is metabolized and excreted in the urine; a major metabolic product was 4-acetylamino-2-aminoanisole. The LD50 range in rats of aqueous solutions of 4-MMPD was 400–500 mg/kg. No gross tissue abnormalities were reported in subchronic feeding or dermal studies. 4-MMPD was not an ocular irritant when tested at 2.5%, but was a mild skin irritant when tested at the same concentration. The dermal application of hair dye formulations containing up to 4.0% 4-MMPD were negative for both embryotonic toxicity and teratogenic effects. The results of numerous mutagenic studies vary between the assay system used. 4-MMPD was noncarcinogenic in four dermal carcinogenic studies, but was carcinogenic to both rats and mice in feeding studies. On the basis of the information included in this report, it is concluded that 4-Methoxy-m-Phenylenediamine, 4-Methoxy-m-Phenylenediamine Sulfate, and 4-Methoxy-m-Phenylenediamine HCl are unsafe for use in cosmetic products.

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.

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