Daniel C. Liebler

Final Report of the Safety Assessment of Kojic Acid as Used in Cosmetics

Kojic acid functions as an antioxidant in cosmetic products. Kojic acid was not a toxicant in acute, chronic, reproductive, and genotoxicity studies. While some animal data suggested tumor promotion and weak carcinogenicity, kojic acid is slowly absorbed into the circulation from human skin and likely would not reach the threshold at which these effects were seen. The available human sensitization data supported the safety of kojic acid at a use concentration of 2% in leave-on cosmetics. Kojic acid depigmented black guinea pig skin at a concentration of 4%, but this effect was not seen at 1%. The Cosmetic Ingredient Review (CIR) Expert Panel concluded that the 2 end points of concern, dermal sensitization and skin lightening, would not be seen at use concentrations below 1%; therefore, this ingredient is safe for use in cosmetic products up to that level.

Final Amended Safety Assessment of Hydroquinone as Used in Cosmetics

Hydroquinone is an aromatic compound that functions in cosmetics as an antioxidant, fragrance, reducing agent, or polymerization inhibitor. Hydroquinone is also used as a skin bleaching agent. Safety and toxicity information indicate that hydroquinone is dermally absorbed in humans from both aqueous and alcoholic formulations and is excreted mainly as the glucuronide or sulfate conjugates. Hydroquinone is associated with altered immune function in vitro and in vivo in animals and an increased incidence of renal tubule cell tumors and leukemia in F344 rats, but the relevance to humans is uncertain. Quantitatively, however, the use of hydroquinone in cosmetics is unlikely to result in renal neoplasia through this mode of action. Thus, hydroquinone is safe at concentrations of ≤1% in hair dyes and is safe for use in nail adhesives. Hydroquinone should not be used in other leave-on cosmetics.

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

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.

Safety Assessment of Cyclomethicone, Cyclotetrasiloxane, Cyclopentasiloxane, Cyclohexasiloxane, and Cycloheptasiloxane

Cyclomethicone (mixture) and the specific chain length cyclic siloxanes (n = 4-7) reviewed in this safety assessment are cyclic dimethyl polysiloxane compounds. These ingredients have the skin/hair conditioning agent function in common. Minimal percutaneous absorption was associated with these ingredients and the available data do not suggest skin irritation or sensitization potential. Also, it is not likely that dermal exposure to these ingredients from cosmetics would cause significant systemic exposure. The Cosmetic Ingredient Review Expert Panel concluded that these ingredients are safe in the present practices of use and concentration.

Safety Assessment of Propylene Glycol, Tripropylene Glycol, and PPGs as Used in Cosmetics:

Propylene glycol is an aliphatic alcohol that functions as a skin conditioning agent, viscosity decreasing agent, solvent, and fragrance ingredient in cosmetics. Tripropylene glycol functions as a humectant, antioxidant, and emulsion stabilizer. Polypropylene glycols (PPGs), including PPG-3, PPG-7, PPG-9, PPG-12, PPG-13, PPG-15, PPG-16, PPG-17, PPG-20, PPG-26, PPG-30, PPG-33, PPG-34, PPG-51, PPG-52, and PPG-69, function primarily as skin conditioning agents, with some solvent use. The majority of the safety and toxicity information presented is for propylene glycol (PG). Propylene glycol is generally nontoxic and is noncarcinogenic. Clinical studies demonstrated an absence of dermal sensitization at use concentrations, although concerns about irritation remained. The CIR Expert Panel determined that the available information support the safety of tripropylene glycol as well as all the PPGs. The Expert Panel concluded that PG, tripropylene glycol, and PPGs ≥3 are safe as used in cosmetic formulations when formulated to be nonirritating.

Amended safety assessment of formaldehyde and methylene glycol as used in cosmetics.

Formaldehyde and methylene glycol may be used safely in cosmetics if established limits are not exceeded and are safe for use in nail hardeners in the present practices of use and concentration, which include instructions to avoid skin contact. In hair-smoothing products, however, in the present practices of use and concentration, formaldehyde and methylene glycol are unsafe. Methylene glycol is continuously converted to formaldehyde, and vice versa, even at equilibrium, which can be easily shifted by heating, drying, and other conditions to increase the amount of formaldehyde. This rapid, reversible formaldehyde/methylene glycol equilibrium is distinguished from the slow, irreversible release of formaldehyde resulting from the so-called formaldehyde releaser preservatives, which are not addressed in this safety assessment (formaldehyde releasers may continue to be safely used in cosmetics at the levels established in their individual Cosmetic Ingredient Review safety assessments).

Safety assessment of Vitis vinifera (grape)-derived ingredients as used in cosmetics.

The Cosmetic Ingredient Review Expert Panel (Panel) assessed the safety of 24 Vitis vinifera (grape)-derived ingredients and found them safe in the present practices of use and concentration in cosmetics. These ingredients function in cosmetics mostly as skin-conditioning agents, but some function as antioxidants, flavoring agents, and/or colorants. The Panel reviewed the available animal and clinical data to determine the safety of these ingredients. Additionally, some constituents of grapes have been assessed previously for safety as cosmetic ingredients by the Panel, and others are compounds that have been discussed in previous Panel safety assessments.

Final Report of the Cosmetic Ingredient Review Expert Panel on the Safety Assessment of Dicarboxylic Acids, Salts, and Esters:

The CIR Expert Panel assessed the safety of dicarboxylic acids and their salts and esters as used in cosmetics. Most dicarboxylic acids function in cosmetics as pH adjusters or fragrance ingredients, but the functions of most of the salts in cosmetics are not reported. Some of the esters function as skin conditioning or fragrance ingredients, plasticizers, solvents, or emollients. The Expert Panel noted gaps in the available safety data for some of the dicarboxylic acid and their salts and esters in this safety assessment. The available data on many of the ingredients are sufficient, however, and similar structural activity relationships, biologic functions, and cosmetic product usage suggest that the available data may be extrapolated to support the safety of the entire group. The Panel concluded that the ingredients named in this report are safe in the present practices of use and concentration.

Safety Assessment of 1,2-Glycols as Used in Cosmetics

Caprylyl glycol and related 1,2-glycols are used mostly as skin and hair conditioning agents and viscosity agents in cosmetic products, and caprylyl glycol and pentylene glycol also function as cosmetic preservatives. The Cosmetic Ingredient Review (CIR) Expert Panel noted that, while these ingredients are dermally absorbed, modeling data predicted decreased skin penetration of longer chain 1,2-glycols. Because the negative oral toxicity data on shorter chain 1,2-glycols and genotoxicity data support the safety of the 1,2-glycols reviewed in this safety assessment, the Panel concluded that these ingredients are safe in the present practices of use and concentration described in this safety assessment.

Safety Assessment of Citric Acid, Inorganic Citrate Salts, and Alkyl Citrate Esters as Used in Cosmetics:

The CIR Expert Panel (Panel) assessed the safety of citric acid, 12 inorganic citrate salts, and 20 alkyl citrate esters as used in cosmetics, concluding that these ingredients are safe in the present practices of use and concentration. Citric acid is reported to function as a pH adjuster, chelating agent, or fragrance ingredient. Some of the salts are also reported to function as chelating agents, and a number of the citrates are reported to function as skin-conditioning agents but other functions are also reported. The Panel reviewed available animal and clinical data, but because citric acid, calcium citrate, ferric citrate, manganese citrate, potassium citrate, sodium citrate, diammonium citrate, isopropyl citrate, stearyl citrate, and triethyl citrate are generally recognized as safe direct food additives, dermal exposure was the focus for these ingredients in this cosmetic ingredient safety assessment.