Alcohol Denat. is the generic term used by the
cosmetics industry to describe denatured alcohol. Alcohol Denat. and various specially denatured (SD)
alcohols are used as cosmetic ingredients in a wide variety of products. Many denaturants have been previously considered, on an individual basis, as cosmetic ingredients by the Cosmetic Ingredient Review (CIR) Expert Panel, whereas others, including
Brucine and
Brucine Sulfate,
Denatonium Benzoate, and
Quassin, have not previously been evaluated.
Quassin is a bitter
alkaloid obtained from the wood of Quassia amara.
Quassin has been used as an insect antifeedant and
insecticide and several studies demonstrate its effectiveness. At oral doses up to 1000 mg/kg using rats,
Quassin was not toxic in acute and short-term tests, but some reversible piloerection, decrease in motor activity, and a partial loss of righting reflex were found in mice at 500 mg/kg. At 1000 mg/kg given intraperitoneally (i.p.), all mice died within 24 h of receiving treatment. In a cytotoxicity test with brine shrimp, 1 mg/ml of
Quassin did not possess any cytotoxic or antiplasmodial activity.
Quassin administered to rat Leydig cells in vitro at concentrations of 5-25 ng/ml inhibited both the basal and
luteinizing hormone (LH)-stimulated
testosterone secretion in a dose-related fashion.
Quassin at doses up to 2.0 g/kg in
drinking water using rats produced no significant effect on the
body weights, but the mean weights of the testes, seminal vesicles, and epididymides were significantly reduced, and the weights of the anterior pituitary glands were significantly increased. The sperm counts and levels of LH,
follicle-stimulating hormone (FSH), and
testosterone were significantly lower in groups treated with
Quassin.
Brucine is a derivative of 2-hydroxystrychnine. Swiss-Webster mice given
Brucine base, 30 ml/kg, had an acute oral LD(50) of 150 mg/kg, with central nervous system depression followed by convulsions and
seizures in some cases. In those animals that died, respiratory arrest was the cause. The acute i.p. LD(50) for 15 ml/kg of
Brucine base was 62.0 mg/kg, with central nervous system depression prior to the onset of convulsions, just as with oral
Brucine. The acute intravenous (i.v.) LD(50) was 12.0 mg/kg.
Brucine was nonmutagenic in an Ames assay at levels up to 6666 mu g/plate, with and without metabolic activation. In a repeat-insult patch test, for a hair care product containing 47% SD Alcohol 40 (95%), it was reported that
Brucine Sulfate may be considered a nonprimary
irritant and a nonprimary sensitizer. Three different
sunscreen products (35% SD Alcohol 40-B, 72.4% SD Alcohol 40, and 74.5% SD Alcohol 40) did not show any signs of
photoallergy in human subjects. Also, these three formulas did not exhibit any evidence of
phototoxicity in humans.
Denatonium Benzoate is a bitter substance detectable at a concentration of 10 ppb, discernibly bitter at 50 ppb, and unpleasantly bitter
at 10 ppm. The distribution of topically applied
lidocaine, a topical
anesthetic chemically related to
Denatonium Benzoate demonstrated that virtually no
lidocaine appears in the plasma, suggesting that the larger
Denatonium Benzoate molecule also would have little or no systemic exposure.
Denatonium Benzoate (0.1%) did not show adverse effects in 10 rats in an acute inhalation toxicity test and 0.005% to 0.05% was nonirritating to ocular mucosa in 6 albino rabbits. The acute oral LD(50) for the male rats was 640 mg/kg and for females, 584 mg/kg. The LD(50) for the male rabbits was 508 mg/kg and for the female rabbits, 640 mg/kg. In two chronic toxicity studies,
Denatonium Benzoate was administered (by gavage) at 1.6, 8, and 16 mg/kg/day, one using cynomologus monkeys and the other rats, resulted in no compound-related toxicity. The toxicity of SD
Alcohols has also been tested, with implications for the particular denaturant used. An irritation test of 55.65% SD Alcohol 40-B denatured with
Denatonium Benzoate using rabbits produced minimal effects. A spray formula containing 12% SD Alcohol 40-B was found to be nonirritating when evaluated for vaginal mucosal irritation in New Zealand white rabbits. Cosmetic formulations containing SD Alcohol 40-B (denatured with
Denatonium Benzoate) were not sensitizers in repeated insult patch tests. A gel formula containing 29% SD Alcohol 40-B and a spray liquid containing 12% SD Alcohol 40-B did not induce
photoallergy, dermal sensitization, or phototoxic response in human subjects. Although the absorption of
ethanol (aka Alcohol for purposes of cosmetic ingredient labeling) occurs through skin,
ethanol does not appear to affect the integrity of the skin barrier nor reach a very high systemic concentration following dermal exposure.
Ethanol may be found in the bloodstream as a result of inhalation exposure and ingestion. Topically applied,
ethanol can act as a penetration enhancer. Most of the systemic toxicity of
ethanol appears to be associated with chronic abuse of alcohol. Although
ethanol is denatured to make it unfit for consumption, there have been reports of intentional and unintentional consumption of products containing denatured alcohol.
Ethanol is a reproductive and developmental toxicant.
Ethanol is genotoxic in some test systems and it has been proposed that the genotoxic effects of
ethanol are mediated via its metabolite,
acetaldehyde. A brief summary is provided of the effects of chronic ingestion of alcohol including intoxication, liver damage, brain damage, and possible carcinogenicity. The CIR Expert Panel recognizes that certain ingredients in this group are reportedly used in a given product category, but the concentration of use is not available. Because dermal application or inhalation of cosmetic products containing these ingredients will not produce significant systemic exposure to
ethanol, the CIR Expert Panel concluded that safety of the ingredients should be predicated on the safety of the denaturants used. The Panel considered that the adverse effects known to be associated with Alcohol ingestion included in this safety assessment do not suggest a concern for Alcohol Denat. or SD
Alcohols because of the presence of the denaturants, which are added for the express purpose of making the Alcohol unpotable. The CIR Expert Panel has previously conducted safety assessments of t-
Butyl Alcohol,
Diethyl Phthalate,
Methyl Alcohol,
Salicylic Acid,
Sodium Salicylate, and
Methyl Salicylate, in which each was affirmed safe or safe with qualifications. Given their use as denaturants are at low concentrations of use in Alcohol, the CIR Expert Panel determined that Alcohol Denat. denatured with t-
Butyl Alcohol,
Diethyl Phthalate,
Methyl Alcohol,
Salicylic Acid,
Sodium Salicylate, and
Methyl Salicylate is safe as used in cosmetic formulations with no qualifications. Likewise, because they are denatured with either t-
Butyl Alcohol,
Diethyl Phthalate, or
Methyl Alcohol, SD
Alcohols 3-A, 30, 39-B, 39-C, and 40-C all are considered safe as used. The Panel considered the available data for
Denatonium Benzoate and SD Alcohol 40-B to be sufficient to support the safety of these ingredients in
cosmetics.
Denatonium Benzoate is sufficiently bitter that it is an effective denaturant at only 0.0006%. The Panel recognized that data on dermal penetration of
Denatonium Benzoate were not available, but considered that the available data on
lidocaine, a smaller structurally related chemical, indicates that dermal exposure does not result in measurable systemic exposure. The available data, however, were not sufficient to support the safety of
Quassin,
Brucine, and
Brucine Sulfate, Alcohol Denat. denatured with those denaturants, or SD Alcohol 39 and SD Alcohol 40 (SD
Alcohols denatured with
Quassin,
Brucine, and/or
Brucine Sulfate), and in order for the Expert Panel to reach a conclusion for these denaturants, additional data are needed.