Test guidelines for in vitro assessment of dermal absorption and percutaneous penetration of cosmetic ingredients. European Cosmetic, Toiletry and Perfumery Association.
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Numerous cosmetics are used on a daily basis by men, women, and children. Despite a few adverse reactions, cosmetics are a remarkably safe group of products.
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The CIR's 13-year history of cosmetic-ingredient safety review appears to have successfully accomplished its goal of reviewing in a scientific manner the safety of cosmetic chemical ingredients. The method of prioritization has allowed for the identification of the most frequently used and the most biologically active chemicals. To date, 310 cosmetic ingredients have been reviewed, and 33 ingredients are under current review. Although CIR does not have a safety-evaluation report available for every cosmetic ingredient in use, it has proved that CIR is a system of documentation, review, and analysis that can be used to address any safety problem that may exist with any cosmetic ingredient.
The distribution of allergic contact sensitization to cosmetic ingredients was studied in an unselected population, living in Western Copenhagen, Denmark. Ready-to-apply patch tests were mailed to 793 adults, and 567 (71.5%) participated. The tests were read two days after application. Sensitization to one or more of the cosmetic ingredients included in the test was diagnosed in 3.2% of the males and in 4.2% of the females. Old age was associated with an insignificantly higher probability of sensitization (p = 0.06). When adjusted for sex and age, the probability of sensitization was increased by a factor 2.3 among those reporting a history of cosmetic-related skin symptoms as compared to those who did not (p = 0.08). Among males, current daily use of cosmetics was less probable among those sensitized than among those not sensitized (p = 0.02). Contact sensitization to cosmetic ingredients was relatively frequent in the general population. Sex was not an important risk factor for sensitization to cosmetic ingredients.
The cosmetic industry, with the advice of individuals familiar with food and drug safety assessment, set up a Cosmetic Ingredient Review panel of experts and an attendant staff in the fall of 1976, which began to function in July 1977. Its structure and role were carefully developed by a steering committee to assure the independence and credibility of the expert panel's deliberations and decisions and the ultimate publication of a final report on each of many ingredients. That report must conclude 1) that there is reasonable certainty that the ingredient is safe under conditions of use, 2) that it is unsafe, or 3) that the evidence is inadequate to make such a judgment. There is considerable variability in the adequacy of the safety assessments or the assessments of safety in the literature and unpublished reports on ingredients that have been reviewed to date.
As part of our investigation into mutagenic effects of environmental compounds, we studied chemicals allowed as ingredients of cosmetics according to the guidelines of the Council of the European Communities (27 July 1976). We used three systems, the Salmonella/microsome test, the Basc test on Drosophila and the micronucleus test on mouse bone marrow. Of the 31 chemicals tested, 15 were mutagenic in the Ames test; and of these, 5 were also mutagenic in the Basc test and 2 in the micronucleus test.
The purpose of this paper is to report on the ability of an in-house porcine corneal opacity and permeability assay (PCOP) to predict eye irritation for cosmetic ingredients. Preliminary studies showed that the PCOP assay could accurately predict eye irritation class for liquid and water soluble materials. To broaden our experience a larger study on 50 cosmetic ingredients of this group was conducted. A prediction model (PM) was obtained based on only one endpoint-permeability measured after 30-min exposure O.D.30. This PM allows to distinguish nonirritating compounds (if O.D.30 < 0.35) from irritating (if O.D.30 > or = 0.35). Forty-nine of the 50 ingredients tested in the PCOP assay were accurately classified. The agreement was high (concordance 98%-kappa = 0.96). For 43 of the test substances an equation PM was obtained to predict the MAS. Despite satisfactory statistical coefficients this algorithm is not recommended due to wide 95% confidence intervals. These results confirm the usefulness of the PCOP for water-soluble cosmetic ingredients to discriminate nonirritants (MAS < or = 15) and irritants (MAS >15). For this type of ingredients the PCOP seems to be better than the BCOP to predict irritation class. Future work will be done to compare the BCOP and PCOP performances and to develop an appropriate protocol for water insoluble compounds.
Since the basic domain of human immunodeficiency virus type I (HIV-1) transactivator of transcription (TAT) protein was reported to possess the ability to traverse biological membranes efficiently, various therapeutic proteins have been attached to TAT for the purpose of therapy. In this study, the tripeptide GKH (glycine-lysine-histidine) derived from parathyroid hormone (PTH), known as lipolytic peptide, was attached to 9-poly lysine (TAT) to be used as a cosmetic ingredient in slimming products. TAT-GKH at 10(-5) M induced approximately 37.6% and 41.5% maximal lipolytic effects in cultured 3T3-L1 differentiated adipocytes and in epididymal adipocytes isolated from rats, respectively, compared with basal lipolysis. The lipolytic effect of GKH was not changed by TAT-GKH fusion. In cytotoxicity tests, there was no cytotoxicity in any dose concentration of TAT-GKH. We confirmed that TAT-GKH induced lipolytic activity by GKH without cytotoxicity and with the possibility of its use as a safe cosmetic ingredient. TAT-GKH elevated penetration into excised hairless mice skin 36 times more efficiently than GKH. TAT-GKH can be used as a cosmetic ingredient in slimming products, with both penetration enhancement and lipolytic effect without cytotoxicity.
Diethyl phthalate (DEP; CAS No. 84-66-2) has many industrial uses, as a solvent and vehicle for fragrance and cosmetic ingredients and subsequent skin contact. This review focuses on its safety in use as a solvent and vehicle for fragrance and cosmetic ingredients. Available data are reviewed for acute toxicity, eye irritation, dermal irritation, dermal sensitization, phototoxicity, photoallergenicity, percutaneous absorption, kinetics, metabolism, subchronic toxicity, teratogenicity, reproductive toxicity, estrogenic potential, genetic toxicity, chronic toxicity, carcinogenicity, in vitro toxicity, ecotoxicity, environmental fate and potential human exposure. No toxicological endpoints of concern have been identified. Comparison of estimated exposure (0.73 mg/kg/day) from dermal applications of fragrances and cosmetic products with other accepted industrial (5 mg/m(3) in air) and consumer exposures (350 mg/l in water; 0.75 mg/kg/day oral exposure) indicates no significant toxic liability for the use of DEP in fragrances and cosmetic products.
United States federal regulations require ingredient listing on cosmetics labeled after November 30, 1976. Standardized ingredient nomenclature from a reference text will be utilized to minimize confusion which might arise if various synonyms for chemical names were used. This new information on cosmetics labeling will assist physicians in the diagnosis of cosmetic-related dermatoses. It should facilitate the patch testing procedure by enabling the dermatologist to focus attention on suspect ingredients early in the evaluation. Once the identify of offending ingredients in a cosmetic has been determined for a particular patient, the individual will have the opportunity to avoid those ingredients and related ingredients in future purchases of cosmetics.
The Scientific Committee on Cosmetology (SCC) of the Commission of the European Communities was established in 1978 to assist the Commission in the application of the 76/768 Directive, which regulates the production and marketing of cosmetics products. The Committee has been asked to update the general guidelines, defined in 1982, for testing cosmetics ingredients with the aim of ensuring consumers' safety. In the present paper the full document approved by the SCC in October 1990 is reported. This new document is based on the experience of the Committee over the last 10 years, during which more than 400 cosmetics ingredients have been evaluated. The document also highlights the need to proceed to define standard methods to be used to assess dermal absorption and phototoxicity--areas in which international guidelines have not yet been approved. The document also includes some comments made by the author in order to explain better the position of the Committee in relation to certain items.
The acute cytotoxicities of four cosmetic ingredients: a preservative, imidazolidinylurea (IU) and three mild surfactants, cocamido propyl hydroxy sultaine (CAS), magnesium laureth sulfate (Mg LES), and decyl glucoside (APG) were studied using sea urchin eggs. The cellular targets of these compounds were identified by studying the effects on calcium homeostasis, intracellular pH, sodium and potassium contents, protein and DNA synthesis, and protein phosphorylation. These compounds inhibited the first cleavage of sea urchin eggs in a dose-dependent fashion with half maximal doses (IC50) from 30 microg/ml for Mg LES, 60 microg/ml for IU, 83 microg/ml for CAS, to above 400 microg/ml for APG. The time at which a compound showed the greatest toxicity to the cell cycle was definable for APG (between 20 and 50 min postfertilization) and IU (from fertilization to 50 min later); the other compounds being toxic throughout division. Compounds exhibited toxicity to a wide range of cellular targets. IU, the least toxic, mainly operates through inhibition of protein and DNA syntheses. CAS and Mg LES produced nonspecific cytotoxicity related to alterations of membrane and endomembrane permeabilities resulting in ionic disequilibrium (Na+, K+, Ca2+) and inhibition of intracellular storage of Ca2+. The APG effect mainly involved intracellular pH and DNA synthesis, a hypothesis suggested by the narrow postfertilization period of maximal toxicity.
Certain commercially available cosmetic products have been found to contain the ingredient urocanic acid. We have shown that the solar irradiation in vitro of one such lotion resulted in the formation of cis urocanic acid. The irradiated lotion, when applied topically to the skin of hairless mice, systemically suppressed the normal contact hypersensitivity reaction to 2,4-dinitrofluorobenzene by 68%. In addition, mice exposed to a minimally erythemal dose of ultraviolet B (280-320 nm) radiation, normally sub-immunosuppressive, showed a 56% suppression of the contact hypersensitivity reaction if they were irradiated through the topically applied cosmetic lotion.
Previous study showed that the cosmetic ingredient chemical azulene and its derivative gauiazulene exhibited photomutagenicity four- to five-fold higher than spontaneous mutation in Salmonella typhimurium TA102. In this study, phototoxicity including photogenotoxicity of azulene in human Jurkat T-cells is reported. When the cell suspensions are irradiated by light (UVA plus visible light) in the presence of azulene, an azulene dose-dependent cellular DNA damage is observed. At the highest azulene concentration of 50 microM, the average DNA fragmentation is 33 +/- 10%, determined by single cell gel electrophoresis (Comet assay). Cell viability assay using fluorescein diacetate indicates that the cells could endure the damage and remain viable. Further study revealed that the combination of light and azulene can cause single-strand cleavage on pure PhiX174 plasmid DNA in solution. Studies using scavengers reveal that singlet oxygen and free radicals are involved in causing DNA cleavage. This suggests that the photomutagenicity of azulene in S. typhimurium TA102 could be due to DNA fragmentation caused by the concurrent exposure to azulene and light.
A review of the procedures, methods used, and the data that are required to evaluate the safety of cosmetic ingredients is presented. The results of the program and the limitations placed upon the use of some ingredients are discussed.
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