Tocopherol and its several ester and ether derivatives all function as antioxidants in cosmetic formulations; they also have other functions, such as skin conditioning. Tocopheryl Acetate, Tocopherol, and Tocopheryl Linoleate are used in 2673 formulations, generally at concentrations of up to 36%, 5%, and 2%, respectively, although Tocopheryl Acetate is 100% of vitamin E oil. Tocophersolan, Tocopheryl Linoleate/Oleate, Tocopheryl Nicotinate, Tocopheryl Succinate, Dioleyl Tocopheryl Methylsilanol, and Potassium Ascorbyl Tocopheryl Phosphate, combined, are used in 36 formulations at concentrations lower than those reported for the frequently used ingredients. Tocopherol may be isolated from vegetable oils or synthesized using isophytol and methylhydroquinone. Tocopherol, Tocopheryl Acetate, Tocopheryl Linoleate, and Tocopheryl Succinate all were absorbed in human skin. In rat skin, Tocopheryl Acetate is hydrolyzed to Tocopherol. Tocopherol is a natural component of cell membranes thought to protect against oxidative damage. Tocopherol, Tocopheryl Acetate, and Tocopheryl Succinate each were reported to protect against ultraviolet radiation-induced skin damage. These ingredients are generally not toxic in animal feeding studies, although very high doses (>2 g/kg/day) have hemorrhagic activity. These ingredients are generally not irritating or sensitizing to skin or irritating to eyes, although a Tocopheryl Acetate did produce sensitization in one animal test, and Tocophersolan was a slight eye irritant in an animal test. Reproductive and developmental toxicity tests in animals using Tocopherol, Tocopheryl Acetate, Tocopheryl Succinate, and Tocophersolan were all negative or showed some effect of reducing toxicity. Tocopherol, Tocopheryl Acetate, Tocopheryl Succinate, and Dioleyl Tocopheryl Methylsilanol were almost uniformly negative. These ingredients exhibit antimutagenic activity consistent with their antioxidant properties. Tocopherol was not carcinogenic. The ability of Tocopherol, Tocopheryl Acetate, and Tocopheryl Succinate to modulate the carcinogenic effect of other agents (e.g., tumor promotion) has been extensively studied. One study showing tumor promotion in mice may be discounted as not reproducible and not consistent with the large volume of data suggesting that the antioxidant properties of these agents protect against tumor induction. Specifically, the frequent use of Tocopherol as a negative control in other tumor promotion studies suggests that Tocopherol is not a tumor promoter. Tocopherol has been shown to reduce the photocarcinogenic effect of ultraviolet radiation in mice. Similar studies with Tocopheryl Acetate and Tocopheryl Succinate, however, demonstrated some enhancement of photocarcinogenesis, although the effect was not dose related. In clinical studies, Tocopherol, Tocopheryl Acetate, and Tocopheryl Nicotinate were not irritants or sensitizers. A report of a large number of positive patch-tests to Tocopheryl Linoleate in one cosmetic product were considered to result from a contaminant or metabolite. The Cosmetic Ingredient Review Expert Panel considered that these data provide an adequate basis on which to conclude that Tocopherol, Tocophersolan, Tocopheryl Acetate, Tocopheryl Linoleate, Tocopheryl Linoleate/Oleate, Tocopheryl Nicotinate, Tocopheryl Succinate, Dioleyl Tocopheryl Methylsilanol, and Potassium Ascorbyl Tocopheryl Phosphate are safe as used in cosmetic formulations. Although there were no inhalation toxicity data, these ingredients are used at such low concentrations in hair sprays that no inhalation toxicity risk was considered likely. Because methylhydroquinone is used in the chemical synthesis of Tocopherol, there was concern that hydroquinone may be present as an impurity. In such cases, residual levels of hydroquinone would be expected to be limited to those achieved by good manufacturing practices.

Dilauryl thiodipropionate (DLTDP), dicetyl thiodipropionate, dimyristyl thiodipropionate, distearyl thiodipropionate, and ditridecyl thiodipropionate are dialkyl esters of their respective alcohols and thiodipropionic acid (TDPA) used in cosmetics. Ingested DLTDP was excreted in the urine as TDPA. Single-dose acute oral and parenteral studies and subchronic and chronic repeated dose oral studies did not suggest significant toxicity. Neither DLTDP nor TDPA was irritating to animal skin or eyes and they were not sensitizers. TDPA was neither a teratogen nor a reproductive toxicant. Genotoxicity studies were negative for TDPA and DLTDP. Clinical testing demonstrated some evidence of irritation but no sensitization or photosensitization. The Cosmetic Ingredient Review Expert Panel considered that the data from DLTDP reasonably may be extrapolated to the other dialkyl esters and concluded that these ingredients were safe for use in cosmetic products that are formulated to be nonirritating.

HC Orange No. 1 is used as a colorant in semipermanent hair dyes. The highest concentration reported to be used is 0.15%, but information from manufacturers suggested that higher concentrations may be used in the future. Skin penetration through cadaver skin was 1.28% at 24 hours. In studies using rats, acute oral exposure studies produced little toxicity, and short-term toxicity studies produced reduced body weight and increased liver and kidney weights, relative to controls in animals fed 0.5% HC Orange No. 1. There was no evidence of reproductive or developmental toxicity in rats fed up to 1.25% HC Orange No. 1 or in a multigeneration study using rats in which 0.15% HC Orange No. 1 was painted on the skin. While evidence suggests this ingredient is a mild ocular irritant, no skin irritation, sensitization, or photosensitization was seen in animal or clinical tests. The preponderance of data (four out offive studies) indicate that this ingredient is not genotoxic. Hepatocellular and parathyroid hyperplasia were noted in the dermal carcinogenicity study, but the overall findings were clearly negative. Because the highest concentration tested that produced no significant sensitization in clinical tests was 3%, the Expert Panel concluded that safety could be assured only at levels ≤3%. The Expert Panel recognized that this concentration may be greater than that currently used in hair dye formulations.

Biotin is a water-soluble vitamin used as a hair-conditioning agent and a skin-conditioning agent in many cosmetic products at concentrations ranging from 0.0001% to 0.6%. Although Biotin does absorb some ultraviolet (UV) radiation, the absorption shows no peaks in the UVA or UVB region. Biotin is rapidly metabolized and excreted in urine. Little acute oral toxicity is seen in animal tests. Short-term and subchronic toxicity studies likewise found no evidence of toxicity. Although intradermal injection of a small quantity of Biotin (0.1 ml) into guinea pig skin did not produce skin irritation, Biotin (0.1% at pH 7.3) did produce slight, transient ocular irritation in rabbit eyes. Biotin was not mutagenic in bacterial tests, but positive results were found in a Tradescantia micronucleus test. There was evidence of an increase in the number of resorptions in rats receiving Biotin by subcutaneous injection, with concomitant decreases in fetal, uterine, and placental weights. Another study of mice receiving Biotin orally or by subcutaneous injection found no differences between control and treatment groups. Although there is one case study reporting an urticarial reaction in the literature, there are a very large number of individuals exposed to Biotin on a daily basis, and there is not a parallel appearance of irritation, sensitization, or other adverse reactions. Based on these available data, it was concluded that Biotin is safe as used in cosmetic formulations.