Safety Assessment of Hops as Used in Cosmetics.

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of Humulus Lupulus (Hops) Extract (reported functions include antimicrobial agent and hair conditioning agent) and Humulus Lupulus (Hops) Oil (reported function is fragrance). The Panel reviewed the relevant data related to these ingredients. Because final product formulations may contain multiple botanicals, each containing the same constituents of concern, formulators are advised to be aware of these constituents and to avoid reaching levels that may be hazardous to consumers. For these ingredients, the Panel was concerned about the presence of 8-prenylnaringenin, ß-myrcene, and quercetin in cosmetics, which could result in estrogenic effects, dermal irritation, and genotoxicity, respectively. Industry should use current good manufacturing practices to limit impurities and constituents of concern. The Panel concluded that Humulus Lupulus (Hops) Extract and Humulus Lupulus (Hops) Oil are safe in cosmetics in the present practices of use and concentration when formulated to be non-sensitizing.

Safety Assessment of Helianthus annuus (Sunflower)-Derived Ingredients as Used in Cosmetics.

This is a review of the scientific literature and unpublished data that are relevant for assessing the safety of 12 Helianthus annuus (sunflower)-derived ingredients as used in cosmetics. Because final product formulations may contain multiple botanicals, each containing similar constituents of concern, formulators are advised to be aware of these constituents and to avoid levels that may be hazardous to consumers. Helianthus annuus (sunflower)-derived ingredients may contain allergens, including 2S albumins and sesquiterpene lactones. Industry should use current good manufacturing practices (cGMP) to limit impurities and constituents of concern. The Expert Panel for Cosmetic Ingredient Safety (Panel) concluded that 9 Helianthus annuus (sunflower) seed- and flower-derived ingredients are safe as used in cosmetics in the present practices of use and concentration described in this safety assessment. The data are insufficient to evaluate the safety of 3 ingredients that are derived from other plant parts.

Safety Assessment of Ethers and Esters of Ascorbic Acid as Used in Cosmetics.

The Expert Panel for Cosmetic Ingredient Safety (Panel) reviewed the safety of 7 ethers and esters of ascorbic acid, which collectively function as antioxidants, skin-conditioning agents, skin protectants, fragrance ingredients, and skin bleaching agents in cosmetic products. The Panel reviewed relevant data relating to the safety of these ingredients, and concluded that the ethers and esters of ascorbic acid are safe in the present practices of use and concentration, as described in this safety assessment.

Safety Assessment of Plant-Derived Proteins and Peptides as Used in Cosmetics.

The Expert Panel for Cosmetic Ingredient Safety (Panel) reviewed the safety of 19 plant-derived proteins and peptides, which function mainly as skin and/or hair conditioning agents in personal care products. The Panel concluded that 18 plant-derived proteins and peptides are safe as used in the present practices of use and concentration as described in this safety assessment, while the data on Hydrolyzed Maple Sycamore Protein are insufficient to determine safety.

Safety Assessment of Phosphoric Acid and Its Salts as Used in Cosmetics.

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of Phosphoric Acid and its salts (31 ingredients), which are reported to function as buffering agents, corrosion inhibitors, chelating agents, and pH adjusters in cosmetic products. The Panel reviewed data relating to the safety of these ingredients and concluded that Phosphoric Acid and its salts are safe in the present practices of use and concentration in cosmetics when formulated to be nonirritating.

Safety Assessment of Polyaminopropyl Biguanide (Polyhexamethylene Biguanide Hydrochloride) as Used in Cosmetics.

The Expert Panel for Cosmetic Ingredient Safety (Panel) reviewed the safety of Polyaminopropyl Biguanide (polyhexamethylene biguanide hydrochloride), which functions as a preservative in cosmetic products. The Panel reviewed relevant data relating to the safety of this ingredient and concluded that Polyaminopropyl Biguanide is safe in cosmetics in the present practices of use and concentration described in the safety assessment, when formulated to be nonirritating and nonsensitizing, which may be based on a quantitative risk assessment or other accepted methodologies. The Panel also concluded that the data are insufficient to determine the safety of Polyaminopropyl Biguanide in products that may be incidentally inhaled.

Safety Assessment of Ceramides as Used in Cosmetics.

The Expert Panel for Cosmetic Ingredient Safety (Panel) reviewed the safety of ceramides, which function in cosmetics primarily as hair-conditioning agents and skin-conditioning agents-miscellaneous. The Panel considered relevant data related to these ingredients. The Panel concluded that ceramides were safe in cosmetics in the present practices of use and concentration described in this safety assessment.

Safety Assessment of Fatty Acid Amidopropyl Dimethylamines as Used in Cosmetics.

The Cosmetic Ingredient Review Expert Panel (Panel) reviewed the safety of fatty acid amidopropyl dimethylamines, which function primarily as antistatic agents in cosmetic products. The relevant animal and human data reviewed for these ingredients indicate that they are potential dermal sensitizers that may be due in part by the sensitizing impurity, 3,3-dimethylaminopropylamine. The Panel concluded that fatty acid amidopropyl dimethylamines were safe as cosmetic ingredients when they are formulated to be nonsensitizing, which may be based on a quantitative risk assessment.

Amended Safety Assessment of Methylisothiazolinone as Used in Cosmetics.

The Cosmetic Ingredient Review Expert Panel (Panel) reviewed the safety of methylisothiazolinone (MI), which functions as a preservative. The Panel reviewed relevant animal and human data provided in this safety assessment and in a previously published safety assessment of MI and concluded that MI is safe for use in rinse-off cosmetic products at concentrations up to 100 ppm and safe in leave-on cosmetic products when they are formulated to be nonsensitizing, which may be determined based on a quantitative risk assessment.

Safety Assessment of PEGs Cocamine and Related Ingredients as Used in Cosmetics.

The Cosmetic Ingredient Review Expert Panel assessed the safety of 47 polyethylene glycols (PEGs) cocamine and related ingredients, which are reported to function mostly as surfactants and antistatic agents. The Panel reviewed the relevant data and developed a framework to satisfy previously identified data deficiencies for this group of materials as well as extend the scope of related materials covered by the analysis. The irritation potential of these ingredients is consistent with the surface active properties that are characteristic of surfactants. The Panel concluded that the PEGs cocamine and related ingredients were safe as ingredients in cosmetic formulations in the current practices of use and concentration when formulated to be nonirritating.

The Cosmetic Ingredient Review Program-Expert Safety Assessments of Cosmetic Ingredients in an Open Forum.

The Cosmetic Ingredient Review (CIR) is a nonprofit program to assess the safety of ingredients in personal care products in an open, unbiased, and expert manner. Cosmetic Ingredient Review was established in 1976 by the Personal Care Products Council (PCPC), with the support of the US Food and Drug Administration (USFDA) and the Consumer Federation of America (CFA). Cosmetic Ingredient Review remains the only scientific program in the world committed to the systematic, independent review of cosmetic ingredient safety in a public forum. Cosmetic Ingredient Review operates in accordance with procedures modeled after the USFDA process for reviewing over-the-counter drugs. Nine voting panel members are distinguished, such as medical professionals, scientists, and professors. Three nonvoting liaisons are designated by the USFDA, CFA, and PCPC to represent government, consumer, and industry, respectively. The annual rate of completing safety assessments accelerated from about 100 to more than 400 ingredients by implementing grouping and read-across strategies and other approaches. As of March 2017, CIR had reviewed 4,740 individual cosmetic ingredients, including 4,611 determined to be safe as used or safe with qualifications, 12 determined to be unsafe, and 117 ingredients for which the information is insufficient to determine safety. Examples of especially challenging safety assessments and issues are presented here, including botanicals. Cosmetic Ingredient Review continues to strengthen its program with the ongoing cooperation of the USFDA, CFA, the cosmetics industry, and everyone else interested in contributing to the process.

Safety Assessment of Cross-Linked Alkyl Acrylates as Used in Cosmetics.

The Cosmetic Ingredient Review (CIR) Expert Panel assessed the safety of cross-linked alkyl acrylates as used in cosmetics. The 23 cross-linked alkyl acrylates included in this safety assessment are reported to function as absorbents, film formers, emulsion stabilizers, viscosity increasing agents, suspending agents, binders, and/or skin-conditioning agents. The Panel reviewed available animal and clinical data, as well as information from previous CIR reports on monomer components. Because data were not available for the individual ingredients, and because residual monomer may be present, the Panel extrapolated from previous reports to support safety. The Panel concluded that cross-linked alkyl acrylates are safe in the present practices of use and concentration, provided that they are not polymerized in benzene. For those ingredients polymerized in benzene, the data available were insufficient to make a determination of safety. A risk assessment for the amount of benzene present would be needed.

Safety Assessment of Alumina and Aluminum Hydroxide as Used in Cosmetics.

This is a safety assessment of alumina and aluminum hydroxide as used in cosmetics. Alumina functions as an abrasive, absorbent, anticaking agent, bulking agent, and opacifying agent. Aluminum hydroxide functions as a buffering agent, corrosion inhibitor, and pH adjuster. The Food and Drug Administration (FDA) evaluated the safe use of alumina in several medical devices and aluminum hydroxide in over-the-counter drugs, which included a review of human and animal safety data. The Cosmetic Ingredient Review (CIR) Expert Panel considered the FDA evaluations as part of the basis for determining the safety of these ingredients as used in cosmetics. Alumina used in cosmetics is essentially the same as that used in medical devices. This safety assessment does not include metallic or elemental aluminum as a cosmetic ingredient. The CIR Expert Panel concluded that alumina and aluminum hydroxide are safe in the present practices of use and concentration described in this safety assessment.

Safety Assessment of Talc as Used in Cosmetics.

The Cosmetic Ingredient Review Expert Panel (Panel) assessed the safety of talc for use in cosmetics. The safety of talc has been the subject of much debate through the years, partly because the relationship between talc and asbestos is commonly misunderstood. Industry specifications state that cosmetic-grade talc must contain no detectable fibrous, asbestos minerals. Therefore, the large amount of available animal and clinical data the Panel relied on in assessing the safety of talc only included those studies on talc that did not contain asbestos. The Panel concluded that talc is safe for use in cosmetics in the present practices of use and concentration (some cosmetic products are entirely composed of talc). Talc should not be applied to the skin when the epidermal barrier is missing or significantly disrupted.

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).

Monomethylarsonic acid and dimethylarsinic acid: developmental toxicity studies with risk assessment.

BACKGROUND: The toxicity of arsenic compounds is highly dependent on the valence and methylation state of the compound. Although there is extensive published literature on the potential developmental toxicity of inorganic arsenic compounds, little exists on organic arsenic compounds and, in particular, studies conducted in accordance with conventional regulatory guidelines appropriate for risk assessment are rare. The organic arsenic compounds, monomethylarsonic acid (MMAV) and dimethylarsinic acid (DMAV, also called cacodylic acid), are the active ingredients in pesticide products that are used mainly for weed control. MMAV and DMAV are also metabolites of inorganic arsenic formed intracellularly by most living organisms (animals, plants and bacteria). In mammals, this occurs predominantly in liver cells. METHODS: Conventional developmental toxicity studies of orally administered MMAV and DMAV in the Sprague-Dawley rat and New Zealand White rabbit were conducted in commercial contract laboratories in the late 1980 s for regulatory compliance. The results of these studies are summarized and presented to broaden the data available in the public domain. RESULTS: In both species, data shows an absence of dose-related effects at organic arsenic exposures that were not maternally toxic. MMAV doses of 0, 10, 100, and 500 mg/kg/day (rat) and 0, 1, 3, 7, and 12 mg/kg/day (rabbit) and DMAV doses of 0, 4, 12, and 36 mg/kg/day (rat) and 0, 3, 12, and 48 mg/kg/day (rabbit) were administered by oral gavage daily during organogenesis (Gestation Day [GD] 6-15, rat; GD 7-19, rabbit) and the litters examined at maternal sacrifice (GD 20, rat; GD 29, rabbit). After treatment with MMAV, maternal and fetal toxicity were observed at the highest doses of 500 mg/kg/day (rat) and 12 mg/kg/day (rabbit), but no treatment-related developmental toxicity at the lower doses, even in the presence of minimal maternal toxicity in the rat at 100 mg/kg/d. There was no evidence of teratogenicity associated with MMAV treatment. With DMAV, maternal and developmental toxicity were observed in the rat at 36 mg/kg/day, with a higher than spontaneous incidence of fetuses with diaphragmatic hernia. In the rabbit at 48 mg/kg/day, there was marked maternal toxicity, culminating for most females in abortion and with no surviving fetuses for evaluation. There was no treatment-related maternal or developmental toxicity in the rat or rabbit at 12 mg/kg/day. Based on pregnancy outcome, the developmental toxicity no observed adverse effect level (NOAEL) for orally administered MMAV were 100 and 7 mg/kg/day in the rat and rabbit, respectively, and for DMAV were 12 mg/kg/day in both species. CONCLUSIONS: Margins of exposure estimated based on conservative estimates of daily intakes of arsenic in all of its forms indicate that exposure to MMAV or DMAV at environmentally relevant exposure levels, by the oral route (the environmentally relevant route of exposure) is unlikely to pose a risk to pregnant women and their offspring.