Development and economic evaluation of an eco-friendly biocatalytic synthesis of emollient esters.

During the past decades the understanding and prospects of enzyme-catalysed reactions have been massively widened and there are a number of implemented large-scale enzymatic processes mainly based in the use of commercial biocatalysts. As it might happen that the same process can be successfully carried out by different commercial lipases, the election of the biocatalyst must rely on productivity and economic considerations. This work presents productiveness and direct operation cost evaluation as a key tool for the selection between two commercial lipase catalysts, the versatile but expensive Novozym® 435 and a much more economical option, Lipozyme® TL IM, in the synthesis of spermaceti, a mixture of emollient esters with cosmetic applications. Proving that Novozym® 435 leads to minimum savings of 10% with respect to the cheapest immobilized derivative, biocatalyst cost does not appear to be the major contribution to the economics of the processes under study, due to their great capacity to be recovered and reused. At laboratory scale, the biggest economic investment is caused by substrates, which can be massively reduced at industrial scale by using bulk reagents. In such case, energy cost may be the major contribution to the process economy. This work proposes an optimized process ready to be scaled-up in order to accurately determine the energetic requirements of the possible industrial enzymatic synthesis.

Stability Assessment of Topical Amitriptyline Extemporaneously Compounded with Lipoderm Base, PLO Gel Mediflo 30, and Emollient Cream.

Extemporaneous topical compounds for neuropathic pain offers an alternative or adjunct approach to existing therapies for patients. Assigning evidence-based beyond-use dating prior to dispensing topical medications is a legal requirement by pharmacy governing bodies. The purpose of this study was to utilize a validated stability-indicating high-performance liquid chromatography assay to determine beyond-use dating of topical amitriptyline in three different bases (Lipoderm Base, PLO Gel Mediflo 30, Emollient Cream) at three different temperatures [room temperature (25°C), refrigeration (4°C), and high temperature (40°C)]. Amitriptyline was stable after 90 days at room temperature in both Lipoderm Base and PLO Gel Mediflo 30. However, it was not stable at 40°C in Emollient Cream, irrespective of storage conditions.

Safety Assessment of Plant-Derived Fatty Acid Oils.

The Cosmetic Ingredient Review Expert Panel (Panel) assessed the safety of 244 plant-derived fatty acid oils as used in cosmetics. Oils are used in a wide variety of cosmetic products for their skin conditioning, occlusive, emollient, and moisturizing properties. Since many of these oils are edible, and their systemic toxicity potential is low, the review focused on potential dermal effects. The Panel concluded that the 244 plant-derived fatty acid oils are safe as used in cosmetics.

Safety Assessment of Panax spp Root-Derived Ingredients as Used in Cosmetics.

The Cosmetic Ingredient Review Expert Panel (Panel) reviewed the safety of 13 Panax spp root-derived ingredients as used in cosmetics. Panax "spp" indicates that multiple species within the genus are used in cosmetics, but not all species within that genus. Four species are being considered in this safety assessment. These ingredients function mostly as skin-conditioning agents-miscellaneous, fragrance ingredients, skin-conditioning agents-humectant, skin-conditioning agents-emollient, and cosmetic astringents. The Panel reviewed available data related to these ingredients and addressed the issue of pulegone, a constituent of these ingredients and other ingredients, such as peppermint oil. The Panel concluded that these Panax spp root-derived ingredients are safe in the practices of use and concentration as given in this safety assessment.

Safety assessment of bis-diglyceryl polyacyladipate-2 and bis-diglyceryl polyacyladipate-1 as used in cosmetics.

The Cosmetic Ingredient Review Expert Panel assessed the safety of bis-diglyceryl polyacyladipate-2 and bis-diglyceryl polyacyladipate-1 as used in cosmetics, finding that these ingredients are safe in cosmetic formulations in the present practices of use and concentration. Both ingredients are lanolin substitutes and are reported to function in cosmetics as skin-conditioning agents--emollients. The Panel reviewed available animal and clinical data in making its determination of safety.

Safety assessment of isoparaffins as used in cosmetics.

The safety of isoparaffins as used in cosmetic products is reviewed in this safety assessment. These ingredients function mostly as solvents and also function as emollients in the 0001% to 90% concentration range. The Cosmetic Ingredient Review (CIR) Expert Panel has reviewed relevant animal and clinical data and concluded that these ingredients are safe in the present practices of use and concentration described in this safety assessment.

Use of emollients in the treatment of dry skin conditions.

Dry skin conditions are often not considered important by health professionals, and as a consequence treatments are frequently under-prescribed. As a result of this, problems with untreated dry skin can lead to a variety of issues. Conditions such as pruritus and ichthyosis vulgaris can be distressing, while ezcema and psoriasis can lead to more serious consequences such as fissures and infections and can result in a reduced quality of life and social isolation. However, with appropriate treatments such as emollient therapy, the incidences of these conditions occurring can be reduced. Despite a wide range of choice available on the market, choosing an effective emollient which will help aid concordance is often difficult. In order to achieve this, several factors need to be considered in conjunction with the product selection. This article discusses the various factors that nurses need to consider when advising patients on which emollient to use as part of their skin care regimen, in order to improve concordance and patient outcomes.

Final report on the amended safety assessment of diisopropyl dimer dilinoleate, dicetearyl dimer dilinoleate, diisostearyl dimer dilinoleate, dioctyl dimer dilinoleate, dioctyldodecyl dimer dilinoleate, and ditridecyl dimer dilinoleate.

Diisopropyl Dimer Dilinoleate, Dicetearyl Dimer Dilinoleate, Diisostearyl Dimer Dilinoleate, Dioctyl Dimer Dilinoleate, Dioctyldodecyl Dimer Dilinoleate, and Ditridecyl Dimer Dilinoleate are diesters of their respective alcohols and dilinoleic acid. They function as skin-conditioning agents in a variety of cosmetic products at concentrations around 10%, but may be used at concentrations up to 53% in lipsticks. These ingredients do not absorb radiation in the ultraviolet (UV) UVA or UVB range and the only impurities expected are <0.5% dilinoleic acid, <0.1% isopropyl alcohol or <1% isostearyl alcohol, and/or small amounts of dilinoleic acid and cetearyl alcohol or octyldodecanol, depending on which diester is used. The potential skin penetration of these ingredients was evaluated using an estimate of the octanol/water partition coefficient (logP of 17.7) based on the structure of Diisopropyl Dimer Dilinoleate. This is consistent with the insolubility of these ingredients in water. Safety test data on dilinoleic acid (no adverse effects) were considered relevant because dilinoleic acid is a component of these diesters and a likely breakdown product. The acute oral and dermal LD(50) values for rats of Diisopropyl, Diisostearyl, and Dioctyldodecyl Dimer Dilinoleate were >5.0 g/kg. In a subchronic feeding study, macrophage aggregation was seen in the mesenteric lymph node at the lowest dose level (0.1% in the diet). These ingredients did not produce skin or ocular irritation in animal tests, nor were they comedogenic. Ames testing, clastogenesis in human lymphocytes in culture, and L5178Y mouse lymphoma cell forward mutations were all negative, indicating no dilinoleic acid genotoxicity. No carcinogenicity or reproductive/developmental toxicity data were available; however, structural alerts that would suggest a mutagenic or carcinogenic risk are absent. Significant reproductive/developmental toxicity or other systemic toxicity is not expected with these ingredients because they remain on the skin surface. In clinical studies, cosmetic formulations containing these ingredients did not produce skin irritation or sensitization, although one report of sensitization to dilinoleic acid appeared in the case literature. The Panel did note that the concentration of use of Diisopropyl Dimer Dilinoleate was reportedly as high as 53% in lipsticks, but that the highest concentration tested for irritation/sensitization is 27%. Given the size of these molecules, their relative insolubility in water, their lipophilic nature, and the absence of any significant case reports of allergic reactions, a use concentration of 53% is not likely to be associated with any adverse effects. Accordingly, these diesters were considered safe as used in cosmetic products.

Final report on the safety assessment of stearoxy dimethicone, dimethicone, methicone, amino bispropyl dimethicone, aminopropyl dimethicone, amodimethicone, amodimethicone hydroxystearate, behenoxy dimethicone, C24-28 alkyl methicone, C30-45 alkyl methicone, C30-45 alkyl dimethicone, cetearyl methicone, cetyl dimethicone, dimethoxysilyl ethylenediaminopropyl dimethicone, hexyl methicone, hydroxypropyldimethicone, stearamidopropyl dimethicone, stearyl dimethicone, stearyl methicone, and vinyldimethicone.

Dimethicone is a fluid mixture of fully methylated linear siloxane polymers end-blocked with trimethylsiloxy units. Methicone is a linear monomethyl polysiloxane. The other dimethicones and methicones covered in this review are siloxane polymers of Dimethicone and Methicone. Most of these ingredients function as conditioning agents in cosmetic formulations at current concentrations of use of < or =15%. Clinical and animal absorption studies reported that Dimethicone was not absorbed following oral or dermal exposure. Dimethicone, Methicone, and Vinyldimethicone were not acutely toxic following oral exposure. No adverse reactions were found in rabbits following short-term dermal dosing with 6% to 79% Dimethicone, yet adverse effects were noted with a hand cream formulation containing 1% Dimethicone, suggesting something else in the preparation was toxic. Mice and rats were dosed for 90 days with up to 10% Dimethicone without adverse effect. Dimethicone did not produce adverse effects in acute and short-term inhalation-route studies, Methicone and Vinyldimethicone were negative in acute exposure studies using rats, but Hexyl Methicone was toxic to rats at 5 mg/L delivered in small particle (mean diameter of 0.29 micro) aerosols. Most dermal irritation studies using rabbits classified Dimethicone as a minimal irritant. Dimethicone (tested undiluted and at 79%) was not a sensitizer in four assays using mice and guinea pigs. It was not a sensitizer at 5.0% in a clinical repeated insult patch test using 83 panelists. Most ocular irritation studies using rabbits classified Dimethicone as a mild to minimal irritant. Dimethicone was tested in numerous oral-dose (using rats) and dermal-dose (using rats, rabbits, and monkeys) reproductive and developmental toxicity studies. In a few studies, treated males had significantly decreased body weight and/or decreased testes or seminal vesicles weights. No treatment-related adverse findings were noted in dosed pregnant females or fetuses. Dimethicone was negative in all genotoxicity assays. It was negative in both an oral (tested at 91%) and dermal (tested at an unknown concentration) dose carcinogenicity assay using mice. The Cosmetic Ingredient Review (CIR) Expert Panel considered it unlikely that any of these polymers would be significantly absorbed into the skin due to their large molecular weight. Although adverse effects were noted in one inhalation study with small aerosol particles, the expected particle sizes for cosmetic products would primarily be in the range of 60 to 80 micro, and less than 1% would be under 10 micro, which is an upper limit for respirable particles. Overall, the safety test data support the safety of these ingredients at the concentrations they are known to be used in cosmetic formulations. Accordingly, the CIR Expert Panel was of the opinion that Stearoxy Dimethicone, Dimethicone, Methicone, Amino Bispropyl Dimethicone, Aminopropyl Dimethicone, Amodimethicone, Amodimethicone Hydroxystearate, Behenoxy Dimethicone, C24-28 Alkyl Methicone, C30-45 Alkyl Methicone, C30-45 Alkyl Dimethicone, Cetearyl Methicone, Cetyl Dimethicone, Dimethoxysilyl Ethylenediaminopropyl Dimethicone, Hexyl Methicone, Hydroxypropyldimethicone, Stearamidopropyl Dimethicone, Stearyl Dimethicone, Stearyl Methicone, and Vinyldimethicone are safe as used in cosmetic formulations.

Assessment of the influence of use on ecotoxicological characteristics of synthetic ester lubricants.

Synthetic ester lubricants need optimisation about their technical and their ecotoxicological characteristics. To determine the ecotoxicological potential the required examinations can be based on the procedure for a risk assessment of chemicals. At present risk classification of lubricant oils is carried out with new oil fluids that are normally prepared before application in aqueous bioassays. In order to improve the ecotoxicological characteristics of some lubricant oils, the quality of the preparation method has been optimised. The resulting preparation protocol leads to aqueous extracts of the oil fluids that can be tested using biological assays. The extent of the changes of the chemical composition caused by the use as well as the ecotoxicological effects caused by additives have to be taken into consideration. For this reason various used lubricants are tested in addition to new oil fluids. In this work various lubricant samples were examined with standardised bacterial growth assays with Vibrio fischeri and Pseudomonas putida, luminescence inhibition assay with V. fischeri, survival assay with Daphnia magna and algal growth inhibition assay with Scenedesmus subspicatus. The chemical characterisation of the aqueous extracts included the determination of pH, conductivity, heavy metals, the content of dissolved organic carbon, inorganic anions and the content of phosphorus. The results emphasize the thesis that environmentally acceptable lubricants can undergo a change of their ecotoxicological potential during the use. Some of the substances that are normally added to base fluids in order to enhance the applicability of the oils may possess a high toxicological potential.

Final report on the safety assessment of acetyl triethyl citrate, acetyl tributyl citrate, acetyl trihexyl citrate, and acetyl trioctyl citrate.

Acetyl Triethyl Citrate, Acetyl Tributyl Citrate, Acetyl Trihexyl Citrate, and Acetyl Trioctyl Citrate all function as plasticizers in cosmetics. Additionally, the Trihexyl and Trioctyl forms are described as skin-conditioning agents-emollients, although there are currently no reported uses of Acetyl Trihexyl Citrate or Acetyl Trioctyl Citrate. Acetyl Triethyl Citrate and Acetyl Tributyl Citrate are used in nail products at concentrations up to 7%. Recognizing that there are no reported uses of Acetyl Trihexyl or Trioctyl Citrate, if they were to be used in the future, their concentration of use is expected to be no higher than that reported for Acetyl Triethyl and Tributyl Citrate. These ingredients were sufficiently similar in structure that safety test data on one were considered applicable to all. Approximately 99% of orally administered Acetyl Tributyl Citrate is excreted-intermediate metabolites include acetyl citrate, monobutyl citrate, acetyl monobutyl citrate, dibutyl citrate, and acetyl dibutyl citrate. In acute, short-term, subchronic, and chronic feeding studies, these ingredients were relatively nontoxic. Differences from controls were either not statistically significant or not related to any organ toxicity. Ocular exposures produced moderate reactions that cleared by 48 hours after instillation. Dermal application was not toxic in rabbits. In a guinea pig maximization test, Acetyl Triethyl Citrate was a sensitizer whereas Acetyl Tributyl Citrate was not. Limited clinical testing of Acetyl Triethyl Citrate and Acetyl Tributyl Citrate was negative for both skin irritation and sensitization. These clinical data were considered more relevant than the guinea pig maximization data, suggesting to the Cosmetic Ingredient Review Expert Panel that none of these ingredients would be a sensitizer. Physiologic effects noted with intravenous delivery of Acetyl Triethyl Citrate or Acetyl Tributyl Citrate include dose-related decreases in blood pressure and intestinal muscular spasms. These ingredients were not genotoxic in bacterial or mammalian test systems. No significant differences in tumor induction (lymphomas) were noted in rats fed Acetyl Tributyl Citrate for 2 year. Acetyl Tributyl Citrate was not a developmental or reproductive toxicant in studies in mice and rats. Based on all the available data, these ingredients were considered safe as used in cosmetics.