Prevalence of Surfactant in the Contact Allergen Management Program.

BACKGROUND: Surfactants are common ingredients in topical products, which can cause both irritant and allergic contact dermatitis. OBJECTIVE: The aim of this study was to determine the prevalence of 12 common groups of surfactants and 12 common individual surfactants among products in each category in the American Contact Dermatitis Society Contact Allergen Management Program (CAMP). METHODS: The American Contact Dermatitis Society CAMP was queried for the 12 surfactant groups and the 12 individual surfactants. RESULTS: The laureth/pareth sulfate group was the most prevalent surfactant group in CAMP products (17.9%). Laureth/pareth sulfates were the most common surfactant group in all product categories, except household and eye care products. The betaine/sultaine group (13.5%) and glucosides (10.0%) were also found in a significant proportion of CAMP products. Oleamidopropyl dimethylamine has the highest positive reaction rate (3.5%) but was tied for the lowest prevalence (0.20%) of the 12 individual surfactants studied. In contrast, cocamidopropyl betaine has a lower positive reaction rate (1.6%) with a higher prevalence (10.4%). CONCLUSIONS: Surfactants were commonly found across all product types in CAMP. This study provides important information on allergen and irritant exposures in care products.

Opportunities for Bio-Based Solvents Created as Petrochemical and Fuel Products Transition towards Renewable Resources.

The global bio-based chemical market is growing in size and importance. Bio-based solvents such as glycerol and 2-methyltetrahydrofuran are often discussed as important introductions to the conventional repertoire of solvents. However adoption of new innovations by industry is typically slow. Therefore it might be anticipated that neoteric solvent systems (e.g., ionic liquids) will remain niche, while renewable routes to historically established solvents will continue to grow in importance. This review discusses bio-based solvents from the perspective of their production, identifying suitable feedstocks, platform molecules, and relevant product streams for the sustainable manufacturing of conventional solvents.

Design of Block Copolymer Costabilized Nonionic Microemulsions and Their In Vitro and In Vivo Assessment as Carriers for Sustained Regional Delivery of Ibuprofen via Topical Administration.

Nonionic surfactants (caprylocaproyl macrogol-8 glycerides, octoxynol-12, polysorbate-20, and polyethylene glycol-40 hydrogenated castor oil) (47.03%, w/w), costabilizer (poloxamer 407) (12%-20%, w/w), oil (isopropyl myristate) (5.22%, w/w), water (q.s. ad 100%, w/w), and ibuprofen (5%, w/w) were used to develop oil-in-water microemulsions with Newtonian flow behavior, low viscosity (from 368 ± 38 to 916 ± 46 mPa s), and average droplet size from 14.79 ± 0.31 to 16.54 ± 0.75 nm. Ibuprofen in vitro release from the microemulsions was in accordance with zero-order kinetics (R0(2) > 0.99) for at least 12 h. The maximum drug release rate (3.55%h(-1) ) was from the microemulsion M3 comprising 16%, w/w of poloxamer 407. The release rate of ibuprofen from the reference hydrogel followed Higuchi kinetics (RH(2) > 0.99), and drug amount released after the 6th hour was negligible. In a rat model of inflammation, the microemulsion M3 was significantly more efficacious than the reference hydrogel in exerting antihyperalgesic effects in prophylactic topical treatment, whereas they were comparable in therapeutic treatment as well as in producing antiedematous effect in both protocols. No obvious skin irritation was observed in in vivo studies. The developed nonionic surfactants-based microemulsions containing the optimal concentration of poloxamer 407 could be promising carriers for sustained regional delivery of ibuprofen via topical administration.

Sucrose esters as natural surfactants in drug delivery systems--a mini-review.

Sucrose esters (SEs) are widely used in the food and cosmetic industries and there has recently been great interest in their applicability in different pharmaceutical fields. They are natural and biodegradable excipients with well-known emulsifying and solubilizing behavior. Currently the most common pharmaceutical applications of SEs are for the enhancement of drug dissolution and drug absorption/permeation, and in controlled-release systems. Although the number of articles on SEs is continuously increasing, they have not yet been widely used in the pharmaceutical industry. The aim of this review is to discuss and summarize some of the findings and applications of SEs in different areas of drug delivery. The article highlights the main properties of SEs and focuses on their use in pharmaceutical technology and on their regulatory and toxicological status.

Occurrence of anionic surfactants in treated sewage: risk assessment to aquatic environment.

A comparative evaluation of occurrence of and risk to aquatic environment due to anionic surfactants (AS) in treated effluents from three main treatment processes, i.e. activated sludge process (ASP), oxidation pond (OP), and upflow anaerobic sludge blanket reactor (UASBR) is presented. UASBR effluents contained substantial concentrations of AS (4.25-5.91mg/L as average AS removal was not found to exceed 18%). Post-treatment of UASBR effluent using 1-1.6 days detention, anaerobic polishing ponds (PP) was also found quite ineffective. In UASBR-PP combine, AS reduced only up to 30%. Effluents from OP based sewage treatment plants (STPs) also contained significant concentrations of AS. On the contrary, effluent AS or linear alkylbenzene sulfonate (LAS) concentrations recorded in ASP effluents were quite low (less than 0.2mg/L). Unlike UASBR, LAS or AS removals greater than 99% are achieved in ASP. Treated effluents from UASBR and OP based STPs when discharged to aquatic ecosystems are likely to cause substantial risk to aquatic environment due to the presence of AS while effluents from ASP are not supposed to pose risk. Need to find an effective aerobic post-treatment unit to UASBR for desired removal of AS is emphasized.

Assessment of drug-lipid complex formation by a high-throughput Langmuir-balance and correlation to phospholipidosis.

Phospholipidosis, the accumulation of phospholipids in cells, is a relatively frequent side effect of cationic amphiphilic drugs. In response to the industry need, several methods have been recently published for the prediction of the phospholipidosis-inducing potential of drug candidates. We describe here a high-throughput physicochemical approach, which is based on the measurement of drug-phospholipid complex formation observed by their effect on the critical micelle concentration (CMC) of a short-chain acidic phospholipid. The relative change due to the drug, CMC(DL)/CMC(L) provides a direct measure of the energy of the drug-phospholipid association, irrespective of the nature of the interaction. Comparison of results for 53 drugs to human data, animal testing, cell culture assays, and other screening methods reveals very good correlation to their phospholipidosis-inducing potential. The method is well suited for screening already in early phases of drug discovery.

Skin capacitance imaging and corneosurfametry. A comparative assessment of the impact of surfactants on stratum corneum.

Silicon image sensor (SIS) technology was recently introduced as an innovative tool (SkinChip, L'Oréal) providing sensitive imaging of the skin capacitance. This method can detect discrete focal variations in skin surface hydration, and thus early discrete manifestations of skin irritation induced by surfactants. In the present in vivo study, 2 neat and diluted shampoos, and 5% and 10% sodium laurylsulfate solutions were tested on human skin. Each surfactant solution was gently rubbed on the skin using wet hair wicks mimicking the casual use of a shampoo on the scalp. Clinical and SIS evaluations were carried out. In addition, the same products were tested using the ex vivo corneosurfametry bioassay performed on human stratum corneum (SC) harvested by cyanoacrylate skin surface strippings. The colourimetric index of mildness (CIM) was measured on these samples. The product reactivity with the SC was recognized by darker skin capacitance images, and by both lowered SkinChip-generated values and lowered CIM values. The extent in changes varied according to the nature of the test products and their concentrations. The SkinChip image changes likely corresponded to the acute surfactant-induced water swelling of the corneocytes. Skin capacitance imaging and corneosurfametry allow to disclose discrete surfactant-induced alterations of corneocytes.

Assessment of the potential irritation and photoirritation of novel amino acid-based surfactants by in vitro methods as alternative to the animal tests.

The ultraviolet-A radiation damage effects on skin and eyes will be increased by phototoxic compounds which could be present in pharmaceutical or cosmetic formulations. Great efforts have been made in the last years to find surfactants to replace those with phototoxic potential in commercial use. Series of different in vitro models for phototoxicity, included to validated neutral red uptake (NRU) 3T3 phototoxicity assay are useful screening tools. The phototoxic effects of a novel family of glycerol amino acid-based surfactant compounds were examined via these assays. Human red blood cells and two immortalised cell lines, murine fibroblast cell line 3T3, and one human keratinocyte cell line, HaCaT, were the in vitro models employed to predict potential photoirritation. The phototoxic end-points assessed were hemolysis (human red blood cell test) and resazurin transformation to resorufin and NRU in cell culture methods. The results suggest that no phototoxic effects by any new amino acid derived-surfactants, could be identified.

Assessment of bioconcentration and secondary poisoning of surfactants.

The relevance of the bioconcentration behaviour of surfactants for the secondary poisoning assessment and for the risk characterisation in the bird and mammalian food chain has been investigated. The approach used is described in the recently revised EU Technical Guidance Document for the Risk Assessment of Substances. The results demonstrate that, based on experimentally derived bioconcentration factors, environmental concentrations and effects in animals, there is a clear level of safety for both linear alkylbenzene sulphonate (LAS) and alcohol ethoxylates (AE), the most important surfactants by volume. To assess other surfactants used in detergents, a bioconcentration factor that would need to be attained for secondary poisoning to be of concern has been estimated from predicted environmental concentrations and known long-term effects data in animals. Based on the known structural similarity of these surfactants to LAS and AE and the ubiquitous nature of the enzymatic systems that are present in biotransformation processes in organisms, it is concluded that bioconcentration of these surfactants to these levels is highly unlikely. Therefore the potential for secondary poisoning effects of these surfactants is extremely low.

Effects and risk assessment of linear alkylbenzene sulfonates in agricultural soil. 1. Short-term effects on soil microbiology.

Linear alkylbenzene sulfonates (LAS) may occur in sewage sludge that is applied to agricultural soil, in which LAS can be inhibitory to biological activity. As a part of a broader risk assessment of LAS in the terrestrial environment, we tested the short-term effects of aqueous LAS on microbial parameters in a sandy agricultural soil that was incubated for up to 11 d. The assays included 10 microbial soil parameters; ethylene degradation; potential ammonium oxidation; potential dehydrogenase activity; beta-glucosidase activity; iron reduction; the populations of cellulolytic bacteria, fungi and actinomycetes; the basal soil respiration; and the phospholipid fatty acid (PLFA) content. Except for beta-glucosidase activity, basal respiration, and total PLFA content, all soil parameters were sensitive to LAS, with EC10 values in the range of less than 8 to 22 mg/kg dry weight. This probably reflected a similar mode of LAS toxicity, ascribed to cell membrane interactions, and showed that sensitivity to LAS was common for various soil microorganisms. The extracellular beta-glucosidase activity was rather insensitive to LAS (ECI10, 47 mg/kg dry wt), whereas the basal soil respiration was not inhibited even at 793 mg/kg dry weight. This was interpreted as a combined response of inhibited and stimulated compartments of the microbial community. The PLFA content, surprisingly, showed no decrease even at 488 mg/kg. In conclusion, LAS inhibited specific microbial activities, although this could not be deduced from the basal respiration or the total PLFA content. The lowest EC10 values for microbial soil parameters were slightly higher than the predicted no-effect concentrations recently derived for plants and soil fauna (approximately 5 mg/kg dry wt).

Effects and risk assessment of linear alkylbenzene sulfonates in agricultural soil. 3. Sublethal effects on soil invertebrates.

Sewage sludge applied to agricultural soils often contains considerable amounts of linear alkylbenzene sulfonates (LAS). Toxic effects of LAS on soil organisms should, therefore. be evaluated to ensure safe use of sewage sludge as a fertilizer. In this study, dose-response relationships for the toxicity of Na-LAS to six species of soil invertebrates (survival, reproduction, and growth) were established using a sandy, agricultural soil as test substrate. In general, toxic effects on reproduction and growth appeared when the concentration in soil exceeded 40 to 60 mg/kg. Reproduction was approximately fourfold more sensitive in earthworms and enchytracids than in springtails and mites. It is argued that this difference in sensitivity is related to the dependency of soil pore water, which is high in the annelids but comparatively low in the arthropods.

Effects and risk assessment of linear alkylbenzene sulfonates in agricultural soil. 2. Effects on soil microbiology as influenced by sewage sludge and incubation time.

The anionic surfactant linear alkylbenzene sulfonate (LAS) may inhibit soil microorganisms and may occur in agricultural soil through the application of sewage sludge. For five microbial parameters (microbial biomass C and the potentials of iron reduction, ammonium oxidation, dehydrogenase activity, and arylsulfatase activity), we compared the effects of aqueous LAS and LAS-spiked sewage sludge added to existing levels of 0, 3, 8, 22, 22, 62, 174, and 488 mg/kg soil (dry wt) in a Danish sandy agricultural soil that was incubated for 5 d to eight weeks. Arylsulfatase activity (measured after four weeks of incubation) was rather insensitive to LAS, with an EC 10 of 222 and more than 488 mg/kg in soil samples treated with aqueous LAS and LAS-spiked sewage sludge, respectively. For the other microbial parameters, the short-term effects (approximately one to two weeks) of aqueous LAS were characterized by an EC10 in the range of 3 to 39 mg/kg. Application of LAS via sewage sludge generally reduced the short-term effects for the microbial parameters, and the EC10 for LAS in sludge-amended soil after approximately one to two weeks of incubation ranged from less than 8 to 102 mg/kg. Recovery potential was seen for most microbial parameters as a result of prolonged incubation, both under conditions of LAS persistence (anaerobic conditions, the iron-reduction test) and LAS depletion (aerobic incubations, all other assays). In conclusion, the short-term inhibitory effects of LAS on soil microbiology were decreased in the presence of sewage sludge and by a prolonged (two to eight weeks) laboratory incubation period.

Final report on the safety assessment of Cocoyl Sarcosine, Lauroyl Sarcosine, Myristoyl Sarcosine, Oleoyl Sarcosine, Stearoyl Sarcosine, Sodium Cocoyl Sarcosinate, Sodium Lauroyl Sarcosinate, Sodium Myristoyl Sarcosinate, Ammonium Cocoyl Sarcosinate, and Ammonium Lauroyl Sarcosinate.

This safety assessment addresses cosmetic ingredients that are N-acyl derivatives of sarcosine and are generally referred to as acyl sarcosines, and those that are salts, known generally as acyl sarcosinates. Previous assessments have addressed the safety of each of the fatty acids that appear in these acyl sarcosines and sarcosinates (Coconut Acid, Oleic Acid, Lauric Acid, and Myristic Acid). In each case the fatty acid was either safe for use or safe as used in cosmetic formulations. Acyl sarcosines are considered modified fatty acids with greater solubility and increased acidity of the carboxylic acid group compared to the parent fatty acid. They are used in a large number of cosmetic formulations as hair-conditioning agents and surfactant-cleansing agents. In soaps, concentrations are reported to be as high as 12.9%. These ingredients have low oral toxicity in rats. Although cytotoxic to Chinese hamster cells in culture, acyl sarcosines and sarcosinates are not mutagenic in those cells, nor in bacterial cells in culture. Carcinogenicity data were not available. These ingredients are nonirritating and nonsensitizing to animal and human skin, although they can enhance the penetration of other ingredients through the skin. For that reason, caution should be exhibited in formulating cosmetic products that contain these ingredients in combination with other ingredients whose safety is based on their lack of absorption or where dermal absorption is a concern (e.g., HC Yellow No. 4, Disperse Yellow 3). Because sarcosine can be nitrosated to form N-nitrososarcosine, a known animal carcinogen, these ingredients should not be used in cosmetic products in which N-nitroso compounds may be formed. With the above caveat, and based on the available data, it was concluded that these acyl sarcosines and sarcosinates are safe as used in rinse-off products. They may be safely used in leave-on products at concentrations up to 5%, the highest concentration tested in clinical irritation and sensitization studies. Oleoyl Sarcosine is used as a corrosion inhibitor in some aerosol products, at extremely low concentrations. In this circumstance, the ingredient is not being used as a cosmetic ingredient and this report is not intended to limit that use. Because of the absence of data on inhalation toxicity, however, it was concluded that the available data were not sufficient to support the safety of acyl sarcosines and sarcosinates as cosmetic ingredients in products where they are likely to be inhaled.

Final report on the safety assessment of Cetethyl Morpholinium Ethosulfate.

Cetethyl Morpholinium Ethosulfate is a quaternary salt used as an antistatic agent and as a surfactant in several hair care products. The concentration at which this ingredient is used is unknown, although data reported in 1984 indicated a maximum concentration of 1%. In an inhalation toxicity study, the approximate lethal concentration of Cetethyl Morpholinium Ethosulfate was 0.403 mg/mm3. This ingredient was shown to be a severe ocular irritant in an animal study. No other safety test data on this ingredient were available. These data were clearly insufficient to support the safety of Cetethyl Morpholinium Ethosulfate in cosmetics. Data available on Morpholine were summarized, but these data themselves were insufficient to support safety. The data needed in order to complete the safety assessment of Cetethyl Morpholinium Ethosulfate include: methods of manufacture and impurities, especially nitrosamines; current concentration of use; skin penetration; if there is significant skin penetration, then both a 28-day dermal toxicity study to assess general skin and systemic toxicity and a reproductive and developmental toxicity study are needed; two genotoxicity studies, at least one in a mammalian system, if positive, then a 2-year dermal carcinogenisis study using National Toxicology Program (NTP) methods may be needed; ultraviolet (UV) absorption data, if significantly absorbed, then photosensitization data are needed; dermal irritation and sensitization; and ocular toxicity, if available.

Shielded corneosurfametry and corneoxenometry: novel bioassays for the assessment of skin barrier products.

OBJECTIVES: One of the most frequent occupational and environmental insults to the skin is linked to chronic exposure to weak irritants. There is a need for new predictive tests assessing the efficacy of barrier creams. METHODS: Shielded variants of corneosurfametry and corneoxenometry are introduced as novel ex vivo bioassays applicable for comparing protection to surfactants and organic solvents. RESULTS: Both bioassays showed good reproducibility for each offending agent and skin-protective products. Significant differences in efficacy were indicated between the presumptive barrier products. CONCLUSIONS: Shielded corneosurfametry and corneoxenometry may be convenient bioassays to compare the protection afforded by topical products against specific offending compounds to the skin. They avoid animal testing and toxicological hazards in human testing. In addition, they are cheap, rapid and reproducible.

Quantitative in vitro assessment of N-alkyl sulphate-induced cytotoxicity in human keratinocytes (HaCaT). Comparison with in vivo human irritation tests.

A spontaneously immortalized human keratinocyte line, HaCaT, was used as an in vitro model to predict the cutaneous irritation of anionic surfactants. For this purpose, a number of sodium salts of N-alkyl sulphates with hydrocarbon chain lengths varying between C8 and C16 were studied for possible cytotoxic effects. The endpoints used to assess toxicity were uptake of the vital dye neutral red (NR) and cell morphology criteria 24 h after dosing. A linear proportionality between keratinocyte number and NR uptake was established. All tested surfactants had cytotoxic effects as demonstrated by a decreased NR uptake, which showed a clear dose-response relationship. Concentrations resulting in 50% inhibition of NR uptake (IC-50) ranged from 0.15 mmol (sodium lauryl sulphate, C12) to 1.23 mmol (sodium octyl sulphate, C8). The in vitro cytotoxicity data were highly reproducible when the test was repeated after several weeks. The cytotoxicity data from these assays were compared with the irritant responses (as evaluated by measurement of erythema and transepidermal water loss) obtained after 24 h application of the same compounds (300 microliters of 20 mmol aqueous solution) to the volar forearm of human volunteers. There were significant linear correlations between the IC-50 values and both barrier damage (transepidermal water loss) and erythema (as evaluated by skin colour reflectance measurements). For the test substances, however, the sensitivity of the in vitro system was between 10 and 100 times higher than that observed in human skin in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)