Abstract  The role of oleic acid in the modulation of gap junction permeability was studied in cultured rat astrocytes by the scrape-loading/Lucifer yellow transfer technique. Incubation with oleic acid caused a dose-dependent inhibition of gap junction permeability by 79.5% at 50 mu M, and no further inhibition was observed by increasing the oleic acid concentration to 100 mu M. The oleic acid-mediated inhibition of gap junction permeability was reversible and was prevented by bovine serum albumin. The potency of oleic acid-related compounds in inhibiting gap junction permeability was arachidonic acid > oleic acid > oleyl alcohol > palmitoleic acid > stearic acid > octanol > caprylic acid > palmitic acid > methyloleyl ester. Oleic acid and arachidonic acid, but not methyloleyl ester, increased glucose uptake by astrocytes. Neither-oleic acid nor arachidonic acid increased glucose uptake in the poorly coupled glioma C6 cells. These results support that the inhibition of gap junction permeability is associated with the increase in glucose uptake. We suggest that oleic acid may be a physiological mediator of the transduction pathway leading to the inhibition of intercellular communication.

Abstract  Eighteen potential penetration enhancers, some at concentrations that might be used for that purpose, have been examined to evaluate their irritancy potential on nude mouse skin. A biopsy technique was employed followed by histological examination. Up to 50% glycerol, 10% hydroxyethyl lactamide (HELA), 10% oleyl alcohol, 10% Solketal, 10% glycofurol, 100% tetrahydrofurfuryl alcohol (THFA) and 10% urea induced no discernible change in the histological appearance of the skin whereas 100% dimethyl sulphoxide (DMSO), 100% dimethyl formamide (DMF), 100% N-methyl-2-pyrrolidone, 10% Azone, 10% oleic acid, 10% methyl laurate, 10% benzyl alcohol and 10% glycerol formal caused severe skin irritation.

Abstract  The Oleth family of ingredients are the polyethylene glycol (PEG) ethers of oleyl alcohol. They are manufactured by the ethoxylation of oleyl alcohol with the number of moles of ethylene oxide corresponding to the average polyethylene glycol chain length desired. Not all of the polymer chain lengths covered in this assessment are currently reported to be used, but all are listed as cosmetic ingredients and may have been used in the past and could be used in the future. Oleths are surfactants used as emulsifying, cleansing, and solubilizing agents in cosmetic formulations. Limited safety test data are available on ingredients in the Oleth family, all consistent with surfactant properties. In feeding studies, Oleth-20 was associated with reduced body weight gain. Hepatic lesions in one exposure group were not found in any other exposure group, but were found in the controls. Oleth-20 and Oleth-10 were found to have moderate ocular irritation potential, and Oleth-10 was considered to be a cumulative skin irritant. Toxicity data, including reproductive and developmental toxicity, carcinogenesis data, and clinical testing data, available from previous safety assessments on Polyethylene Glycol and Oleyl Alcohol, were summarized. The principal finding related to PEGs, based on clinical data in burn patients, is that PEGs were mild irritant/sensitizers and there was evidence of nephrotoxicity. No such effects were seen in animal studies on intact skin. Cosmetic manufacturers should adjust product formulations containing Polyethylene Glycol to minimize any untoward effects when products are used on damaged skin. Although metabolites of ethylene glycol monoalkyl ethers are reproductive and developmental toxins, it was considered unlikely that the relevant metabolites would be found in or produced from the use of Oleths in cosmetic formulations. Of concern was the possible presence of 1,4-dioxane and ethylene oxide impurities. The importance of using the necessary purification procedures to remove these impurities was stressed. Based on particle size and cosmetic use considerations, it was not considered that these ingredients, in formulation, are respirable. Based in part on the limited data available on Oleths included in the report and on the previous reviews of Polyethylene Glycol and Oleyl Alcohol, it was concluded that Oleth-2, -3, -4, -5, -6,-7,-8,-9,-10,-11,-12,-15,-16,-20,-23, -25, -30, -40, -44, and, -50 are safe in the present practices of use.

Abstract  A young woman being treated for linear scleroderma became allergic to fluocinonide (Lidex) cream while using it with occlusion. She was able to continue treatment with fluocinonide ointment without an adverse reaction. Patch testing with the ingredients of the cream demonstrated sensitization to an impurity in commercial stearyl alcohol and irritation from propylene glycol. The woman had no adverse reactions to fluocinonide ointment because this preparation contains no stearyl alcohol and very little propylene glycol. This case reemphasizes the important role of vehicles in contact allergy and indicates that allergic sensitization may be induced despite the presence of a potent topical steroid.

Abstract  Effectiveness of certain long carbon chain aliphatic alcohols as ovicides and larvicides was investigated under laboratory conditions against eggs and larvae of Aedes aegypti and Aedes scutellaris. Out of the eight alcohols tested, three (1-decanol, 1-undecanol and 1-dodecanol) proved to be very effective. The hatching of mosquito eggs was inhibited at a dosage of 5 to 7 litres/hectare. First, third and fourth instar larvae were killed at a dosage of 3 to 7 litres/hectare. First instar larvae were more sensitive to the alcohols than the older larvae. The shorter carbon chain alcohols (2-mercapto-ethanol, 1-butanol, benzyl alcohol and 2-octanol) proved unsatisfactory due to their volatility and solubility. Longer carbon chain alcohols (1-tetradecanol, 1-hexadecanol and 1-octadecanol), Which are solid and wax-like at room temperature, proved unsatisfactory when dissolved in hexane and applied to eggs and larvae.

Abstract  A 96 h LC50 value of >0.4 mg/L was determined for the effect of the test substance on mortality of the fish O. mykiss. The water solubility of octadecanol is 0.0011 mg/L at 25oC [SIDS dossier on 1-octadecanol, 1993b; Budavari, 1996], therefore the LC50 value is >0.0011 mg/L, The water solubility of octadecanol is 0.0011 mg/L at 25oC [SIDS dossier on 1-octadecanol, 1993b; Budavari, 1996], therefore the LC50 value is >0.0011 mg/L (>LoS), i.e. the test substance was not toxic at the LoS.

Abstract  SIDS INITIAL ASSESSMENT: There is need for further work. SHORT SUMMARY OF THE REASONS WHICH SUPPORT THE RECOMMENDATION: The substance is firmly bound to sediments, and therefore anaerobic biodegradation can be an important factor. A 21-day test in daphnids indicated that the substance may be toxic at a range of between 1 and 3mg/l. FURTHER WORK RECOMMENDED: Determination of anaerobic biodegradability. Depending on the results of this test, it may be considered whether or not long-term fish toxicity testing is required.

Abstract  Behenyl alcohol is a saturated 22-carbon, long-chain aliphatic alcohol, which has potential for use in foods as an oil-structuring and -solidifying agent in fats. Previously completed studies with behenyl alcohol indicated an absence of mutagenic or genotoxic potential. In addition, subchronic toxicity studies in rats and dogs reported no adverse effects following gross and histopathological examinations. Compound-related effects were limited to the observation of pale feces in dogs treated with high doses of behenyl alcohol, and were attributable to unabsorbed behenyl alcohol. The reproductive effects of behenyl alcohol were investigated in a fertility and reproduction study, and an embryonic development study in rats and rabbits, respectively. No evidence of maternal or fetal toxicity was observed in either study. Behenyl alcohol demonstrated no effects on the fertility or reproduction of rats dosed up to 1000 mg/kg body weight. Similarly, behenyl alcohol had no reproductive effects on rabbits treated with doses up to 2000 mg/kg body weight. The observation of pale feces was the only compound-related effect reported, limited to rabbits treated with 2000 mg behenyl alcohol/kg body weight. Based on these findings, there is no evidence to suggest that behenyl alcohol is teratogenic or embryotoxic.

Abstract  The effects of alkyl alcohols and related chemicals on the ultrastructure of mitochondria in the rat hepatocyte were studied. The following three different groups of chemicals were tested: Group 1: alkyl alcohols with straight carbon chains (ethanol, 1-propanol, 1-butanol, 1-pentanol, 1-octanol, 1-dodecanol and 1-octadecanol); Group 2: tert- and cyclo-compounds (tert-butanol, cyclo-pentanol, and cyclo-hexanol); and Group 3: polyhydroxy alcohols (ethylene glycol, propylene glycol, 1, 3-propanediol, glycerol and pentaerythritol). Results obtained were summarized as follows: 1) Ethanol, 1-propanol, 1-butanol, 1-pentanol and 1-octanol had essentially the same effects on the mitochondrial ultrastructure: a mixed population of small and enlarged mitochondria with poorly developed cristae; 1-dodecanol induced ultrastructural changes of mitochondria of two distinct types: a mixed population of small and enlarged mitochondria with poorly developed cristae in some hepatocytes and remarkably enlarged mitochondria with well-developed cristate in others; and 1-octadecanol induced remarkably enlarged mitochondria in all hepatocytes. 2) Chemicals belonging to group 2 and group 3 induced essentially the same changes as those induced by 1-octadecanol. More than one month was required to induce those changes. The mechanism by which those ultrastructural mitochondrial changes were induced is not clear, but the present results may suggest that the hydroxy group (-OH) common to all these chemicals in some way accounts for the phenomenon.

Abstract  A 46 year old male metalworker was seen with a 3 year history of eczema of both hands. The eczema cleared within several weeks of absence from work. Patch tests conducted 2 years earlier had been negative. New patch tests were done with the German Contact Dermatitis Group standard series, two preservative series and a metal and metalworking series. Positive reactions seen for p-phenylenediamine (106503), p-aminobenzene (62533), and gold-sodium-thiosulfate (10233882) were not considered clinically relevant. A repetitive open application test using cutting fluid induced eczematous lesions. Patch tests with three concentrations of the fluid were also positive.Further patch tests using the components of the cutting fluid gave positive reactions to 2-amino-ethanol (141435) and oleyl-alcohol (143282). A previous report of 2-amino-ethanol occupational contact dermatitis in metalworkers was cited. Reports of sensitization to oleyl-alcohol were also cited, but none involved cutting fluids. No cross sensitivity to ethanol (64175) was observed in this patient. The author concludes that the patient had developed occupational contact dermatitis to 2-amino-ethanol and oleyl-alcohol in the metal cutting fluid.

Abstract  Long-chain fatty acids are important nutrients, but obesity is the most common nutritional disorder in humans. In this study we investigated the effect of oleyl alcohol on the intestinal long-chain fatty acid absorption in rats. We administered [14C]oleic acid and oleyl alcohol as lipid emulsion intraduodenally in unanesthetized lymph-cannulated rats and measured the lymphatic output of oleic acid. Second, we orally administered lipid emulsion with a stomach tube and measured the luminal and mucosal oleic acid residues. Furthermore, rats were fed oleyl alcohol as a dietary component for 20 days, and fecal lipid and the weight of adipose tissues were measured. In lymph-cannulated rats, triglyceride and [14C]oleic acid output in the lymph were significantly lower in the presence of oleyl alcohol when compared with the absence of oleyl alcohol in a dose-dependent manner. The radioactivity remaining in the intestinal lumen was more strongly detected in rats that had been orally administered oleyl alcohol than in the controls. The feces of rats fed an oleyl-alcohol-added diet contained much higher amounts of lipids, and the weights of their adipose tissues were significantly lower than in the control group. These results suggest that oleyl alcohol inhibits the rat gastrointestinal absorption of long-chain fatty acids in vivo.

Abstract  Castor oil is widely used as an emollient in lipsticks, particularly make-up removers and moisturizers. It is also used as a base for some topical medicaments, as well as a purgative (I). Angioedema, rhinitis, asthma and rashes due to castor oil during its extraction from the seeds of Ricinus communis (Euphorbiaceae) and oral administration of the oil have been reported (2). Oleyl alcohol is used as an emulsifier and emollient in lipsticks, hair applications and topical medicament bases, superfatting agent, solvent for essential oils and in the manufacture of paper and printing ink (3). Tosti et al. (4) found that oleyl alcohol was the most common cause of contact dermatitis from fatty alcohols.

Abstract  Both assays demonstrated a lack of mutagenic activity by behenyl alcohol. No significant and reproducible increases in the number of revertants were found in any strain and behenyl alcohol treatment group combination relative to the solvent control. In addition, no concentration-dependent enhancement of the revertant number occurred, and no differences were observed between behenyl alcohol treatments with or without metabolic activation. Strain text description: S. typhimurium strains TA1535, TA1537, TA1538, TA98, and TA100 Criteria for Postive Results: For a test substance to be considered positive in tester strain TA100, at least a twofold increase was required in the number of reversions. In tester strains TA1535, TA1537, TA1538, and TA98, a test substance was considered positive when the number of reversions was at least three times higher than the spontaneous reversion rate. In addition, a dose-dependent increase in the number of revertants was regarded as an indication of possible mutagenic potential, regardless of whether the highest dose induced a two- to threefold increase in the number of revertants. Genotoxic Effect: Negative

Abstract  IPA COPYRIGHT: ASHP A male hairdressing formulation produced eye irritancy during test marketing despite negative toxicity screening tests in rabbits and squirrel monkeys. The adverse effects were detected during a 10-month test market period, during which 20 complaints of eye irritation were received. This represented 1 complaint for every 8,500 hair preparations sold. Irritation was observed after exposure to rain or snow. The dressing, a solid transparent microemulsion, produced reversible visual blurring, corneal pitting, itching and pain. Similar responses were noted in human volunteers when an aqueous solution of the ethoxylated oleyl alcohol constituent of the dressing was instilled in the eye.

Abstract  A standardized, feasible test system for assessing the environmental behavior of chemicals in ecotoxicological terms and for setting up priority lists was described earlier. 14C chemicals were used in environmentally relevant concentrations. The bioaccumulation potential of chemicals was determined from tests with algae and fish; mammalian retention and elimination were investigated in a test with rats. Information about biodegradability, metabolism, accumulation, and bound residues was provided by the activated sludge test, while the possibility of photomineralization of the organic compounds was studied by irradiation with uv light of wavelength above 290 nm. The presentation of the data is by ranking in tables: they are either ranked in order of decreasing accumulation in the algae, fish, rat, and activated sludge tests (lipophilic substances such as hexachlorobenzene, chlorinated biphenyls, aldrin, etc., displaying the highest accumulation, are on top of the lists); or they are ranked in order of increasing degradability in the activated sludge and photomineralization tests (the most persistent chemicals thus again are on the top of the list). The data obtained from the accumulation tests are correlated with respective physicochemical properties of the chemicals and the results of the tests are compared with one another for ecotoxicological profile assessment.

Abstract  A test system is described for assessing the mineralization of 14C-radiolabeled compounds to carbon dioxide (CO2) and methane (CH4) under anaerobic conditions. Environmentally realistic concentrations of test chemicals were incubated with anaerobic digester sludge in sealed vessels at 35 °C. The headspace of these vessels was continuously purged with nitrogen, which was passed through a series of potassium hydroxide (KOH) scrubbers to trap 14CO2. This effluent gas was mixed with oxygen and passed through a combustion tube containing cupric oxide at 800 °C to convert 14CH4 to 14CO2, which was subsequently trapped in a second series of KOH traps. Trapping efficiency was 97.1 ± 5% for 14CO2 and 108 ± 13% for 14CH4. The system was used to evaluate the mineralization of several organic chemicals including glucose, palmitic acid, hexadecanol, and two surfactants, alkyl ethoxylate sulfate (AES) and alkyl sulfate (AS), in anaerobic digester sludge. Total yields of 14CH4 and 14CO2 from these compounds exceeded 80%, and the total mass balances generally exceeded 95%. Mineralization of hexadecanol was described by a simple first-order production equation, while that of the other compounds was best described by a three-half-order model. This system provided excellent recovery of radioactive gases and consequently excellent mass balances. Given the reproduction of in situ condition and the realistic ratio of test material to biomass, the test system also generated relevant kinetic data. It, therefore, has application for demonstrating the significance of biodegradation as a removal mechanism during anaerobic digestion as well as determining the completeness of anaerobic biodegradation.

Abstract  A 96 h LC50 value of >1000 mg/L tested with Water Accomodated Fractions (WAFs) has been calculated for the effects of docosan-1 -ol on Oncorhynchus mykiss. This result signifies that the test substance is not expected to be toxic at the limit of solubility. Due to the very low water solubility of the substance, the test was conducted with WAFs.The WAFs used in this study were filtered. This is the only experimental value available for this endpoint and therefore has been selected as key.

Abstract  SIDS dossiers already existed for 1-Dodecanol (CAS 112-53-8) and 1-Octadecanol (CAS 112-92-5) (published in 1998 and 1995 respectively); the present document updates and extends the earlier ones; brings in new information, and therefore replaces it. No conclusions drawn in the earlier review are amended. Available data for these substances are compiled in SIDS dossiers related to each CAS number. The reliability of each data point has been considered during this period of review, in accordance with the guidance of the Fraunhofer Institut für Toxikologie und Aerosolforschung. The following standard reliability codes, defined by Klimisch et al. (1997)1, apply, in accordance with the SIDS guidance: (1) Valid without restriction (2) Valid with restrictions (3) Invalid (4) Not assignable. Results considered to be Invalid are not used in the discussions or conclusions in this report. However, results which are of Non-assignable reliability may be fully valid, although insufficient details were available to be sure of this; therefore reliability (4) results are used in this report. The reliability code of each data point is given. Key studies are flagged in the SIDS dossiers. These are studies with the highest reliability/adequacy. If several studies showed comparable reliability/ adequacy, the study with the lowest LC/LD/EC50 or NOEC/ NOAEL has been indicated as the key study. For some endpoints, fully reliable results are not available and it has been necessary to use a weight of evidence including results of studies of non-assignable reliability. In such cases the results are identified as key studies as they are of high importance to the data set. For transparency, some study summaries in the SIDS dossier have been transferred from the previously published version of IUCLID or from the previous SIDS submission. In some cases, it has not been possible to retrieve the original literature/study reports using the reported citation or as a result of literature searching. In some cases, change of business ownership meant that internal study reports cited in previous summaries could not be accessed. In some other cases, e.g. certain non-SIDS endpoints, and in areas where a very large amount of literature has been published, it was not considered necessary to pursue all individual published sources due to weight of evidence of more reliable results. In all cases, reliability (4) applies, because the original documentation has not been reviewed in the development of the dossier. Such results are clearly identified in the SIDS dossier and more details are given therein.

Abstract  The rat oral LD50 for Nacol 22 RD is >10g/kg. At this dose level there was no evidence of toxicity in any of the parameters monitored.