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Query: UMLS:C0920652 (skin irritant)
 188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The oil derived from the seed of the Ricinus communis plant and its primary constituent, Ricinoleic Acid, along with certain of its salts and esters function primarily as skin-conditioning agents, emulsion stabilizers, and surfactants in cosmetics, although other functions are described. Ricinus Communis (Castor) Seed Oil is the naming convention for castor oil used in cosmetics. It is produced by cold pressing the seeds and subsequent clarification of the oil by heat. Castor oil does not contain ricin because ricin does not partition into the oil. Castor oil and Glyceryl Ricinoleate absorb ultraviolet (UV) light, with a maximum absorbance at 270 nm. Castor oil and Hydrogenated Castor Oil reportedly were used in 769 and 202 cosmetic products, respectively, in 2002; fewer uses were reported for the other ingredients in this group. The highest reported use concentration (81%) for castor oil is associated with lipstick. Castor oil is classified by Food and Drug Administration (FDA) as generally recognized as safe and effective for use as a stimulant laxative. The Joint Food and Agriculture Organization (FAO)/World Health Organization (WHO) Expert Committee on Food Additives established an acceptable daily castor oil intake (for man) of 0 to 0.7 mg/kg body weight. Castor oil is hydrolyzed in the small intestine by pancreatic enzymes, leading to the release of glycerol and Ricinoleic Acid, although 3,6-epoxyoctanedioic acid, 3,6-epoxydecanedioic acid, and 3,6-epoxydodecanedioic acid also appear to be metabolites. Castor oil and Ricinoleic Acid can enhance the transdermal penetration of other chemicals. Although chemically similar to prostaglandin E(1), Ricinoleic Acid did not have the same physiological properties. These ingredients are not acute toxicants, and a National Toxicology Program (NTP) subchronic oral toxicity study using castor oil at concentrations up to 10% in the diet of rats was not toxic. Other subchronic studies of castor oil produced similar findings. Undiluted castor oil produced minimal ocular toxicity in one study, but none in another. Undiluted castor oil was severely irritating to rabbit skin in one study, only slightly irritating in another, mildly irritating to guinea pig and rat skin, but not irritating to miniature swine skin. Ricinoleic Acid was nonirritating in mice and in one rabbit study, but produced well-defined erythema at abraded and intact skin sites in another rabbit study. Zinc Ricinoleate was not a sensitizer in guinea pigs. Neither castor oil nor Sodium Ricinoleate was genotoxic in bacterial or mammalian test systems. Ricinoleic Acid produced no neoplasms or hyperplasia in one mouse study and was not a tumor promoter in another mouse study, but did produce epidermal hyperplasia. Castor oil extract had a strong suppressive effect on S(180) body tumors and ARS ascites cancer in male Kunming mice. No dose-related reproductive toxicity was found in mice fed up to 10% castor oil for 13 weeks. Female rats injected intramuscularly with castor oil on the first day after estrus had suppressed ovarian folliculogenesis and anti-implantation and abortive effects. Castor oil used as a vehicle control in rats receiving subcutaneous injections had no effect on spermatogenesis. A methanol extract of Ricinus communis var. minor seeds (ether-soluble fraction) produced anti-implantation, anticonceptive, and estrogenic activity in rats and mice. Clinically, castor oil has been used to stimulate labor. Castor oil is not a significant skin irritant, sensitizer, or photosensitizer in human clinical tests, but patients with occupational dermatoses may have a positive reaction to castor oil or Ricinoleic Acid. The instillation of a castor oil solution into the eyes of nine patients resulted in mild and transient discomfort and minor epithelial changes. In another study involving 100 patients, the instillation of castor oil produced corneal epithelial cell death and continuity breaks in the epithelium. Because castor oil contains Ricinoleic Acid as the primary fatty acid group, the Cosmetic Ingredient Review (CIR) Expert Panel considered the safety test data on the oil broadly applicable to this entire group of cosmetic ingredients. The available data demonstrate few toxic effects. Although animal studies indicate no significant irritant or sensitization potential, positive reactions to Ricinoleic Acid in selected populations with identified dermatoses did suggest that sensitization reactions may be higher in that population. Overall, however, the clinical experience suggests that sensitization reactions are seen infrequently. In the absence of inhalation toxicity data on these ingredients, the Panel determined that these ingredients can be used safely in aerosolized cosmetic products because the particle sizes produced are not respirable. Overall, the CIR Expert Panel concluded that these cosmetic ingredients are safe in the practices of use and concentrations as described in this safety assessment.
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PMID:Final report on the safety assessment of Ricinus Communis (Castor) Seed Oil, Hydrogenated Castor Oil, Glyceryl Ricinoleate, Glyceryl Ricinoleate SE, Ricinoleic Acid, Potassium Ricinoleate, Sodium Ricinoleate, Zinc Ricinoleate, Cetyl Ricinoleate, Ethyl Ricinoleate, Glycol Ricinoleate, Isopropyl Ricinoleate, Methyl Ricinoleate, and Octyldodecyl Ricinoleate. 1808 Aug 73

The ECVAM-funded skin irritation validation study (SIVS) was initiated in 2003, with the aim to evaluate whether the EpiDerm, EPISKIN and the SIFT alternative methods were able to reliably identify skin irritant and non-irritant chemicals, and could therefore be candidates for replacing the rabbit Draize test for skin irritation. The primary goal of the study was to evaluate the predictive capacity of the assays with regard to the EU classification system, which employs the risk phrases, "R38", for skin irritants, and "no label" for non-irritants. A secondary objective was the retrospective analysis of the data, to assess whether the in vitro tests would be able to discriminate between strong irritants (category 2), mild irritants (category 3) and non-irritants (no category), as defined by the OECD and United Nations proposal for a Globally Harmonised System (GHS) for the classification and labelling of dermal irritancy. A Chemicals Selection Sub-Committee (CSSC) was appointed to identify test chemicals to be used in the SIVS, for which existing, high quality in vivo data were available, with which to correlate the in vitro measurements. Since chemicals from the European Centre for the Ecotoxicology and Toxicology of Chemicals (ECETOC) database of reference chemicals for skin irritation/skin corrosion had been extensively used in preceding studies, the CSSC made use of novel sources for potential test chemicals. The first source of chemicals screened was the New Chemicals Database (NCD), which is the central archive within the EU notification scheme for 'new' commercial chemicals. Data registered in the NCD originate from standard assays, submitted in compliance with the legislation which regulates the marketing of industrial chemicals, and are subject to quality assurance by the competent authorities of the EU Member States. In addition, to obtain 'existing' chemicals which were readily available from major manufacturing and/or distribution sources, additional databases were surveyed, such as the Toxic Substance Control Act (TSCA) database maintained by the US Environmental Protection Agency (EPA), and the ECETOC database, with the exclusion of the chemicals used in the previous optimisation and prevalidation phases. A total of approximately 3500 chemicals from the NCD and 1600 from the additional databases were screened. Pre-determined selection criteria were applied, primarily to ensure the quality of the in vivo data and the practicability of their use in testing. Overall, the number of chemicals fulfilling the CSSC selection criteria was found to be limited, particularly in the case of GHS category 2 chemicals. However, a total set of 60 chemicals were selected and proposed to the Management Team of the SIVS for independent coding and supply to the participating laboratories. The selected chemicals: i) represented statistically justified sample sizes for distinguishing R38 from no-label chemicals; ii) provided a balanced representation of the three GHS categories, to allow for the post hoc evaluation of the performance of the assays for that classification system; and iii) acknowledged, to a certain degree, the large prevalence known to exist for chemicals which have oedema and erythema scores of 0. The selected chemicals represented a variety of molecular structures, functional chemical groups, and effect and use categories, as well as a wide range of physico-chemical properties. They represented a challenging set of chemicals, relevant to current industrial commerce, with which to validate the alternative methods.
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PMID:The ECVAM international validation study on in vitro tests for acute skin irritation: selection of test chemicals. 1818 68

An in vitro cell culture approach was evaluated for its ability to provide data pertinent to the assessment of skin irritation potential. The hypothesis of this approach is that a direct toxic insult to the epidermal keratinocyte in vivo may lead to release of inflammatory mediators, which are responsible for initiation of a local primary skin irritant reaction. This paper presents data on the cytotoxic potential of a number of structurally unrelated chemicals (chloroform, 2-methoxyethanol, 2-butoxyethylacetate, toluene, 1-butanol, acetaldehyde, n-hexane, sodium dodecyl sulfate, benzalkonium chloride, silver nitrate, dibutyltin dichloride and tributyltin chloride). Cytotoxicity (neutral red uptake and intracellular acid phosphatase activity) of a number of structurally unrelated chemicals, representative of a wide range of skin irritation potential, was evaluated in cultures of rat and human epidermal keratinocytes. The sensitivity of human and rat keratinocytes to the test chemicals was very similar, irrespective of the endpoint of cytotoxicity. The neutral red uptake assay appeared more generally applicable to the diverse range of chemical structures represented in this study, since not all test chemicals elicited an early increase in intracellular acid phosphatase activity. The results were very encouraging, as a good correlation was evident between cytotoxicity in rat keratinocytes and the degree of erythema and oedema associated with an in vivo skin irritant response in rabbits. Keratinocyte cytotoxicity data may provide an indication of the potential of a chemical to induce a severe skin irritant reaction, or if a chemical is more likely to be a marginal or non-irritant. However, the data illustrate that such assays appear unable to discriminate correctly between more subtle classes of irritancy, such as non-irritant, mild, moderate or severe. Available human in vivo skin irritation data were insufficient to conclude which cell type is preferable for evaluation of human skin irritation potential.
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PMID:Use of human and rat keratinocyte cultures to assess skin irritation potential. 2065 Feb 13

A specific, mechanistic, in vitro approach for the assessment of human skin irritation potential is outlined for the evaluation of surfactants and the results compared with in vivo human patch test data. The level of free available surfactant monomer and the solubilization of the corn protein zein in vitro were confirmed to be related to surfactant in vivo human skin irritation potential. In vitro cytotoxicity to monolayer keratinocyte cultures could not discriminate between the moderate human skin irritant sodium dodecyl sulfate (SDS) and the mild irritants cocamidopropylbetaine (CA) and Polysorbate 20 (P20). An in vitro stratified differentiated human epidermal equivalent (HEE) exhibited reduced cytotoxicity to the test chemicals, compared with monolayer culture responses, and was able to discriminate between the toxic potential of SDS and CA. Stimulation of interleukin-1alpha release from the A431 human keratinocyte cell line reflected in vivo erythema scores more closely than cytotoxic potential, and coincided with nitric oxide production by macrophages upon exposure to A431-conditioned medium. Combination of these mechanistic assays has allowed a profile of likely in vivo human responses to be approximated. Additional knowledge of skin penetrability and rate of recovery from toxic damage would affirm these predictions.
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PMID:Human keratinocyte cultures in an in vitro approach for the assessment of surfactant-induced irritation. 2065 97


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