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Local Lymph Node (local + lymph_node)
Selected AbstractsAutoxidation of linalyl acetate, the main component of lavender oil, creates potent contact allergensCONTACT DERMATITIS, Issue 1 2008Maria Sköld Background:, Fragrances are among the most common causes of allergic contact dermatitis. We have in previous studies shown that linalool, present in lavender oil, autoxidizes on air exposure, forming allergenic oxidation products. Oxidized linalool was found to be a frequent cause of contact allergy in a patch test study on consecutive dermatitis patients. Linalyl acetate, the main component of lavender oil is commonly used as a fragrance chemical in scented products. Because of structural similarities, linalyl acetate should also be susceptible to oxidation on air exposure, forming similar oxidation products as linalool. Objective:, The aim of the present study was to investigate the autoxidation of linalyl acetate and the influence of oxidation on its sensitizing potency. Methods:, Analyses were performed using gas chromatography, nuclear magnetic resonance spectrometry and mass spectrometry. Sensitizing potencies of compounds were determined using the local lymph node assay (LLNA) in mice. Results:, Analyses showed that the content of linalyl acetate decreased over time on air exposure and other compounds were formed. Hydroperoxides, an epoxide and an alcohol were identified as oxidation products from linalyl acetate. In the LLNA, linalyl acetate of high purity showed a weak sensitizing potency (EC3 25%). Autoxidation increased the sensitizing potency of linalyl acetate, and a 10 weeks oxidized sample gave an EC3 value of 3.6%. As for linalool, the hydroperoxides were shown to be the oxidation products with the highest sensitizing potency. Conclusion:, It is concluded that autoxidation of the weakly allergenic linalyl acetate leads to formation of allergenic oxidation products. [source] The local lymph node assay and the assessment of relative potency: status of validationCONTACT DERMATITIS, Issue 2 2007David A. Basketter For the prediction of skin sensitization potential, the local lymph node assay (LLNA) is a fully validated alternative to guinea-pig tests. More recently, information from LLNA dose,response analyses has been used to assess the relative potency of skin sensitizing chemicals. These data are then deployed for risk assessment and risk management. In this commentary, the utility and validity of these relative potency measurements are reviewed. It is concluded that the LLNA does provide a valuable assessment of relative sensitizing potency in the form of the estimated concentration of a chemical required to produce a threefold stimulation of draining lymph node cell proliferation compared with concurrent controls (EC3 value) and that all reasonable validation requirements have been addressed successfully. EC3 measurements are reproducible in both intra- and interlaboratory evaluations and are stable over time. It has been shown also, by several independent groups, that EC3 values correlate closely with data on relative human skin sensitization potency. Consequently, the recommendation made here is that LLNA EC3 measurements should now be regarded as a validated method for the determination of the relative potency of skin sensitizing chemicals, a conclusion that has already been reached by a number of independent expert groups. [source] Information derived from sensitization test methods: test sensitivity, false positives and false negativesCONTACT DERMATITIS, Issue 1 2007David A. Basketter Predictive toxicology tests for the prospective identification of skin-sensitizing chemicals are well known and have been used for many years. However, of these, only the local lymph node assay (LLNA) has actually undergone formal independent assessment to determine the accuracy of the predictions, particularly with respect to the likelihood of false positives and false negatives. Often, efforts to increase the sensitivity of a test (reducing false negatives) tend to increase the number of false positives. In this short review, these issues are discussed in particular relation to the 3 predictive tests available in regulatory toxicology, the guinea-pig maximization test, the occluded patch test of Buehler and the LLNA. A key perspective is that no predictive test is without limitations; having a good appreciation of these limitations is necessary for making the best use of the information derived from these methods. [source] Predictive identification of human skin sensitization thresholdsCONTACT DERMATITIS, Issue 5 2005David A. Basketter For years, methods have been available for the predictive identification of chemicals that possess the intrinsic potential to cause skin sensitization. However, many have proven less suitable for the determination of relative sensitizing potency. In this respect, the local lymph node assay (LLNA) has been shown to have a number of important advantages. Through interpolation of LLNA dose,response data, the concentration of a chemical required to produce a threshold positive response (a 3-fold increase in activity compared with concurrent vehicle controls, the EC3 value) can be measured. The robustness of this parameter has been demonstrated rigorously in terms of inter- and intralaboratory reproducibility. Additionally, the relationship between potency estimates from the LLNA and an appreciation of human potency based on clinical experience has been reported previously. In the present investigations, we have sought to consolidate further our understanding of the association between EC3 values and human skin-sensitization potency by undertaking a thorough and extensive analysis of existing human predictive assays, particularly where dose,response information is available, from historical human repeated insult patch tests (HRIPTs). From these human data, information on the approximate threshold for the induction of skin sensitization in the HRIPT was determined for 26 skin-sensitizing chemicals. These data were then compared with LLNA-derived EC3 values. The results from each assay, expressed as dose per unit area (,g/cm2), revealed a clear linear relationship between the 2 values, thereby substantiating further the utility of LLNA EC3 values for prediction of the relative human sensitizing potency of newly identified skin sensitizers. [source] Evaluation of the skin sensitizing potency of chemicals by using the existing methods and considerations of relevance for elicitationCONTACT DERMATITIS, Issue 1 2005David A. Basketter The Technical Committee of Classification and Labelling dealing with harmonized classification of substances and classification criteria under Directive 67/548/EEC on behalf of the European Commission nominated an expert group on skin sensitization in order to investigate further the possibility for potency consideration of skin sensitizers for future development of the classification criteria. All substances and preparations should be classified on the basis of their intrinsic properties and should be labelled accordingly with the rules set up in the Directive 67/548/EEC. The classification should be the same under their full life cycle and in the case that there is no harmonized classification the substance or preparation should be self-classified by the manufacturer in accordance with the same criteria. The Directive does not apply to certain preparations in the finished state, such as medical products, cosmetics, food and feeding stuffs, which are subject to specific community legislation. The main questions that are answered in this report are whether it would be possible to give detailed guidance on how to grade allergen potency based on the existing methods, whether such grading could be translated into practical thresholds and whether these could be set for both induction and elicitation. Examples are given for substances falling into various potency groups for skin sensitization relating to results from the local lymph node assay, the guinea pig maximization test, the Buehler method and human experience. [source] Allergenicity evaluation of Bioban CS-1135 in experimental animalsCONTACT DERMATITIS, Issue 6 2004Tetsuo Yamano An industrial preservative, Bioban CS-1135, was evaluated for its contact allergenicity by means of multiple-dose guinea-pig maximization test and non-radioactive murine local lymph node assay. In the guinea-pig test, an induction dose of 0.5% Bioban CS-1135 sensitized all animals of the group. The dose,response study of the elicitation phase determined a minimum elicitation dose of 5% for positive skin reactions. In the murine assay, Bioban CS-1135 at doses of 10% and more exerted significant effects on lymphoid cell proliferation. Although the data clearly designated Bioban CS-1135 as a skin sensitizer, its relative potency was ranked lowest among skin-sensitizing biocides previously evaluated in this laboratory. [source] A chemical dataset for evaluation of alternative approaches to skin-sensitization testingCONTACT DERMATITIS, Issue 5 2004G. Frank Gerberick Allergic contact dermatitis resulting from skin sensitization is a common occupational and environmental health problem. In recent years, the local lymph node assay (LLNA) has emerged as a practical option for assessing the skin-sensitization potential of chemicals. In addition to accurate identification of skin sensitizers, the LLNA can also provide a reliable measure of relative sensitization potency, information that is pivotal in successful management of human health risks. However, even with the significant animal welfare benefits provided by the LLNA, there is interest still in the development of non-animal test methods for skin sensitization. Here, we provide a dataset of chemicals that have been tested in the LLNA and the activity of which correspond with what is known of their potential to cause skin sensitization in humans. It is anticipated that this will be of value to other investigators in the evaluation and calibration of novel approaches to skin-sensitization testing. The materials that comprise this dataset encompass both the chemical and biological diversity of known chemical allergens and provide also examples of negative controls. It is hoped that this dataset will accelerate the development, evaluation and eventual validation of new approaches to skin-sensitization testing. [source] The human skin/chick chorioallantoic membrane model accurately predicts the potency of cosmetic allergensEXPERIMENTAL DERMATOLOGY, Issue 4 2009Dan Slodownik Abstract:, The current standard method for predicting contact allergenicity is the murine local lymph node assay (LLNA). Public objection to the use of animals in testing of cosmetics makes the development of a system that does not use sentient animals highly desirable. The chorioallantoic membrane (CAM) of the chick egg has been extensively used for the growth of normal and transformed mammalian tissues. The CAM is not innervated, and embryos are sacrificed before the development of pain perception. The aim of this study was to determine whether the sensitization phase of contact dermatitis to known cosmetic allergens can be quantified using CAM-engrafted human skin and how these results compare with published EC3 data obtained with the LLNA. We studied six common molecules used in allergen testing and quantified migration of epidermal Langerhans cells (LC) as a measure of their allergic potency. All agents with known allergic potential induced statistically significant migration of LC. The data obtained correlated well with published data for these allergens generated using the LLNA test. The human-skin CAM model therefore has great potential as an inexpensive, non-radioactive, in vivo alternative to the LLNA, which does not require the use of sentient animals. In addition, this system has the advantage of testing the allergic response of human, rather than animal skin. [source] Vehicle effects on skin sensitizing potency of four chemicals: assessment using the local lymph node assayINTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 2 2001Z M Wright Synopsis The murine local lymph node assay (LLNA) can be used to determine the relative skin sensitizing potency of chemicals via interpolation of the quantitative dose response data generated. Using this approach we have demonstrated previously that the vehicle matrix in which a chemical allergen is encountered on the skin can have a significant influence on sensitizing potency. Estimates of relative potency are calculated from LLNA dose responses as a function of the mathematically derived EC3 value, this being the concentration estimated to induce a stimulation index (SI) of 3. To investigate further the influence of application vehicle on sensitizing potency, the LLNA has been used to examine the activity of four recognized human contact allergens: isoeugenol and cinnamic aldehyde, two fragrance chemicals; 3-dimethylaminopropylamine (a sensitizing impurity of cocamidopropyl betaine, a surfactant used in shower gel) and dibromodicyanobutane (the sensitizing component of Euxyl K 400, a preservative used in cosmetics). The four chemicals were applied in each of seven different vehicles (acetone: olive oil [4 : 1]; dimethylsulphoxide; methylethylketone; dimethyl formamide; propylene glycol; and both 50 : 50 and 90 : 10 mixtures of ethanol and water). It was found that the vehicle in which a chemical is presented to the epidermis can have a marked effect on sensitizing activity. EC3 values ranged from 0.9 to 4.9% for isoeugenol, from 0.5 to 1.7% for cinnamic aldehyde, from 1.7 to > 10% for dimethylaminopropylamine and from 0.4 to 6.4% for dibromodicyanobutane. These data confirm that the vehicle in which a chemical is encountered on the skin has an important influence on the relative skin sensitizing potency of chemicals and may have a significant impact on the acquisition of allergic contact dermatitis. The data also demonstrate the utility of the LLNA as a method for the prediction of these effects and thus for the development of more accurate risk assessments. Résumé Le test local des ganglions lymphatiques murins (LLNA) peut être utilisé pour déterminer le potentiel relatif de sensibilisation de la peau de produits chimiques, par interpolation des données quantitatives de dose/réponse obtenues. En utilisant cette approche, nous avions démontré précédemment que la matrice vecteur par laquelle un allergène chimique est mis en contact avec la peau peut avoir une influence significative sur le potentiel de sensibilisation. Des estimations d'activité relative sont calculées à partir des doses/réponses de LLNA en fonction de la valeur EC3 dérivée mathématiquement, celle-ci étant la concentration estimée comme induisant un indice de stimulation (IS) de 3. Pour examiner plus avant l'influence du vecteur d'application sur l'activité de sensibilisation, on a utilisé le LLNA pour déterminer l'activité de quatre allergènes de contact humains reconnus: isoeugénol et aldéhyde cinnamique, deux substances chimiques de parfumerie; la 3-diméthylaminopropylamine (une impureté sensibilisante de la cocamidopropyl bétaïne, un tensioactif utilisé dans les gels douches) et le dibromodicyanobutane (le composant sensibilisant de Euxyl K 400, un conservateur utilisé dans les cosmétiques). Les quatre produits chimiques ont été appliqués dans chacun de sept vecteurs différents (acétone: huile d'olive [4: 1]; diméthylsulfoxyde; méthyléthylcétone; diméthylformamide; propy- lène glycol; et deux mélanges 50: 50 et 90: 10 d'éthanol et d'eau). On observe que le vecteur dans lequel le produit chimique est présentéà l'épiderme peut avoir un effet marqué sur l'activité sensibilisatrice. Les valeurs EC3 vont de 0,9 à 4,9 % pour l'isoeugénol, de 0,5 à 1,7 % pour l'aldéhyde cinnamique, de 1,7 à > 10 % pour la diméthylaminopropylamine et de 0,4 à 6,4 % pour le dibromodicyanobutane. Ces données confirment que le vecteur dans lequel un produit chimique est mis en contact avec la peau a une influence importante sur le potentiel relatif de sensibilisation de la peau des produits chimiques, et peut avoir un impact significatif sur l'apparition de dermatite allergique par contact. Les données démontrent aussi l'utilité du LLNA comme méthode de prévision de ces effets et donc pour le développement d'évaluations plus précises des risques. [source] Skin sensitization, false positives and false negatives: experience with guinea pig assaysJOURNAL OF APPLIED TOXICOLOGY, Issue 5 2010David A. Basketter Abstract The advent of the local lymph node assay (LLNA), and efforts to develop in vitro alternatives for the identification of skin sensitizing chemicals has focused attention on the issue of false positive and false negative results. In essence, the question becomes ,what is the gold standard?' In this context, attention has focused primarily on the LLNA as this is now the preferred assay for skin sensitization testing. However, for many years prior to introduction of the LLNA, the guinea pig maximization test and the occluded patch test of Buehler were the methods of choice. In order to encourage a more informed dialogue about the relative performance, accuracy and applicability of the LLNA and guinea pig tests, we have here considered the extent to which guinea pig methods were themselves subject to false positives and negative results. We describe and discuss here well-characterized examples of instances where both false negatives (including abietic acid and eugenol) or false positives (including vanillin and sulfanilic acid) have been recorded in guinea pig tests. These and other examples are discussed with particular reference to the fabrication of a gold standard dataset that is required for the validation of in vitro alternatives. Copyright © 2010 John Wiley & Sons, Ltd. [source] Skin sensitization potency of isoeugenol and its dimers evaluated by a non-radioisotopic modification of the local lymph node assay and guinea pig maximization testJOURNAL OF APPLIED TOXICOLOGY, Issue 4 2008Masahiro Takeyoshi Abstract Allergic contact dermatitis is the serious unwanted effect arising from the use of consumer products such as cosmetics. Isoeugenol is a fragrance chemical with spicy, carnation-like scent, is used in many kinds of cosmetics and is a well-known moderate human sensitizer. It was previously reported that the dimerization of eugenol yielded two types of dimer possessing different sensitization potencies. This study reports the differences in skin sensitization potencies for isoeugenol and two types of dimer, , -O-4-dilignol and dehydrodiisoeugenol (DIEG), as evaluated by the non-radioisotopic local lymph node assay (non-RI LLNA) and guinea pig maximization test. In the guinea pig maximization test, isoeugenol, , -O-4-dilignol and DIEG were classified as extreme, weak and moderate sensitizers, respectively. As for the results of non-RI LLNA, the EC3 for isoeugenol, , -O-4-dilignol and DIEG were calculated as 12.7%, >30% and 9.4%, respectively. The two types of isoeugenol dimer showed different sensitizing activities similar to the case for eugenol dimers. A reduction of sensitization potency achieved by dimerization may lead to developing safer cosmetic ingredients. Isoeugenol dimers are not currently used for fragrance chemicals. However, the dimerization of isoeugenol may yield a promising candidate as a cosmetic ingredient with low sensitization risk. The data may also provide useful information for the structure-activity relationship (SAR) in skin sensitization. Copyright © 2007 John Wiley & Sons, Ltd. [source] Advantage of using CBA/N strain mice in a non-radioisotopic modification of the local lymph node assayJOURNAL OF APPLIED TOXICOLOGY, Issue 1 2006Masahiro Takeyoshi Abstract The murine local lymph node assay (LLNA) is currently recognized as a stand-alone test method for determining the skin sensitizing potential of chemicals. It has been incorporated into the official test guidelines published by some authorities, including the OECD. To avoid the use of radioisotopes, efforts have been made recently to develop non-radioisotopic modifications of the LLNA. A non-radioisotopic modification of the LLNA was developed previously using 5-bromo-2,-deoxyuridine (BrdU) incorporation (non-RI LLNA). However, the non-RI LLNA was found to be somewhat less sensitive than the standard assay. This study reports the advantage of using mice of the CBA/N strain in the non-RI LLNA to improve the sensitivity of this method. The non-RI LLNA was performed using CBA/JN and CBA/N mice exposed to one of four confirmed skin sensitizers, 2,4-dinitrochlorobenzene (DNCB), eugenol (EG), isoeugenol (IEG) or , -hexylcinnamic aldehyde (HCA), and to one non-sensitizer, propylene glycol (PG). The EC3 values for DNCB, IEG, EG, HCA and PG were calculated to be 0.1%, 9.6%, 40.6%, 45.5% and >50% in CBA/JN mice and 0.08%, 1.9%, 10.7%, 20.3% and >50% in CBA/N mice, respectively. The EC3 values for DNCB, IEG, EG, HCA and PG in the standard LLNA using CBA/Ca mice and radioisotopes were reported elsewhere as being 0.08%, 1.3%, 13.0%, 8.0% and >50%, respectively. The EC3 values derived from the CBA/N mice in the non-RI LLNA were nearly equivalent to the EC3 values obtained using the standard radioisotopic LLNA with CBA/Ca mice. These data suggest that the use of CBA/N mice may provide a realistic opportunity to develop a version of the LLNA that does not have a requirement for the use of radioisotopes, but which nevertheless has sensitivity approaching, or comparable to, the standard method. Copyright © 2005 John Wiley & Sons, Ltd. [source] Allergenicity testing of supermethrin, phenoxyacetic acid and DNCB using in vivo and in vitro modifications of the local lymph node assays, maximization and epicutaneous testingJOURNAL OF APPLIED TOXICOLOGY, Issue 4 2001M. Kuricova Abstract The purpose of this study was to compare two methods of testing for allergenicity: in vivo and in vitro modifications of local lymph node assays (LLNA) in mice and the maximization and epicutaneous skin tests in guinea pigs as per the Organization for Economic Cooperation and Development (1981). Two pesticides,the synthetic pyrethroid insecticide supermethrin (SM) and the herbicide phenoxyacetic acid (PAA),were evaluated using this testing battery. 1-Chloro-2,4-dinitrobenzene (DNCB) was selected as a reference allergen for the local lymph node assay. In vitro modification of LLNA proliferative response per standard cell count in lymphocyte cultures derived from treated Balb/c mice did not differ from control mice. Results of the in vivo modification showed that treatment with 50% PAA and 50% SM resulted in a lower proliferation response of lymphocytes in lymph nodes compared with control animals. The vigour of the proliferative response varied more in in vivo modification of LLNA. Stimulation indices were <3, so PAA and SM did not indicate classification as allergens. Lymphocyte proliferation in 1% DNCB-activated lymph nodes was approximately fivefold higher than in those derived from control mice. Proliferation response in vitro calculated as stimulation index was higher in DNCB-treated mice than those observed in vivo, but differences were not dramatic. Auricular lymph node weight and cellularity in mice treated with PAA and SM were similar to controls. The DNCB stimulation index for lymph node cellularity was 5.5. Lymph node weight was three times higher in comparison with controls. In the maximization test in guinea pigs SM and PAA acid resulted in 40% and 50% of animals demonstrating sensitization, respectively. Epicutaneous administration resulted in weaker reaction. Both SM and PAA are mildly strong sensitizers by this battery. Copyright © 2001 John Wiley & Sons, Ltd. [source] Adrenocortical carcinoma with delayed cutaneous metastasisJOURNAL OF CUTANEOUS PATHOLOGY, Issue 7 2008Elizabeth K. Satter Adrenal cortical carcinoma (ACC) is an uncommon and aggressive malignancy. Patients often have metastatic disease at initial presentation, with the most common sites being the liver, local lymph nodes, lungs, peritoneum and bone. Despite a high frequency of metastases, there are only isolated reports of ACC that have metastasized to the skin. Herein, we report a case of an 82-year-old woman who presented with a cyst-like lesion on her back, which on biopsy proved to be ACC metastatic from a primary tumor diagnosed 30 years previously. [source] A retrospective study of outcome of Mohs' micrographic surgery for cutaneous squamous cell carcinoma using formalin fixed sectionsBRITISH JOURNAL OF DERMATOLOGY, Issue 4 2000R.J. Turner The surgical management of recurrent or large squamous cell carcinoma (SCC) can be challenging as tumours often extend beyond visible margins. Micrographic surgery is a potentially effective method of ensuring complete clearance of tumour. A retrospective study of all cases of SCC treated by micrographic surgery in this department between 1986 and 1996 has been done. Sixty-one patients were treated using a formalin-fixed paraffin-embedded tissue technique with a median follow-up of 4 years. In two cases there was local recurrence and in three others metastasis to local lymph nodes. The overall cure rate was 92% (56 of 61), which compares favourably with published series using chemosurgery and frozen tissue techniques. The results show that this technique of micrographic surgery is a satisfactory and cost-effective alternative to conventional frozen section techniques in the treatment of SCC. The formalin-fixed tissue method has the advantage of providing high-quality permanent histological sections using existing conventional pathology services. [source] Local excision and endoscopic posterior mesorectal resection versus low anterior resection in T1 rectal cancer,BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 3 2008I. Tarantino Background: Rectum-preserving endoscopic posterior mesorectal resection (EPMR) removes the local lymph nodes in a minimally invasive manner and completes tumour staging after transanal local excision (TE). The aim of this study was to compare the morbidity and mortality of TE and EPMR with those of low anterior resection (LAR) in patients with T1 rectal cancer. Methods: Between 1996 and 2006 EPMR was performed 6 weeks after TE in 18 consecutive patients with a T1 rectal cancer. Morbidity and mortality were recorded prospectively and compared with those in a group of 17 patients treated by LAR. Lymph node involvement and local recurrence rate were analysed in both groups. Results: Two major and three minor complications were noted after EPMR, and four major and four minor complications after LAR (P = 0·402 for major and P = 0·691 for minor complications). Median number of lymph nodes removed was 7 (range 1,22) for EPMR and 11 (range 2,36) for LAR (P = 0·132). Two of 25 patients with a low-risk rectal cancer were node positive. No patient developed locoregional recurrence. Conclusion: EPMR after TE is a safe option for T1 rectal cancer. This two-stage procedure has a lower morbidity than LAR and may reduce locoregional recurrence compared with TE alone. Copyright © 2008 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] | ||||||||||