Mechanistic applicability domain classification of a local lymph node assay dataset for skin sensitization.

Science.gov (United States)

Roberts, David W; Patlewicz, Grace; Kern, Petra S; Gerberick, Frank; Kimber, Ian; Dearman, Rebecca J; Ryan, Cindy A; Basketter, David A; Aptula, Aynur O

2007-07-01

The goal of eliminating animal testing in the predictive identification of chemicals with the intrinsic ability to cause skin sensitization is an important target, the attainment of which has recently been brought into even sharper relief by the EU Cosmetics Directive and the requirements of the REACH legislation. Development of alternative methods requires that the chemicals used to evaluate and validate novel approaches comprise not only confirmed skin sensitizers and non-sensitizers but also substances that span the full chemical mechanistic spectrum associated with skin sensitization. To this end, a recently published database of more than 200 chemicals tested in the mouse local lymph node assay (LLNA) has been examined in relation to various chemical reaction mechanistic domains known to be associated with sensitization. It is demonstrated here that the dataset does cover the main reaction mechanistic domains. In addition, it is shown that assignment to a reaction mechanistic domain is a critical first step in a strategic approach to understanding, ultimately on a quantitative basis, how chemical properties influence the potency of skin sensitizing chemicals. This understanding is necessary if reliable non-animal approaches, including (quantitative) structure-activity relationships (Q)SARs, read-across, and experimental chemistry based models, are to be developed.

Evaluation of a high-throughput peptide reactivity format assay for assessment of the skin sensitization potential of chemicals

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Chin Lin eWong

2016-03-01

Full Text Available The direct peptide reactivity assay (DPRA is a validated method for in vitro assessment of the skin sensitization potential of chemicals. In the present work, we describe a peptide reactivity assay using 96-well plate format and systematically identified the optimal assay conditions for accurate and reproducible classification of chemicals with known sensitizing capacity. The aim of the research is to ensure that the analytical component of the peptide reactivity assay is robust, accurate and reproducible in accordance with criteria that are used for the validation of bioanalytical methods. Analytical performance was evaluated using quality control samples (QCs; heptapeptides at low, medium and high concentrations and incubation of control chemicals (chemicals with known sensitization capacity, weak, moderate, strong, extreme and non-sensitizers with each of three synthetic heptapeptides, viz Cor1-C420 (Ac-NKKCDLF, cysteine- (Ac-RFAACAA and lysine- (Ac-RFAAKAA containing heptapeptides. The optimal incubation temperature for all three heptapeptides was 25°C. Apparent heptapeptide depletion was affected by vial material composition. Incubation of test chemicals with Cor1-C420, showed that peptide depletion was unchanged in polypropylene vials over 3-days storage in an autosampler but this was not the case for borosilicate glass vials. For cysteine-containing heptapeptide, the concentration was not stable by day 3 post-incubation in borosilicate glass vials. Although the lysine-containing heptapeptide concentration was unchanged in both polypropylene and borosilicate glass vials, the apparent extent of lysine-containing heptapeptide depletion by ethyl acrylate, differed between polypropylene (24.7% and glass (47.3% vials. Additionally, the peptide-chemical complexes for Cor1-C420-cinnamaldehyde and cysteine-containing heptapeptide-2,4-dinitrochlorobenzene were partially reversible during 3-days of autosampler storage. These observations further

QSAR Study of Skin Sensitization Using Local Lymph Node Assay Data

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Eugene Demchuk

2004-01-01

Full Text Available Abstract: Allergic Contact Dermatitis (ACD is a common work-related skin disease that often develops as a result of repetitive skin exposures to a sensitizing chemical agent. A variety of experimental tests have been suggested to assess the skin sensitization potential. We applied a method of Quantitative Structure-Activity Relationship (QSAR to relate measured and calculated physical-chemical properties of chemical compounds to their sensitization potential. Using statistical methods, each of these properties, called molecular descriptors, was tested for its propensity to predict the sensitization potential. A few of the most informative descriptors were subsequently selected to build a model of skin sensitization. In this work sensitization data for the murine Local Lymph Node Assay (LLNA were used. In principle, LLNA provides a standardized continuous scale suitable for quantitative assessment of skin sensitization. However, at present many LLNA results are still reported on a dichotomous scale, which is consistent with the scale of guinea pig tests, which were widely used in past years. Therefore, in this study only a dichotomous version of the LLNA data was used. To the statistical end, we relied on the logistic regression approach. This approach provides a statistical tool for investigating and predicting skin sensitization that is expressed only in categorical terms of activity and nonactivity. Based on the data of compounds used in this study, our results suggest a QSAR model of ACD that is based on the following descriptors: nDB (number of double bonds, C-003 (number of CHR3 molecular subfragments, GATS6M (autocorrelation coefficient and HATS6m (GETAWAY descriptor, although the relevance of the identified descriptors to the continuous ACD QSAR has yet to be shown. The proposed QSAR model gives a percentage of positively predicted responses of 83% on the training set of compounds, and in cross validation it correctly identifies 79% of

A fluorescence high throughput screening method for the detection of reactive electrophiles as potential skin sensitizers

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Skin sensitization is an important toxicological end-point in the risk assessment of chemical allergens. Because of the complexity of the biological mechanisms associated with skin sensitization integrated approaches combining different chemical, biological and in silico methods are recommended to r...

QSAR models of human data can enrich or replace LLNA testing for human skin sensitization

OpenAIRE

Alves, Vinicius M.; Capuzzi, Stephen J.; Muratov, Eugene; Braga, Rodolpho C.; Thornton, Thomas; Fourches, Denis; Strickland, Judy; Kleinstreuer, Nicole; Andrade, Carolina H.; Tropsha, Alexander

2016-01-01

Skin sensitization is a major environmental and occupational health hazard. Although many chemicals have been evaluated in humans, there have been no efforts to model these data to date. We have compiled, curated, analyzed, and compared the available human and LLNA data. Using these data, we have developed reliable computational models and applied them for virtual screening of chemical libraries to identify putative skin sensitizers. The overall concordance between murine LLNA and human skin ...

Local lymph node assay (LLNA) for detection of sensitization capacity of chemicals.

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Gerberick, G Frank; Ryan, Cindy A; Dearman, Rebecca J; Kimber, Ian

2007-01-01

The local lymph node assay (LLNA) is a murine model developed to evaluate the skin sensitization potential of chemicals. The LLNA is an alternative approach to traditional guinea pig methods and in comparison provides important animal welfare benefits. The assay relies on measurement of events induced during the induction phase of skin sensitization, specifically lymphocyte proliferation in the draining lymph nodes which is a hallmark of a skin sensitization response. Since its introduction the LLNA has been the subject of extensive evaluation on a national and international scale, and has been successfully validated and incorporated worldwide into regulatory guidelines. Experience gained in recent years has demonstrated that adherence to published procedures and guidelines for the LLNA (e.g., with respect to dose and vehicle selection) is critical for the successful conduct and eventual interpretation of the data. In addition to providing a robust method for skin sensitization hazard identification, the LLNA has proven very useful in assessing the skin sensitizing potency of test chemicals, and this has provided invaluable information to risk assessors. The primary method to make comparisons of the relative potency of chemical sensitizers is to use linear interpolation to estimate the concentration of chemical required to induce a stimulation index of three relative to concurrent vehicle-treated controls (EC3). In certain situations where there are available less than optimal dose response data a log-linear extrapolation method can be used to estimate an EC3 value which can reduce significantly the need for repeat testing of chemicals. The LLNA, when conducted according to published guidelines, provides a robust method for skin sensitization testing that not only provides reliable hazard identification information but also data necessary for effective risk assessment and risk management.

Infrared sensing based sensitive skin

Institute of Scientific and Technical Information of China (English)

CAO Zheng-cai; FU Yi-li; WANG Shu-guo; JIN Bao

2006-01-01

Developed robotics sensitive skin is a modularized, flexible, mini-type array of infrared sensors with data processing capabilities, which can be used to cover the body of a robot. Depending on the infrared sensors and periphery processing circuit, robotics sensitive skin can in real-time provide existence and distance information about obstacles for robots within sensory areas. The methodology of designing sensitive skin and the algorithm of a mass of IR data fusion are presented. The experimental results show that the multi-joint robot with this sensitive skin can work autonomously in an unknown environment.

The local lymph node assay and skin sensitization testing.

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Kimber, Ian; Dearman, Rebecca J

2010-01-01

The mouse local lymph node assay (LLNA) is a method for the identification and characterization of skin sensitization hazards. In this context the method can be used both to identify contact allergens, and also determine the relative skin sensitizing potency as a basis for derivation of effective risk assessments.The assay is based on measurement of proliferative responses by draining lymph node cells induced following topical exposure of mice to test chemicals. Such responses are known to be causally and quantitatively associated with the acquisition of skin sensitization and therefore provide a relevant marker for characterization of contact allergic potential.The LLNA has been the subject of exhaustive evaluation and validation exercises and has been assigned Organization for Economic Cooperation and Development (OECD) test guideline 429. Herein we describe the conduct and interpretation of the LLNA.

Dendritic cells and skin sensitization: Biological roles and uses in hazard identification

International Nuclear Information System (INIS)

Ryan, Cindy A.; Kimber, Ian; Basketter, David A.; Pallardy, Marc; Gildea, Lucy A.; Gerberick, G. Frank

2007-01-01

Recent advances have been made in our understanding of the roles played by cutaneous dendritic cells (DCs) in the induction of contact allergy. A number of associated changes in epidermal Langerhans cell phenotype and function required for effective skin sensitization are providing the foundations for the development of cellular assays (using DC and DC-like cells) for skin sensitization hazard identification. These alternative approaches to the identification and characterization of skin sensitizing chemicals were the focus of a Workshop entitled 'Dendritic Cells and Skin Sensitization: Biological Roles and Uses in Hazard Identification' that was given at the annual Society of Toxicology meeting held March 6-9, 2006 in San Diego, California. This paper reports information that was presented during the Workshop

A cell-based in vitro alternative to identify skin sensitizers by gene expression

International Nuclear Information System (INIS)

Hooyberghs, Jef; Schoeters, Elke; Lambrechts, Nathalie; Nelissen, Inge; Witters, Hilda; Schoeters, Greet; Heuvel, Rosette van den

2008-01-01

The ethical and economic burden associated with animal testing for assessment of skin sensitization has triggered intensive research effort towards development and validation of alternative methods. In addition, new legislation on the registration and use of cosmetics and chemicals promote the use of suitable alternatives for hazard assessment. Our previous studies demonstrated that human CD34 + progenitor-derived dendritic cells from cord blood express specific gene profiles upon exposure to low molecular weight sensitizing chemicals. This paper presents a classification model based on this cell type which is successful in discriminating sensitizing chemicals from non-sensitizing chemicals based on transcriptome analysis of 13 genes. Expression profiles of a set of 10 sensitizers and 11 non-sensitizers were analyzed by RT-PCR using 9 different exposure conditions and a total of 73 donor samples. Based on these data a predictive dichotomous classifier for skin sensitizers has been constructed, which is referred to as . In a first step the dimensionality of the input data was reduced by selectively rejecting a number of exposure conditions and genes. Next, the generalization of a linear classifier was evaluated by a cross-validation which resulted in a prediction performance with a concordance of 89%, a specificity of 97% and a sensitivity of 82%. These results show that the present model may be a useful human in vitro alternative for further use in a test strategy towards the reduction of animal use for skin sensitization

Filling the concept with data: integrating data from different in vitro and in silico assays on skin sensitizers to explore the battery approach for animal-free skin sensitization testing.

Science.gov (United States)

Natsch, Andreas; Emter, Roger; Ellis, Graham

2009-01-01

Tests for skin sensitization are required prior to the market launch of new cosmetic ingredients. Significant efforts are made to replace the current animal tests. It is widely recognized that this cannot be accomplished with a single in vitro test, but that rather the integration of results from different in vitro and in silico assays will be needed for the prediction of the skin sensitization potential of chemicals. This has been proposed as a theoretical scheme so far, but no attempts have been made to use experimental data to prove the validity of this concept. Here we thus try for the first time to fill this widely cited concept with data. To this aim, we integrate and report both novel and literature data on 116 chemicals of known skin sensitization potential on the following parameters: (1) peptide reactivity as a surrogate for protein binding, (2) induction of antioxidant/electrophile responsive element dependent luciferase activity as a cell-based assay; (3) Tissue Metabolism Simulator skin sensitization model in silico prediction; and (4) calculated octanol-water partition coefficient. The results of the in vitro assays were scaled into five classes from 0 to 4 to give an in vitro score and compared to the local lymph node assay (LLNA) data, which were also scaled from 0 to 4 (nonsensitizer/weak/moderate/strong/extreme). Different ways of evaluating these data have been assessed to rate the hazard of chemicals (Cooper statistics) and to also scale their potency. With the optimized model an overall accuracy for predicting sensitizers of 87.9% was obtained. There is a linear correlation between the LLNA score and the in vitro score. However, the correlation needs further improvement as there is still a relatively high variation in the in vitro score between chemicals belonging to the same sensitization potency class.

In chemico skin sensitization risk assessment of botanical ingredients.

Science.gov (United States)

Avonto, Cristina; Chittiboyina, Amar G; Sadrieh, Nakissa; Vukmanovic, Stanislav; Khan, Ikhlas A

2018-03-24

Skin sensitization risk assessment of botanical ingredients is necessary for consumers' protection and occupational hazard identification. There are currently very few available alternative methods that can assist in the evaluation of complex mixtures. Chemical methods can provide essential information in a timely manner and thus help to reduce the need for in vivo testing, and they can complement and facilitate targeted in vitro assays. In the present work, the applicability of the high-throughput screening with dansyl cysteamine (DCYA) method for the systematic evaluation of skin sensitization of complex botanicals was explored. Botanical ingredients of four unrelated plant species were obtained and tested with the high-throughput fluorescence method at three concentrations. To illustrate the minimal matrix effects of the tested extracts on the developed method, the least DCYA-reactive extract (Rosa canina) was spiked with known sensitizers at different concentrations. The data obtained from the four plant extracts and the spiking experiments with known sensitizers, suggest that the high-throughput screening-DCYA method can be successfully applied for estimating the skin sensitization potential of complex botanical matrices. This is the first report of an attempt to develop a versatile in chemico method for the rapid detection of reactive skin sensitizers in complex botanical extracts, which could complement the battery of existing validated, non-animal methods. Copyright © 2018 John Wiley & Sons, Ltd.

Performance of a novel keratinocyte-based reporter cell line to screen skin sensitizers in vitro

International Nuclear Information System (INIS)

Emter, Roger; Ellis, Graham; Natsch, Andreas

2010-01-01

In vitro tests are needed to replace animal tests to screen for the skin sensitization potential of chemicals. Skin sensitizers are electrophilic molecules and the Nrf2-electrophile-sensing pathway comprising the repressor protein Keap1, the transcription factor Nrf2 and the antioxidant response element (ARE) is emerging as a toxicity pathway induced by skin sensitizers. Previously, we screened a large set of chemicals in the reporter cell line AREc32, which contains an eight-fold repeat of the rat GSTA2 ARE-sequence upstream of a luciferase reporter gene in the human breast cancer cell line MCF7. This approach was now further developed to bring it closer to the conditions in the human skin and to propose a fully standardized assay. To this end, a luciferase reporter gene under control of a single copy of the ARE-element of the human AKR1C2 gene was stably inserted into HaCaT keratinocytes. A standard operating procedure was developed whereby chemicals are routinely tested at 12 concentrations in triplicate for significant induction of gene activity. We report results from this novel assay on (i) a list of reference chemicals published by ECVAM, (ii) the ICCVAM list of chemicals for validation of alternative endpoints in the LLNA and (iii) on a more general list of 67 chemicals derived from the ICCVAM database. For comparison, peptide reactivity data are presented for the same chemicals. The results indicate a good predictive value of this approach for hazard identification. Its technical simplicity, the high-throughput format and the good predictivity may make this assay a candidate for rapid validation to meet the tight deadline to replace animal tests for skin sensitization by 2013 set by the European authorities.

Prediction of Skin Sensitization with a Particle Swarm Optimized Support Vector Machine

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Chenzhong Cao

2009-07-01

Full Text Available Skin sensitization is the most commonly reported occupational illness, causing much suffering to a wide range of people. Identification and labeling of environmental allergens is urgently required to protect people from skin sensitization. The guinea pig maximization test (GPMT and murine local lymph node assay (LLNA are the two most important in vivo models for identification of skin sensitizers. In order to reduce the number of animal tests, quantitative structure-activity relationships (QSARs are strongly encouraged in the assessment of skin sensitization of chemicals. This paper has investigated the skin sensitization potential of 162 compounds with LLNA results and 92 compounds with GPMT results using a support vector machine. A particle swarm optimization algorithm was implemented for feature selection from a large number of molecular descriptors calculated by Dragon. For the LLNA data set, the classification accuracies are 95.37% and 88.89% for the training and the test sets, respectively. For the GPMT data set, the classification accuracies are 91.80% and 90.32% for the training and the test sets, respectively. The classification performances were greatly improved compared to those reported in the literature, indicating that the support vector machine optimized by particle swarm in this paper is competent for the identification of skin sensitizers.

Prediction of Skin Sensitization with a Particle Swarm Optimized Support Vector Machine

Science.gov (United States)

Yuan, Hua; Huang, Jianping; Cao, Chenzhong

2009-01-01

Skin sensitization is the most commonly reported occupational illness, causing much suffering to a wide range of people. Identification and labeling of environmental allergens is urgently required to protect people from skin sensitization. The guinea pig maximization test (GPMT) and murine local lymph node assay (LLNA) are the two most important in vivo models for identification of skin sensitizers. In order to reduce the number of animal tests, quantitative structure-activity relationships (QSARs) are strongly encouraged in the assessment of skin sensitization of chemicals. This paper has investigated the skin sensitization potential of 162 compounds with LLNA results and 92 compounds with GPMT results using a support vector machine. A particle swarm optimization algorithm was implemented for feature selection from a large number of molecular descriptors calculated by Dragon. For the LLNA data set, the classification accuracies are 95.37% and 88.89% for the training and the test sets, respectively. For the GPMT data set, the classification accuracies are 91.80% and 90.32% for the training and the test sets, respectively. The classification performances were greatly improved compared to those reported in the literature, indicating that the support vector machine optimized by particle swarm in this paper is competent for the identification of skin sensitizers. PMID:19742136

Chemical peeling in ethnic/dark skin.

Science.gov (United States)

Roberts, Wendy E

2004-01-01

Chemical peeling for skin of color arose in ancient Egypt, Mesopotamia, and other ancient cultures in and around Africa. Our current fund of medical knowledge regarding chemical peeling is a result of centuries of experience and research. The list of agents for chemical peeling is extensive. In ethnic skin, our efforts are focused on superficial and medium-depth peeling agents and techniques. Indications for chemical peeling in darker skin include acne vulgaris, postinflammatory hyperpigmentation, melasma, scarring, photodamage, and pseudofolliculitis barbae. Careful selection of patients for chemical peeling should involve not only identification of Fitzpatrick skin type, but also determining ethnicity. Different ethnicities may respond unpredictably to chemical peeling regardless of skin phenotype. Familiarity with the properties each peeling agent used is critical. New techniques discussed for chemical peeling include spot peeling for postinflammatory hyperpigmentation and combination peels for acne and photodamage. Single- or combination-agent chemical peels are shown to be efficacious and safe. In conclusion, chemical peeling is a treatment of choice for numerous pigmentary and scarring disorders arising in dark skin tones. Familiarity with new peeling agents and techniques will lead to successful outcomes.

Effect of chemical peeling on the skin in relation to UV irradiation.

Science.gov (United States)

Funasaka, Yoko; Abdel-Daim, Mohamed; Kawana, Seiji; Nishigori, Chikako

2012-07-01

Chemical peeling is one of the dermatological treatments available for certain cutaneous diseases and conditions or improvement of cosmetic appearance of photoaged skin. However, it needs to be clarified whether the repetitive procedure of chemical peeling on photodamaged skin is safe and whether the different chemicals used for peeling results in similar outcomes or not. In this article, we reviewed the effect of peeling or peeling agents on the skin in relation to ultraviolet (UV) radiation. The pretreatment of peeling agents usually enhance UV sensitivity by inducing increased sunburn cell formation, lowering minimum erythematous dose and increasing cyclobutane pyrimidine dimers. However, this sensitivity is reversible and recovers to normal after 1-week discontinuation. Using animals, the chronic effect of peeling and peeling agents was shown to prevent photocarcinogenesis. There is also an in vitro study using culture cells to know the detailed mechanisms of peeling agents, especially on cell proliferation and apoptotic changes via activating signalling cascades and oxidative stress. It is important to understand the effect of peeling agents on photoaged skin and to know how to deal with UV irradiation during the application of peeling agents and treatment of chemical peeling in daily life. © 2012 John Wiley & Sons A/S.

The pilosebaceous unit—a phthalate-induced pathway to skin sensitization

International Nuclear Information System (INIS)

Simonsson, Carl; Stenfeldt, Anna-Lena; Karlberg, Ann-Therese; Ericson, Marica B.; Jonsson, Charlotte A.M.

2012-01-01

Allergic contact dermatitis (ACD) is caused by low-molecular weight compounds called haptens. It has been shown that the potency of haptens can depend on the formulation in which they are applied on the skin. Specifically the sensitization potency of isothiocyanates, a group of haptens which can be released from e.g. adhesive tapes and neoprene materials, increases with the presence of phthalates; however, the underlying mechanisms are not clear. A better understanding of the mechanisms governing the potency of haptens is important, e.g. to improve the risk assessment and the formulation of chemicals in consumer products. In this study we have explored phthalate-induced effects on the sensitization potency, skin distribution, and reactivity of fluorescent model isothiocyanate haptens using non-invasive two-photon microscopy to provide new insights regarding vehicle effects in ACD. The data presented in this paper indicate that the sensitization potency of isothiocyanates increases when applied in combination with dibutylphthalate due to a specific uptake via the pilosebaceous units. The results highlight the importance of shunt pathways when evaluating the bioavailability of skin sensitizers. The findings also indicate that vehicle-dependent hapten reactivity towards stratum corneum proteins regulates the bioavailability, and thus the potency, of skin sensitizers. -- Highlights: ► Vehicle effects on sensitization potency were investigated in the LLNA. ► In vivo cutaneous absorption of contact sensitizers was visualized using TPM. ► Sensitizing potency of isothiocyanates depends on the presence of a phthalate. ► Phthalate induced cutaneous absorption via the pilosebaceous units. ► Vehicle-dependent reactivity regulates sensitization potency.

The pilosebaceous unit—a phthalate-induced pathway to skin sensitization

Energy Technology Data Exchange (ETDEWEB)

Simonsson, Carl, E-mail: carl.simonsson@chem.gu.se [Department of Chemistry and Molecular Biology, University of Gothenburg, SE-412 96, Gothenburg (Sweden); Stenfeldt, Anna-Lena; Karlberg, Ann-Therese [Department of Chemistry and Molecular Biology, University of Gothenburg, SE-412 96, Gothenburg (Sweden); Ericson, Marica B., E-mail: marica.ericson@physics.gu.se [Department of Physics, University of Gothenburg, SE-412 96, Gothenburg (Sweden); Jonsson, Charlotte A.M. [Department of Chemistry and Molecular Biology, University of Gothenburg, SE-412 96, Gothenburg (Sweden)

2012-10-01

Allergic contact dermatitis (ACD) is caused by low-molecular weight compounds called haptens. It has been shown that the potency of haptens can depend on the formulation in which they are applied on the skin. Specifically the sensitization potency of isothiocyanates, a group of haptens which can be released from e.g. adhesive tapes and neoprene materials, increases with the presence of phthalates; however, the underlying mechanisms are not clear. A better understanding of the mechanisms governing the potency of haptens is important, e.g. to improve the risk assessment and the formulation of chemicals in consumer products. In this study we have explored phthalate-induced effects on the sensitization potency, skin distribution, and reactivity of fluorescent model isothiocyanate haptens using non-invasive two-photon microscopy to provide new insights regarding vehicle effects in ACD. The data presented in this paper indicate that the sensitization potency of isothiocyanates increases when applied in combination with dibutylphthalate due to a specific uptake via the pilosebaceous units. The results highlight the importance of shunt pathways when evaluating the bioavailability of skin sensitizers. The findings also indicate that vehicle-dependent hapten reactivity towards stratum corneum proteins regulates the bioavailability, and thus the potency, of skin sensitizers. -- Highlights: ► Vehicle effects on sensitization potency were investigated in the LLNA. ► In vivo cutaneous absorption of contact sensitizers was visualized using TPM. ► Sensitizing potency of isothiocyanates depends on the presence of a phthalate. ► Phthalate induced cutaneous absorption via the pilosebaceous units. ► Vehicle-dependent reactivity regulates sensitization potency.

Development of an in vitro skin sensitization test based on ROS production in THP-1 cells.

Science.gov (United States)

Saito, Kazutoshi; Miyazawa, Masaaki; Nukada, Yuko; Sakaguchi, Hitoshi; Nishiyama, Naohiro

2013-03-01

Recently, it has been reported that reactive oxygen species (ROS) produced by contact allergens can affect dendritic cell migration and contact hypersensitivity. The aim of the present study was to develop a new in vitro assay that could predict the skin sensitizing potential of chemicals by measuring ROS production in THP-1 (human monocytic leukemia cell line) cells. THP-1 cells were pre-loaded with a ROS sensitive fluorescent dye, 5-(and 6-)-chloromethyl-2', 7'-dichlorodihydrofluorescein diacetate, acetyl ester (CM-H2DCFDA), for 15min, then incubated with test chemicals for 30min. The fluorescence intensity was measured by flow cytometry. For the skin sensitizers, 25 out of 30 induced over a 2-fold ROS production at more than 90% of cell viability. In contrast, increases were only seen in 4 out of 20 non-sensitizers. The overall accuracy for the local lymph node assay (LLNA) was 82% for 50 chemicals tested. A correlation was found between the estimated concentration showing 2-fold ROS production in the ROS assay and the EC3 values (estimated concentration required to induce positive response) of the LLNA. These results indicated that the THP-1 cell-based ROS assay was a rapid and highly sensitive detection system able to predict skin sensitizing potentials and potency of chemicals. Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical stability and in chemico reactivity of 24 fragrance ingredients of concern for skin sensitization risk assessment.

Science.gov (United States)

Avonto, Cristina; Wang, Mei; Chittiboyina, Amar G; Vukmanovic, Stanislav; Khan, Ikhlas A

2018-02-01

Twenty-four pure fragrance ingredients have been identified as potential concern for skin sensitization. Several of these compounds are chemically unstable and convert into reactive species upon exposure to air or light. In the present work, a systematic investigation of the correlation between chemical stability and reactivity has been undertaken. The compounds were subjected to forced photodegradation for three months and the chemical changes were studied with GC-MS. At the end of the stability study, two-thirds of the samples were found to be unstable. The generation of chemically reactive species was investigated using the in chemico HTS-DCYA assay. Eleven and fourteen compounds were chemically reactive before and after three months, respectively. A significant increase in reactivity upon degradation was found for isoeugenol, linalool, limonene, lyral, citronellol and geraniol; in the same conditions, the reactivity of hydroxycitronellal decreased. The non-reactive compounds α-isomethyl ionone, benzyl alcohol, amyl cinnamal and farnesol became reactive after photo-oxidative degradation. Overall, forced degradation resulted in four non-reactive fragrance compounds to display in chemico thiol reactivity, while ten out of 24 compounds remained inactive. Chemical degradation does not necessarily occur with generation of reactive species. Non-chemical activation may be involved for the 10 stable unreactive compounds. Copyright © 2017 Elsevier Ltd. All rights reserved.

Migration of human antigen-presenting cells in a human skin graft onto nude mice model after contact sensitization

NARCIS (Netherlands)

Hoefakker, S.; Balk, H.P.; Boersma, W.J.A.; Joost, T. van; Notten, W.R.F.; Claassen, E.

1995-01-01

Fluorescent contact chemical allergens provoke sensitization after application on both syngeneic and allogeneic skin grafts in mice. We attempted to determine whether the functional activity in a contact sensitization response of human skin graft was affected at the level of antigen uptake and

Electrocutaneous sensitivity: effects of skin temperature.

Science.gov (United States)

Larkin, W D; Reilly, J P

1986-01-01

The effect of human skin temperature on electrocutaneous sensitivity was examined using brief capacitive discharges. Stimuli were designed to ensure that sensory effects would be independent of skin resistance and would reflect underlying neural excitability as closely as possible. Skin temperature was manipulated by immersing the forearm in circulating hot or cold air. Detection thresholds on the arm and fingertip were raised by cooling, but were not altered by heating. Temperature-related sensitivity shifts were described by the same multiplicative factors for both threshold and suprathreshold levels. The temperature coefficient (Q10) for cutaneous sensitivity under these conditions was approximately 1.3.

Biodegradable Polymers Induce CD54 on THP-1 Cells in Skin Sensitization Test.

Science.gov (United States)

Jung, Yeon Suk; Kato, Reiko; Tsuchiya, Toshie

2011-01-01

Currently, nonanimal methods of skin sensitization testing for various chemicals, biodegradable polymers, and biomaterials are being developed in the hope of eliminating the use of animals. The human cell line activation test (h-CLAT) is a skin sensitization assessment that mimics the functions of dendritic cells (DCs). DCs are specialized antigen-presenting cells, and they interact with T cells and B cells to initiate immune responses. Phenotypic changes in DCs, such as the production of CD86 and CD54 and internalization of MHC class II molecules, have become focal points of the skin sensitization test. In this study, we used h-CLAT to assess the effects of biodegradable polymers. The results showed that several biodegradable polymers increased the expression of CD54, and the relative skin sensitizing abilities of biodegradable polymers were PLLG (75 : 25) < PLLC (40 : 60) < PLGA (50 : 50) < PCG (50 : 50). These results may contribute to the creation of new guidelines for the use of biodegradable polymers in scaffolds or allergenic hazards.

Biodegradable Polymers Induce CD54 on THP-1 Cells in Skin Sensitization Test

Directory of Open Access Journals (Sweden)

Yeon Suk Jung

2011-01-01

Full Text Available Currently, nonanimal methods of skin sensitization testing for various chemicals, biodegradable polymers, and biomaterials are being developed in the hope of eliminating the use of animals. The human cell line activation test (h-CLAT is a skin sensitization assessment that mimics the functions of dendritic cells (DCs. DCs are specialized antigen-presenting cells, and they interact with T cells and B cells to initiate immune responses. Phenotypic changes in DCs, such as the production of CD86 and CD54 and internalization of MHC class II molecules, have become focal points of the skin sensitization test. In this study, we used h-CLAT to assess the effects of biodegradable polymers. The results showed that several biodegradable polymers increased the expression of CD54, and the relative skin sensitizing abilities of biodegradable polymers were PLLG (75 : 25 < PLLC (40 : 60 < PLGA (50 : 50 < PCG (50 : 50. These results may contribute to the creation of new guidelines for the use of biodegradable polymers in scaffolds or allergenic hazards.

Multivariate Models for Prediction of Human Skin Sensitization ...

Science.gov (United States)

One of the lnteragency Coordinating Committee on the Validation of Alternative Method's (ICCVAM) top priorities is the development and evaluation of non-animal approaches to identify potential skin sensitizers. The complexity of biological events necessary to produce skin sensitization suggests that no single alternative method will replace the currently accepted animal tests. ICCVAM is evaluating an integrated approach to testing and assessment based on the adverse outcome pathway for skin sensitization that uses machine learning approaches to predict human skin sensitization hazard. We combined data from three in chemico or in vitro assays - the direct peptide reactivity assay (DPRA), human cell line activation test (h-CLAT) and KeratinoSens TM assay - six physicochemical properties and an in silico read-across prediction of skin sensitization hazard into 12 variable groups. The variable groups were evaluated using two machine learning approaches , logistic regression and support vector machine, to predict human skin sensitization hazard. Models were trained on 72 substances and tested on an external set of 24 substances. The six models (three logistic regression and three support vector machine) with the highest accuracy (92%) used: (1) DPRA, h-CLAT and read-across; (2) DPRA, h-CLAT, read-across and KeratinoSens; or (3) DPRA, h-CLAT, read-across, KeratinoSens and log P. The models performed better at predicting human skin sensitization hazard than the murine

CON4EI: SkinEthic™ Human Corneal Epithelium Eye Irritation Test (SkinEthic™ HCE EIT) for hazard identification and labelling of eye irritating chemicals.

Science.gov (United States)

Van Rompay, A R; Alépée, N; Nardelli, L; Hollanders, K; Leblanc, V; Drzewiecka, A; Gruszka, K; Guest, R; Kandarova, H; Willoughby, J A; Verstraelen, S; Adriaens, E

2018-06-01

Assessment of ocular irritancy is an international regulatory requirement and a necessary step in the safety evaluation of industrial and consumer products. Although a number of in vitro ocular irritation assays exist, none are capable of fully categorizing chemicals as a stand-alone assay. Therefore, the CEFIC-LRI-AIMT6-VITO CON4EI (CONsortium for in vitro Eye Irritation testing strategy) project was developed with the goal of assessing the reliability of eight in vitro/alternative test methods as well as establishing an optimal tiered-testing strategy. One of the in vitro assays selected was the validated SkinEthic™ Human Corneal Epithelium Eye Irritation Test method (SkinEthic™ HCE EIT). The SkinEthic™ HCE EIT has already demonstrated its capacity to correctly identify chemicals (both substances and mixtures) not requiring classification and labelling for eye irritation or serious eye damage (No Category). The goal of this study was to evaluate the performance of the SkinEthic™ HCE EIT test method in terms of the important in vivo drivers of classification. For the performance with respect to the drivers all in vivo Cat 1 and No Cat chemicals were 100% correctly identified. For Cat 2 chemicals the liquids and the solids had a sensitivity of 100% and 85.7%, respectively. For the SkinEthic™ HCE EIT test method, 100% concordance in predictions (No Cat versus No prediction can be made) between the two participating laboratories was obtained. The accuracy of the SkinEthic™ HCE EIT was 97.5% with 100% sensitivity and 96.9% specificity. The SkinEthic™ HCE EIT confirms its excellent results of the validation studies. Copyright © 2017. Published by Elsevier Ltd.

Ultrastructural observations of chemical peeling for skin rejuvenation (ultrastructural changes of the skin due to chemical peeling).

Science.gov (United States)

Omi, Tokuya; Sato, Shigeru; Numano, Kayoko; Kawana, Seiji

2010-02-01

Chemical peeling of the skin is commonly used as a means to treat photoaging, but the mechanism underlying its efficacy has not yet been fully clarified. We recently conducted chemical peeling of the skin with glycolic acid and lactic acid and observed it at the ultrastructural level. No changes in the horny layer or the upper epidermal layer were observed but there was dissociation and vacuolation between the basal cells and increases in vimentin filaments within fibroblasts and endothelial cells were seen. These findings suggest that chemical peeling of the skin with this type of agent directly induces collagen formation within the dermis and thus directly stimulates remodeling of the dermis.

Experimental studies on the nature of sensitive skin.

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Kligman, A M; Sadiq, Iqbal; Zhen, Yaxian; Crosby, Marilyn

2006-11-01

In the USA, Europe and Japan 40 to 50% of women report that they have sensitive skin, defined as abnormal sub-clinical sensory responses to drugs, cosmetics and toiletries in the absence of visible signs of irritation. Itching, burning, stinging and tightness are the commonest complaints, which mainly afflict women. Manufacturers of skin care products have made available a large variety of products which are designed for persons with sensitive skin. Such products are not required by regulatory agencies to submit evidence of safety and efficacy, allowing marketers to make claims that are often exaggerated, irrational and even preposterous. The consumer with self-assessed sensitive skin has no way of judging which products are likely to be most beneficial and least harmful. The marketplace is awash with products for which there is no evidence that the rosy claims have been substantiated by appropriate testing procedures. There is no internationally accepted consensus regarding the criteria which define sensitive skin. Many papers have been published in the last 15 years, mainly originating from industry, which express widely differing views regarding what constitutes sensitive skin. For some, any adverse reaction to a product topically applied to sensitive skin, including breakouts, redness, scaling etc., a panoply of adverse reactions which is virtually meaningless. Others include environmental factors as causative, including cold, dry wind, heat and high humidity, solar radiation, etc., which add to the manifest complexities of the subject. This is the first paper in a series which provides a comprehensive review of the subject, emphasizing the all too many controversies and confusions arising from the lack of a consensus regarding the identification, classification, epidemiology, prevalence and pathogenesis of sensitive skin. Sensitive skin is a biologic reality and not a psychological, fashionable fantasy on the part of impressionable women. There is an urgent

The local lymph node assay and skin sensitization: a cut-down screen to reduce animal requirements?

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Kimber, Ian; Dearman, Rebecca J; Betts, Catherine J; Gerberick, G Frank; Ryan, Cindy A; Kern, Petra S; Patlewicz, Grace Y; Basketter, David A

2006-04-01

The local lymph node assay (LLNA), an alternative approach to skin-sensitizing testing, has made a significant contribution to animal welfare by permitting a reduction and refinement of animal use. Although there is clearly an aspiration to eliminate the use of animals in such tests, it is appropriate also to consider other opportunities for refinement and reduction of animal use. We have therefore explored the use of a modified version of the LLNA for screening purposes when there is a need to evaluate the sensitizing activity of a large number of chemicals, as will be the case under the auspices of registration, evaluation and authorization of chemicals (REACH). Using an existing LLNA database of 211 chemicals, we have examined whether a cut-down assay comprising a single high-dose group and a concurrent vehicle control would provide a realistic approach for screening chemicals for sensitizing potential. The analyses reported here suggest this is the case. We speculate that the animal welfare benefits may be enhanced further by reducing the number of animals per experimental group. However, a detailed evaluation will be necessary to provide reassurance that a reduction in group size would provide adequate sensitivity across a range of skin sensitization potencies.

Application of BALB/c mouse in the local lymph node assay:BrdU-ELISA for the prediction of the skin sensitizing potential of chemicals.

Science.gov (United States)

Hou, Fenxia; Xing, Caihong; Li, Bin; Cheng, Juan; Chen, Wei; Zhang, Man

2015-01-01

Allergic contact dermatitis (ACD) is a skin disease characterized by eczema and itching. A considerable proportion of chemicals induce ACD in humans. More than 10,000 substances should be tested for skin sensitization potential under the Registration, Evaluation, Authorization and Restriction of Chemical substances (REACH) regulation. The Local Lymph Node Assay (LLNA) has been designated as the first-choice in vivo assay for sensitization testing by REACH. The LLNA:BrdU-ELISA is a validated non-radioactive modification to the LLNA. For both the LLNA and the LLNA:BrdU-ELISA, CBA/JN mouse is the preferred mouse strain recommended in the regulatory guidelines. However, the availability of CBA/JN mouse in China is only limited to a few animal suppliers, which makes the mouse difficult to obtain. BALB/c mouse, which is widely commercially available, is considered for alternative use but it can only be used in the assay after it has been evaluated by formal validation study. Thus, a validation study was conducted in our laboratory to determine if BALB/c mouse could also be used in the LLNA:BrdU-ELISA. Forty-three test substances including 32 LLNA sensitizers and 11 LLNA non-sensitizers, their vehicles and each concentration used were the same as that used in the formal validation study for the LLNA:BrdU-ELISA using CBA/JN mouse. Female BALB/c mice of 8-10 weeks old were randomly allocated to groups (four mice per group). The test substance (25 μl) or the vehicle alone was applied to the dorsum of both ears daily for 3 consecutive days. A single intraperitoneal injection of 0.5 ml of BrdU (10mg/ml) solution was given on day 5. On day 6, a pair of auricular lymph nodes from each mouse was excised, weighed and stored at -20°C until BrdU-ELISA was conducted. This validation study for the LLNA:BrdU-ELISA using BALB/c mouse correctly identified 30 of 31 sensitizers and 8 of 11 non-sensitizers. The accuracy, sensitivity, specificity, false positive rate, false negative rate

Estimating skin sensitization potency from a single dose LLNA.

Science.gov (United States)

Roberts, David W

2015-04-01

Skin sensitization is an important aspect of safety assessment. The mouse local lymph node assay (LLNA) developed in the 1990 s is an in vivo test used for skin sensitization hazard identification and characterization. More recently a reduced version of the LLNA (rLLNA) has been developed as a means of identifying, but not quantifying, sensitization hazard. The work presented here is aimed at enabling rLLNA data to be used to give quantitative potency information that can be used, inter alia, in modeling and read-across approaches to non-animal based potency estimation. A probit function has been derived enabling estimation of EC3 from a single dose. This has led to development of a modified version of the rLLNA, whereby as a general principle the SI value at 10%, or at a lower concentration if 10% is not testable, is used to calculate the EC3. This version of the rLLNA has been evaluated against a selection of chemicals for which full LLNA data are available, and has been shown to give EC3 values in good agreement with those derived from the full LLNA. Copyright © 2015 Elsevier Inc. All rights reserved.

A fluorescence high throughput screening method for the detection of reactive electrophiles as potential skin sensitizers

Energy Technology Data Exchange (ETDEWEB)

Avonto, Cristina; Chittiboyina, Amar G. [National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, University, MS 38677 (United States); Rua, Diego [The Center for Food Safety and Applied Nutrition, US Food and Drug Administration, College Park, MD 20740 (United States); Khan, Ikhlas A., E-mail: ikhan@olemiss.edu [National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, University, MS 38677 (United States); Division of Pharmacognosy, Department of BioMolecular Sciences, School of Pharmacy, The University of Mississippi, University, MS 38677 (United States)

2015-12-01

Skin sensitization is an important toxicological end-point in the risk assessment of chemical allergens. Because of the complexity of the biological mechanisms associated with skin sensitization, integrated approaches combining different chemical, biological and in silico methods are recommended to replace conventional animal tests. Chemical methods are intended to characterize the potential of a sensitizer to induce earlier molecular initiating events. The presence of an electrophilic mechanistic domain is considered one of the essential chemical features to covalently bind to the biological target and induce further haptenation processes. Current in chemico assays rely on the quantification of unreacted model nucleophiles after incubation with the candidate sensitizer. In the current study, a new fluorescence-based method, ‘HTS-DCYA assay’, is proposed. The assay aims at the identification of reactive electrophiles based on their chemical reactivity toward a model fluorescent thiol. The reaction workflow enabled the development of a High Throughput Screening (HTS) method to directly quantify the reaction adducts. The reaction conditions have been optimized to minimize solubility issues, oxidative side reactions and increase the throughput of the assay while minimizing the reaction time, which are common issues with existing methods. Thirty-six chemicals previously classified with LLNA, DPRA or KeratinoSens™ were tested as a proof of concept. Preliminary results gave an estimated 82% accuracy, 78% sensitivity, 90% specificity, comparable to other in chemico methods such as Cys-DPRA. In addition to validated chemicals, six natural products were analyzed and a prediction of their sensitization potential is presented for the first time. - Highlights: • A novel fluorescence-based method to detect electrophilic sensitizers is proposed. • A model fluorescent thiol was used to directly quantify the reaction products. • A discussion of the reaction workflow

A fluorescence high throughput screening method for the detection of reactive electrophiles as potential skin sensitizers

International Nuclear Information System (INIS)

Avonto, Cristina; Chittiboyina, Amar G.; Rua, Diego; Khan, Ikhlas A.

2015-01-01

Skin sensitization is an important toxicological end-point in the risk assessment of chemical allergens. Because of the complexity of the biological mechanisms associated with skin sensitization, integrated approaches combining different chemical, biological and in silico methods are recommended to replace conventional animal tests. Chemical methods are intended to characterize the potential of a sensitizer to induce earlier molecular initiating events. The presence of an electrophilic mechanistic domain is considered one of the essential chemical features to covalently bind to the biological target and induce further haptenation processes. Current in chemico assays rely on the quantification of unreacted model nucleophiles after incubation with the candidate sensitizer. In the current study, a new fluorescence-based method, ‘HTS-DCYA assay’, is proposed. The assay aims at the identification of reactive electrophiles based on their chemical reactivity toward a model fluorescent thiol. The reaction workflow enabled the development of a High Throughput Screening (HTS) method to directly quantify the reaction adducts. The reaction conditions have been optimized to minimize solubility issues, oxidative side reactions and increase the throughput of the assay while minimizing the reaction time, which are common issues with existing methods. Thirty-six chemicals previously classified with LLNA, DPRA or KeratinoSens™ were tested as a proof of concept. Preliminary results gave an estimated 82% accuracy, 78% sensitivity, 90% specificity, comparable to other in chemico methods such as Cys-DPRA. In addition to validated chemicals, six natural products were analyzed and a prediction of their sensitization potential is presented for the first time. - Highlights: • A novel fluorescence-based method to detect electrophilic sensitizers is proposed. • A model fluorescent thiol was used to directly quantify the reaction products. • A discussion of the reaction workflow

Multivariate Models for Prediction of Human Skin Sensitization Hazard

Science.gov (United States)

Strickland, Judy; Zang, Qingda; Paris, Michael; Lehmann, David M.; Allen, David; Choksi, Neepa; Matheson, Joanna; Jacobs, Abigail; Casey, Warren; Kleinstreuer, Nicole

2016-01-01

One of ICCVAM’s top priorities is the development and evaluation of non-animal approaches to identify potential skin sensitizers. The complexity of biological events necessary to produce skin sensitization suggests that no single alternative method will replace the currently accepted animal tests. ICCVAM is evaluating an integrated approach to testing and assessment based on the adverse outcome pathway for skin sensitization that uses machine learning approaches to predict human skin sensitization hazard. We combined data from three in chemico or in vitro assays—the direct peptide reactivity assay (DPRA), human cell line activation test (h-CLAT), and KeratinoSens™ assay—six physicochemical properties, and an in silico read-across prediction of skin sensitization hazard into 12 variable groups. The variable groups were evaluated using two machine learning approaches, logistic regression (LR) and support vector machine (SVM), to predict human skin sensitization hazard. Models were trained on 72 substances and tested on an external set of 24 substances. The six models (three LR and three SVM) with the highest accuracy (92%) used: (1) DPRA, h-CLAT, and read-across; (2) DPRA, h-CLAT, read-across, and KeratinoSens; or (3) DPRA, h-CLAT, read-across, KeratinoSens, and log P. The models performed better at predicting human skin sensitization hazard than the murine local lymph node assay (accuracy = 88%), any of the alternative methods alone (accuracy = 63–79%), or test batteries combining data from the individual methods (accuracy = 75%). These results suggest that computational methods are promising tools to effectively identify potential human skin sensitizers without animal testing. PMID:27480324

Is skin penetration a determining factor in skin sensitization ...

Science.gov (United States)

Summary:Background. It is widely accepted that substances that cannot penetrate through the skin will not be sensitisers. Thresholds based on relevant physicochemical parameters such as a LogKow > 1 and a MW 1 is a true requirement for sensitisation.Methods. A large dataset of substances that had been evaluated for their skin sensitisation potential, together with measured LogKow values was compiled from the REACH database. The incidence of skin sensitisers relative to non-skin sensitisers below and above the LogKow = 1 threshold was evaluated. Results. 1482 substances with associated skin sensitisation outcomes and measured LogKow values were identified. 305 substances had a measured LogKow self-evident truth borne out from the widespread misconception that the ability to efficiently penetrate the stratum corneum is a key determinant of skin sensitisation potential and potency. Using the REACH data extracted to test out the validity of common assumptions in the skin sensitization AOP. Builds on trying to develop a proof of concept IATA

Skin acceptability of a cosmetic moisturizer formulation in female subjects with sensitive skin

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Nisbet SJ

2018-04-01

Full Text Available Stephanie J Nisbet Skin Health Medical Affairs, GSK Consumer Healthcare, Weybridge, Surrey, UK Purpose: This 3-week, open-label, noncomparative clinical study evaluated the skin acceptability of a cosmetic moisturizer in subjects with sensitive skin, by monitoring adverse events (AEs and cutaneous discomfort related to normal usage.Materials and methods: Female subjects aged between 18–60 years, with Fitzpatrick phototype classification I–IV and sensitive skin, verified by a positive reaction on the stinging test at screening, were included. Subjects applied the moisturizer to their face and body twice daily for 21±2 days at home and recorded study product usage and feelings of cutaneous discomfort (eg, dryness, prickling, stinging, and itching in a diary; any AEs were reported to the clinic. At study end, skin acceptability of the moisturizer was investigator-assessed based on the nature of AEs and subjects’ self-reported feelings of discomfort, and by clinical evaluation of skin reactions in the area of moisturizer application (appearance of erythema, formation of edema, and skin desquamation; scored according to an adapted Draize and Kligman scale. Only subjects with a treatment compliance of ≥80% were included in the final analysis.Results: In total, 35 subjects initiated and completed the study; all were compliant to the minimum study product usage. Per investigator clinical dermatological assessment at study end, none of the 35 subjects had skin reactions in the area of moisturizer application and there were no reported AEs. One subject reported sensations of mild prickling and itching immediately after applying the moisturizer (not classified as AEs, which spontaneously remitted after complete absorption of the product and were noted only in exposed areas. These events were considered by the investigator as being possibly/probably related to the use of study product; however, no clinical signs of skin reaction were observed in

Comparative analysis of skin sensitization potency of acrylates (methyl acrylate, ethyl acrylate, butyl acrylate, and ethylhexyl acrylate) using the local lymph node assay.

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Dearman, Rebecca J; Betts, Catherine J; Farr, Craig; McLaughlin, James; Berdasco, Nancy; Wiench, Karin; Kimber, Ian

2007-10-01

There are currently available no systematic experimental data on the skin sensitizing properties of acrylates that are of relevance in occupational settings. Limited information from previous guinea-pig tests or from the local lymph node assay (LLNA) is available; however, these data are incomplete and somewhat contradictory. For those reasons, we have examined in the LLNA 4 acrylates: butyl acrylate (BA), ethyl acrylate (EA), methyl acrylate (MA), and ethylhexyl acrylate (EHA). The LLNA data indicated that all 4 compounds have some potential to cause skin sensitization. In addition, the relative potencies of these acrylates were measured by derivation from LLNA dose-response analyses of EC3 values (the effective concentration of chemical required to induce a threefold increase in proliferation of draining lymph node cells compared with control values). On the basis of 1 scheme for the categorization of skin sensitization potency, BA, EA, and MA were each classified as weak sensitizers. Using the same scheme, EHA was considered a moderate sensitizer. However, it must be emphasized that the EC3 value for this chemical of 9.7% is on the borderline between moderate (10%) categories. Thus, the judicious view is that all 4 chemicals possess relatively weak skin sensitizing potential.

Dermal safety assessment of Arm & Hammer laundry products formulated for sensitive skin.

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Frederick, Douglas M; Vorwerk, Linda; Gupta, Archana; Ghassemi, Annahita

2017-09-01

The prevalence of sensitive skin among the general population in industrialized countries is reported to be over 50%. Sensitive skin subjects often report significant reactions to contact with cosmetics, soaps and other consumer products. This paper describes the overall skin compatibility and mildness program for a newly developed, lightly fragranced, colorant free laundry product (i.e. Arm & Hammer™ Sensitive Skin plus Skin-Friendly Fresh Scent), specially formulated for individuals with sensitive skin. The skin mildness of the product was compared to Arm & Hammer™ Free & Clear liquid laundry detergent with no fragrance or colorant, and an established history of safe use by sensitive skin consumers. The test material was a liquid laundry product with a light scent formulated for sensitive skin consumers (Arm & Hammer™ Sensitive Skin plus Skin-Friendly Fresh Scent). The product was compared to commercially marketed products for sensitive skin with a history of skin safety in the marketplace, including: a very similar product formulation (Arm & Hammer™ Free & Clear with no fragrance), and several selected competitors' products. Studies were conducted among individuals with self-assessed sensitive skin (based on a questionnaire) using standard protocols for the Human Repeat Insult Patch Test (HRIPT), 10-Day Cumulative Irritation, the Wrist Band Wear test, and the Safety In-Use testing. Responses in all protocols were evaluated by visual scoring of potential dermatologic reactions, and recording any sensory effects at the time of the examination. In addition, sensory effects collected from panelists' daily diaries were also evaluated. The HRIPT confirmed that neither the fragrance alone, nor the product formulation with fragrance, induced contact sensitization in sensitive skin subjects. The 10-Day cumulative irritation study conducted using sensitive skin subjects showed highly favorable skin compatibility, and the test product was comparable to the control

Chemical and engineering approaches to enable organic field-effect transistors for electronic skin applications.

Science.gov (United States)

Sokolov, Anatoliy N; Tee, Benjamin C-K; Bettinger, Christopher J; Tok, Jeffrey B-H; Bao, Zhenan

2012-03-20

Skin is the body's largest organ and is responsible for the transduction of a vast amount of information. This conformable material simultaneously collects signals from external stimuli that translate into information such as pressure, pain, and temperature. The development of an electronic material, inspired by the complexity of this organ is a tremendous, unrealized engineering challenge. However, the advent of carbon-based electronics may offer a potential solution to this long-standing problem. In this Account, we describe the use of an organic field-effect transistor (OFET) architecture to transduce mechanical and chemical stimuli into electrical signals. In developing this mimic of human skin, we thought of the sensory elements of the OFET as analogous to the various layers and constituents of skin. In this fashion, each layer of the OFET can be optimized to carry out a specific recognition function. The separation of multimodal sensing among the components of the OFET may be considered a "divide and conquer" approach, where the electronic skin (e-skin) can take advantage of the optimized chemistry and materials properties of each layer. This design of a novel microstructured gate dielectric has led to unprecedented sensitivity for tactile pressure events. Typically, pressure-sensitive components within electronic configurations have suffered from a lack of sensitivity or long mechanical relaxation times often associated with elastomeric materials. Within our method, these components are directly compatible with OFETs and have achieved the highest reported sensitivity to date. Moreover, the tactile sensors operate on a time scale comparable with human skin, making them ideal candidates for integration as synthetic skin devices. The methodology is compatible with large-scale fabrication and employs simple, commercially available elastomers. The design of materials within the semiconductor layer has led to the incorporation of selectivity and sensitivity within

An improvement of LLNA:DA to assess the skin sensitization potential of chemicals.

Science.gov (United States)

Zhang, Hongwei; Shi, Ying; Wang, Chao; Zhao, Kangfeng; Zhang, Shaoping; Wei, Lan; Dong, Li; Gu, Wen; Xu, Yongjun; Ruan, Hongjie; Zhi, Hong; Yang, Xiaoyan

2017-01-01

We developed a modified local lymph node assay based on ATP (LLNA:DA), termed the Two-Stage LLNA:DA, to further reduce the animal numbers in the identification of sensitizers. In the Two-Stage LLNA:DA procedure, 13 chemicals ranging from non-sensitizers to extreme sensitizers were selected. The first stage used reduced LLNA:DA (rLLNA:DA) to screen out sensitive chemicals. The second stage used LLNA:DA based on OECD 442 (A) to classify those potential sensitizers screened out in the first stage. In the first stage, the SIs of the methyl methacrylate, salicylic acid, methyl salicylate, ethyl salicylate, isopropanol and propanediol were below 1.8 and need not to be tested in the second step. Others continued to be tested by LLNA:DA. In the second stage, sodium lauryl sulphate and xylene were classified as weak sensitizers. a-hexyl cinnamic aldehyde and eugenol were moderate sensitizers. Benzalkonium chloride and glyoxal were strong sensitizers, and phthalic anhydride was an extreme sensitizer. The 9/9, 11/12, 10/11, and 8/13 (positive or negative only) categories of the Two-Stage LLNA:DA were consistent with those from the other methods (LLNA, LLNA:DA, GPMT/BT and HMT/HPTA), suggesting that Two-Stage LLNA:DA have a high coincidence rate with reported data. In conclusion, The Two-Stage LLNA:DA is in line with the "3R" rules, and can be a modification of LLNA:DA but needs more study.

Assessment of the skin sensitization potency of eugenol and its dimers using a non-radioisotopic modification of the local lymph node assay.

Science.gov (United States)

Takeyoshi, Masahiro; Noda, Shuji; Yamazaki, Shunsuke; Kakishima, Hiroshi; Yamasaki, Kanji; Kimber, Ian

2004-01-01

Allergic contact dermatitis is a serious health problem. There is a need to identify and characterize skin sensitization hazards, particularly with respect to relative potency, so that accurate risk assessments can be developed. For these purposes the murine local lymph node assay (LLNA) was developed. Here, we have investigated further a modi fi cation of this assay, non-radioisotopic LLNA, which in place of tritiated thymidine to measure lymph node cell proliferation employs incorporation of 5-bromo-2'-deoxyuridine. Using this method we have examined the skin sensitizing activity of eugenol, a known human contact allergen, and its dimers 2,2'-dihydroxyl-3,3'-dimethoxy-5,5'-diallyl-biphenyl (DHEA) and 4,5'-diallyl-2'-hydroxy-2,3'-dimethoxy phenyl ether (DHEB). Activity in the guinea pig maximization test (GPMT) also measured. On the basis of GPMT assays, eugenol was classified as a mild skin sensitizer, DHEA as a weak skin sensitizer and DHEB as an extreme skin sensitizer. In the non-radioisotopic LLNA all chemicals were found to give positive responses insofar as each was able to provoke a stimulation index (SI) of >or=3 at one or more test concentrations. The relative skin sensitizing potency of these chemicals was evaluated in the non-radioisotopic LLNA by derivation of an ec(3) value (the concentration of chemical required to provoke an SI of 3). The ec(3) values calculated were 25.1% for eugenol, >30% for DHEA and 2.3% for DHEB. Collectively these data suggest that assessments of relative potency deriving from non-radioisotopic LLNA responses correlate well with evaluations based on GPMT results. These investigations provide support for the proposal that the non-radioisotopic LLNA may serve as an effective alternative to the GPMT where there is a need to avoid the use of radioisotopes. Copyright 2004 John Wiley & Sons, Ltd.

Skin care products can aggravate epidermal function: studies in a murine model suggest a pathogenic role in sensitive skin

OpenAIRE

Li, Z; Hu, L; Elias, PM; Man, M-Q

2018-01-01

Sensitive skin is defined as a spectrum of unpleasant sensations in response to a variety of stimuli. However, only some skin care products provoke cutaneous symptoms in individuals with sensitive skin. Hence, it would be useful to identify products that could provoke cutaneous symptoms in individuals with sensitive skin.To assess whether vehicles, as well as certain branded skin care products, can alter epidermal function following topical applications to normal mouse skin.Following topical ...

Chemical peeling in ethnic skin: an update.

Science.gov (United States)

Salam, A; Dadzie, O E; Galadari, H

2013-10-01

With the growth of cosmetic dermatology worldwide, treatments that are effective against skin diseases and augment beauty without prolonged recovery periods, or exposing patients to the risks of surgery, are increasing in popularity. Chemical peels are a commonly used, fast, safe and effective clinic room treatment that may be used for cosmetic purposes, such as for fine lines and photoageing, but also as primary or adjunct therapies for acne, pigmentary disorders and scarring. Clinicians are faced with specific challenges when using peels on ethnic skin (skin of colour). The higher risk of postinflammatory dyschromias and abnormal scarring makes peels potentially disfiguring. Clinicians should therefore have a sound knowledge of the various peels available and their safety in ethnic skin. This article aims to review the background, classification, various preparations, indications, patient assessment and complications of using chemical peels in ethnic skin. © 2013 The Authors BJD © 2013 British Association of Dermatologists.

Chemical signals of fish skin for the attachment response of Acanthostomum brauni cercariae.

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Haas, W; de Nuñez, M O

1988-01-01

The chemical signals of the skin surface of fish, which stimulate the attachment responses of Acanthostomum brauni cercariae, were identified by offering chemicals and fish-skin extracts in agarose substrates to the cercariae. Smaller molecules such as amino acids, fatty acids, monosaccharides, electrolytes, urea, and carbonate solutions did not stimulate attachments, but hyaluronic acid had some effects. Bovine submaxillary glycoproteins had a strong stimulating activity that disappeared after neuraminidase digestion. The stimulating components of the skin surface of fish were hydrophilic substances with molecular weights of more than 10,000. They were sensitive to neuraminidase digestion but not to hyaluronidase digestion and thus can be identified as glycoproteins. A. brauni cercariae respond only to the complete glycoprotein molecules and not to their monosaccharide components. The known attachment triggers of other cercariae are small molecules. Large glycoproteins as host signals for A. brauni cercariae may be an adaptation to muddy habitats, where various substances with low molecular weights may interfere with the host identification.

High sensitivity optical measurement of skin gloss.

Science.gov (United States)

Ezerskaia, Anna; Ras, Arno; Bloemen, Pascal; Pereira, Silvania F; Urbach, H Paul; Varghese, Babu

2017-09-01

We demonstrate a low-cost optical method for measuring the gloss properties with improved sensitivity in the low gloss regime, relevant for skin gloss properties. The gloss estimation method is based on, on the one hand, the slope of the intensity gradient in the transition regime between specular and diffuse reflection and on the other on the sum over the intensities of pixels above threshold, derived from a camera image obtained using unpolarized white light illumination. We demonstrate the improved sensitivity of the two proposed methods using Monte Carlo simulations and experiments performed on ISO gloss calibration standards with an optical prototype. The performance and linearity of the method was compared with different professional gloss measurement devices based on the ratio of specular to diffuse intensity. We demonstrate the feasibility for in-vivo skin gloss measurements by quantifying the temporal evolution of skin gloss after application of standard paraffin cream bases on skin. The presented method opens new possibilities in the fields of cosmetology and dermatopharmacology for measuring the skin gloss and resorption kinetics and the pharmacodynamics of various external agents.

Machine Learning Approaches for Predicting Human Skin Sensitization Hazard

Science.gov (United States)

One of ICCVAM’s top priorities is the development and evaluation of non-animal approaches to identify potential skin sensitizers. The complexity of biological events necessary for a substance to elicit a skin sensitization reaction suggests that no single in chemico, in vit...

The choice of sensitive skin layer responsible for aftereffects of daily irradiation of the skin

International Nuclear Information System (INIS)

Keirim-Markus, I.B.

1992-01-01

The choice of sensitive human skin layer manifesting in delayed period after daily irradiation of the human skin (stochastic and determined effects) was evaluated. It was established that delayed aftereffects of daily radiation of the skin manifested as epidem damages. This layer of papilla derma of 10-15 mg/cm 2 thick situated at the great part of body surface, 15 mg/cm 2 on dorsal side of hands and 40 mg/cm 2 on palms and pillows of the fingers. Sensitive layer of skin dosimeter for a control of daily irradiation of people must have the same geometry

Skin care products can aggravate epidermal function: studies in a murine model suggest a pathogenic role in sensitive skin.

Science.gov (United States)

Li, Zhengxiao; Hu, Lizhi; Elias, Peter M; Man, Mao-Qiang

2018-02-01

Sensitive skin is defined as a spectrum of unpleasant sensations in response to a variety of stimuli. However, only some skin care products provoke cutaneous symptoms in individuals with sensitive skin. Hence, it would be useful to identify products that could provoke cutaneous symptoms in individuals with sensitive skin. To assess whether vehicles, as well as certain branded skin care products, can alter epidermal function following topical applications to normal mouse skin. Following topical applications of individual vehicle or skin care product to C57BL/6J mice twice daily for 4 days, transepidermal water loss (TEWL) rates, stratum corneum (SC) hydration and skin surface pH were measured on treated versus untreated mouse skin with an MPA5 device and pH 900 pH meter. Our results show that all tested products induced abnormalities in epidermal functions of varying severity, including elevations in TEWL and skin surface pH, and reduced SC hydration. Our results suggest that mice can serve as a predictive model that could be used to evaluate the potential safety of skin care products in humans with sensitive skin. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Immune sensitization to methylene diphenyl diisocyanate (MDI resulting from skin exposure: albumin as a carrier protein connecting skin exposure to subsequent respiratory responses

Directory of Open Access Journals (Sweden)

Redlich Carrie A

2011-03-01

Full Text Available Abstract Background Methylene diphenyl diisocyanate (MDI, a reactive chemical used for commercial polyurethane production, is a well-recognized cause of occupational asthma. The major focus of disease prevention efforts to date has been respiratory tract exposure; however, skin exposure may also be an important route for inducing immune sensitization, which may promote subsequent airway inflammatory responses. We developed a murine model to investigate pathogenic mechanisms by which MDI skin exposure might promote subsequent immune responses, including respiratory tract inflammation. Methods Mice exposed via the skin to varying doses (0.1-10% w/v of MDI diluted in acetone/olive oil were subsequently evaluated for MDI immune sensitization. Serum levels of MDI-specific IgG and IgE were measured by enzyme-linked immunosorbant assay (ELISA, while respiratory tract inflammation, induced by intranasal delivery of MDI-mouse albumin conjugates, was evaluated based on bronchoalveolar lavage (BAL. Autologous serum IgG from "skin only" exposed mice was used to detect and guide the purification/identification of skin proteins antigenically modified by MDI exposure in vivo. Results Skin exposure to MDI resulted in specific antibody production and promoted subsequent respiratory tract inflammation in animals challenged intranasally with MDI-mouse albumin conjugates. The degree of (secondary respiratory tract inflammation and eosinophilia depended upon the (primary skin exposure dose, and was maximal in mice exposed to 1% MDI, but paradoxically limited in mice receiving 10-fold higher doses (e.g. 10% MDI. The major antigenically-modified protein at the local MDI skin exposure site was identified as albumin, and demonstrated biophysical changes consistent with MDI conjugation. Conclusions MDI skin exposure can induce MDI-specific immune sensitivity and promote subsequent respiratory tract inflammatory responses and thus, may play an important role in MDI asthma

Multiple chemical sensitivity

DEFF Research Database (Denmark)

Tran, Marie Thi Dao; Arendt-Nielsen, Lars; Kupers, Ron

2013-01-01

BACKGROUND: Multiple Chemical Sensitivity (MCS) is a chronic condition characterized by recurrent, non-specific symptoms in response to chemically unrelated exposures in non-toxic concentrations. Although the pathophysiology of MCS remains unknown, central sensitization may be an important factor...

Impact of chemical peeling combined with negative pressure on human skin.

Science.gov (United States)

Kim, S J; Kang, I J; Shin, M K; Jeong, K H; Baek, J H; Koh, J S; Lee, S J

2016-10-01

In vivo changes in skin barrier function after chemical peeling with alpha hydroxyacids (AHAs) have been previously reported. However, the additional effects of physical treatment with chemical agents on skin barrier function have not been adequately studied. This study measured the degree of acute skin damage and the time required for skin barrier repair using non-invasive bioengineering methods in vivo with human skin to investigate the additional effect of a 4% AHA chemical jet accelerated at supersonic velocities. Thirteen female subjects (average age: 29.54 ± 4.86 years) participated in this study. The faces of the subjects were divided into half according to the block randomization design and were then assigned to receive AHA peeling alone or AHA peeling combined with pneumatic pressure on each side of the face. Transepidermal water loss (TEWL), skin colour and skin blood flow were evaluated at baseline and at 30 min, 2, 5 and 7 days after treatment. The TEWL and skin blood flow were significantly increased after 30 min in chemodermabrasion compared with chemical peeling alone (P peeling alone (P < 0.05). Chemodermabrasion can temporarily impair skin barriers, but it is estimated that it can enhance the skin barrier function after 7 days compared to the use of a chemical agent alone. In addition, chemodermabrasion has a more effective impact in the dermis and relatively preserves the skin barrier. © 2016 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Multivariate Models for Prediction of Skin Sensitization Hazard in Humans

Science.gov (United States)

One of ICCVAM’s highest priorities is the development and evaluation of non-animal approaches to identify potential skin sensitizers. The complexity of biological events necessary for a substance to elicit a skin sensitization reaction suggests that no single alternative me...

State of the art in non-animal approaches for skin sensitization testing: from individual test methods towards testing strategies.

Science.gov (United States)

Ezendam, Janine; Braakhuis, Hedwig M; Vandebriel, Rob J

2016-12-01

estimate of the potency sub-category of a skin sensitizer as well, but these approaches need further independent evaluation with a new dataset of chemicals. To conclude, this update shows that the field of non-animal approaches for skin sensitization has evolved greatly in recent years and that it is possible to predict skin sensitization hazard without animal testing.

Plasmonic light-sensitive skins of nanocrystal monolayers

Science.gov (United States)

Akhavan, Shahab; Gungor, Kivanc; Mutlugun, Evren; Demir, Hilmi Volkan

2013-04-01

We report plasmonically coupled light-sensitive skins of nanocrystal monolayers that exhibit sensitivity enhancement and spectral range extension with plasmonic nanostructures embedded in their photosensitive nanocrystal platforms. The deposited plasmonic silver nanoparticles of the device increase the optical absorption of a CdTe nanocrystal monolayer incorporated in the device. Controlled separation of these metallic nanoparticles in the vicinity of semiconductor nanocrystals enables optimization of the photovoltage buildup in the proposed nanostructure platform. The enhancement factor was found to depend on the excitation wavelength. We observed broadband sensitivity improvement (across 400-650 nm), with a 2.6-fold enhancement factor around the localized plasmon resonance peak. The simulation results were found to agree well with the experimental data. Such plasmonically enhanced nanocrystal skins hold great promise for large-area UV/visible sensing applications.

Chemical Decontamination of Campylobacter jejuni on Chicken Skin and Meat

DEFF Research Database (Denmark)

Riedel, Charlotte Tandrup; Brøndsted, Lone; Rosenquist, Hanne

2009-01-01

This study evaluated the effectiveness of 11 chemical compounds to reduce Campylobacter jejuni on chicken skin and meat samples dipped in chemical solutions. Treatment of skin samples for 1 min using tartaric acid (2%) and caprylic acid sodium salt (5%) caused reductions of C. jejuni NCTC11168...... effective, indicating that some cells may recover after a 1-min treatment with these chemicals. An increase in treatment time to 15 min resulted in higher effectiveness of trisodium phosphate and formic acid. Interestingly, when reduction of the C. jejuni population was compared on chicken skin and meat...

Comparison of the skin sensitizing potential of unsaturated compounds as assessed by the murine local lymph node assay (LLNA) and the guinea pig maximization test (GPMT).

Science.gov (United States)

Kreiling, R; Hollnagel, H M; Hareng, L; Eigler, D; Lee, M S; Griem, P; Dreessen, B; Kleber, M; Albrecht, A; Garcia, C; Wendel, A

2008-06-01

The skin sensitization potential of eight unsaturated and one saturated lipid (bio)chemicals was tested in both the LLNA and the GPMT to address the hypothesis that chemicals with unsaturated carbon-carbon double bonds may result in a higher number of unspecific (false positive) results in the LLNA compared to the GPMT. Seven substances (oleic acid, linoleic acid, linolenic acid, undecylenic acid, maleic acid, squalene and octinol) gave clear positive results in the LLNA (stimulation index (SI)> or = 3) and thus would require labelling as skin sensitizer. Fumaric acid and succinic acid gave clearly negative results. In the GPMT, besides some sporadic skin reactions, reproducible skin reactions indicating an allergic response were found in a few animals for four test substances. Based on the GPMT results, only undecylenic acid would have to be classified and labelled as a skin sensitizer according to the European Dangerous Substance Directive (67/548/EEC) (results for linoleic acid were inconclusive), while the other seven test substances would not require labelling. Possible mechanisms for unspecific skin cell stimulation and lymph node responses are discussed. In conclusion, the suitability of the LLNA for unsaturated compounds bearing structural similarity to the tested substances should be carefully considered and the GPMT should remain available as an accepted test method for skin sensitization hazard identification.

Chemical ecology of interactions between human skin microbiota and mosquitoes

NARCIS (Netherlands)

Verhulst, N.O.; Takken, W.; Dicke, M.; Schraa, G.; Smallegange, R.C.

2010-01-01

Microbiota on the human skin plays a major role in body odour production. The human microbial and chemical signature displays a qualitative and quantitative correlation. Genes may influence the chemical signature by shaping the composition of the microbiota. Recent studies on human skin microbiota,

Prognostic value of asymptomatic skin sensitization to aeroallergens

DEFF Research Database (Denmark)

Bødtger, Uffe

2004-01-01

condition affecting 8-30% of the population when using a local standard panel of aeroallergens. Clinically, immediate but not late-phase reactions are induced by allergen challenge. Absent eosinophil stimulation and migration and low IL-5 levels appear to be sentinel mechanisms. Prospective studies show...... positive skin test must be ruled out before allergen avoidance measures are initiated. SUMMARY: Surprisingly few papers exist on asymptomatic skin sensitization epidemiology and immunology, despite the intriguing question as to why symptoms do not develop in IgE-sensitized patients. It is a common...

EPA Releases Draft Policy to Reduce Animal Testing for Skin Sensitization

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The document, Draft Interim Science Policy: Use of Alternative Approaches for Skin Sensitization as a Replacement for Laboratory Animal Testing, describes the science behind the non-animal alternatives that can now be used to identify skin sensitization.

Tailoring force sensitivity and selectivity by microstructure engineering of multidirectional electronic skins

Science.gov (United States)

Park, Jonghwa; Kim, Jinyoung; Hong, Jaehyung; Lee, Hochan; Lee, Youngoh; Cho, Seungse; Kim, Sung-Woo; Kim, Jae Joon; Kim, Sung Youb; Ko, Hyunhyub

2018-04-01

Electronic skins (e-skins) with high sensitivity to multidirectional mechanical stimuli are crucial for healthcare monitoring devices, robotics, and wearable sensors. In this study, we present piezoresistive e-skins with tunable force sensitivity and selectivity to multidirectional forces through the engineered microstructure geometries (i.e., dome, pyramid, and pillar). Depending on the microstructure geometry, distinct variations in contact area and localized stress distribution are observed under different mechanical forces (i.e., normal, shear, stretching, and bending), which critically affect the force sensitivity, selectivity, response/relaxation time, and mechanical stability of e-skins. Microdome structures present the best force sensitivities for normal, tensile, and bending stresses. In particular, microdome structures exhibit extremely high pressure sensitivities over broad pressure ranges (47,062 kPa-1 in the range of <1 kPa, 90,657 kPa-1 in the range of 1-10 kPa, and 30,214 kPa-1 in the range of 10-26 kPa). On the other hand, for shear stress, micropillar structures exhibit the highest sensitivity. As proof-of-concept applications in healthcare monitoring devices, we show that our e-skins can precisely monitor acoustic waves, breathing, and human artery/carotid pulse pressures. Unveiling the relationship between the microstructure geometry of e-skins and their sensing capability would provide a platform for future development of high-performance microstructured e-skins.

Non-animal methods to predict skin sensitization (I): the Cosmetics Europe database.

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Hoffmann, Sebastian; Kleinstreuer, Nicole; Alépée, Nathalie; Allen, David; Api, Anne Marie; Ashikaga, Takao; Clouet, Elodie; Cluzel, Magalie; Desprez, Bertrand; Gellatly, Nichola; Goebel, Carsten; Kern, Petra S; Klaric, Martina; Kühnl, Jochen; Lalko, Jon F; Martinozzi-Teissier, Silvia; Mewes, Karsten; Miyazawa, Masaaki; Parakhia, Rahul; van Vliet, Erwin; Zang, Qingda; Petersohn, Dirk

2018-05-01

Cosmetics Europe, the European Trade Association for the cosmetics and personal care industry, is conducting a multi-phase program to develop regulatory accepted, animal-free testing strategies enabling the cosmetics industry to conduct safety assessments. Based on a systematic evaluation of test methods for skin sensitization, five non-animal test methods (DPRA (Direct Peptide Reactivity Assay), KeratinoSens TM , h-CLAT (human cell line activation test), U-SENS TM , SENS-IS) were selected for inclusion in a comprehensive database of 128 substances. Existing data were compiled and completed with newly generated data, the latter amounting to one-third of all data. The database was complemented with human and local lymph node assay (LLNA) reference data, physicochemical properties and use categories, and thoroughly curated. Focused on the availability of human data, the substance selection resulted nevertheless resulted in a high diversity of chemistries in terms of physico-chemical property ranges and use categories. Predictivities of skin sensitization potential and potency, where applicable, were calculated for the LLNA as compared to human data and for the individual test methods compared to both human and LLNA reference data. In addition, various aspects of applicability of the test methods were analyzed. Due to its high level of curation, comprehensiveness, and completeness, we propose our database as a point of reference for the evaluation and development of testing strategies, as done for example in the associated work of Kleinstreuer et al. We encourage the community to use it to meet the challenge of conducting skin sensitization safety assessment without generating new animal data.

Asymptomatic skin sensitization to birch predicts later development of birch pollen allergy in adults

DEFF Research Database (Denmark)

Bodtger, Uffe; Poulsen, Lars K.; Malling, Hans-Jørgen

2003-01-01

The skin prick test is the allergologic test of choice, but asymptomatic skin sensitization to aeroallergens is common. However, no data in the literature describe the clinical phenotype of asymptomatic sensitized adults.......The skin prick test is the allergologic test of choice, but asymptomatic skin sensitization to aeroallergens is common. However, no data in the literature describe the clinical phenotype of asymptomatic sensitized adults....

Multivariate Models for Prediction of Human Skin Sensitization Hazard.

Science.gov (United States)

One of the lnteragency Coordinating Committee on the Validation of Alternative Method's (ICCVAM) top priorities is the development and evaluation of non-animal approaches to identify potential skin sensitizers. The complexity of biological events necessary to produce skin sensiti...

Discrimination of skin sensitizers from non-sensitizers by interleukin-1α and interleukin-6 production on cultured human keratinocytes.

Science.gov (United States)

Jung, Daun; Che, Jeong-Hwan; Lim, Kyung-Min; Chun, Young-Jin; Heo, Yong; Seok, Seung Hyeok

2016-09-01

In vitro testing methods for classifying sensitizers could be valuable alternatives to in vivo sensitization testing using animal models, such as the murine local lymph node assay (LLNA) and the guinea pig maximization test (GMT), but there remains a need for in vitro methods that are more accurate and simpler to distinguish skin sensitizers from non-sensitizers. Thus, the aim of our study was to establish an in vitro assay as a screening tool for detecting skin sensitizers using the human keratinocyte cell line, HaCaT. HaCaT cells were exposed to 16 relevant skin sensitizers and 6 skin non-sensitizers. The highest dose used was the dose causing 75% cell viability (CV75) that we determined by an MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The levels of extracellular production of interleukin-1α (IL-1α) and IL-6 were measured. The sensitivity of IL-1α was 63%, specificity was 83% and accuracy was 68%. In the case of IL-6, sensitivity: 69%, specificity: 83% and accuracy: 73%. Thus, this study suggests that measuring extracellular production of pro-inflammatory cytokines IL-1α and IL-6 by human HaCaT cells may potentially classify skin sensitizers from non-sensitizers. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Skin lesions in Lorestan province chemically wounded combatants

Directory of Open Access Journals (Sweden)

roghaye Jebraili

2004-01-01

Findings: All of the studied cases with mean age of 39.26 years old had skin manifestations among which the most common symptoms were itching , burning ,dry skin , scaling. From view point of lesions, the most common signs were erythema (81% , excoriation (87.9% and pruritic papules (49.5%. Final diagnosis in 78% of the patients was chronic dermatitis and in 7.7% of them was seborrhoeic dermatitis and in 8.8% both chronic and seborrhoeic dermatitis were observed .During exposure to chemical gases only 37.9% of these combatants had used special masks and 40% had properly worn special clothes to protect themselves which covered their body completely , but rest of them had either used protection instruments improperly or had not used them at all. Most of the lesions were in trunk , lower extremities , abdomen , head and neck .78% of the cases had multiple lesions Conclusion: Regarding the results of this study all of the chemical wounded combatants of Lorestan province suffer from different degrees of skin lesions , although more than half of them were not aware of kind and nature of the chemical gases , but it is suggested to do further studies on long-term effects of these chemical gases.

Prediction of skin sensitization potency using machine learning approaches.

Science.gov (United States)

Zang, Qingda; Paris, Michael; Lehmann, David M; Bell, Shannon; Kleinstreuer, Nicole; Allen, David; Matheson, Joanna; Jacobs, Abigail; Casey, Warren; Strickland, Judy

2017-07-01

The replacement of animal use in testing for regulatory classification of skin sensitizers is a priority for US federal agencies that use data from such testing. Machine learning models that classify substances as sensitizers or non-sensitizers without using animal data have been developed and evaluated. Because some regulatory agencies require that sensitizers be further classified into potency categories, we developed statistical models to predict skin sensitization potency for murine local lymph node assay (LLNA) and human outcomes. Input variables for our models included six physicochemical properties and data from three non-animal test methods: direct peptide reactivity assay; human cell line activation test; and KeratinoSens™ assay. Models were built to predict three potency categories using four machine learning approaches and were validated using external test sets and leave-one-out cross-validation. A one-tiered strategy modeled all three categories of response together while a two-tiered strategy modeled sensitizer/non-sensitizer responses and then classified the sensitizers as strong or weak sensitizers. The two-tiered model using the support vector machine with all assay and physicochemical data inputs provided the best performance, yielding accuracy of 88% for prediction of LLNA outcomes (120 substances) and 81% for prediction of human test outcomes (87 substances). The best one-tiered model predicted LLNA outcomes with 78% accuracy and human outcomes with 75% accuracy. By comparison, the LLNA predicts human potency categories with 69% accuracy (60 of 87 substances correctly categorized). These results suggest that computational models using non-animal methods may provide valuable information for assessing skin sensitization potency. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Impacts of chemical enhancers on skin permeation and deposition of terbinafine.

Science.gov (United States)

Erdal, Meryem Sedef; Peköz, Ayca Yıldız; Aksu, Buket; Araman, Ahmet

2014-08-01

The addition of chemical enhancers into formulations is the most commonly employed approach to overcome the skin barrier. The objective of this work was to evaluate the effect of vehicle and chemical enhancers on the skin permeation and accumulation of terbinafine, an allylamine antifungal drug. Terbinafine (1% w/w) was formulated as a Carbopol 934 P gel formulation in presence and absence of three chemical enhancers, nerolidol, dl-limonene and urea. Terbinafine distribution and deposition in stratum corneum (SC) and skin following 8-h ex vivo permeation study was determined using a sequential tape stripping procedure. The conformational order of SC lipids was investigated by ATR-FTIR spectroscopy. Nerolidol containing gel formulation produced significantly higher enhancement in terbinafine permeation through skin and its skin accumulation was increased. ATR-FTIR results showed enhancer induced lipid bilayer disruption in SC. Urea resulted in enhanced permeation of terbinafine across the skin and a balanced distribution to the SC was achieved. But, dl-limonene could not minimize the accumulation of terbinafine in the upper SC. Nerolidol dramatically improved the skin permeation and deposition of terbinafine in the skin that might help to optimize targeting of the drug to the epidermal sites as required for both of superficial and deep cutaneous fungal infections.

Non-animal methods to predict skin sensitization (II): an assessment of defined approaches *.

Science.gov (United States)

Kleinstreuer, Nicole C; Hoffmann, Sebastian; Alépée, Nathalie; Allen, David; Ashikaga, Takao; Casey, Warren; Clouet, Elodie; Cluzel, Magalie; Desprez, Bertrand; Gellatly, Nichola; Göbel, Carsten; Kern, Petra S; Klaric, Martina; Kühnl, Jochen; Martinozzi-Teissier, Silvia; Mewes, Karsten; Miyazawa, Masaaki; Strickland, Judy; van Vliet, Erwin; Zang, Qingda; Petersohn, Dirk

2018-05-01

Skin sensitization is a toxicity endpoint of widespread concern, for which the mechanistic understanding and concurrent necessity for non-animal testing approaches have evolved to a critical juncture, with many available options for predicting sensitization without using animals. Cosmetics Europe and the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods collaborated to analyze the performance of multiple non-animal data integration approaches for the skin sensitization safety assessment of cosmetics ingredients. The Cosmetics Europe Skin Tolerance Task Force (STTF) collected and generated data on 128 substances in multiple in vitro and in chemico skin sensitization assays selected based on a systematic assessment by the STTF. These assays, together with certain in silico predictions, are key components of various non-animal testing strategies that have been submitted to the Organization for Economic Cooperation and Development as case studies for skin sensitization. Curated murine local lymph node assay (LLNA) and human skin sensitization data were used to evaluate the performance of six defined approaches, comprising eight non-animal testing strategies, for both hazard and potency characterization. Defined approaches examined included consensus methods, artificial neural networks, support vector machine models, Bayesian networks, and decision trees, most of which were reproduced using open source software tools. Multiple non-animal testing strategies incorporating in vitro, in chemico, and in silico inputs demonstrated equivalent or superior performance to the LLNA when compared to both animal and human data for skin sensitization.

Skin rejuvenating effects of chemical peeling: a study in photoaged hairless mice.

Science.gov (United States)

Han, Sung Hyup; Kim, Hong Jig; Kim, Si Yong; Kim, You Chan; Choi, Gwang Seong; Shin, Jeong Hyun

2011-09-01

Chemical peeling is a dermatologic treatment for skin aging. However, the mechanism by which the chemical peel achieves its results is not clear. We investigated the effects of chemical peeling and the mechanism of wrinkle reduction in photoaged hairless mice skin. After inducing photoaged skin in hairless mice by repetitive ultraviolet-B irradiation applied over 14 weeks, we applied trichloroacetic acid (TCA) 30%, TCA 50%, and phenol on areas of the same size on the backs of the mice. Punch biopsies were obtained 7, 14, 28, and 60 days after the procedure for histologic and immunohistochemical analyses. Histologic examination showed an increase in dermal thickness, collagen fibers, and elastic fibers in the dermis of intervention groups compared with control groups. These increases were maintained significantly for 60 days. This study demonstrates that chemical peeling reduces wrinkles and regenerates skin by increasing dermal thickness and the amount of collagen and elastic fibers in photoaged skin. © 2011 The International Society of Dermatology.

Novel approach for classifying chemicals according to skin sensitizing potency by non-radioisotopic modification of the local lymph node assay.

Science.gov (United States)

Takeyoshi, Masahiro; Iida, Kenji; Shiraishi, Keiji; Hoshuyama, Satsuki

2005-01-01

The murine local lymph node assay (LLNA) is currently recognized as a stand-alone sensitization test for determining the sensitizing potential of chemicals, and it has the advantage of yielding a quantitative endpoint that can be used to predict the sensitization potency of chemicals. The EC3 has been proposed as a parameter for classifying chemicals according to the sensitization potency. We previously developed a non-radioisotopic endpoint for the LLNA based on 5-bromo-2'-deoxyuridine (BrdU) incorporation (non-RI LLNA), and we are proposing a new procedure to predict the sensitization potency of chemicals based on comparisons with known human contact allergens. Nine chemicals (i.e. diphencyclopropenone, p-phenylenediamine, glutaraldehyde, cinnamicaldehyde, citral, eugenol, isopropyl myristate, propyleneglycol and hexane) categorized as human contact allergen classes 1-5 were tested by the non-RI LLNA with the following reference allergens: 2,4-dinitrochlorobenzene (DNCB) as a class 1 human contact allergen, isoeugenol as a class 2 human contact allergen and alpha-hexylcinnamic aldehyde (HCA) as a class 3 human contact allergen. Consequently, nine test chemicals were almost assigned to their correct allergen class. The results suggested that the new procedure for non-RI LLNA can provide correct sensitization potency data. Sensitization potency data are useful for evaluating the sensitization risk to humans of exposure to new chemical products. Accordingly, this approach would be an effective modification of LLNA with regard to its experimental design. Moreover, this procedure can be applied also to the standard LLNA with radioisotopes and to other modifications of the LLNA. Copyright 2005 John Wiley & Sons, Ltd.

Probabilistic derivation of the interspecies assessment factor for skin sensitization.

NARCIS (Netherlands)

Bil, W; Schuur, A G; Ezendam, J; Bokkers, B G H

An interspecies sensitization assessment factor (SAF) is used in the quantitative risk assessment (QRA) for skin sensitization when a murine-based NESIL (No Expected Sensitization Induction Level) is taken as point of departure. Several studies showed that, on average, the murine sensitization

Inventory of the chemicals and the exposure of the workers' skin to these at two leather factories in Indonesia.

Science.gov (United States)

Febriana, Sri Awalia; Jungbauer, Frank; Soebono, Hardyanto; Coenraads, Pieter-Jan

2012-07-01

Tannery workers are exposed to hazardous chemicals. Tannery work is outsourced to newly industrialized countries (NICs) where attention into occupational health hazards is limited. In this study, we investigated the skin exposure to hazardous chemicals in tannery workers and determined the prevalence of occupational skin diseases (OSDs) at tanneries in a NIC. A cross-sectional study on the observation of the working process and an inventory and risk assessment of the chemicals used. Classification of chemicals as potential sensitizers/irritants and a qualitative assessment of exposure to these chemicals. Workers were examined and interviewed using Nordic Occupational Skin Questionnaire-2002/LONG. The risk of OSDs at the investigated tanneries was mainly related to the exposure of the workers' skin to chemicals in hot and humid environmental conditions. In 472 workers, 12% reported a current OSD and 9% reported a history of OSD. In 10% of all cases, an OSD was confirmed by a dermatologist and 7.4% had an occupational contact dermatitis (OCD). We observed that personal protective equipment (PPE) used was mainly because of skin problems in the past and not as a primary protection against OSD. We observed a high frequency and prolonged exposure to many skin hazardous factors in tannery work although PPE was relatively easily available and which was generally used as a secondary preventative measure. The observed point-prevalence in this study was at the same level as that reported for other high-risk OSDs in Western countries and other tanneries in NICs. However, the observed point-prevalence in this study was lower than that reported in India and Korea. The results of our study and those of other studies at tanneries from other NICs were probably influenced by Healthy Worker Survivor Effect (HWSE).

Prediction of Skin Sensitization Potency Using Machine Learning Approaches

Science.gov (United States)

Replacing animal tests currently used for regulatory hazard classification of skin sensitizers is one of ICCVAM’s top priorities. Accordingly, U.S. federal agency scientists are developing and evaluating computational approaches to classify substances as sensitizers or nons...

Gentle cleansing and moisturizing for patients with atopic dermatitis and sensitive skin.

Science.gov (United States)

Cheong, Wai Kwong

2009-01-01

Atopic dermatitis is a common condition characterized by pruritus, inflammation, and dryness of the skin. Inflammation disrupts the barrier function of the stratum corneum, predisposing the skin to be dry, and increases susceptibility to irritants and secondary bacterial infection. Sensitive skin is common, reported by 40-50% of women and 30% of men in the US, Europe, and Japan. Basic requirements in managing eczema and sensitive skin include effective cleansers that do not compromise skin barrier integrity, alleviation of skin dryness, and restoration of skin barrier function through the use of therapeutic moisturizers. The selection of a skin cleanser is therefore an important part of managing these conditions. Studies have reported clinical improvement with the use of soap-free cleansers in combination with topical treatments. While topical corticosteroids and immunosuppressive agents are mainstays of treatment for atopic dermatitis, therapeutic moisturizers are important adjuncts. Moisturizers improve skin hydration, reduce susceptibility to irritation, restore the integrity of the stratum corneum, and enhance the efficacy of topical corticosteroids.

Sunburn, Thermal, and Chemical Injuries to the Skin.

Science.gov (United States)

Monseau, Aaron J; Reed, Zebula M; Langley, Katherine Jane; Onks, Cayce

2015-12-01

Sunburn, thermal, and chemical injuries to the skin are common in the United States and worldwide. Initial management is determined by type and extent of injury with special care to early management of airway, breathing, and circulation. Fluid management has typically been guided by the Parkland formula, whereas some experts now question this. Each type of skin injury has its own pathophysiology and resultant complications. All primary care physicians should have at least a basic knowledge of management of acute and chronic skin injuries. Copyright © 2015 Elsevier Inc. All rights reserved.

The abdominal skin of female Sprague-Dawley rats is more sensitive than the back skin to drug-induced phototoxicity.

Science.gov (United States)

Kuga, Kazuhiro; Yasuno, Hironobu; Sakai, Yumi; Harada, Yumiko; Shimizu, Fumi; Miyamoto, Yumiko; Takamatsu, Yuki; Miyamoto, Makoto; Sato, Keiichiro

2017-11-01

In vivo phototoxicity studies are important to predict drug-induced phototoxicity in humans; however, a standard methodology has not established. To determine differences in sensitivity to drug-induced phototoxicity among various skin sites, we evaluated phototoxic reactions in the back and abdominal skin of female Sprague-Dawley rats orally dosed with phototoxic drugs (pirfenidone, 8-methoxysoraren, doxycycline, and lomefloxacin) or a non-phototoxic drug (gatifloxacin) followed by solar-simulated light irradiation comprising 18J/cm 2 ultraviolet A. Tissue reactions were evaluated by macroscopic and microscopic examination and immunohistochemistry for γ-H2AX, and tissue concentrations of pirfenidone, doxycycline, and lomefloxacin were measured by tandem mass spectrometry. In addition, the thicknesses of the skin layers at both sites were measured in drug-naïve rats. The abdominal skin showed more severe reactions to all phototoxic drugs than the back skin, whereas the minimal erythema dose in drug-naïve rats and skin concentrations of each drug were comparable between the sites. Furthermore, histopathological lesions and γ-H2AX-positive cells in the abdominal skin were detected in deeper layers than in the back skin. The stratum corneum and dermis in the abdominal skin were significantly thinner than in the back skin, indicating a difference in the depth of light penetration and potentially contributing to the site differences observed in sensitivity to phototoxicity. Gatifloxacin did not induce any phototoxic reactions at either site. In conclusion, the abdominal skin is more sensitive to drug-induced phototoxicity than the back skin and may represent a preferable site for irradiation in this rat phototoxicity model. Copyright © 2017 Elsevier Inc. All rights reserved.

Endogenous UVA-photosensitizers: mediators of skin photodamage and novel targets for skin photoprotection.

Science.gov (United States)

Wondrak, Georg T; Jacobson, Myron K; Jacobson, Elaine L

2006-02-01

Endogenous chromophores in human skin serve as photosensitizers involved in skin photocarcinogenesis and photoaging. Absorption of solar photons, particularly in the UVA region, induces the formation of photoexcited states of skin photosensitizers with subsequent generation of reactive oxygen species (ROS), organic free radicals and other toxic photoproducts that mediate skin photooxidative stress. The complexity of endogenous skin photosensitizers with regard to molecular structure, pathways of formation, mechanisms of action, and the diversity of relevant skin targets has hampered progress in this area of photobiology and most likely contributed to an underestimation of the importance of endogenous sensitizers in skin photodamage. Recently, UVA-fluorophores in extracellular matrix proteins formed posttranslationally as a consequence of enzymatic maturation or spontaneous chemical damage during chronological and actinic aging have been identified as an abundant source of light-driven ROS formation in skin upstream of photooxidative cellular stress. Importantly, sensitized skin cell photodamage by this bystander mechanism occurs after photoexcitation of sensitizers contained in skin structural proteins without direct cellular photon absorption thereby enhancing the potency and range of phototoxic UVA action in deeper layers of skin. The causative role of photoexcited states in skin photodamage suggests that direct molecular antagonism of photosensitization reactions using physical quenchers of photoexcited states offers a novel chemopreventive opportunity for skin photoprotection.

Touch perceptions across skin sites: differences between sensitivity, direction discrimination and pleasantness

Directory of Open Access Journals (Sweden)

Rochelle eAckerley

2014-02-01

Full Text Available Human skin is innervated with different tactile afferents over the body, which are found at varying densities. We investigate how the relationships between tactile pleasantness, sensitivity and discrimination differ across the skin. Tactile pleasantness was assessed by stroking a soft brush over the skin, using five velocities (0.3, 1, 3, 10, 30 cm s-1, known to differentiate hedonic touch, and pleasantness ratings were gained. The ratings velocity-profile is known to correlate with firing in unmyelinated C-tactile afferents. Tactile sensitivity thresholds were determined using monofilament force detection and the tactile discrimination level was obtained in the direction discrimination of a moving probe; both tasks readily activate myelinated touch receptors. Perceptions were measured over five skin sites: forehead, arm, palm, thigh and shin. The assessment of tactile pleasantness over the skin resulted in a preference for the middle velocities (1-10 cm s-1, where higher ratings were gained compared to the slowest and fastest velocities. This preference in tactile pleasantness was found across all the skin sites, apart from at the palm, where no decrease in pleasantness for the faster stroking velocities was seen. We find that tactile sensitivity and discrimination vary across the skin, where the forehead and palm show increased acuity. Tactile sensitivity and discrimination levels also correlated significantly, although the tactile acuity did not relate to the perceived pleasantness of touch. Tactile pleasantness varied in a subtle way across skin sites, where the middle velocities were always rated as the most pleasant, but the ratings at hairy skin sites were more receptive to changes in stroking velocity. We postulate that although the mechanoreceptive afferent physiology may be different over the skin, the perception of pleasant touch can be interpreted using all of the available incoming somatosensory information in combination with

A genomic biomarker signature can predict skin sensitizers using a cell-based in vitro alternative to animal tests

Directory of Open Access Journals (Sweden)

Albrekt Ann-Sofie

2011-08-01

Full Text Available Abstract Background Allergic contact dermatitis is an inflammatory skin disease that affects a significant proportion of the population. This disease is caused by an adverse immune response towards chemical haptens, and leads to a substantial economic burden for society. Current test of sensitizing chemicals rely on animal experimentation. New legislations on the registration and use of chemicals within pharmaceutical and cosmetic industries have stimulated significant research efforts to develop alternative, human cell-based assays for the prediction of sensitization. The aim is to replace animal experiments with in vitro tests displaying a higher predictive power. Results We have developed a novel cell-based assay for the prediction of sensitizing chemicals. By analyzing the transcriptome of the human cell line MUTZ-3 after 24 h stimulation, using 20 different sensitizing chemicals, 20 non-sensitizing chemicals and vehicle controls, we have identified a biomarker signature of 200 genes with potent discriminatory ability. Using a Support Vector Machine for supervised classification, the prediction performance of the assay revealed an area under the ROC curve of 0.98. In addition, categorizing the chemicals according to the LLNA assay, this gene signature could also predict sensitizing potency. The identified markers are involved in biological pathways with immunological relevant functions, which can shed light on the process of human sensitization. Conclusions A gene signature predicting sensitization, using a human cell line in vitro, has been identified. This simple and robust cell-based assay has the potential to completely replace or drastically reduce the utilization of test systems based on experimental animals. Being based on human biology, the assay is proposed to be more accurate for predicting sensitization in humans, than the traditional animal-based tests.

A genomic biomarker signature can predict skin sensitizers using a cell-based in vitro alternative to animal tests

Science.gov (United States)

2011-01-01

Background Allergic contact dermatitis is an inflammatory skin disease that affects a significant proportion of the population. This disease is caused by an adverse immune response towards chemical haptens, and leads to a substantial economic burden for society. Current test of sensitizing chemicals rely on animal experimentation. New legislations on the registration and use of chemicals within pharmaceutical and cosmetic industries have stimulated significant research efforts to develop alternative, human cell-based assays for the prediction of sensitization. The aim is to replace animal experiments with in vitro tests displaying a higher predictive power. Results We have developed a novel cell-based assay for the prediction of sensitizing chemicals. By analyzing the transcriptome of the human cell line MUTZ-3 after 24 h stimulation, using 20 different sensitizing chemicals, 20 non-sensitizing chemicals and vehicle controls, we have identified a biomarker signature of 200 genes with potent discriminatory ability. Using a Support Vector Machine for supervised classification, the prediction performance of the assay revealed an area under the ROC curve of 0.98. In addition, categorizing the chemicals according to the LLNA assay, this gene signature could also predict sensitizing potency. The identified markers are involved in biological pathways with immunological relevant functions, which can shed light on the process of human sensitization. Conclusions A gene signature predicting sensitization, using a human cell line in vitro, has been identified. This simple and robust cell-based assay has the potential to completely replace or drastically reduce the utilization of test systems based on experimental animals. Being based on human biology, the assay is proposed to be more accurate for predicting sensitization in humans, than the traditional animal-based tests. PMID:21824406

The relationship between CD86/CD54 expression and THP-1 cell viability in an in vitro skin sensitization test--human cell line activation test (h-CLAT).

Science.gov (United States)

Sakaguchi, Hitoshi; Ashikaga, Takao; Miyazawa, Masaaki; Kosaka, Nanae; Ito, Yuichi; Yoneyama, Katsurako; Sono, Sakiko; Itagaki, Hiroshi; Toyoda, Hidekazu; Suzuki, Hiroyuki

2009-04-01

Recent regulations for cosmetics in Europe prohibit animal testing for evaluating the sensitization potential of chemicals to improve animal welfare. Yet, there is not an acceptable Organization for Economic Co-operation and Development non-animal skin sensitization test method. Several in vitro skin sensitization methods that focus on the activation of Langerhans cells, including human cell lines, are being evaluated as possible alternatives. In our previous study, we optimized our human cell line activation test (h-CLAT) using THP-1 cells (monocytic leukemia cell line) and conducted an inter-laboratory study. We found that measuring CD86/CD54 expression may be useful for predicting skin sensitization. The aim of this study was to confirm the relationship between CD86/CD54 expression and THP-1 cell viability in the h-CLAT. In this study, 21 allergens (e.g., dinitrochlorobenzene, p-phenylenediamine, Ni) and 8 non-allergens (e.g., SLS, lactic acid) were evaluated. For each chemical, more than 10 concentrations that gave a predicted cell viability range of 20-95% were used. The data showed that expression patterns of CD86/CD54 differed depending on chemical. For most allergens, cytotoxicity (65-90% cell viability) was needed for enhancement of CD86/CD54 expression. The criteria of "CD86 > or = 150 or CD54 > or = 200" resulted in an accuracy of 93%, which confirms appropriate cut-off criteria for h-CLAT. Furthermore, a good correlation was observed between EC3 of local lymph node assay and EC150(CD86) or EC200(CD54) of h-CLAT (12 or 16 chemicals, respectively), which would provide a useful estimate of allergic potency. These findings suggest that h-CLAT would be a good robust in vitro skin sensitization test.

Quantitative relationship between the local lymph node assay and human skin sensitization assays.

Science.gov (United States)

Schneider, K; Akkan, Z

2004-06-01

The local lymph node assay (LLNA) is a new test method which allows for the quantitative assessment of sensitizing potency in the mouse. Here, we investigate the quantitative correlation between results from the LLNA and two human sensitization tests--specifically, human repeat insult patch tests (HRIPTs) and human maximization tests (HMTs). Data for 57 substances were evaluated, of which 46 showed skin sensitizing properties in human tests, whereas 11 yielded negative results in humans. For better comparability data from mouse and human tests were transformed to applied doses per skin area, which ranged over four orders of magnitude for the substances considered. Regression analysis for the 46 human sensitizing substances revealed a significant positive correlation between the LLNA and human tests. The correlation was better between LLNA and HRIPT data (n=23; r=0.77) than between LLNA and HMT data (n=38; r=0.65). The observed scattering of data points is related to various uncertainties, in part associated with insufficiencies of data from older HMT studies. Predominantly negative results in the LLNA for another 11 substances which showed no skin sensitizing activity in human maximization tests further corroborate the correspondence between LLNA and human tests. Based on this analysis, the LLNA can be considered a reliable basis for relative potency assessments for skin sensitizers. Proposals are made for the regulatory exploitation of the LLNA: four potency groups can be established, and assignment of substances to these groups according to the outcome of the LLNA can be used to characterize skin sensitizing potency in substance-specific assessments. Moreover, based on these potency groups, a more adequate consideration of sensitizing substances in preparations becomes possible. It is proposed to replace the current single concentration limit for skin sensitizers in preparations, which leads to an all or nothing classification of a preparation as sensitizing to

IATA-Bayesian Network Model for Skin Sensitization Data

Data.gov (United States)

U.S. Environmental Protection Agency — Since the publication of the Adverse Outcome Pathway (AOP) for skin sensitization, there have been many efforts to develop systematic approaches to integrate the...

Development of LLNA:DAE: a new local lymph node assay that includes the elicitation phase, discriminates borderline-positive chemicals, and is useful for cross-sensitization testing.

Science.gov (United States)

Yamashita, Kunihiko; Shinoda, Shinsuke; Hagiwara, Saori; Itagaki, Hiroshi

2014-02-01

We developed a new local lymph node assay (LLNA) that includes the elicitation phase termed LLNA:DAE for discrimination of borderline-positive chemicals as classified by the LLNA modified by Daicel based on ATP content (LLNA:DA) and for cross-sensitization testing. Although the LLNA:DA method could help identify skin sensitizers, some skin irritants classified as non-sensitizers by the LLNA were classified as borderline positive. In addition, the evaluation for the cross-sensitization potential between chemicals was impossible. In the LLNA:DAE procedure, test group of mice received four applications of chemicals on the dorsum of the right ear for induction and one application on the dorsum of the left ear for elicitation. Control group of mice received one chemical application on the dorsum of the left ear. We evaluated the sensitizing potential by comparing the weights of the lymph nodes from the left ears between the two groups. The results of using the LLNA:DAE method to examine 24 chemicals, which contained borderline-positive chemicals, were consistent with those from the LLNA method, except for nickel chloride (NiCl2). Two chemical pairs, 2,4-dinitrochlorobenzene (DNCB) with 2,4-dinitrofluorobenzene (DNFB) and hydroquinone (HQ) with p-benzoquinone (p-BQ), showed clear cross-sensitization with each other, while another chemical pair, DNFB with hexylcinnamic aldehyde (HCA) did not. Taken together, our results suggest that the LLNA:DAE method is useful for discriminating borderline-positive chemicals and for determining chemical cross-sensitization.

Identification of Lilial as a fragrance sensitizer in a perfume by bioassay-guided chemical fractionation and structure-activity relationships.

Science.gov (United States)

Arnau, E G; Andersen, K E; Bruze, M; Frosch, P J; Johansen, J D; Menné, T; Rastogi, S C; White, I R; Lepoittevin, J P

2000-12-01

Fragrance materials are among the most common causes of allergic contact dermatitis. The aim of this study was to identify in a perfume fragrance allergens not included in the fragrance mix, by use of bioassay-guided chemical fractionation and chemical analysis/structure-activity relationships (SARs). The basis for the investigation was a 45-year-old woman allergic to her own perfume. She had a negative patch test to the fragrance mix and agreed to participate in the study. Chemical fractionation of the perfume concentrate was used for repeated patch testing and/or repeated open application test on the pre-sensitized patient. The chemical composition of the fractions giving a positive patch-test response and repeated open application test reactions was obtained by gas chromatography-mass spectrometry. From the compounds identified, those that contained a "structural alert" in their chemical structure, indicating an ability to modify skin proteins and thus behave as a skin sensitizer, were tested on the patient. The patient reacted positively to the synthetic fragrance p-t-butyl-alpha-methylhydrocinnamic aldehyde (Lilial), a widely used fragrance compound not present in the fragrance mix. The combination of bioassay-guided chemical fractionation and chemical analysis/structure-activity relationships seems to be a valuable tool for the investigation of contact allergy to fragrance materials.

Skin Sensitive Difference of Human Body Sections under Clothing-Smirnov Test of Skin Surface Temperatures' Dynamic Changing

Institute of Scientific and Technical Information of China (English)

LI Jun; WU Hai-yan; WANG Yun-yi

2004-01-01

Skin sensitive difference of human body sections under clothing is the theoretic foundation of thermal insulation clothing design.By a new method of researching on clothing comfort perception,the skin temperature live changing procedure of human body sections affected by the same cold stimulation is inspected.Furthermore with the Smirnov test the skin temperatures dynamic changing patterns of main human body sections are obtained.

Skin sensitizer identification by IL-8 secretion and CD86 expression on THP-1 cells.

Science.gov (United States)

Parise, Carolina Bellini; Sá-Rocha, Vanessa Moura; Moraes, Jane Zveiter

2015-12-25

Substantial progress has been made in the development of alternative methods for skin sensitization in the last decade in several countries around the world. Brazil is experiencing an increasing concern about using animals for product development, since the publication of the Law 9605/1998, which prohibits the use of animals when an alternative method is available. In this way, an in vitro test to evaluate allergenic potential is a pressing need.This preliminary study started setting the use of myelomonocytic THP-1 cell line, according to the human cell line activation test (h-CLAT), already under validation process. We found that 48-h chemical exposure was necessary to identify 22 out of 23 sensitizers by the analyses of CD86 expression. In addition, the CD54 expression analyses presented a poor efficiency to discriminate sensitizers from non-sensitizers in our conditions. In view of these results, we looked for changes of pro-inflammatory interleukin profile. The IL-8 secretion analyses after 24-h chemical incubation seemed to be an alternative for CD54 expression assessing.Altogether, our findings showed that the combination of the analyses of CD86 expression and IL-8 secretion allowed predicting allergenicity.

Measurements of skin friction in water using surface stress sensitive films

International Nuclear Information System (INIS)

Crafton, J W; Fonov, S D; Jones, E G; Goss, L P; Forlines, R A; Fontaine, A

2008-01-01

The measurement of skin friction on hydrodynamic surfaces is of significant value for the design of advanced naval technology, particularly at high Reynolds numbers. Here we report on the development of a new sensor for measurement of skin friction and pressure that operates in both air and water. This sensor is based on an elastic polymer film that deforms under the action of applied normal and tangential loads. Skin friction and pressure gradients are determined by monitoring these deformations and then solving an inverse problem using a finite element model of the elastic film. This technique is known as surface stress sensitive films. In this paper, we describe the development of a sensor package specifically designed for two-dimensional skin friction measurements at a single point. The package has been developed with the goal of making two-dimensional measurements of skin friction in water. Quantitative measurements of skin friction are performed on a high Reynolds number turbulent boundary layer in the 12 inch water tunnel at Penn State University. These skin friction measurements are verified by comparing them to measurements obtained with a drag plate as well as by performing two-dimensional velocity measurements above the sensor using a laser Doppler velocimetry system. The results indicate that the sensor skin friction measurements are accurate to better than 5% and repeatable to better than 2%. The directional sensitivity of the sensor is demonstrated by positioning the sensor at several orientations to the flow. A final interesting feature of this sensor is that it is sensitive to pressure gradients, not to static pressure changes. This feature should prove useful for monitoring the skin friction on a seafaring vessel as the operating depth is changed

High sensitivity optical measurement of skin gloss

NARCIS (Netherlands)

Ezerskaia, A.; Ras, Arno; Bloemen, Pascal; Pereira, S.F.; Urbach, Paul; Varghese, Babu

2017-01-01

We demonstrate a low-cost optical method for measuring the gloss properties with improved sensitivity in the low gloss regime, relevant for skin gloss properties. The gloss estimation method is based on, on the one hand, the slope of the intensity gradient in the transition regime between

The use of ex vivo human skin tissue for genotoxicity testing

Energy Technology Data Exchange (ETDEWEB)

Reus, Astrid A.; Usta, Mustafa [TNO Triskelion BV, Utrechtseweg 48, 3704 HE, Zeist (Netherlands); Krul, Cyrille A.M., E-mail: cyrille.krul@tno.nl [TNO, Utrechtseweg 48, 3704 HE Zeist (Netherlands)

2012-06-01

As a result of the chemical legislation concerning the registration, evaluation, authorization and restriction of chemicals (REACH), and the Seventh Amendment to the Cosmetics Directive, which prohibits animal testing in Europe for cosmetics, alternative methods for safety evaluation of chemicals are urgently needed. Current in vitro genotoxicity assays are not sufficiently predictive for the in vivo situation, resulting in an unacceptably high number of misleading positives. For many chemicals and ingredients of personal care products the skin is the first site of contact, but there are no in vitro genotoxicity assays available in the skin for additional evaluation of positive or equivocal responses observed in regulatory in vitro genotoxicity assays. In the present study ex vivo human skin tissue obtained from surgery was used for genotoxicity evaluation of chemicals by using the comet assay. Fresh ex vivo human skin tissue was cultured in an air–liquid interface and topically exposed to 20 chemicals, including true positive, misleading positive and true negative genotoxins. Based on the results obtained in the present study, the sensitivity, specificity and accuracy of the ex vivo skin comet assay to predict in vivo genotoxicity were 89%, 90% and 89%, respectively. Donor and experimental variability were mainly reflected in the magnitude of the response and not the difference between the presence and absence of a genotoxic response. The present study indicates that human skin obtained from surgery is a promising and robust model for safety evaluation of chemicals that are in direct contact with the skin. -- Highlights: ► We use human skin obtained from surgery for genotoxicity evaluation of chemicals. ► We use the comet assay as parameter for genotoxicity in ex vivo human skin. ► Sensitivity, specificity and accuracy to predict in vivo genotoxins are determined. ► Sensitivity, specificity and accuracy are 89%, 90% and 90%, respectively. ► The method

The use of ex vivo human skin tissue for genotoxicity testing

International Nuclear Information System (INIS)

Reus, Astrid A.; Usta, Mustafa; Krul, Cyrille A.M.

2012-01-01

As a result of the chemical legislation concerning the registration, evaluation, authorization and restriction of chemicals (REACH), and the Seventh Amendment to the Cosmetics Directive, which prohibits animal testing in Europe for cosmetics, alternative methods for safety evaluation of chemicals are urgently needed. Current in vitro genotoxicity assays are not sufficiently predictive for the in vivo situation, resulting in an unacceptably high number of misleading positives. For many chemicals and ingredients of personal care products the skin is the first site of contact, but there are no in vitro genotoxicity assays available in the skin for additional evaluation of positive or equivocal responses observed in regulatory in vitro genotoxicity assays. In the present study ex vivo human skin tissue obtained from surgery was used for genotoxicity evaluation of chemicals by using the comet assay. Fresh ex vivo human skin tissue was cultured in an air–liquid interface and topically exposed to 20 chemicals, including true positive, misleading positive and true negative genotoxins. Based on the results obtained in the present study, the sensitivity, specificity and accuracy of the ex vivo skin comet assay to predict in vivo genotoxicity were 89%, 90% and 89%, respectively. Donor and experimental variability were mainly reflected in the magnitude of the response and not the difference between the presence and absence of a genotoxic response. The present study indicates that human skin obtained from surgery is a promising and robust model for safety evaluation of chemicals that are in direct contact with the skin. -- Highlights: ► We use human skin obtained from surgery for genotoxicity evaluation of chemicals. ► We use the comet assay as parameter for genotoxicity in ex vivo human skin. ► Sensitivity, specificity and accuracy to predict in vivo genotoxins are determined. ► Sensitivity, specificity and accuracy are 89%, 90% and 90%, respectively. ► The method

An in vitro test to screen skin sensitizers using a stable THP-1-derived IL-8 reporter cell line, THP-G8.

Science.gov (United States)

Takahashi, Toshiya; Kimura, Yutaka; Saito, Rumiko; Nakajima, Yoshihiro; Ohmiya, Yoshihiro; Yamasaki, Kenshi; Aiba, Setsuya

2011-12-01

Several studies have suggested that interleukin (IL)-8 can serve as a biomarker for discrimination of skin sensitizers from nonsensitizers. We established a stable THP-1-derived IL-8 reporter cell line, THP-G8, which harbors SLO and SLR luciferase genes under the control of IL-8 and glyceraldehyde 3-phosphate dehydrogenase promoters, respectively. After 6 h treatment with chemicals, normalized SLO luciferase activity (nSLO-LA) was calculated by dividing SLO-LA by SLR-LA, and the fold induction of nSLO-LA (FInSLO-LA) was calculated by dividing nSLO-LA of chemically treated cells by that of nontreated cells. The nSLO-LA of THP-G8 cells increased in response to lipopolysaccharide (LPS) and several sensitizers. The FInSLO-LA in THP-G8 cells induced by LPS or sensitizers positively correlated with their induction of IL-8 messenger RNA in THP-1 cells. The nSLO-LA value of THP-G8 cells was significantly increased (FInSLO-LA ≥ 1.4) by 13 of the 15 sensitizers as well as by 5 of the 7 nonsensitizers. Interestingly, pretreatment with N-acetylcysteine suppressed the increase in FInSLO-LA induced by all sensitizers (inhibition index (II) ≤ 0.8) but did not suppress that induced by most of the nonsensitizers. We then evaluated the performance of this assay using values of FInSLO-LA ≥ 1.4 and II ≤ 0.8 in at least two of three independent experiments as the criteria of a sensitizer, which resulted in test accuracies of 82% for the 22 chemicals used and of 88% for the chemicals proposed by European Center for the Validation of Alternative Methods. This newly developed assay is a candidate replacement for animal tests of skin sensitization because of its accuracy, convenience, and high throughput performance.

Prediction of the contact sensitizing potential of chemicals using analysis of gene expression changes in human THP-1 monocytes.

Science.gov (United States)

Arkusz, Joanna; Stępnik, Maciej; Sobala, Wojciech; Dastych, Jarosław

2010-11-10

The aim of this study was to find differentially regulated genes in THP-1 monocytic cells exposed to sensitizers and nonsensitizers and to investigate if such genes could be reliable markers for an in vitro predictive method for the identification of skin sensitizing chemicals. Changes in expression of 35 genes in the THP-1 cell line following treatment with chemicals of different sensitizing potential (from nonsensitizers to extreme sensitizers) were assessed using real-time PCR. Verification of 13 candidate genes by testing a large number of chemicals (an additional 22 sensitizers and 8 nonsensitizers) revealed that prediction of contact sensitization potential was possible based on evaluation of changes in three genes: IL8, HMOX1 and PAIMP1. In total, changes in expression of these genes allowed correct detection of sensitization potential of 21 out of 27 (78%) test sensitizers. The gene expression levels inside potency groups varied and did not allow estimation of sensitization potency of test chemicals. Results of this study indicate that evaluation of changes in expression of proposed biomarkers in THP-1 cells could be a valuable model for preliminary screening of chemicals to discriminate an appreciable majority of sensitizers from nonsensitizers. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Fate of chemicals in skin after dermal application: does the in vitro skin reservoir affect the estimate of systemic absorption?

International Nuclear Information System (INIS)

Yourick, Jeffrey J.; Koenig, Michael L.; Yourick, Debra L.; Bronaugh, Robert L.

2004-01-01

Recent international guidelines for the conduct of in vitro skin absorption studies put forward different approaches for addressing the status of chemicals remaining in the stratum corneum and epidermis/dermis at the end of a study. The present study investigated the fate of three chemicals [dihydroxyacetone (DHA), 7-(2H-naphtho[1,2-d]triazol-2-yl)-3-phenylcoumarin (7NTPC), and disperse blue 1 (DB1)] in an in vitro absorption study. In these studies, human and fuzzy rat skin penetration and absorption were determined over 24 or 72 h in flow-through diffusion cells. Skin penetration of these chemicals resulted in relatively low receptor fluid levels but high skin levels. For DHA, penetration studies found approximately 22% of the applied dose remaining in the skin (in both the stratum corneum and viable tissue) as a reservoir after 24 h. Little of the DHA that penetrates into skin is actually available to become systemically absorbed. 7NTPC remaining in the skin after 24 h was approximately 14.7% of the applied dose absorbed. Confocal laser cytometry studies with 7NTPC showed that it is present across skin in mainly the epidermis and dermis with intense fluorescence around hair. For DB1, penetration studies found approximately 10% (ethanol vehicle) and 3% (formulation vehicle) of the applied dose localized in mainly the stratum corneum after 24 h. An extended absorption study (72 h) revealed that little additional DB1 was absorbed into the receptor fluid. Skin levels should not be considered as absorbed material for DHA or DB1, while 7NTPC requires further investigation. These studies illustrate the importance of determining the fate of chemicals remaining in skin, which could significantly affect the estimates of systemically available material to be used in exposure estimates. We recommend that a more conclusive means to determine the fate of skin levels is to perform an extended study as conducted for DB1

Evaluation of a topical treatment for the relief of sensitive skin

Directory of Open Access Journals (Sweden)

Heinicke IR

2015-07-01

Full Text Available Ingrid R Heinicke,1 Damian H Adams,2 Tanya M Barnes,1 Kerryn A Greive1 1Ego Pharmaceuticals, Braeside, VIC, Australia; 2Mawson Institute, University of South Australia, Mawson Lakes, SA, Australia Background: Approximately, 50% of the population claim to have sensitive skin, which has created an important challenge for dermatologists and the cosmetic industry. This study evaluates the properties of QV Face Rescue Gel (Rescue Gel that contains a combination of moisturizing and anti-irritant ingredients, and which is used to relieve the symptoms of sensitive facial skin. Methods: The ability of Rescue Gel to induce collagen types I and III in cultured neonatal human foreskin fibroblasts compared to transforming growth factor beta 1, a known potent inducer of collagen types I and III, was measured using immunofluorescence staining. Furthermore, healthy volunteers were recruited to measure the potential for Rescue Gel to reduce erythema induced by solar-simulated ultraviolet radiation on the skin compared to 0.5% hydrocortisone cream (positive control as well as it's ability to decrease transepidermal water loss compared to baseline levels. In addition, the formulation was tested for its potential to be 1 nonstinging using a facial sting/discomfort assay performed on volunteers who reacted positively to lactic acid, 2 nonirritating as determined by repeat insult patch tests, and 3 noncomedogenic. Results: Rescue Gel significantly induced collagen types I and III in cultured human foreskin fibroblasts similarly to transforming growth factor beta 1. In volunteers, Rescue Gel was shown to significantly reduce erythema induced by solar-simulated ultraviolet radiation similarly to 0.5% hydrocortisone, and to significantly reduce transepidermal water loss compared to baseline levels. Further, the formulation was found to be nonstinging, nonirritating, and noncomedogenic. No adverse events were observed. Conclusion: In this study, Rescue Gel has been shown

CADRE-SS, an in Silico Tool for Predicting Skin Sensitization Potential Based on Modeling of Molecular Interactions.

Science.gov (United States)

Kostal, Jakub; Voutchkova-Kostal, Adelina

2016-01-19

Using computer models to accurately predict toxicity outcomes is considered to be a major challenge. However, state-of-the-art computational chemistry techniques can now be incorporated in predictive models, supported by advances in mechanistic toxicology and the exponential growth of computing resources witnessed over the past decade. The CADRE (Computer-Aided Discovery and REdesign) platform relies on quantum-mechanical modeling of molecular interactions that represent key biochemical triggers in toxicity pathways. Here, we present an external validation exercise for CADRE-SS, a variant developed to predict the skin sensitization potential of commercial chemicals. CADRE-SS is a hybrid model that evaluates skin permeability using Monte Carlo simulations, assigns reactive centers in a molecule and possible biotransformations via expert rules, and determines reactivity with skin proteins via quantum-mechanical modeling. The results were promising with an overall very good concordance of 93% between experimental and predicted values. Comparison to performance metrics yielded by other tools available for this endpoint suggests that CADRE-SS offers distinct advantages for first-round screenings of chemicals and could be used as an in silico alternative to animal tests where permissible by legislative programs.

An Animal Model of Trichloroethylene-Induced Skin Sensitization in BALB/c Mice.

Science.gov (United States)

Wang, Hui; Zhang, Jia-xiang; Li, Shu-long; Wang, Feng; Zha, Wan-sheng; Shen, Tong; Wu, Changhao; Zhu, Qi-xing

2015-01-01

Trichloroethylene (TCE) is a major occupational hazard and environmental contaminant that can cause multisystem disorders in the form of occupational medicamentosa-like dermatitis. Development of dermatitis involves several proinflammatory cytokines, but their role in TCE-mediated dermatitis has not been examined in a well-defined experimental model. In addition, few animal models of TCE sensitization are available, and the current guinea pig model has apparent limitations. This study aimed to establish a model of TCE-induced skin sensitization in BALB/c mice and to examine the role of several key inflammatory cytokines on TCE sensitization. The sensitization rate of dorsal painted group was 38.3%. Skin edema and erythema occurred in TCE-sensitized groups, as seen in 2,4-dinitrochlorobenzene (DNCB) positive control. Trichloroethylene sensitization-positive (dermatitis [+]) group exhibited increased thickness of epidermis, inflammatory cell infiltration, swelling, and necrosis in dermis and around hair follicle, but ear painted group did not show these histological changes. The concentrations of serum proinflammatory cytokines including tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-2 were significantly increased in 24, 48, and 72 hours dermatitis [+] groups treated with TCE and peaked at 72 hours. Deposition of TNF-α, IFN-γ, and IL-2 into the skin tissue was also revealed by immunohistochemistry. We have established a new animal model of skin sensitization induced by repeated TCE stimulations, and we provide the first evidence that key proinflammatory cytokines including TNF-α, IFN-γ, and IL-2 play an important role in the process of TCE sensitization. © The Author(s) 2015.

In vitro assessment of skin sensitization, photosensitization and phototoxicity potential of commercial glyphosate-containing formulations.

Science.gov (United States)

de Ávila, Renato Ivan; Teixeira, Gabriel Campos; Veloso, Danillo Fabrini Maciel Costa; Moreira, Larissa Cleres; Lima, Eliana Martins; Valadares, Marize Campos

2017-12-01

This study evaluated the applicability of a modified Direct Peptide Reactivity Assay (DPRA) (OECD N° 442C, 2015) through the 10-fold reduction of reaction volume (micro-DPRA, mDPRA) for skin sensitization evaluation of six commercial glyphosate-containing formulations. In addition, another modification of DPRA was proposed by adding a UVA (5J/cm 2 ) irradiation step, namely photo-mDPRA, to better characterize (photo)sensitizer materials. The phototoxicity profile of pesticides was also evaluated using the 3T3 Neutral Red Uptake Phototoxicity Test (3T3-NRU-PT) (OECD N° 432, 2004). The mDPRA could represent an environmentally acceptable test approach, since it reduces costs and organic waste. Peptide depletion was greater in photo-mDPRA and changed the reactivity class of each test material, in comparison to mDPRA. Thus, the association of mDPRA with photo-mDPRA was better for correctly characterizing human (photo)sensitizer substances and pesticides. In general, cysteine depletion was greater than that of lysine for all materials tested in both mDPRA and photo-mDPRA. Furthermore, while 3T3-NRU-PT is unable to predict (photo)sensitizers, it was capable of correctly identifying the phototoxic potential of the tested agrochemical formulations. In conclusion, mDPRA plus photo-mDPRA and 3T3-NRU-PT seem to be preliminary non-animal test batteries for skin (photo)sensitization/phototoxicity assessment of chemicals, agrochemical formulations and their ingredients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Integrated Computational Solution for Predicting Skin Sensitization Potential of Molecules.

Directory of Open Access Journals (Sweden)

Konda Leela Sarath Kumar

Full Text Available Skin sensitization forms a major toxicological endpoint for dermatology and cosmetic products. Recent ban on animal testing for cosmetics demands for alternative methods. We developed an integrated computational solution (SkinSense that offers a robust solution and addresses the limitations of existing computational tools i.e. high false positive rate and/or limited coverage.The key components of our solution include: QSAR models selected from a combinatorial set, similarity information and literature-derived sub-structure patterns of known skin protein reactive groups. Its prediction performance on a challenge set of molecules showed accuracy = 75.32%, CCR = 74.36%, sensitivity = 70.00% and specificity = 78.72%, which is better than several existing tools including VEGA (accuracy = 45.00% and CCR = 54.17% with 'High' reliability scoring, DEREK (accuracy = 72.73% and CCR = 71.44% and TOPKAT (accuracy = 60.00% and CCR = 61.67%. Although, TIMES-SS showed higher predictive power (accuracy = 90.00% and CCR = 92.86%, the coverage was very low (only 10 out of 77 molecules were predicted reliably.Owing to improved prediction performance and coverage, our solution can serve as a useful expert system towards Integrated Approaches to Testing and Assessment for skin sensitization. It would be invaluable to cosmetic/ dermatology industry for pre-screening their molecules, and reducing time, cost and animal testing.

Two-tiered keratinocyte assay: IL-18 production by NCTC2544 cells to determine the skin sensitizing capacity and an epidermal equivalent assay to determine sensitizer potency

DEFF Research Database (Denmark)

Teunis, Marc; Corsini, Emanuela; Smits, Mieke

2012-01-01

the use of animals. The aim of the EU FP6 Integrated Project Sens-it-iv was to develop and optimize an integrated testing strategy consisting of in vitro, human cell based assays which will closely mimic sensitization mechanisms in vivo. These assays should be an alternative approach to the LLNA. The NCTC...... method to the LLNA. Both assays are based on the use of human keratinocytes, which have been shown, over the last two decades, to play a key role in all phases of skin sensitization. First, 4 known chemicals were tested during a transferability study in which 6 laboratories participated. Three...

Identification of Lilial as a fragrance sensitizer in a perfume by bioassay-guided chemical fractionation and structure-activity relationships

DEFF Research Database (Denmark)

Arnau, E G; Andersen, Klaus Ejner; Bruze, M

2000-01-01

Fragrance materials are among the most common causes of allergic contact dermatitis. The aim of this study was to identify in a perfume fragrance allergens not included in the fragrance mix, by use of bioassay-guided chemical fractionation and chemical analysis/structure-activity relationships...... (SARs). The basis for the investigation was a 45-year-old woman allergic to her own perfume. She had a negative patch test to the fragrance mix and agreed to participate in the study. Chemical fractionation of the perfume concentrate was used for repeated patch testing and/or repeated open application......" in their chemical structure, indicating an ability to modify skin proteins and thus behave as a skin sensitizer, were tested on the patient. The patient reacted positively to the synthetic fragrance p-t-butyl-alpha-methylhydrocinnamic aldehyde (Lilial), a widely used fragrance compound not present in the fragrance...

Reactive skin decontamination lotion (RSDL) for the decontamination of chemical warfare agent (CWA) dermal exposure.

Science.gov (United States)

Schwartz, M D; Hurst, C G; Kirk, M A; Reedy, S J D; Braue, E H

2012-08-01

Rapid decontamination of the skin is the single most important action to prevent dermal absorption of chemical contaminants in persons exposed to chemical warfare agents (CWA) and toxic industrial chemicals (TICs) as a result of accidental or intentional release. Chemicals on the skin may be removed by mechanical means through the use of dry sorbents or water. Recent interest in decontamination systems which both partition contaminants away from the skin and actively neutralize the chemical has led to the development of several reactive decontamination solutions. This article will review the recently FDA-approved Reactive Skin Decontamination Lotion (RSDL) and will summarize the toxicity and efficacy studies conducted to date. Evidence of RSDL's superior performance against vesicant and organophosphorus chemical warfare agents compared to water, bleach, and dry sorbents, suggests that RSDL may have a role in mass human exposure chemical decontamination in both the military and civilian arenas.

Preventive effect of chemical peeling on ultraviolet induced skin tumor formation.

Science.gov (United States)

Abdel-Daim, Mohamed; Funasaka, Yoko; Kamo, Tsuneyoshi; Ooe, Masahiko; Matsunaka, Hiroshi; Yanagita, Emmy; Itoh, Tomoo; Nishigori, Chikako

2010-10-01

Chemical peeling is one of the dermatological treatments available for certain cutaneous diseases and conditions or improvement of cosmetic appearance of photoaged skin. We assessed the photochemopreventive effect of several clinically used chemical peeling agents on the ultraviolet (UV)-irradiated skin of hairless mice. Chemical peeling was done using 35% glycolic acid dissolved in distilled water, 30% salicylic acid in ethanol, 10% or 35% trichloroacetic acid (TCA) in distilled water at the right back of UV-irradiated hairless mice every 2 weeks in case of glycolic acid, salicylic acid, and 10% TCA and every 4 weeks in case of 35% TCA for totally 18 weeks after the establishment of photoaged mice by irradiation with UVA+B range light three times a week for 10 weeks at a total dose of 420 J/cm(2) at UVA and 9.6 J/cm(2) at UVB. Tumor formation was assessed every week. Skin specimens were taken from treated and non-treated area for evaluation under microscopy, evaluation of P53 expression, and mRNA expression of cyclooxygenase (COX)-2. Serum level of prostaglandin E(2) was also evaluated. All types of chemical peeling reduced tumor formation in treated mice, mostly in the treated area but also non-treated area. Peeling suppressed clonal retention of p53 positive abnormal cells and reduced mRNA expression of COX-2 in treated skin. Further, serum prostaglandin E(2) level was decreased in chemical peeling treated mice. These results indicate that chemical peeling with glycolic acid, salicylic acid, and TCA could serve tumor prevention by removing photodamaged cells. Copyright © 2010 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Type I allergy to natural rubber latex and type IV allergy to rubber chemicals in health care workers with glove-related skin symptoms.

Science.gov (United States)

Nettis, E; Assennato, G; Ferrannini, A; Tursi, A

2002-03-01

It has been established that there are type I and type IV allergens in latex gloves. The purpose of the study was to establish the prevalence of rubber glove-induced skin symptoms among health care workers in one Italian hospital. Health care workers (n = 1584) were evaluated using a written questionnaire and 295 respondents with glove-induced skin symptoms were tested. We performed: skin prick test with latex glove extract and commercial latex, and environmental and food allergens; glove use test; patch tests with a rubber additive series; and RASTs. Hospital employees who used or had used latex gloves at work were 1294. Three hundred and sixteen (24.4%) reported glove-induced symptoms, namely, cutaneous symptoms in all the cases and non-cutaneous symptoms in 105 subjects (8.1%). Twenty-seven of the 295 symptomatic employees tested (9.1%) were latex sensitive. Thirty-one patients (10.5%) exhibited positive patch test to rubber-related allergens. The most positive readings were obtained from the Thiuram mix and the Carba mix, with 12 and 9 positivities, respectively. The risk factors for latex skin sensitization were: a previous history of atopy and asthma; history of surgery; pre-existing hand dermatitis; work-related symptoms; and positive skin tests to common inhalant and certain foods (P skin complaints of latex gloves are related to skin irritation rather than to allergy. The immediate allergy to latex and the delayed allergy to rubber chemicals suggest that all the health care workers with glove-related dermatitis should undergo both skin prick test and glove use test to detect type I hypersensitivity to latex, and patch test to detect type IV hypersensitivity to rubber chemicals.

Contrasting effects of ultraviolet-A and ultraviolet B exposure on induction of contact sensitivity in human skin

DEFF Research Database (Denmark)

Skov, Lone; Hansen, Henrik; Barker, J. N.

1997-01-01

Ultraviolet-B (UVB), in addition to direct effects on DNA, induces immunological changes in the skin that predispose to the development of skin cancer. Whether ultraviolet-A (UVA) induces similar changes is unknown. This effect can be investigated in humans in vivo using epicutaneous antigens...... as a model of tumour antigens. Volunteers (n = 46) were randomly assigned to received no sensitization, sensitization with the allergen diphenylcyclopropenone (DPCP) on non-UV-exposed normal skin, or sensitization with DPCP on skin exposed to three minimal erythema doses (MED) of either UVA or UVB radiation...... the immunization rate compared with sensitization on non-irradiated skin (P UVA radiation did not result in a decreased immunization rate compared with non-irradiated skin. These results indicate that in humans erythemagenic...

Skin sensitization potency of methyl methacrylate in the local lymph node assay: comparisons with guinea-pig data and human experience.

Science.gov (United States)

Betts, Catherine J; Dearman, Rebecca J; Heylings, Jon R; Kimber, Ian; Basketter, David A

2006-09-01

There is compelling evidence that contact allergens differ substantially (by 4 or 5 orders of magnitude) with respect to their inherent skin-sensitizing potency. Relative potency can now be measured effectively using the mouse local lymph node assay (LLNA) and such data form the basis of risk assessment and risk management strategies. Such determinations also facilitate distinctions being drawn between the prevalence of skin sensitization to a particular contact allergen and inherent potency. The distinction is important because chemicals that are implicated as common causes of contact allergy are not necessarily potent sensitizers. One example is provided by nickel that is undoubtedly a common cause of allergic contact dermatitis, but is a comparatively weak sensitizer in predictive tests. In an attempt to explore other examples of contact allergens where there may exist a discrepancy between prevalence and potency, we describe here analyses conducted with methyl methacrylate (MMA). Results of LLNA studies have been interpreted in the context of historical clinical data on occupational allergic contact dermatitis associated with exposure to MMA.

SKIN SENSITIZATION AND ALLERGIC CONTACT DERMATITIS (BASIC COURSE): THE GLOBAL REGULATORY ENVIRONMENT - CONTINUING EDUCATION COURSE; 1 OF 4 SPEAKERS FOR AN SOT BASIC COURSE

Science.gov (United States)

New regulations have emerged in recent years giving guidance on how best to conduct skin sensitization testing on new chemical entities. For example, recently The Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) in the U.S. and the European Ce...

Wearable, Flexible, and Multifunctional Healthcare Device with an ISFET Chemical Sensor for Simultaneous Sweat pH and Skin Temperature Monitoring.

Science.gov (United States)

Nakata, Shogo; Arie, Takayuki; Akita, Seiji; Takei, Kuniharu

2017-03-24

Real-time daily healthcare monitoring may increase the chances of predicting and diagnosing diseases in their early stages which, currently, occurs most frequently during medical check-ups. Next-generation noninvasive healthcare devices, such as flexible multifunctional sensor sheets designed to be worn on skin, are considered to be highly suitable candidates for continuous real-time health monitoring. For healthcare applications, acquiring data on the chemical state of the body, alongside physical characteristics such as body temperature and activity, are extremely important for predicting and identifying potential health conditions. To record these data, in this study, we developed a wearable, flexible sweat chemical sensor sheet for pH measurement, consisting of an ion-sensitive field-effect transistor (ISFET) integrated with a flexible temperature sensor: we intend to use this device as the foundation of a fully integrated, wearable healthcare patch in the future. After characterizing the performance, mechanical flexibility, and stability of the sensor, real-time measurements of sweat pH and skin temperature are successfully conducted through skin contact. This flexible integrated device has the potential to be developed into a chemical sensor for sweat for applications in healthcare and sports.

The sensitization potential of sunscreen after ablative fractional skin resurfacing using modified human repeated insult patch test.

Science.gov (United States)

Boonchai, Waranya; Sathaworawong, Angkana; Wongpraparut, Chanisada; Wanitphakdeedecha, Rungsima

2015-10-01

Ablative fractional skin resurfacing has become popular and proven to be useful in treating scars, photoaging and wrinkles. Although post-inflammatory hyperpigmentation (PIH) is the most common complication especially in dark-skinned patients like Asian. Several modalities have been used to overcome the PIH. To determine the sensitization potential of sunscreen applied immediately after ablative fractional skin resurfacing. Sixty volunteers were recruited. Of these 30 subjects were from previous ablative fractional skin resurfacing study who applied broad-spectrum sunscreen containing anti-inflammatory agent starting on the first day after resurfacing and another 30 non-resurfacing subjects had applied the same sunscreen on the intact skin. All subjects were patch/photopatch tested for sensitization study by using modified human repeated insult patch test (HRIPT). There were significantly higher sensitization rate of UV-filter, octocrylene and the sunscreen in resurfacing group than in non-resurfacing group. Early application of sunscreen after ablative fractional skin resurfacing has increased the incidence of sensitization potential of sunscreen. The sunscreen is recommended to start using from D3 after fractional ablative skin resurfacing to ensure the complete recovery of skin barrier and minimize the risk of sensitization.

Tolerance of fragranced and fragrance-free facial cleansers in adults with clinically sensitive skin.

Science.gov (United States)

Draelos, Zoe D; Fowler, Joseph; Larsen, Walter G; Hornby, Sidney; Walters, Russel M; Appa, Yohini

2015-10-01

Although mild, fragrance-free, nonfoaming cleansers generally are recommended for individuals with sensitive skin, many consumers choose fragranced foaming cleansers. The addition of hydrophobically modified polymers (HMPs) to mild facial cleansers has been shown to improve product tolerability in individuals with sensitive skin while facilitating foaming. The objective of the 2 studies reported here was to assess the tolerability of a mild, HMP-containing, foaming facial cleanser with a fragrance that was free of common allergens and irritating essential oils in patients with sensitive skin. In the first study, 8 participants with clinically diagnosed fragrance sensitivity used a gentle foaming HMP-containing facial cleanser with or without fragrance for 3 weeks. Both cleansers improved global disease severity, irritation, and erythema with similar cleansing effectiveness. The second study was a 3-week, prospective, double-blind, randomized, 2-center study of 153 participants with clinically diagnosed sensitive skin. In this study, the fragranced gentle foaming cleanser with HMP was as well tolerated as a benchmark gentle, fragrance-free, nonfoaming cleanser. Itching, irritation, and desquamation were most improved from baseline in both groups. The participant-rated effectiveness of the cleanser with HMP was similar or better than the benchmark cleanser after 3 weeks of use. In conclusion, the gentle facial cleanser with HMPs and a fragrance offers a new option for adults with sensitive skin who may prefer, and commonly use, a fragranced and foaming product.

Development of an artificial neural network model for risk assessment of skin sensitization using human cell line activation test, direct peptide reactivity assay, KeratinoSens™ and in silico structure alert parameter.

Science.gov (United States)

Hirota, Morihiko; Ashikaga, Takao; Kouzuki, Hirokazu

2018-04-01

It is important to predict the potential of cosmetic ingredients to cause skin sensitization, and in accordance with the European Union cosmetic directive for the replacement of animal tests, several in vitro tests based on the adverse outcome pathway have been developed for hazard identification, such as the direct peptide reactivity assay, KeratinoSens™ and the human cell line activation test. Here, we describe the development of an artificial neural network (ANN) prediction model for skin sensitization risk assessment based on the integrated testing strategy concept, using direct peptide reactivity assay, KeratinoSens™, human cell line activation test and an in silico or structure alert parameter. We first investigated the relationship between published murine local lymph node assay EC3 values, which represent skin sensitization potency, and in vitro test results using a panel of about 134 chemicals for which all the required data were available. Predictions based on ANN analysis using combinations of parameters from all three in vitro tests showed a good correlation with local lymph node assay EC3 values. However, when the ANN model was applied to a testing set of 28 chemicals that had not been included in the training set, predicted EC3s were overestimated for some chemicals. Incorporation of an additional in silico or structure alert descriptor (obtained with TIMES-M or Toxtree software) in the ANN model improved the results. Our findings suggest that the ANN model based on the integrated testing strategy concept could be useful for evaluating the skin sensitization potential. Copyright © 2017 John Wiley & Sons, Ltd.

Occupational skin hazards and prevalence of occupational skin diseases in shoe manufacturing workers in Indonesia.

Science.gov (United States)

Febriana, Sri Awalia; Soebono, Hardyanto; Coenraads, Pieter-Jan

2014-02-01

Shoe manufacturing workers are exposed daily to an extensive range of potential physical and chemical occupational hazards. Shoe manufacturing in Indonesia is one of the industrial sectors that has shown sustained growth amongst the newly industrialized countries (NICs). In this study, we investigated the possible potential exposure of the workers to physical and occupational hazards and determined the prevalence of occupational skin diseases at a shoe manufacturing factory in Indonesia. A cross-sectional study on the observation of the working process and an inventory and risk assessment of exposure to the chemicals used. Classification of chemicals as potential sensitizers/irritants and qualitative assessments of these chemicals were done. Workers were examined and interviewed using the Nordic Occupational Skin Questionnaire-2002/LONG. The risk of Occupational skin diseases (OSD) at the shoe factory was mainly related to the exposure of the workers' skin to potential physical and chemical hazards in hot and humid environmental conditions. From a total of 514 workers, 8.5 % reported current OSD and 4.8 % reported a history of OSD. Occupational skin diseases were diagnosed in 29 % of the workers by dermatologists and 7.6 % had an occupational contact dermatitis (OCD). Of the 39 workers with contact dermatitis, 33 consented to being patch tested, 14 (3 %) workers showed a positive results and considered as having an occupational allergic contact dermatitis (OACD) and 25 (4.9 %) had an occupational irritant contact dermatitis (OICD). We observed a repeated and prolonged exposure of the workers to numerous physical and chemical skin hazards at this factory.

Skin sensitization potency of isoeugenol and its dimers evaluated by a non-radioisotopic modification of the local lymph node assay and guinea pig maximization test.

Science.gov (United States)

Takeyoshi, Masahiro; Iida, Kenji; Suzuki, Keiko; Yamazaki, Shunsuke

2008-05-01

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, beta-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, beta-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, beta-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 (c) 2007 John Wiley & Sons, Ltd.

The physico-chemical properties of pangas catfish (Pangasius pangasius) skin gelatin

Science.gov (United States)

Pradarameswari, K. A.; Zaelani, K.; Waluyo, E.; Nurdiani, R.

2018-04-01

Gelatin can be used as emulsifier and stabilizer in food products. Until now, the most widely used raw materials for the production of gelatin industry are cow bone, cow skin and pig skin. Fish gelatin has been highlighted as a better alternative to replace mammals gelatin based on ethical and religious perspective. Fish gelatin was extracted from Pangas catfish skin to determine its physico-chemical properties. Different temperatures (45 °C, 50 °C, 55 °C) were employed during gelatin extraction. Higher temperature increased the yield and fat contents of Pangas catfish skin gelatin. In contrary, higher water, protein, ash contents were observed during lower temperature. Temperature significantly (p fish skin gelatin. Based on the FTIR spectrum catfish skin gelatin functional groups can be identified as N-H, O-H, C = H, C-O and C-H.

High sensitivity optical measurement of skin gloss

OpenAIRE

Ezerskaia, Anna; Ras, Arno; Bloemen, Pascal; Pereira, Silvania F.; Urbach, H. Paul; Varghese, Babu

2017-01-01

We demonstrate a low-cost optical method for measuring the gloss properties with improved sensitivity in the low gloss regime, relevant for skin gloss properties. The gloss estimation method is based on, on the one hand, the slope of the intensity gradient in the transition regime between specular and diffuse reflection and on the other on the sum over the intensities of pixels above threshold, derived from a camera image obtained using unpolarized white light illumination. We demonstrate the...

Multiple Chemical Sensitivity

DEFF Research Database (Denmark)

Junge, Anne Gram

Et voksende antal mennesker i Danmark oplever at være overfølsomme over for dufte og kemikalier. Imidlertid er den tilskrevne diagnose Multiple Chemical Sensitivity (MCS) ikke medicinsk anerkendt i Danmark pga. mangel på organiske og patofysiologisk basis for symptomerne. Dette speciale bygger på...

Prevalence and effects of multiple chemical sensitivities in Australia

Directory of Open Access Journals (Sweden)

Anne Steinemann

2018-06-01

Full Text Available Multiple chemical sensitivities (MCS is a medical condition associated with exposure to common chemical pollutants. The aims of this study are to assess the prevalence of MCS, its overlaps with asthma and fragrance sensitivity, and its health and societal effects in Australia. Data were collected in June 2016 using an on-line survey with a representative national sample (N = 1098 of adults (ages 18–65 in Australia. Results found that, across the country, 6.5% report medically diagnosed MCS, 18.9% report chemical sensitivity (being unusually sensitive to everyday chemicals and chemically formulated products, and 19.9% either or both. Among people with MCS, 74.6% also have diagnosed asthma or an asthma-like condition, and 91.5% have fragrance sensitivity, reporting health problems (such as migraine headaches when exposed to fragranced consumer products (such as air fresheners and cleaning supplies. In addition, among people with MCS, 77.5% are prevented from access to places because of fragranced products, 52.1% lost workdays or a job in the past year due to fragranced product exposure in the workplace, and 55.4% report health effects considered potentially disabling. Results indicate that MCS is a widespread disease, affecting an estimated 1 million adult Australians, with chemical sensitivity affecting another 2 million. Reducing chemical exposure to problematic sources, such as fragranced consumer products, is critical to reduce adverse effects. Keywords: MCS, Multiple chemical sensitivities, Chemical sensitivity, Asthma, Fragrance sensitivity, Fragranced consumer products

Multiple Chemical Sensitivity

DEFF Research Database (Denmark)

Dantoft, Thomas Meinertz

Multiple chemical sensitivity (MCS) is a chronic disorder characterized by reports of symptoms from various organ systems attributed by the individuals to exposure to common odors and airborne chemicals in doses far below those known to induce toxic effects. There exists a general lack of knowledge......, significantly reduced levels of IL-13 in the MCS group and no group differences in the allergen specific IgE measures. The differences were independent of factors such as sex, age, Body Mass Index, asthma, smoking, depression, anxiety and allergen-specific IgE. In conclusion, the study identified a distinct...

Role of the Slug Transcription Factor in Chemically-Induced Skin Cancer

Directory of Open Access Journals (Sweden)

Kristine von Maltzan

2016-02-01

Full Text Available The Slug transcription factor plays an important role in ultraviolet radiation (UVR-induced skin carcinogenesis, particularly in the epithelial-mesenchymal transition (EMT occurring during tumor progression. In the present studies, we investigated the role of Slug in two-stage chemical skin carcinogenesis. Slug and the related transcription factor Snail were expressed at high levels in skin tumors induced by 7,12-dimethylbenz[α]anthracene application followed by 12-O-tetradecanoylphorbol-13-acetate (TPA treatment. TPA-induced transient elevation of Slug and Snail proteins in normal mouse epidermis and studies in Slug transgenic mice indicated that Slug modulates TPA-induced epidermal hyperplasia and cutaneous inflammation. Although Snail family factors have been linked to inflammation via interactions with the cyclooxygenase-2 (COX-2 pathway, a pathway that also plays an important role in skin carcinogenesis, transient TPA induction of Slug and Snail appeared unrelated to COX-2 expression. In cultured human keratinocytes, TPA induced Snail mRNA expression while suppressing Slug expression, and this differential regulation was due specifically to activation of the TPA receptor. These studies show that Slug and Snail exhibit similar patterns of expression during both UVR and chemical skin carcinogenesis, that Slug and Snail can be differentially regulated under some conditions and that in vitro findings may not recapitulate in vivo results.

Ultrastructural demonstration of chemical modification of melanogenesis in hairless mouse skin

International Nuclear Information System (INIS)

Nishimura, M.; Gellin, G.A.; Hoshino, S.; Epstein, J.H.; Epstein, W.L.; Fukuyama, K.

1982-01-01

We investigated chemical and physical modifications of the genetically determined ultrastructure of melanosomes. The flank skin of hairless mice was treated with ultraviolet energy (UV) shorter than 320 nm or with a combination of a photosensitizer and UV (PUVA treatment). All melanosomes in the induced melanocytes and those in resident melanocytes in the ear skin showed eumelanogenesis, although the degree of melanin deposition differed considerably according to the induction process. Eumelanogenesis was most advanced in the resident melanocytes while PUVA-induced melanocytes showed more immature premelanosomes. We then topically applied 4-tertiary butyl catechol on the skin. The depigmenting agent caused an appearance of pheomelanosomes. The alteration in melanogenesis was seen most distinctly in premelanosomes of the PUVA-induced cells. Altered ultrastructure was also observed in matured melanosomes; this change was most apparent in the resident melanocytes. These findings indicate that cells with eumelanogenesis may undergo pheomelanogenesis. The present study demonstrated effects of chemicals on genetically determined function of melanocytes by quantitative analysis of melanosome ultrastructure

Evaluation of the skin sensitization potential of chemicals using expression of co-stimulatory molecules, CD54 and CD86, on the naive THP-1 cell line.

Science.gov (United States)

Yoshida, Y; Sakaguchi, H; Ito, Y; Okuda, M; Suzuki, H

2003-04-01

It has been known that dendritic cells (DCs) including Langerhans cells (LCs) play a critical role in the skin sensitization process. Many attempts have been made to develop in vitro sensitization tests that employ DCs derived from peripheral blood mononuclear cells (PBMC-DC) or CD34+ hematopoietic progenitor cells (CD34+ HPC) purified from cord blood or bone marrow. However, the use of the DCs in in vitro methods has been difficult due to the nature of these cells such as low levels in the source and/or donor-to-donor variability. In our studies, we employed the human monocytic leukemia cell line, THP-1, in order to avoid some of these difficulties. At the start, we examined whether treatment of the cells with various cytokines could produce DCs from THP-1. Treatment of THP-1 cells with cytokines such as GM-CSF, IL-4, TNF-alpha, and/or PMA did induce some phenotypic changes in THP-1 cells that were characteristic of DCs. Subsequently, responses to a known sensitizer, dinitrochlorobenzene (DNCB), and a non-sensitizer, dimethyl sulfoxide (DMSO) or sodium lauryl sulfate (SLS), on the expression of co-stimulatory molecules, CD54 and CD86, were examined between the naive cells and the cytokine-treated cells. Interestingly, the naive THP-1 cells responded only to DNCB and the response to the sensitizer was more distinct than cytokine-treated THP-1 cells. Similar phenomena were also observed in the human myeloid leukemia cell line, KG-1. Furthermore, with treatment of DNCB, naive THP-1 cells showed augmented expression of HLA, CD80 and secretion of IL-1 beta. The response of THP-1 cells to a sensitizer was similar to that of LCs/DCs. Upon demonstrating the differentiation of monocyte cells in our system, we then evaluated a series of chemicals, including known sensitizers and non-sensitizers, for their potential to augment CD54 and CD86 expression on naive THP-1 cells. Indeed, known sensitizers such as PPD and 2-MBT significantly augmented CD54 and CD86 expression in a

Chemically sensitive interfaces on SAW devices

Energy Technology Data Exchange (ETDEWEB)

Ricco, A.J.; Martin, S.J. [Sandia National Labs., Albuquerque, NM (United States); Crooks, R.M.; Xu, Chuanjing [Texas A and M Univ., College Station, TX (United States); Allred, R.E. [Adherent Technologies, Inc., Albuquerque, NM (United States)

1993-11-01

Using surface acoustic wave (SAW) devices, three approaches to the effective use of chemically sensitive interfaces that are not highly chemically selective have been examined: (1) molecular identification from time-resolved permeation transients; (2) using multifrequency SAW devices to determine the frequency dependence of analyte/film interactions; (3) use of an array of SAW devices bearing diverse chemically sensitive interfaces to produce a distinct response pattern for each analyte. In addition to their well-known sensitivity to mass changes (0.0035 monolayer of N{sub 2} can be measured), SAW devices respond to the mechanical and electronic properties of thin films, enhancing response information content but making a thorough understanding of the perturbation critical. Simultaneous measurement of changes in frequency and attenuation, which can provide the information necessary to determine the type of perturbation, are used as part of the above discrimination schemes.

Genetic susceptibility factors for multiple chemical sensitivity revisited

DEFF Research Database (Denmark)

Berg, Nikolaj Drimer; Rasmussen, Henrik Berg; Linneberg, Allan

2010-01-01

of this study was to investigate genetic susceptibility factors for MCS and self-reported chemical sensitivity in a population sample. Ninety six MCS patients and 1,207 controls from a general population divided into four severity groups of chemical sensitivity were genotyped for variants in the genes encoding......Multiple chemical sensitivity (MCS) is characterised by adverse effects due to exposure to low levels of chemical substances. Various genes, especially genes of importance to the metabolism of xenobiotic compounds, have been associated with MCS, but findings are inconsistent. The purpose...... significant (OR=1.2, p=0.28). Fast arylamine N-acetyltransferase 2 metaboliser status was associated with severity of chemical sensitivity only in the most severely affected group in the population sample (OR=3.1, p=0.04). The cholecystokinin 2 receptor allele with 21 CT repeats was associated with MCS when...

Changes in the radiation sensitivity of mouse skin during fractionated and prolonged treatments

International Nuclear Information System (INIS)

Ruifrok, A.C.C.; Mason, K.A.; Hunter, N.; Thames, H.D.

1994-01-01

Reactions of the skin of the right thigh of mice were used as an experimental model to test possible changes in the radiosensitivity of mouse skin, as represented by changes in the linear-quadratic (LQ) model parameters α and β, as a function of fractionation interval and overall treatment time. In the first series of experiments, variable numbers of 3-Gy fractions with intervals of 6, 24 or 48 h were applied, followed by top-up doses to increase the skin damage to a level that could be scored. The results showed that mouse skin is more sensitive to 3-Gy fractions applied with 48-h intervals than to 3-Gy fractions applied with 6- or 24-h intervals. In the second series of experiments we used single-dose or fractonated test treatments for previously unirradiated mice and mice treated with priming doses of 10, 20 or 30 Gy given 1-18 days before the test treatment. The sensitivity appeared to be higher after intervals of 14-18 days than after 1-10 days after priming treatments of 20 and 30 Gy. The increased sensitivity 18 days after 20 Gy was mainly the result of an increase in the β component of the LQ model; higher values of α were also determined. We conclude that the radiosensitivity of mouse skin is higher during a radiation-induced proliferative response. 28 refs., 3 figs., 7 tabs

Integrating non-animal test information into an adaptive testing strategy - skin sensitization proof of concept case.

Science.gov (United States)

Jaworska, Joanna; Harol, Artsiom; Kern, Petra S; Gerberick, G Frank

2011-01-01

There is an urgent need to develop data integration and testing strategy frameworks allowing interpretation of results from animal alternative test batteries. To this end, we developed a Bayesian Network Integrated Testing Strategy (BN ITS) with the goal to estimate skin sensitization hazard as a test case of previously developed concepts (Jaworska et al., 2010). The BN ITS combines in silico, in chemico, and in vitro data related to skin penetration, peptide reactivity, and dendritic cell activation, and guides testing strategy by Value of Information (VoI). The approach offers novel insights into testing strategies: there is no one best testing strategy, but the optimal sequence of tests depends on information at hand, and is chemical-specific. Thus, a single generic set of tests as a replacement strategy is unlikely to be most effective. BN ITS offers the possibility of evaluating the impact of generating additional data on the target information uncertainty reduction before testing is commenced.

Prediction of skin sensitizers using alternative methods to animal experimentation.

Science.gov (United States)

Johansson, Henrik; Lindstedt, Malin

2014-07-01

Regulatory frameworks within the European Union demand that chemical substances are investigated for their ability to induce sensitization, an adverse health effect caused by the human immune system in response to chemical exposure. A recent ban on the use of animal tests within the cosmetics industry has led to an urgent need for alternative animal-free test methods that can be used for assessment of chemical sensitizers. To date, no such alternative assay has yet completed formal validation. However, a number of assays are in development and the understanding of the biological mechanisms of chemical sensitization has greatly increased during the last decade. In this MiniReview, we aim to summarize and give our view on the recent progress of method development for alternative assessment of chemical sensitizers. We propose that integrated testing strategies should comprise complementary assays, providing measurements of a wide range of mechanistic events, to perform well-educated risk assessments based on weight of evidence. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Mechano-sensitive nociceptors are required to detect heat pain thresholds and cowhage itch in human skin.

Science.gov (United States)

Weinkauf, B; Dusch, M; van der Ham, J; Benrath, J; Ringkamp, M; Schmelz, M; Rukwied, R

2016-02-01

Mechano-sensitive and mechano-insensitive C-nociceptors in human skin differ in receptive field sizes and electrical excitation thresholds, but their distinct functional roles are yet unclear. After blocking the lateral femoral cutaneous nerve (NCFL) in eight healthy male subjects (3-mL Naropin(®) 1%), we mapped the skin innervation territory being anaesthetic to mechanical pin prick but sensitive to painful transcutaneous electrical stimuli. Such 'differentially anaesthetic zones' indicated that the functional innervation with mechano-sensitive nociceptors was absent but the innervation with mechano-insensitive nociceptors remained intact. In these areas, we explored heat pain thresholds, low pH-induced pain, cowhage- and histamine-induced itch, and axon reflex flare. In differentially anaesthetic skin, heat pain thresholds were above the cut-off of 50°C (non-anaesthetized skin 47 ± 0.4°C). Pain ratings to 30 μL pH 4 injections were reduced compared to non-anaesthetized skin (48 ± 9 vs. 79 ± 6 VAS; p pain. The mechano-sensitive nociceptors are crucial for cowhage-induced itch and for the assessment of heat pain thresholds. © 2015 European Pain Federation - EFIC®

Are basophil histamine release and high affinity IgE receptor expression involved in asymptomatic skin sensitization?

DEFF Research Database (Denmark)

Jensen, Bettina Margrethe; Assing, K; Jensen, Lone Hummelshøj

2006-01-01

Immunoglobulin (Ig)E-sensitized persons with positive skin prick test, but no allergy symptoms, are classified as being asymptomatic skin sensitized (AS). The allergic type 1 disease is dependant on IgE binding to the high affinity IgE-receptor (FcepsilonRI) expressed on basophils and mast cells....

A study of the effects of physical dermabrasion combined with chemical peeling in porcine skin.

Science.gov (United States)

Kang, Boo Kyoung; Choi, Jeong Hwee; Jeong, Ki Heon; Park, Jong Min; Suh, Dong Hye; Lee, Sang Jun; Shin, Min Kyung

2015-02-01

Many comparative studies of chemical peeling and dermabrasion have been reported. However, rare basic scientific data about the immediate effects after combined treatment with chemical peeling and dermabrasion have been confirmed. The aim of this study is to evaluate the effect of the application of physical abrasion in combination with chemical peels. Three pigs were treated with physical abrasion using a water jet device in combination with an α-hydroxy acid solution, and the skin samples of the control received chemical peeling solution alone. The levels of growth factors and neuropeptides were measured with a multiplex immunoassay. Skin treated with physical dermabrasion combined with chemical peeling showed prominent detachment and swelling of the stratum corneum (SC), and fluid collection in the hair follicles. The mean cell count of CD34 positive fibroblasts and mast cells, levels of epidermal growth factor, fibroblast growth factor-2, vascular endothelial growth factor, and neurotensin, were significantly increased in the tissue treated with physical abrasion combined with a chemical peeling agent, compared to the skin in the control. We concluded that physical dermabrasion combined with chemical peeling can be more effective than chemical peeling alone, for the approach through transfollicular routes.

The Clinical Test of Nano gold Cosmetic for Recovering Skin Damage Due to Chemicals: Special Case

Science.gov (United States)

Taufikurohmah, T.; Wardana, A. P.; Tjahjani, S.; Sanjaya, I. G. M.; Baktir, A.; Syahrani, A.

2018-01-01

Manufacturing of Nano gold cosmetics was done at PT. Gizi Indonesia. Clinical trials to cosmetics data supported that cosmetics are able to treat skin health which has been reported partially. For special cases, the recovery process of facial skin damage should also receive attention including cases of facial skin damage caused by chemicals such as phenol, HCl, aqua regia or other harsh chemicals. The problem determined whether the Nano gold is able to recover skin damage due to the harsh chemicals. This clinical trial data on the forms of early skin damage caused by phenol was delivered in the forms of facial photos patients. The recovery progress of facial skin condition was obtained every week for two months. The data included the forms of widespread wounds during the recovery process. This statement supported by anova statistical analysis of the widespread wound changing every week for 8 times. The conclusion is skin damage due to Phenol impregnation can be recovered with the use of Nano gold cosmetics for 8 weeks. This results support the manufacturing of Nano gold cosmetics for the needs of society. It also suggest that Nano gold material can be used for medicine manufacturing in the future.

Evaluation of the skin sensitizing potency of chemicals by using the existing methods and considerations of relevance for elicitation

DEFF Research Database (Denmark)

Basketter, David A; Andersen, Klaus E; Liden, Carola

2005-01-01

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...... 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...

Contact sensitization to common haptens is associated with atopic dermatitis: new insight

DEFF Research Database (Denmark)

Thyssen, J P; Linneberg, A; Engkilde, K

2012-01-01

and questioned about AD Results: The variable "contact sensitization to common chemicals, but not nickel and thimerosal", was significantly associated with atopic dermatitis (OR=2.53; CI95%=1.59-4.04). The higher prevalence of contact sensitization was mainly driven by fragrance chemicals. In a sub......-analysis in non-pierced women, a positive association was also found for nickel sensitization. Nickel and thimerosal sensitization may introduce bias in data analysis since these allergies often develop following skin piercing where the skin compartments are bypassed. Discussion: We suspect that individuals...

Increased Sensitization to Mold Allergens Measured by Intradermal Skin Testing following Hurricanes.

Science.gov (United States)

Saporta, Diego; Hurst, David

2017-01-01

Objective . To report on changes in sensitivity to mold allergens determined by changes in intradermal skin testing reactivity, after exposure to two severe hurricanes. Methods . A random, retrospective allergy charts review divided into 2 groups of 100 patients each: Group A, patients tested between 2003 and 2010 prior to hurricanes, and Group B, patients tested in 2014 and 2015 following hurricanes. Reactivity to eighteen molds was determined by intradermal skin testing. Test results, age, and respiratory symptoms were recorded. Chi-square test determined reactivity/sensitivity differences between groups. Results . Posthurricane patients had 34.6 times more positive results ( p hurricanes ( p hurricanes ( p hurricanes. This supports climatologists' hypothesis that environmental changes resulting from hurricanes can be a health risk as reflected in increased allergic sensitivities and symptoms and has significant implications for physicians treating patients from affected areas.

Chemically Designed Metallic/Insulating Hybrid Nanostructures with Silver Nanocrystals for Highly Sensitive Wearable Pressure Sensors.

Science.gov (United States)

Kim, Haneun; Lee, Seung-Wook; Joh, Hyungmok; Seong, Mingi; Lee, Woo Seok; Kang, Min Su; Pyo, Jun Beom; Oh, Soong Ju

2018-01-10

With the increase in interest in wearable tactile pressure sensors for e-skin, researches to make nanostructures to achieve high sensitivity have been actively conducted. However, limitations such as complex fabrication processes using expensive equipment still exist. Herein, simple lithography-free techniques to develop pyramid-like metal/insulator hybrid nanostructures utilizing nanocrystals (NCs) are demonstrated. Ligand-exchanged and unexchanged silver NC thin films are used as metallic and insulating components, respectively. The interfaces of each NC layer are chemically engineered to create discontinuous insulating layers, i.e., spacers for improved sensitivity, and eventually to realize fully solution-processed pressure sensors. Device performance analysis with structural, chemical, and electronic characterization and conductive atomic force microscopy study reveals that hybrid nanostructure based pressure sensor shows an enhanced sensitivity of higher than 500 kPa -1 , reliability, and low power consumption with a wide range of pressure sensing. Nano-/micro-hierarchical structures are also designed by combining hybrid nanostructures with conventional microstructures, exhibiting further enhanced sensing range and achieving a record sensitivity of 2.72 × 10 4 kPa -1 . Finally, all-solution-processed pressure sensor arrays with high pixel density, capable of detecting delicate signals with high spatial selectivity much better than the human tactile threshold, are introduced.

Defect-engineered graphene chemical sensors with ultrahigh sensitivity.

Science.gov (United States)

Lee, Geonyeop; Yang, Gwangseok; Cho, Ara; Han, Jeong Woo; Kim, Jihyun

2016-05-25

We report defect-engineered graphene chemical sensors with ultrahigh sensitivity (e.g., 33% improvement in NO2 sensing and 614% improvement in NH3 sensing). A conventional reactive ion etching system was used to introduce the defects in a controlled manner. The sensitivity of graphene-based chemical sensors increased with increasing defect density until the vacancy-dominant region was reached. In addition, the mechanism of gas sensing was systematically investigated via experiments and density functional theory calculations, which indicated that the vacancy defect is a major contributing factor to the enhanced sensitivity. This study revealed that defect engineering in graphene has significant potential for fabricating ultra-sensitive graphene chemical sensors.

Numerical simulation study on rolling-chemical milling process of aluminum-lithium alloy skin panel

Science.gov (United States)

Huang, Z. B.; Sun, Z. G.; Sun, X. F.; Li, X. Q.

2017-09-01

Single curvature parts such as aircraft fuselage skin panels are usually manufactured by rolling-chemical milling process, which is usually faced with the problem of geometric accuracy caused by springback. In most cases, the methods of manual adjustment and multiple roll bending are used to control or eliminate the springback. However, these methods can cause the increase of product cost and cycle, and lead to material performance degradation. Therefore, it is of significance to precisely control the springback of rolling-chemical milling process. In this paper, using the method of experiment and numerical simulation on rolling-chemical milling process, the simulation model for rolling-chemical milling process of 2060-T8 aluminum-lithium alloy skin was established and testified by the comparison between numerical simulation and experiment results for the validity. Then, based on the numerical simulation model, the relative technological parameters which influence on the curvature of the skin panel were analyzed. Finally, the prediction of springback and the compensation can be realized by controlling the process parameters.

Predicting skin permeability from complex chemical mixtures

International Nuclear Information System (INIS)

Riviere, Jim E.; Brooks, James D.

2005-01-01

Occupational and environmental exposure to topical chemicals is usually in the form of complex chemical mixtures, yet risk assessment is based on experimentally derived data from individual chemical exposures from a single, usually aqueous vehicle, or from computed physiochemical properties. We present an approach using hybrid quantitative structure permeation relationships (QSPeR) models where absorption through porcine skin flow-through diffusion cells is well predicted using a QSPeR model describing the individual penetrants, coupled with a mixture factor (MF) that accounts for physicochemical properties of the vehicle/mixture components. The baseline equation is log k p = c + mMF + aΣα 2 H + bΣβ 2 H + sπ 2 H + rR 2 + vV x where Σα 2 H is the hydrogen-bond donor acidity, Σβ 2 H is the hydrogen-bond acceptor basicity, π 2 H is the dipolarity/polarizability, R 2 represents the excess molar refractivity, and V x is the McGowan volume of the penetrants of interest; c, m, a, b, s, r, and v are strength coefficients coupling these descriptors to skin permeability (k p ) of 12 penetrants (atrazine, chlorpyrifos, ethylparathion, fenthion, methylparathion, nonylphenol, ρ-nitrophenol, pentachlorophenol, phenol, propazine, simazine, and triazine) in 24 mixtures. Mixtures consisted of full factorial combinations of vehicles (water, ethanol, propylene glycol) and additives (sodium lauryl sulfate, methyl nicotinate). An additional set of 4 penetrants (DEET, SDS, permethrin, ricinoleic acid) in different mixtures were included to assess applicability of this approach. This resulted in a dataset of 16 compounds administered in 344 treatment combinations. Across all exposures with no MF, R 2 for absorption was 0.62. With the MF, correlations increased up to 0.78. Parameters correlated to the MF include refractive index, polarizability and log (1/Henry's Law Constant) of the mixture components. These factors should not be considered final as the focus of these studies

Keratinocyte gene expression profiles discriminate sensitizing and irritating compounds

NARCIS (Netherlands)

Briel, R.J. van de; Pennings, J.L.A.; Baken, K.A.; Pronk, T.E.; Boorsma, A.; Gottschalk, R.; Loveren, H. van

2010-01-01

Many chemicals can induce allergic contact dermatitis. Because evaluation of skin sensitizing potential by animal testing is prohibited for cosmetics, and screening of many chemicals is required within Registration, Evaluation, Authorisation and Restriction of Chemicals, urgent need exists for

Gene expression profiles in auricle skin as a possible additional endpoint for determination of sensitizers: A multi-endpoint evaluation of the local lymph node assay.

Science.gov (United States)

Tsuchiyama, Hiromi; Maeda, Akihisa; Nakajima, Mayumi; Kitsukawa, Mika; Takahashi, Kei; Miyoshi, Tomoya; Mutsuga, Mayu; Asaoka, Yoshiji; Miyamoto, Yohei; Oshida, Keiyu

2017-10-05

The murine local lymph node assay (LLNA) is widely used to test chemicals to induce skin sensitization. Exposure of mouse auricle skin to a sensitizer results in proliferation of local lymph node T cells, which has been measured by in vivo incorporation of H 3 -methyl thymidine or 5-bromo-2'-deoxyuridine (BrdU). The stimulation index (SI), the ratio of the mean proliferation in each treated group to that in the concurrent vehicle control group, is frequently used as a regulatory-authorized endpoint for LLNA. However, some non-sensitizing irritants, such as sodium dodecyl sulfate (SDS) or methyl salicylate (MS), have been reported as false-positives by this endpoint. In search of a potential endpoint to enhance the specificity of existing endpoints, we evaluated 3 contact sensitizers; (hexyl cinnamic aldehyde [HCA], oxazolone [OXA], and 2,4-dinitrochlorobenzene [DNCB]), 1 respiratory sensitizer (toluene 2,4-diisocyanate [TDI]), and 2 non-sensitizing irritants (MS and SDS) by several endpoints in LLNA. Each test substance was applied to both ears of female CBA/Ca mice daily for 3 consecutive days. The ears and auricle lymph node cells were analyzed on day 5 for endpoints including the SI value, lymph node cell count, cytokine release from lymph node cells, and histopathological changes and gene expression profiles in auricle skin. The SI values indicated that all the test substances induced significant proliferation of lymph node cells. The lymph node cell counts showed no significant changes by the non-sensitizers assessed. The inflammatory findings of histopathology were similar among the auricle skins treated by sensitizers and irritants. Gene expression profiles of cytokines IFN-γ, IL-4, and IL-17 in auricle skin were similar to the cytokine release profiles in draining lymph node cells. In addition, the gene expression of the chemokine CXCL1 and/or CXCL2 showed that it has the potential to discriminate sensitizers and non-sensitizing irritants. Our results

Chemical profiling and cytotoxicity assay of bufadienolides in toad venom and toad skin.

Science.gov (United States)

Meng, Qiong; Yau, Lee-Fong; Lu, Jing-Guang; Wu, Zhen-Zhen; Zhang, Bao-Xian; Wang, Jing-Rong; Jiang, Zhi-Hong

2016-07-01

Toad venom and toad skin have been widely used for treating various cancers in China. Bufadienolides are regarded as the main anticancer components of toad venom, but the difference on composition and anticancer activities of bufadienolides between toad venom and toad skin remains unclear. Fractions enriched with free and conjugated bufadienolides were prepared from toad venom and toad skin. Bufadienolides in each fraction were comprehensively profiled by using a versatile UHPLC-TOF-MS method. Relative contents of major bufadienolides were determined by using three bufogenins and one bufotoxin as marker compounds with validated UHPLC-TOF-MS method. Furthermore, cytotoxicity of the fractions was examined by MTT assay. Two fractions, i.e., bufogenin and bufotoxin fractions (TV-F and TV-C) were isolated from toad venom, and one bufotoxin fraction (TS-C) was isolated from toad skin. Totally 56 bufadienolides in these three fractions were identified, and 29 were quantified or semi-quantified. Bufotoxins were identified in both toad venom and toad skin, whereas bufogenins exist only in toad venom. Bufalin-3-conjugated bufotoxins are major components in toad venom, whereas cinobufotalin and cinobufagin-3-conjugated bufotoxins are main bufotoxins in toad skin. MTT assay revealed potent cytotoxicity of all the fractions in an order of TV-F>TV-C>TS-C. Our study represents the most comprehensive investigation on the chemical profiles of toad venom and toad skin from both qualitative and quantitative aspects. Eight bufotoxins were identified in toad skin responsible for the cytotoxicity for the first time. Our research provides valuable chemical evidence for the appropriate processing method, quality control and rational exploration of toad skin and toad venom for the development of anticancer medicines. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Sensitive skin at menopause; dew point and electrometric properties of the stratum corneum.

Science.gov (United States)

Paquet, F; Piérard-Franchimont, C; Fumal, I; Goffin, V; Paye, M; Piérard, G E

1998-01-12

A number of menopausal women experience skin sensitive to various environmental threats. Two panels of 15 menopausal women on or without HRT were compared. We studied the response of their stratum corneum to variations in environmental humidity, either in air or in response to an emollient. Environment dew point and electrometric measurements on the skin were recorded to search for correlations. Data show that the baseline stratum corneum hydration is influenced by the dew point. HRT improves the barrier function of the skin. The use of emollient further extends the improvement in the functional properties of skin in menopausal women. Both HRT and an emollient can counteract in part some of the deleterious effects of cold and dry weather.

Assessment of skin sensitization under REACH: A case report on vehicle choice in the LLNA and its crucial role preventing false positive results.

Science.gov (United States)

Watzek, Nico; Berger, Franz; Kolle, Susanne Noreen; Kaufmann, Tanja; Becker, Matthias; van Ravenzwaay, Bennard

2017-04-01

In the EU, chemicals with a production or import volume in quantities of one metric ton per year or more have to be tested for skin sensitizing properties under the REACH regulation. The murine Local Lymph Node Assay (LLNA) and its modifications are widely used to fulfil the data requirement, as it is currently considered the first-choice method for in vivo testing to cover this endpoint. This manuscript describes a case study highlighting the importance of understanding the chemistry of the test material during testing for 'skin sensitization' of MCDA (mixture of 2,4- and 2,6-diamino-methylcyclohexane) with particular focus on the vehicle used. While the BrdU-ELISA modification of the LLNA using acetone/olive oil (AOO) as vehicle revealed expectable positive results. However, the concentration control analysis unexpectedly revealed an instability of MCDA in the vehicle AOO. Further studies on the reactivity showed MCDA to rapidly react with AOO under formation of various imine structures, which might have caused the positive LLNA result. The repetition of the LLNA using propylene glycol (PG) as vehicle did not confirm the positive results of the LLNA using AOO. Finally, a classification of MCDA as skin sensitizer according to the Globally Harmonized System (GHS) was not justified. Copyright © 2017 Elsevier Inc. All rights reserved.

Pyridoxylamine reactivity kinetics as an amine based nucleophile for screening electrophilic dermal sensitizers

Science.gov (United States)

Chipinda, Itai; Mbiya, Wilbes; Adigun, Risikat Ajibola; Morakinyo, Moshood K.; Law, Brandon F.; Simoyi, Reuben H.; Siegel, Paul D.

2015-01-01

Chemical allergens bind directly, or after metabolic or abiotic activation, to endogenous proteins to become allergenic. Assessment of this initial binding has been suggested as a target for development of assays to screen chemicals for their allergenic potential. Recently we reported a nitrobenzenethiol (NBT) based method for screening thiol reactive skin sensitizers, however, amine selective sensitizers are not detected by this assay. In the present study we describe an amine (pyridoxylamine (PDA)) based kinetic assay to complement the NBT assay for identification of amine-selective and non-selective skin sensitizers. UV-Vis spectrophotometry and fluorescence were used to measure PDA reactivity for 57 chemicals including anhydrides, aldehydes, and quinones where reaction rates ranged from 116 to 6.2 × 10−6 M−1 s−1 for extreme to weak sensitizers, respectively. No reactivity towards PDA was observed with the thiol-selective sensitizers, non-sensitizers and prohaptens. The PDA rate constants correlated significantly with their respective murine local lymph node assay (LLNA) threshold EC3 values (R2 = 0.76). The use of PDA serves as a simple, inexpensive amine based method that shows promise as a preliminary screening tool for electrophilic, amine-selective skin sensitizers. PMID:24333919

Sensory irritation and multiple chemical sensitivity.

Science.gov (United States)

Anderson, R C; Anderson, J H

1999-01-01

Many of the symptoms described in Sick Building Syndrome (SBS) and multiple chemical sensitivity (MCS) resemble the symptoms known to be elicited by airborne irritant chemicals. Irritation of the eye, nose, and throat is common to SBS, MCS, and sensory irritation (SI). Difficulty of breathing is often seen with SBS, MCS, and pulmonary irritation (PI). We therefore asked the question: can indoor air pollutants cause SI and/or PI? In laboratory testing in which mice breathed the dilute volatile emissions of air fresheners, fabric softeners, colognes, and mattresses for 1 h, we measured various combinations of SI and PI as well as airflow decreases (analogous to asthma attacks). Air samples taken from sites associated with repeated human complaints of poor air quality also caused SI, PI, and airflow limitation (AFL) in the mice. In previous publications, we have documented numerous behavior changes in mice (which we formally studied with a functional observational battery) after exposure to product emissions or complaint site air; neurological complaints are a prominent part of SBS and MCS. All together, these data suggest that many symptoms of SBS and MCS can be described as SI, PI, AFL, and neurotoxicity. All these problems can be caused by airborne irritant chemicals such as those emitted by common commercial products and found in polluted indoor air. With some chemical mixtures (e.g., emissions of some fabric softeners, disposable diapers, and vinyl mattress covers) but not others (e.g., emissions of a solid air freshener), the SI response became larger (2- to 4-fold) when we administered a series of two or three 1-h exposures over a 24-h period. Since with each exposure the intensity of the stimulus was constant yet the magnitude of the response increased, we concluded that there was a change in the sensitivity of the mice to these chemicals. The response was not a generalized stress response because it occurred with only some mixtures of irritants and not others

Skin exposure to isocyanates: reasons for concern.

Science.gov (United States)

Bello, Dhimiter; Herrick, Christina A; Smith, Thomas J; Woskie, Susan R; Streicher, Robert P; Cullen, Mark R; Liu, Youcheng; Redlich, Carrie A

2007-03-01

Isocyanates (di- and poly-), important chemicals used worldwide to produce polyurethane products, are a leading cause of occupational asthma. Respiratory exposures have been reduced through improved hygiene controls and the use of less-volatile isocyanates. Yet isocyanate asthma continues to occur, not uncommonly in settings with minimal inhalation exposure but opportunity for skin exposure. In this review we evaluate the potential role of skin exposure in the development of isocyanate asthma. We reviewed the published animal and human literature on isocyanate skin-exposure methods, workplace skin exposure, skin absorption, and the role of skin exposure in isocyanate sensitization and asthma. We selected relevant articles from computerized searches on Medline, U.S. Environmental Protection Agency, Occupational Safety and Health Administration, National Institute for Occupational Safety and Health, and Google databases using the keywords "isocyanate," "asthma," "skin," "sensitization," and other synonymous terms, and our own extensive collection of isocyanate publications. Isocyanate production and use continues to increase as the polyurethane industry expands. There is substantial opportunity for isocyanate skin exposure in many work settings, but such exposure is challenging to quantify and continues to be underappreciated. Isocyanate skin exposure can occur at work, even with the use of personal protective equipment, and may also occur with consumer use of certain isocyanate products. In animals, isocyanate skin exposure is an efficient route to induce sensitization, with subsequent inhalation challenge resulting in asthma-like responses. Several lines of evidence support a similar role for human isocyanate skin exposure, namely, that such exposure occurs and can contribute to the development of isocyanate asthma in certain settings, presumably by inducing systemic sensitization. Integrated animal and human research is needed to better understand the role of skin

Evaluation of a Silicone Membrane as an Alternative to Human Skin for Determining Skin Permeation Parameters of Chemical Compounds.

Science.gov (United States)

Uchida, Takashi; Yakumaru, Masafumi; Nishioka, Keisuke; Higashi, Yoshihiro; Sano, Tomohiko; Todo, Hiroaki; Sugibayashi, Kenji

2016-01-01

We evaluated the effectiveness of a silicone membrane as an alternative to human skin using the skin permeation parameters of chemical compounds. An in vitro permeation study using 15 model compounds was conducted, and permeation parameters comprising permeability coefficient (P), diffusion parameter (DL(-2)), and partition parameter (KL) were calculated from each permeation profile. Significant correlations were obtained in log P, log DL(-2), and log KL values between the silicone membrane and human skin. DL(-2) values of model compounds, except flurbiprofen, in the silicone membrane were independent of the lipophilicity of the model compounds and were 100-fold higher than those in human skin. For antipyrine and caffeine, which are hydrophilic, KL values in the silicone membrane were 100-fold lower than those in human skin, and P values, calculated as the product of a DL(-2) and KL, were similar. For lipophilic compounds, such as n-butyl paraben and flurbiprofen, KL values for silicone were similar to or 10-fold higher than those in human skin, and P values for silicone were 100-fold higher than those in human skin. Furthermore, for amphiphilic compounds with log Ko/w values from 0.5 to 3.5, KL values in the silicone membrane were 10-fold lower than those in human skin, and P values for silicone were 10-fold higher than those in human skin. The silicone membrane was useful as a human skin alternative in an in vitro skin permeation study. However, depending on the lipophilicity of the model compounds, some parameters may be over- or underestimated.

LLNA variability: An essential ingredient for a comprehensive assessment of non-animal skin sensitization test methods and strategies.

Science.gov (United States)

Hoffmann, Sebastian

2015-01-01

The development of non-animal skin sensitization test methods and strategies is quickly progressing. Either individually or in combination, the predictive capacity is usually described in comparison to local lymph node assay (LLNA) results. In this process the important lesson from other endpoints, such as skin or eye irritation, to account for variability reference test results - here the LLNA - has not yet been fully acknowledged. In order to provide assessors as well as method and strategy developers with appropriate estimates, we investigated the variability of EC3 values from repeated substance testing using the publicly available NICEATM (NTP Interagency Center for the Evaluation of Alternative Toxicological Methods) LLNA database. Repeat experiments for more than 60 substances were analyzed - once taking the vehicle into account and once combining data over all vehicles. In general, variability was higher when different vehicles were used. In terms of skin sensitization potential, i.e., discriminating sensitizer from non-sensitizers, the false positive rate ranged from 14-20%, while the false negative rate was 4-5%. In terms of skin sensitization potency, the rate to assign a substance to the next higher or next lower potency class was approx.10-15%. In addition, general estimates for EC3 variability are provided that can be used for modelling purposes. With our analysis we stress the importance of considering the LLNA variability in the assessment of skin sensitization test methods and strategies and provide estimates thereof.

A Prototype Lip Balm: Summary of Three Dermatological Studies Demonstrating Safety and Acceptability for Sensitive Skin.

Science.gov (United States)

Nisbet, Stephanie

Data were generated from three studies to assess the tolerability and acceptability of a prototype cosmetic lip balm. Dermatological assessments of topical compatibility (primary and cumulative irritability and sensitization), photoirritant and topical photosensitizer potential, and acceptability for safe use of a prototype cosmetic lip balm on sensitive skin are summarized. In Study 1, the product was applied to the volunteers' backs under a semiocclusive patch followed by patch removal/reapplication over 6 weeks to assess the irritant and allergic potential of the product. Dermatological assessments were performed at the beginning and end of the study or when there was evidence of positivity or adverse event. Study 2 was conducted by applying the product to the volunteers' backs under a semiocclusive patch, followed by patch removal/reapplication and irradiation of the test area with ultraviolet A (UVA) radiation at various intervals over 5 weeks. Dermatological assessments were performed to assess the product's role in the induction of photoirritancy and photosensitization. Clinical and subjective assessments for acceptability were obtained during Study 3 in volunteers with a diagnosis of sensitive skin and those who used the product as per instructions for use during the study period. The data generated from the three studies demonstrated no evidence of primary or cumulative dermal irritation or of dermal sensitization. In addition, no photoirritation potential or photosensitization potential was observed. As assessed by dermatologic monitoring and subject diary entries, the prototype lip balm did not cause irritation or sensitization reactions when used for 28 days in volunteers with a diagnosis of sensitive skin. Based on these findings, the prototype lip balm can be considered suitable for use for people with sensitive skin.

Assessment of Irritation and Sensitization Potential of Eight Baby Skin Care Products.

Science.gov (United States)

Galzote, Carlos; Thomas, Mini; Sachdev, Mukta

2016-10-01

Ethnic differences in skin sensitivity suggest that greater emphasis be focused on understanding a product's effect in diverse populations. The irritation and/or sensitization potential of 8 baby skin care products in Indian adults were evaluated using cumulative irritation tests (CIT) and human repeat insult patch testing (HRIPT) protocols. Healthy males or females aged 18 to 65 years of Indian ethnicity were treated with each of 6 products (cream, hair oil, lotion, body wash, shampoo, and baby soap) using CIT (n = 25) and HRIPT (n = 200). Baby powder and baby oil were evaluated by CIT (n = 25) and HRIPT (n = 107) in separate studies. CITs were conducted over 14 days; HRIPTs were conducted over 10 weeks. In both CIT and HRIPT, most products were considered mild, with no irritation. Baby soap and powder elicited reactions in the HRIPT induction phase, with positive challenge phase reactions (3 subjects), but were affirmed to be nonallergenic in the rechallenge phase. In these studies, 8 baby skin care products were evaluated by both CIT and HRIPT in Indian adults. The results of the studies indicated that all of the tested products were nonallergenic and nonirritating. J Drugs Dermatol. 2016;15(10):1244-1248.

Chemical sensitivity: pathophysiology or pathopsychology?

Science.gov (United States)

Genuis, Stephen J

2013-05-01

Escalating numbers of people throughout the world are presenting to primary care physicians, allergists, and immunologists with myriad clinical symptoms after low-level exposure to assorted everyday chemicals such as smoke, perfumes, air fresheners, paints, glues, and other products. This clinical state is referred to by various diagnostic labels, including multiple chemical sensitivity disorder, environmental intolerance, chemical sensitivity (CS), and sensitivity-related illness, and has been the subject of much controversy within the health care community. The goal of this study was to provide a brief overview of the etiology, pathogenesis, clinical presentation, and management of CS. An evaluation of the medical community's response to this emerging diagnosis was also explored. This review was prepared by assessing available medical and scientific literature from MEDLINE, as well as by reviewing numerous books, toxicology journals, conference proceedings, government publications, and environmental health periodicals. A primary observation, however, is that there is limited scientific literature available on the issue of CS. The format of a traditional integrated review was chosen because such reviews play a pivotal role in scientific research and professional practice in medical issues with limited primary study and uncharted clinical territory. The sensitization state of CS seems to be initiated by a significant toxic exposure, occurring as a 1-time event, or on surpassing a threshold of toxicity after toxicant accrual from repeated lower-level exposures. Once sensitized through a toxicant-induced loss of tolerance, individuals exposed to inciting triggers such as minute amounts of diverse everyday chemicals may experience various clinical and immune sequelae, sometimes involving lymphocyte, antibody, or cytokine responses. Precautionary avoidance of inciting triggers will prevent symptoms, and desensitization immunotherapy or immune suppression may improve

Non-animal assessment of skin sensitization hazard: Is an integrated testing strategy needed, and if so what should be integrated?

Science.gov (United States)

Roberts, David W; Patlewicz, Grace

2018-01-01

There is an expectation that to meet regulatory requirements, and avoid or minimize animal testing, integrated approaches to testing and assessment will be needed that rely on assays representing key events (KEs) in the skin sensitization adverse outcome pathway. Three non-animal assays have been formally validated and regulatory adopted: the direct peptide reactivity assay (DPRA), the KeratinoSens™ assay and the human cell line activation test (h-CLAT). There have been many efforts to develop integrated approaches to testing and assessment with the "two out of three" approach attracting much attention. Here a set of 271 chemicals with mouse, human and non-animal sensitization test data was evaluated to compare the predictive performances of the three individual non-animal assays, their binary combinations and the "two out of three" approach in predicting skin sensitization potential. The most predictive approach was to use both the DPRA and h-CLAT as follows: (1) perform DPRA - if positive, classify as sensitizing, and (2) if negative, perform h-CLAT - a positive outcome denotes a sensitizer, a negative, a non-sensitizer. With this approach, 85% (local lymph node assay) and 93% (human) of non-sensitizer predictions were correct, whereas the "two out of three" approach had 69% (local lymph node assay) and 79% (human) of non-sensitizer predictions correct. The findings are consistent with the argument, supported by published quantitative mechanistic models that only the first KE needs to be modeled. All three assays model this KE to an extent. The value of using more than one assay depends on how the different assays compensate for each other's technical limitations. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Assessment of phototoxicity, skin irritation, and sensitization potential of polystyrene and TiO2 nanoparticles

Science.gov (United States)

Park, Yoon-Hee; Jeong, Sang Hoon; Yi, Sang Min; Hyeok Choi, Byeong; Kim, Yu-Ri; Kim, In-Kyoung; Kim, Meyoung-Kon; Son, Sang Wook

2011-07-01

The human skin equivalent model (HSEM) is well known as an attractive alternative model for evaluation of dermal toxicity. However, only limited data are available on the usefulness of an HSEM for nanotoxicity testing. This study was designed to investigate cutaneous toxicity of polystyrene and TiO2 nanoparticles using cultured keratinocytes, an HSEM, and an animal model. In addition, we also evaluated the skin sensitization potential of nanoparticles using a local lymph node assay with incorporation of BrdU. Findings from the present study indicate that polystyrene and TiO2 nanoparticles do not induce phototoxicity, acute cutaneous irritation, or skin sensitization. Results from evaluation of the HSEMs correspond well with those from animal models. Our findings suggest that the HSEM might be a useful alternative model for evaluation of dermal nanotoxicity.

Assessment of phototoxicity, skin irritation, and sensitization potential of polystyrene and TiO2 nanoparticles

International Nuclear Information System (INIS)

Park, Yoon-Hee; Jeong, Sang Hoon; Yi, Sang Min; Choi, Byeong Hyeok; Son, Sang Wook; Kim, Yu-Ri; Kim, In-Kyoung; Kim, Meyoung-Kon

2011-01-01

The human skin equivalent model (HSEM) is well known as an attractive alternative model for evaluation of dermal toxicity. However, only limited data are available on the usefulness of an HSEM for nanotoxicity testing. This study was designed to investigate cutaneous toxicity of polystyrene and TiO 2 nanoparticles using cultured keratinocytes, an HSEM, and an animal model. In addition, we also evaluated the skin sensitization potential of nanoparticles using a local lymph node assay with incorporation of BrdU. Findings from the present study indicate that polystyrene and TiO 2 nanoparticles do not induce phototoxicity, acute cutaneous irritation, or skin sensitization. Results from evaluation of the HSEMs correspond well with those from animal models. Our findings suggest that the HSEM might be a useful alternative model for evaluation of dermal nanotoxicity.

Reproducibility of the heat/capsaicin skin sensitization model in healthy volunteers

Directory of Open Access Journals (Sweden)

Cavallone LF

2013-11-01

Full Text Available Laura F Cavallone,1 Karen Frey,1 Michael C Montana,1 Jeremy Joyal,1 Karen J Regina,1 Karin L Petersen,2 Robert W Gereau IV11Department of Anesthesiology, Washington University in St Louis, School of Medicine, St Louis, MO, USA; 2California Pacific Medical Center Research Institute, San Francisco, CA, USAIntroduction: Heat/capsaicin skin sensitization is a well-characterized human experimental model to induce hyperalgesia and allodynia. Using this model, gabapentin, among other drugs, was shown to significantly reduce cutaneous hyperalgesia compared to placebo. Since the larger thermal probes used in the original studies to produce heat sensitization are now commercially unavailable, we decided to assess whether previous findings could be replicated with a currently available smaller probe (heated area 9 cm2 versus 12.5–15.7 cm2.Study design and methods: After Institutional Review Board approval, 15 adult healthy volunteers participated in two study sessions, scheduled 1 week apart (Part A. In both sessions, subjects were exposed to the heat/capsaicin cutaneous sensitization model. Areas of hypersensitivity to brush stroke and von Frey (VF filament stimulation were measured at baseline and after rekindling of skin sensitization. Another group of 15 volunteers was exposed to an identical schedule and set of sensitization procedures, but, in each session, received either gabapentin or placebo (Part B.Results: Unlike previous reports, a similar reduction of areas of hyperalgesia was observed in all groups/sessions. Fading of areas of hyperalgesia over time was observed in Part A. In Part B, there was no difference in area reduction after gabapentin compared to placebo.Conclusion: When using smaller thermal probes than originally proposed, modifications of other parameters of sensitization and/or rekindling process may be needed to allow the heat/capsaicin sensitization protocol to be used as initially intended. Standardization and validation of

Calculating the dermal flux of chemicals with OELs based on their molecular structure: An attempt to assign the skin notation.

Science.gov (United States)

Kupczewska-Dobecka, Małgorzata; Jakubowski, Marek; Czerczak, Sławomir

2010-09-01

Our objectives included calculating the permeability coefficient and dermal penetration rates (flux value) for 112 chemicals with occupational exposure limits (OELs) according to the LFER (linear free-energy relationship) model developed using published methods. We also attempted to assign skin notations based on each chemical's molecular structure. There are many studies available where formulae for coefficients of permeability from saturated aqueous solutions (K(p)) have been related to physicochemical characteristics of chemicals. The LFER model is based on the solvation equation, which contains five main descriptors predicted from chemical structure: solute excess molar refractivity, dipolarity/polarisability, summation hydrogen bond acidity and basicity, and the McGowan characteristic volume. Descriptor values, available for about 5000 compounds in the Pharma Algorithms Database were used to calculate permeability coefficients. Dermal penetration rate was estimated as a ratio of permeability coefficient and concentration of chemical in saturated aqueous solution. Finally, estimated dermal penetration rates were used to assign the skin notation to chemicals. Defined critical fluxes defined from the literature were recommended as reference values for skin notation. The application of Abraham descriptors predicted from chemical structure and LFER analysis in calculation of permeability coefficients and flux values for chemicals with OELs was successful. Comparison of calculated K(p) values with data obtained earlier from other models showed that LFER predictions were comparable to those obtained by some previously published models, but the differences were much more significant for others. It seems reasonable to conclude that skin should not be characterised as a simple lipophilic barrier alone. Both lipophilic and polar pathways of permeation exist across the stratum corneum. It is feasible to predict skin notation on the basis of the LFER and other published

National Prevalence and Effects of Multiple Chemical Sensitivities.

Science.gov (United States)

Steinemann, Anne

2018-03-01

The aim of this study was to assess the prevalence of multiple chemical sensitivities (MCS), its co-occurrence with asthma and fragrance sensitivity, and effects from exposure to fragranced consumer products. A nationally representative cross-sectional population-based sample of adult Americans (n = 1137) was surveyed in June 2016. Among the population, 12.8% report medically diagnosed MCS and 25.9% report chemical sensitivity. Of those with MCS, 86.2% experience health problems, such as migraine headaches, when exposed to fragranced consumer products; 71.0% are asthmatic; 70.3% cannot access places that use fragranced products such as air fresheners; and 60.7% lost workdays or a job in the past year due to fragranced products in the workplace. Prevalence of diagnosed MCS has increased over 300%, and self-reported chemical sensitivity over 200%, in the past decade. Reducing exposure to fragranced products could help reduce adverse health and societal effects.

Skin Barrier Function and Allergens

DEFF Research Database (Denmark)

Engebretsen, Kristiane Aasen; Thyssen, Jacob Pontoppidan

2016-01-01

The skin is an important barrier protecting us from mechanical insults, microorganisms, chemicals and allergens, but, importantly, also reducing water loss. A common hallmark for many dermatoses is a compromised skin barrier function, and one could suspect an elevated risk of contact sensitization...... and skin barrier status. Psoriasis has traditionally been regarded a Th1-dominated disease, but the discovery of Th17 cells and IL-17 provides new and interesting information regarding the pathogenesis of the disease. Research suggests an inverse relationship between psoriasis and CA, possibly due......) and Th2 (AD) have been proposed as an explanation. Finally, there is convincing evidence that exposure to irritants increases the risk of CS, and patients with ICD are, therefore, at great risk of developing CA. Skin irritation leads to the release of IL-1 and TNF-α, which affects the function of antigen...

Physicochemical properties of pH-sensitive hydrogels based on hydroxyethyl cellulose-hyaluronic acid and for applications as transdermal delivery systems for skin lesions.

Science.gov (United States)

Kwon, Soon Sik; Kong, Bong Ju; Park, Soo Nam

2015-05-01

We investigated the physicochemical properties of pH-sensitive hydroxyethyl cellulose (HEC)/hyaluronic acid (HA) complex hydrogels containing isoliquiritigenin (ILTG), and discussed potential applications as transdermal delivery systems for the treatment of skin lesions caused by pH imbalance. HA has skin compatibility and pH functional groups and HEC serves as scaffold to build hydrogels with varied HCE:HA mass ratio. Hydrogels were synthesized via chemical cross-linking, and three-dimensional network structures were characterized via scanning electron microscopy (SEM). The swelling properties and polymer ratios of the hydrogels were investigated at pH values in the range 1-13. HECHA13 (i.e., an HEC:HA mass ratio of 1:3) was found to have optimal rheological and adhesive properties, and was used to investigate the drug release efficiency as a function of pH; the efficiency was greater than 70% at pH 7. Antimicrobial activity assays against Propionibacterium acnes were conducted to take advantage of the pH-sensitive properties of HECHA13. At pH 7, we found that HECHA13, which contained ILTG, inhibited the growth of P. acnes. Furthermore, HECHA13 was found to exhibit excellent permeability into the skin, which penetrated mostly via the hair follicle. These results indicate that this pH-sensitive hydrogel is effective as a transdermal delivery system for antimicrobial therapeutics, with potential applications in the treatment of acne. Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical applicability domain of the Local Lymph Node Assay (LLNA) for skin sensitisation potency. Part 3. Apparent discrepancies between LLNA and GPMT sensitisation potential: False positives or differences in sensitivity?

Science.gov (United States)

Roberts, David W; Schultz, Terry W; Api, Anne Marie

2016-10-01

The Local Lymph Node Assay (LLNA) is the gold standard regulatory toxicology test for skin sensitisation along with the guinea pig maximisation test (GPMT). Compared with the GPMT, LLNA uses fewer animals, it is quantitative, and it gives a numerical prediction of potency. However several concerns have been raised with this assay, mainly related to false positives and false negatives. Over the years, many authors, including the developers of the assay, have presented cases where there have been discrepancies between the GMPT and LLNA results. Several theories have been put forward for these discrepancies, the main one being the "over-sensitivity" of the GPMT. This paper analyses the data from a systematic study, published in three papers from 2008 to 2011, covering several classes of chemicals, in particular unsaturated fatty acids, sugar surfactants and ethoxylated alcohols, with many cases of chemicals testing positive in the LLNA being negative in the GPMT. Based on consideration of reaction chemistry and structural alerts, it is concluded that these discrepancies are not LLNA false positives, but can be rationalised in terms of the different protocols of the assays. Copyright © 2016 Elsevier Inc. All rights reserved.

Skin Bleaching and Dermatologic Health of African and Afro-Caribbean Populations in the US: New Directions for Methodologically Rigorous, Multidisciplinary, and Culturally Sensitive Research.

Science.gov (United States)

Benn, Emma K T; Alexis, Andrew; Mohamed, Nihal; Wang, Yan-Hong; Khan, Ikhlas A; Liu, Bian

2016-12-01

Skin-bleaching practices, such as using skin creams and soaps to achieve a lighter skin tone, are common throughout the world and are triggered by cosmetic reasons that oftentimes have deep historical, economic, sociocultural, and psychosocial roots. Exposure to chemicals in the bleaching products, notably, mercury (Hg), hydroquinone, and steroids, has been associated with a variety of adverse health effects, such as Hg poisoning and exogenous ochronosis. In New York City (NYC), skin care product use has been identified as an important route of Hg exposure, especially among Caribbean-born blacks and Dominicans. However, surprisingly sparse information is available on the epidemiology of the health impacts of skin-bleaching practices among these populations. We highlight the dearth of large-scale, comprehensive, community-based, clinical, and translational research in this area, especially the limited skin-bleaching-related research among non-White populations in the US. We offer five new research directions, including investigating the known and under-studied health consequences among populations for which the skin bleach practice is newly emerging at an alarming rate using innovative laboratory and statistical methods. We call for conducting methodologically rigorous, multidisciplinary, and culturally sensitive research in order to provide insights into the root and the epidemiological status of the practice and provide evidence of exposure-outcome associations, with an ultimate goal of developing potential intervention strategies to reduce the health burdens of skin-bleaching practice.

The respiratory allergen glutaraldehyde in the local lymph node assay: Sensitization by skin exposure, but not by inhalation

International Nuclear Information System (INIS)

Triel, Jos J. van; Bree, Bianca W.J. van; Roberts, David W.; Muijser, Hans; Duistermaat, Evert; Woutersen, Ruud A.; Kuper, C. Frieke

2011-01-01

Previously, a selection of low molecular weight contact and respiratory allergens had tested positive in both a skin and a respiratory local lymph node assay (LLNA), but formaldehyde was negative for sensitization by inhalation. To investigate whether this was due to intrinsic properties of aldehyde sensitizers, the structurally related allergen glutaraldehyde (GA) was tested. BALB/c mice were exposed by inhalation to 6 or 18 ppm GA (respiratory LLNA), both generated as a vapor and as an aerosol. Other groups received 0.25% or 2.5% GA on the skin of the ears (skin LLNA). Lymphocyte proliferation and cytokine production were measured in the draining lymph nodes. GA was positive in the skin LLNA and its cytokine profile (IL-4/IFN-γ) skewed towards a Th2-type immune response with increasing dose. Inhalation exposure did not result in increased lymphocyte proliferation or increased cytokine levels, despite comparable tissue damage (irritation) in the skin and respiratory tract. We hypothesize that the highly reactive and hydrophilic GA oligomerizes in the protein-rich mucous layer of the respiratory tract, which impedes sensitization but still facilitates local irritation. Within the context of risk assessment in respiratory allergy, our results stress the importance of prevention of skin - besides inhalation - exposure to aldehydes like GA.

Expression of surface markers on the human monocytic leukaemia cell line, THP-1, as indicators for the sensitizing potential of chemicals.

Science.gov (United States)

An, Susun; Kim, Seoyoung; Huh, Yong; Lee, Tae Ryong; Kim, Han-Kon; Park, Kui-Lea; Eun, Hee Chul

2009-04-01

Evaluation of skin sensitization potential is an important part of the safety assessment of cosmetic ingredients and topical drugs. Recently, evaluation of changes in surface marker expression induced in dendritic cells (DC) or DC surrogate cell lines following exposure to chemicals represents one approach for in vitro test methods. The study aimed to test the change of expression patterns of surface markers on THP-1 cells by chemicals as a predictive in vitro method for contact sensitization. We investigated the expression of CD54, CD86, CD83, CD80, and CD40 after a 1-day exposure to sensitizers (1-chloro-2,4-dinitrobenzene; 2,4-dinitrofluorobenzene; benzocaine; 5-chloro-2-methyl-4-isothiazolin-3-one; hexyl cinnamic aldehyde; eugenol; nickel sulfate hexahydrate; potassium dichromate; cobalt sulfate; 2-mercaptobenzothiazole; and ammonium tetrachloroplatinate) and non-sensitizers (sodium lauryl sulfate, benzalkonium chloride, lactic acid, salicylic acid, isopropanol, and dimethyl sulphoxide). The test concentrations were 0.1x, 0.5x, and 1x of the 50% inhibitory concentration, and the relative fluorescence intensity was used as an expression indicator. By evaluating the expression patterns of CD54, CD86, and CD40, we could classify the chemicals as sensitizers or non-sensitizers, but CD80 and CD83 showed non-specific patterns of expression. These data suggest that the THP-1 cells are good model for screening contact sensitizers and CD40 could be a useful marker complementary to CD54 and CD86.

Validation of the 3D Skin Comet assay using full thickness skin models: Transferability and reproducibility.

Science.gov (United States)

Reisinger, Kerstin; Blatz, Veronika; Brinkmann, Joep; Downs, Thomas R; Fischer, Anja; Henkler, Frank; Hoffmann, Sebastian; Krul, Cyrille; Liebsch, Manfred; Luch, Andreas; Pirow, Ralph; Reus, Astrid A; Schulz, Markus; Pfuhler, Stefan

2018-03-01

Recently revised OECD Testing Guidelines highlight the importance of considering the first site-of-contact when investigating the genotoxic hazard. Thus far, only in vivo approaches are available to address the dermal route of exposure. The 3D Skin Comet and Reconstructed Skin Micronucleus (RSMN) assays intend to close this gap in the in vitro genotoxicity toolbox by investigating DNA damage after topical application. This represents the most relevant route of exposure for a variety of compounds found in household products, cosmetics, and industrial chemicals. The comet assay methodology is able to detect both chromosomal damage and DNA lesions that may give rise to gene mutations, thereby complementing the RSMN which detects only chromosomal damage. Here, the comet assay was adapted to two reconstructed full thickness human skin models: the EpiDerm™- and Phenion ® Full-Thickness Skin Models. First, tissue-specific protocols for the isolation of single cells and the general comet assay were transferred to European and US-American laboratories. After establishment of the assay, the protocol was then further optimized with appropriate cytotoxicity measurements and the use of aphidicolin, a DNA repair inhibitor, to improve the assay's sensitivity. In the first phase of an ongoing validation study eight chemicals were tested in three laboratories each using the Phenion ® Full-Thickness Skin Model, informing several validation modules. Ultimately, the 3D Skin Comet assay demonstrated a high predictive capacity and good intra- and inter-laboratory reproducibility with four laboratories reaching a 100% predictivity and the fifth yielding 70%. The data are intended to demonstrate the use of the 3D Skin Comet assay as a new in vitro tool for following up on positive findings from the standard in vitro genotoxicity test battery for dermally applied chemicals, ultimately helping to drive the regulatory acceptance of the assay. To expand the database, the validation will

Phthalates in baby skin care products.

Science.gov (United States)

Lampel, Heather P; Jacob, Sharon E

2011-01-01

The systemic toxicity of phthalates has been extensively reported. Although rarely sensitizing, phthalates have been implicated in promoting the development of both atopy and contact dermatitis in animal models. Dermal absorption of phthalates may contribute to overall chemical burden. Infants may be particularly susceptible to chemical exposures. Baby skin care products may be a significant source of phthalate exposure. We measured the phthalate content of 30 skin care products intended for babies and children. Nineteen leave-on and 11 wash-off baby skin care products were analyzed for 17 unique phthalates by an independent laboratory using standard gas chromatographic mass spectrometry. Of 30 products tested, four had phthalate levels above the reporting limit (0.1-0.5 ppm); of these, only one had levels above 1 ppm (44 ppm). There was no statistical significance of phthalate detection in leave-on versus wash-off products (p = .578). The majority (26 of 30) of the baby skin care products analyzed did not have detectable phthalate levels. Four products had detectable phthalate levels. In baby skin care products, levels of the 17 phthalates tested are low overall, but occasional products may contain higher phthalate levels. Monitoring products to ensure safety standards are met may be warranted.

Application of the KeratinoSens™ assay for assessing the skin sensitization potential of agrochemical active ingredients and formulations.

Science.gov (United States)

Settivari, Raja S; Gehen, Sean C; Amado, Ricardo Acosta; Visconti, Nicolo R; Boverhof, Darrell R; Carney, Edward W

2015-07-01

Assessment of skin sensitization potential is an important component of the safety evaluation process for agrochemical products. Recently, non-animal approaches including the KeratinoSens™ assay have been developed for predicting skin sensitization potential. Assessing the utility of the KeratinoSens™ assay for use with multi-component mixtures such as agrochemical formulations has not been previously evaluated and is a significant need. This study was undertaken to evaluate the KeratinoSens™ assay prediction potential for agrochemical formulations. The assay was conducted for 8 agrochemical active ingredients (AIs) including 3 sensitizers (acetochlor, meptyldinocap, triclopyr), 5 non-sensitizers (aminopyralid, clopyralid, florasulam, methoxyfenozide, oxyfluorfen) and 10 formulations for which in vivo sensitization data were available. The KeratinoSens™ correctly predicted the sensitization potential of all the AIs. For agrochemical formulations it was necessary to modify the standard assay procedure whereby the formulation was assumed to have a common molecular weight. The resultant approach correctly predicted the sensitization potential for 3 of 4 sensitizing formulations and all 6 non-sensitizing formulations when compared to in vivo data. Only the meptyldinocap-containing formulation was misclassified, as a result of high cytotoxicity. These results demonstrate the promising utility of the KeratinoSens™ assay for evaluating the skin sensitization potential of agrochemical AIs and formulations. Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical peeling by SA-PEG remodels photo-damaged skin: suppressing p53 expression and normalizing keratinocyte differentiation.

Science.gov (United States)

Dainichi, Teruki; Amano, Satoshi; Matsunaga, Yukiko; Iriyama, Shunsuke; Hirao, Tetsuji; Hariya, Takeshi; Hibino, Toshihiko; Katagiri, Chika; Takahashi, Motoji; Ueda, Setsuko; Furue, Masutaka

2006-02-01

Chemical peeling with salicylic acid in polyethylene glycol vehicle (SA-PEG), which specifically acts on the stratum corneum, suppresses the development of skin tumors in UVB-irradiated hairless mice. To elucidate the mechanism through which chemical peeling with SA-PEG suppresses skin tumor development, the effects of chemical peeling on photodamaged keratinocytes and cornified envelopes (CEs) were evaluated in vivo. Among UVB-irradiated hairless mice, the structural atypia and expression of p53 protein in keratinocytes induced by UVB irradiation were intensely suppressed in the SA-PEG-treated mice 28 days after the start of weekly SA-PEG treatments when compared to that in the control UVB-irradiated mice. Incomplete expression of filaggrin and loricrin in keratinocytes from the control mice was also improved in keratinocytes from the SA-PEG-treated mice. In photo-exposed human facial skin, immature CEs were replaced with mature CEs 4 weeks after treatment with SA-PEG. Restoration of photodamaged stratum corneum by treatment with SA-PEG, which may affect remodeling of the structural environment of the keratinocytes, involved the normalization of keratinocyte differentiation and suppression of skin tumor development. These results suggest that the stratum corneum plays a protective role against carcinogenesis, and provide a novel strategy for the prevention of photo-induced skin tumors.

Non-allergic cutaneous reactions in airborne chemical sensitivity--a population based study.

Science.gov (United States)

Berg, Nikolaj Drimer; Linneberg, Allan; Thyssen, Jacob Pontoppidan; Dirksen, Asger; Elberling, Jesper

2011-06-01

Multiple chemical sensitivity (MCS) is characterised by adverse effects due to exposure to low levels of chemical substances. The aetiology is unknown, but chemical related respiratory symptoms have been found associated with positive patch test. The purpose of this study was to investigate the relationship between cutaneous reactions from patch testing and self-reported severity of chemical sensitivity to common airborne chemicals. A total of 3460 individuals participating in a general health examination, Health 2006, were patch tested with allergens from the European standard series and screened for chemical sensitivity with a standardised questionnaire dividing the participants into four severity groups of chemical sensitivity. Both allergic and non-allergic cutaneous reactions--defined as irritative, follicular, or doubtful allergic reactions--were analysed in relationship with severity of chemical sensitivity. Associations were controlled for the possible confounding effects of sex, age, asthma, eczema, atopic dermatitis, psychological and social factors, and smoking habits. In unadjusted analyses we found associations between allergic and non-allergic cutaneous reactions on patch testing and the two most severe groups of self-reported sensitivity to airborne chemicals. When adjusting for confounding, associations were weakened, and only non-allergic cutaneous reactions were significantly associated with individuals most severely affected by inhalation of airborne chemicals (odds ratio = 2.5, p = 0.006). Our results suggest that individuals with self-reported chemical sensitivity show increased non-allergic cutaneous reactions based on day 2 readings of patch tests. Copyright © 2011 Elsevier GmbH. All rights reserved.

Assessment of phototoxicity, skin irritation, and sensitization potential of polystyrene and TiO{sub 2} nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Park, Yoon-Hee; Jeong, Sang Hoon; Yi, Sang Min; Choi, Byeong Hyeok; Son, Sang Wook [Laboratory of Cell Signaling and Nanomedicine, Department of Dermatology and Division of Brain Korea 21 Project for Biomedical Science, Korea University College of Medicine, Seoul (Korea, Republic of); Kim, Yu-Ri; Kim, In-Kyoung; Kim, Meyoung-Kon [Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul (Korea, Republic of)

2011-07-06

The human skin equivalent model (HSEM) is well known as an attractive alternative model for evaluation of dermal toxicity. However, only limited data are available on the usefulness of an HSEM for nanotoxicity testing. This study was designed to investigate cutaneous toxicity of polystyrene and TiO{sub 2} nanoparticles using cultured keratinocytes, an HSEM, and an animal model. In addition, we also evaluated the skin sensitization potential of nanoparticles using a local lymph node assay with incorporation of BrdU. Findings from the present study indicate that polystyrene and TiO{sub 2} nanoparticles do not induce phototoxicity, acute cutaneous irritation, or skin sensitization. Results from evaluation of the HSEMs correspond well with those from animal models. Our findings suggest that the HSEM might be a useful alternative model for evaluation of dermal nanotoxicity.

The respiratory allergen glutaraldehyde in the local lymph node assay: sensitization by skin exposure, but not by inhalation.

Science.gov (United States)

van Triel, Jos J; van Bree, Bianca W J; Roberts, David W; Muijser, Hans; Duistermaat, Evert; Woutersen, Ruud A; Kuper, C Frieke

2011-01-11

Previously, a selection of low molecular weight contact and respiratory allergens had tested positive in both a skin and a respiratory local lymph node assay (LLNA), but formaldehyde was negative for sensitization by inhalation. To investigate whether this was due to intrinsic properties of aldehyde sensitizers, the structurally related allergen glutaraldehyde (GA) was tested. BALB/c mice were exposed by inhalation to 6 or 18ppm GA (respiratory LLNA), both generated as a vapor and as an aerosol. Other groups received 0.25% or 2.5% GA on the skin of the ears (skin LLNA). Lymphocyte proliferation and cytokine production were measured in the draining lymph nodes. GA was positive in the skin LLNA and its cytokine profile (IL-4/IFN-γ) skewed towards a Th2-type immune response with increasing dose. Inhalation exposure did not result in increased lymphocyte proliferation or increased cytokine levels, despite comparable tissue damage (irritation) in the skin and respiratory tract. We hypothesize that the highly reactive and hydrophilic GA oligomerizes in the protein-rich mucous layer of the respiratory tract, which impedes sensitization but still facilitates local irritation. Within the context of risk assessment in respiratory allergy, our results stress the importance of prevention of skin--besides inhalation-- exposure to aldehydes like GA. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Non-allergic cutaneous reactions in airborne chemical sensitivity--a population based study

DEFF Research Database (Denmark)

Berg, Nikolaj Drimer; Linneberg, Allan; Thyssen, Jacob Pontoppidan

2011-01-01

the relationship between cutaneous reactions from patch testing and self-reported severity of chemical sensitivity to common airborne chemicals. A total of 3460 individuals participating in a general health examination, Health 2006, were patch tested with allergens from the European standard series and screened...... for chemical sensitivity with a standardised questionnaire dividing the participants into four severity groups of chemical sensitivity. Both allergic and non-allergic cutaneous reactions--defined as irritative, follicular, or doubtful allergic reactions--were analysed in relationship with severity of chemical...... most severe groups of self-reported sensitivity to airborne chemicals. When adjusting for confounding, associations were weakened, and only non-allergic cutaneous reactions were significantly associated with individuals most severely affected by inhalation of airborne chemicals (odds ratio = 2.5, p = 0...

Preliminary evaluation of military, commercial and novel skin decontamination products against a chemical warfare agent simulant (methyl salicylate).

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Matar, Hazem; Guerreiro, Antonio; Piletsky, Sergey A; Price, Shirley C; Chilcott, Robert P

2016-01-01

Rapid decontamination is vital to alleviate adverse health effects following dermal exposure to hazardous materials. There is an abundance of materials and products which can be utilised to remove hazardous materials from the skin. In this study, a total of 15 products were evaluated, 10 of which were commercial or military products and five were novel (molecular imprinted) polymers. The efficacies of these products were evaluated against a 10 µl droplet of (14)C-methyl salicylate applied to the surface of porcine skin mounted on static diffusion cells. The current UK military decontaminant (Fuller's earth) performed well, retaining 83% of the dose over 24 h and served as a benchmark to compare with the other test products. The five most effective test products were Fuller's earth (the current UK military decontaminant), Fast-Act® and three novel polymers [based on itaconic acid, 2-trifluoromethylacrylic acid and N,N-methylenebis(acrylamide)]. Five products (medical moist-free wipes, 5% FloraFree™ solution, normal baby wipes, baby wipes for sensitive skin and Diphotérine™) enhanced the dermal absorption of (14)C-methyl salicylate. Further work is required to establish the performance of the most effective products identified in this study against chemical warfare agents.

Food Sensitivity in Children with Acute Urticaria in Skin Prick Test: Single Center Experience

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Hatice Eke Gungor

2015-11-01

Full Text Available Aim: Families of children with acute urticaria often think that there is food allergy in children with urticaria and insist for skin tests. In this study, it was aimed to determine whether skin prick tests are necessary in cases presented with acute urticaria, in whom other causes of acute urticaria are excluded. Material and Method: A test panel involving cow milk, egg white, wheat, hazelnut, peanut, soybean, walnut, sesame, and tuna fish antigens was applied to the children presented with acute urticaria between 1 August 2013 and 1 August 2014, in whom other causes of acute urticaria were excluded and suspected food allergy was reported by parents. Results: Overall, 574 children aged 1-14 years were included to the study. Of the patients, sensitization against at least one food antigen was detected in 22.3% (128/574 of the patients. This rate was found to be 31.9% among those younger than 3 years, while 19.3% in those older than 3 years. Overall, sensitization rates against food allergen in panel were as follows: egg white, 7.3%; wheat, 3.3%; cow milk, 2.7%,; sesame, 2.8%; hazelnut, 2.4%; soybean, 2.3%; peanut, 1.9%, walnut, 1.6%; tuna fish, 1.6%. In general, the history of patients wasn%u2019t compatible with food sensitization detected. Discussion: Sensitization to food allergens is infrequent in children presented with acute urticaria, particularly among those older than 3 years despite expressions of parent and skin prick tests seems to be unnecessary unless strongly suggestive history is present.

Comparative DNA microarray analysis of human monocyte derived dendritic cells and MUTZ-3 cells exposed to the moderate skin sensitizer cinnamaldehyde

International Nuclear Information System (INIS)

Python, Francois; Goebel, Carsten; Aeby, Pierre

2009-01-01

The number of studies involved in the development of in vitro skin sensitization tests has increased since the adoption of the EU 7th amendment to the cosmetics directive proposing to ban animal testing for cosmetic ingredients by 2013. Several studies have recently demonstrated that sensitizers induce a relevant up-regulation of activation markers such as CD86, CD54, IL-8 or IL-1β in human myeloid cell lines (e.g., U937, MUTZ-3, THP-1) or in human peripheral blood monocyte-derived dendritic cells (PBMDCs). The present study aimed at the identification of new dendritic cell activation markers in order to further improve the in vitro evaluation of the sensitizing potential of chemicals. We have compared the gene expression profiles of PBMDCs and the human cell line MUTZ-3 after a 24-h exposure to the moderate sensitizer cinnamaldehyde. A list of 80 genes modulated in both cell types was obtained and a set of candidate marker genes was selected for further analysis. Cells were exposed to selected sensitizers and non-sensitizers for 24 h and gene expression was analyzed by quantitative real-time reverse transcriptase-polymerase chain reaction. Results indicated that PIR, TRIM16 and two Nrf2-regulated genes, CES1 and NQO1, are modulated by most sensitizers. Up-regulation of these genes could also be observed in our recently published DC-activation test with U937 cells. Due to their role in DC activation, these new genes may help to further refine the in vitro approaches for the screening of the sensitizing properties of a chemical.

Stress and skin disease quality of life: the moderating role of anxiety sensitivity social concerns.

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Dixon, L J; Witcraft, S M; McCowan, N K; Brodell, R T

2018-04-01

Stress is an important factor in the onset, exacerbation and reoccurrence of many skin diseases. Little is known about psychological risk factors that affect the association between stress and dermatological conditions. One relevant factor that may modulate this link is anxiety sensitivity (AS) social concerns - the propensity to respond fearfully to anxiety-related sensations (e.g. sweating, flushing) owing to perceived social consequences (e.g. rejection or humiliation). To gain insight into psychological factors affecting skin disease, we examined the moderating role of AS social concerns in the relationship between stress and skin disease quality of life (QoL). Participants [n = 237 (161 female), mean ± SD age 34·18 ± 9·57 years] with active skin disease symptoms were recruited online and completed questionnaires assessing stress, AS social concerns, skin disease QoL and global skin disease symptom severity. AS social concerns moderated the association between stress and skin-related emotional and social functioning in adults with skin disease. Stress was a significant predictor of the impairment associated with skin disease. Stress was linked to skin disease-related emotional and functional impairment associated with skin disease among individuals with high AS social concerns. These results highlight the potential for AS reduction interventions to break the vicious cycle of stress and skin disease symptoms and to improve psychosocial well-being in dermatology patients. © 2017 British Association of Dermatologists.

Skin-Inspired Multifunctional Autonomic-Intrinsic Conductive Self-Healing Hydrogels with Pressure Sensitivity, Stretchability, and 3D Printability.

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Darabi, Mohammad Ali; Khosrozadeh, Ali; Mbeleck, Rene; Liu, Yuqing; Chang, Qiang; Jiang, Junzi; Cai, Jun; Wang, Quan; Luo, Gaoxing; Xing, Malcolm

2017-08-01

The advent of conductive self-healing (CSH) hydrogels, a class of novel materials mimicking human skin, may change the trajectory of the industrial process because of their potential applications in soft robots, biomimetic prostheses, and health-monitoring systems. Here, the development of a mechanically and electrically self-healing hydrogel based on physically and chemically cross-linked networks is reported. The autonomous intrinsic self-healing of the hydrogel is attained through dynamic ionic interactions between carboxylic groups of poly(acrylic acid) and ferric ions. A covalent cross-linking is used to support the mechanical structure of the hydrogel. Establishing a fair balance between the chemical and physical cross-linking networks together with the conductive nanostructure of polypyrrole networks leads to a double network hydrogel with bulk conductivity, mechanical and electrical self-healing properties (100% mechanical recovery in 2 min), ultrastretchability (1500%), and pressure sensitivity. The practical potential of CSH hydrogels is further revealed by their application in human motion detection and their 3D-printing performance. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Environmental issues and work: women with multiple chemical sensitivities.

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Lipson, Juliene G; Doiron, Nathalie

2006-08-01

Multiple chemical sensitivities (MCS) is an acquired condition in which exposure to low levels of chemicals causes symptoms in multiple organ systems. Some 12%-16% of the U.S. population has some level of chemical sensitivity, 80% of whom are women. Attempts to reduce chemical exposures leads to enormous life difficulties at home, school, and workplace. We base our article on an ethnographic study of MCS in the United States and Canada. We describe here themes related to work issues in terms of a general trajectory of becoming sick from work exposures, coping with toxic physical environments and dealing with coworkers and, when unable to continue working, applying for workers' compensation, or disability status, or both.

Probabilistic hazard assessment for skin sensitization potency by dose–response modeling using feature elimination instead of quantitative structure–activity relationships

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McKim, James M.; Hartung, Thomas; Kleensang, Andre; Sá-Rocha, Vanessa

2016-01-01

Supervised learning methods promise to improve integrated testing strategies (ITS), but must be adjusted to handle high dimensionality and dose–response data. ITS approaches are currently fueled by the increasing mechanistic understanding of adverse outcome pathways (AOP) and the development of tests reflecting these mechanisms. Simple approaches to combine skin sensitization data sets, such as weight of evidence, fail due to problems in information redundancy and high dimension-ality. The problem is further amplified when potency information (dose/response) of hazards would be estimated. Skin sensitization currently serves as the foster child for AOP and ITS development, as legislative pressures combined with a very good mechanistic understanding of contact dermatitis have led to test development and relatively large high-quality data sets. We curated such a data set and combined a recursive variable selection algorithm to evaluate the information available through in silico, in chemico and in vitro assays. Chemical similarity alone could not cluster chemicals’ potency, and in vitro models consistently ranked high in recursive feature elimination. This allows reducing the number of tests included in an ITS. Next, we analyzed with a hidden Markov model that takes advantage of an intrinsic inter-relationship among the local lymph node assay classes, i.e. the monotonous connection between local lymph node assay and dose. The dose-informed random forest/hidden Markov model was superior to the dose-naive random forest model on all data sets. Although balanced accuracy improvement may seem small, this obscures the actual improvement in misclassifications as the dose-informed hidden Markov model strongly reduced "false-negatives" (i.e. extreme sensitizers as non-sensitizer) on all data sets. PMID:26046447

An evaluation of selected in silico models for the assessment of skin sensitization potential – performance and practical utility considerations (QSAR conference)

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Skin sensitization remains an important endpoint for consumers, manufacturers and regulators. Although the development of alternative approaches to assess skin sensitization potential has been extremely active over many years, the implication of regulations such as REACH and the ...

Damage and recovery of skin barrier function after glycolic acid chemical peeling and crystal microdermabrasion.

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Song, Ji Youn; Kang, Hyun A; Kim, Mi-Yeon; Park, Young Min; Kim, Hyung Ok

2004-03-01

Superficial chemical peeling and microdermabrasion have become increasingly popular methods for producing facial rejuvenation. However, there are few studies reporting the skin barrier function changes after these procedures. To evaluate objectively the degree of damage visually and the time needed for the skin barrier function to recover after glycolic acid peeling and aluminum oxide crystal microdermabrasion using noninvasive bioengineering methods. Superficial chemical peeling using 30%, 50%, and 70% glycolic acid and aluminum oxide crystal microdermabrasion were used on the volar forearm of 13 healthy women. The skin response was measured by a visual observation and using an evaporimeter, corneometer, and colorimeter before and after peeling at set time intervals. Both glycolic acid peeling and aluminum oxide crystal microdermabrasion induced significant damage to the skin barrier function immediately after the procedure, and the degree of damage was less severe after the aluminum oxide crystal microdermabrasion compared with glycolic acid peeling. The damaged skin barrier function had recovered within 24 hours after both procedures. The degree of erythema induction was less severe after the aluminum oxide crystal microdermabrasion compared with the glycolic acid peeling procedure. The degree of erythema induced after the glycolic acid peeling procedure was not proportional to the peeling solution concentration used. The erythema subsided within 1 day after the aluminum oxide crystal microdermabrasion procedure and within 4 days after the glycolic acid peeling procedure. These results suggest that the skin barrier function is damaged after the glycolic acid peeling and aluminum oxide crystal microdermabrasion procedure but recovers within 1 to 4 days. Therefore, repeating the superficial peeling procedure at 2-week intervals will allow sufficient time for the damaged skin to recover its barrier function.

Assessment of skin barrier function and biochemical changes of ex vivo human skin in response to physical and chemical barrier disruption.

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Döge, Nadine; Avetisyan, Araks; Hadam, Sabrina; Pfannes, Eva Katharina Barbosa; Rancan, Fiorenza; Blume-Peytavi, Ulrike; Vogt, Annika

2017-07-01

Topical dermatotherapy is intended to be used on diseased skin. Novel drug delivery systems even address differences between intact and diseased skin underlining the need for pre-clinical assessment of different states of barrier disruption. Herein, we studied how short-term incubation in culture media compared to incubation in humidified chambers affects human skin barrier function and viability. On both models we assessed different types and intensities of physical and chemical barrier disruption methods with regard to structural integrity, biophysical parameters and cytokine levels. Tissue degeneration and proliferative activity limited the use of tissue cultures to 48h. Viability is better preserved in cultured tissue. Tape-stripping (50×TS) and 4h sodium lauryl sulfate (SLS) pre-treatment were identified as highly reproducible and effective procedures for barrier disruption. Transepidermal water loss (TEWL) values reproducibly increased with the intensity of disruption while sebum content and skin surface pH were of limited value. Interleukin (IL)-6/8 and various chemokines and proteases were increased in tape-stripped skin which was more pronounced in SLS-treated skin tissue extracts. Thus, albeit limited to 48h, cultured full-thickness skin maintained several barrier characteristics and responded to different intensities of barrier disruption. Potentially, these models can be used to assess pre-clinically the efficacy and penetration of anti-inflammatory compounds. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of the performance of the reduced local lymph node assay for skin sensitization testing.

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Ezendam, Janine; Muller, Andre; Hakkert, Betty C; van Loveren, Henk

2013-06-01

The local lymph node assay (LLNA) is the preferred method for classification of sensitizers within REACH. To reduce the number of mice for the identification of sensitizers the reduced LLNA was proposed, which uses only the high dose group of the LLNA. To evaluate the performance of this method for classification, LLNA data from REACH registrations were used and classification based on all dose groups was compared to classification based on the high dose group. We confirmed previous examinations of the reduced LLNA showing that this method is less sensitive compared to the LLNA. The reduced LLNA misclassified 3.3% of the sensitizers identified in the LLNA and misclassification occurred in all potency classes and that there was no clear association with irritant properties. It is therefore not possible to predict beforehand which substances might be misclassified. Another limitation of the reduced LLNA is that skin sensitizing potency cannot be assessed. For these reasons, it is not recommended to use the reduced LLNA as a stand-alone assay for skin sensitization testing within REACH. In the future, the reduced LLNA might be of added value in a weight of evidence approach to confirm negative results obtained with non-animal approaches. Copyright © 2013 Elsevier Inc. All rights reserved.

Screening for skin-sensitizing allergens among patients with clinically suspected allergic contact dermatitis

Directory of Open Access Journals (Sweden)

Zahid Shakoor

2017-09-01

Full Text Available Objectives: To detect common skin-sensitizing agents among patients experiencing allergic contact dermatitis (ACD. Methods: This was a retrospective study of 152 patients with clinically suspected ACD who underwent patch testing in an allergy clinic at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia between January 2012 and February 2015. Of these patients, only 74 (48% patients reacted to one or more contact allergens. This group of patients included 58 (78.4% women and 16 (21.6% men (mean age: 37.8±13.8 years. Patch testing was performed using the thin-layer rapid-use epicutaneous patch test panels. Results: Nickel sulfate was the most common sensitizing agent, with 26 (35.1% patients yielding a positive result; followed by p-phenylenediamine in 17 (22.9%, butyl-tetra-phenol formaldehyde in 12 (16.2%, gold sodium thiosulfate in 10 (13.5%, and thimerosal in 6 (8.1% patients. Nickel reactivity was significantly higher among women (41.4% than among men (12.5% (p less than 0.0001. Similarly, gold reactivity among women (15.5% was also higher than among men (6.2% (p≤0.02. Conclusion: The high level of skin sensitization due to nickel, PPD, and gold in patients with ACD emphasizes the need for measures to decrease exposure to these sensitizing agents.

β-Adrenergic blockade does not impair the skin blood flow sensitivity to local heating in burned and nonburned skin under neutral and hot environments in children.

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Rivas, Eric; McEntire, Serina J; Herndon, David N; Mlcak, Ronald P; Suman, Oscar E

2017-05-01

We tested the hypothesis that propranolol, a drug given to burn patients to reduce hypermetabolism/cardiac stress, may inhibit heat dissipation by changing the sensitivity of skin blood flow (SkBF) to local heating under neutral and hot conditions. In a randomized double-blind study, a placebo was given to eight burned children, while propranolol was given to 13 burned children with similar characteristics (mean±SD: 11.9±3 years, 147±20 cm, 45±23 kg, 56±12% Total body surface area burned). Nonburned children (n=13, 11.4±3 years, 152±15 cm, 52±13 kg) served as healthy controls. A progressive local heating protocol characterized SkBF responses in burned and unburned skin and nonburned control skin under the two environmental conditions (23 and 34°C) via laser Doppler flowmetry. Resting SkBF was greater in burned and unburned skin compared to the nonburned control (main effect: skin, Pburned; 38±36 unburned vs 9±8 control %SkBF max ). No difference was found for maximal SkBF capacity to local heating between groups. Additionally, dose-response curves for the sensitivity of SkBF to local heating were not different among burned or unburned skin, and nonburned control skin (EC 50 , P>.05) under either condition. Therapeutic propranolol does not negatively affect SkBF under neutral or hot environmental conditions and further compromise temperature regulation in burned children. © 2017 John Wiley & Sons Ltd.

Sensitivity and specificity of skin tests in the diagnosis of clarithromycin allergy.

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Mori, Francesca; Barni, Simona; Pucci, Neri; Rossi, Elisabetta; Azzari, Chiara; de Martino, Maurizio; Novembre, Elio

2010-05-01

Clarithromycin is one of the most frequently prescribed oral macrolidic antibiotics in the pediatric population. Suspected adverse reactions to clarithromycin have been frequently described by parents of children examined in pediatric allergy units, but there is a lack of reliable methods available in detecting the presence of specific IgE antibodies. To investigate the prevalence of a clarithromycin allergy in children seen in a pediatric allergy unit using standardized skin tests and oral provocation tests (OPTs). Sixty-four children were referred with a history of a clarithromycin-associated adverse drug reaction. All these children underwent skin tests and OPTs. The nonirritating intradermal skin test concentration for clarithromycin was determined in a control group of 18 children who had tolerated clarithromycin in the previous month. The threshold nonirritating intradermal concentration was established at the 10:2 dilution (0.5 mg/mL). Nine of the 64 children had an immediately positive intradermal response to the 10:2 dilution and only 1 child to the 10:3 dilution (0.05 mg/mL). None had positive skin prick test results or delayed skin responses to intradermal tests. Four of 64 children (6%) with previously described adverse reactions due to clarithromycin intake had a positive OPT reaction. When we correlated the intradermal skin test results to the OPT results, intradermal test sensitivity and specificity were 75% and 90%, respectively. Intradermal tests seem to be useful in allergologic workup in children with suspected clarithromycin hypersensitivity and may help reduce the need for OPTs.

β-adrenergic blockade does not impair the skin blood flow sensitivity to local heating in burned and non-burned skin under neutral and hot environments in children

Science.gov (United States)

Rivas, Eric; McEntire, Serina J.; Herndon, David N.; Mlcak, Ronald P.; Suman, Oscar E.

2017-01-01

Objective Tested the hypothesis that propranolol, a drug given to burn patients to reduce hypermetabolism/cardiac stress, may inhibit heat dissipation by changing the sensitivity of skin blood flow (SkBF) to local heating under neutral and hot conditions. Methods In a randomized double-blind study, a placebo was given to 8 burned children while propranolol was given to 13 burned children with similar characteristics (mean ± SD: 11.9±3y, 147±20cm, 45±23kg, 56±12% TBSA). Non-burned children (n=13, 11.4±3y, 152±15cm, 52±13kg) served as healthy controls. A progressive local heating protocol characterized SkBF responses in burned and unburned skin and non-burned control skin under the two environmental conditions (23°C and 34°C) via laser-Doppler flowmetry. Results Resting SkBF was greater in burned and unburned skin compared to the non-burned control (main effect: skin, Pburned; 38±36 unburned vs 9±8 control %SkBFmax). No difference was found for maximal SkBF capacity to local heating between groups. Additionally, dose response curves for the sensitivity of SkBF to local heating were not different among burned or unburned skin, and non-burned control skin (EC50, P>0.05) under either condition. Conclusion Therapeutic propranolol does not negatively affect SkBF under neutral or hot environmental conditions and further compromise temperature regulation in burned children. PMID:28071840

Evaluation of efficacy of chemical peeling with glycolic acid in hyperpigmentation disorders of the skin

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Supriya P Deshmukh

2012-01-01

Full Text Available Background : Chemical peeling entails application of chemical agents to the skin causing a controlled chemical burn, thereby achieving improved texture and quality of skin. Aim: To evaluate the efficacy of glycolic acid in melasma and other causes of hyperpigmentation. Materials and Methods: A total of 20 patients were included in the study. After adequate priming, application of glycolic acid in various concentrations in biweekly interval for a period of 16 weeks was done. Post-treatment photographs were taken and were subjected to analysis. Results: Melasma constituted 11 patients and hyperpigmentation, ie, post acne marks and freckles due to sun exposure accounted nine patients. Complete resolution of melasma was possible only in one (9% patient and good improvement in four (36.3%, whereas five (45.5% patients showed fair improvement. In cases of hyperpigmentation, three (33% patients showed excellent improvement, one (11% showed good improvement, and five (55.5% patients showed fair improvement. The patients of melasma took an average of 7.33 number of peels to show improvement and those of hyperpigmentation took 4.2 peels. Conclusions: Melasma shows fair to good improvement and requires more number of peels as compared to other causes of hyperpigmentation in skin. Postinflammatory pigmentation shows excellent improvement in the majority of patients.

Potential natural sensitizers extracted from the skin of Canarium odontophyllum fruits for dye-sensitized solar cells

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Lim, Andery; Kumara, N. T. R. N.; Tan, Ai Ling; Mirza, Aminul Huq; Chandrakanthi, R. L. N.; Petra, Mohammad Iskandar; Ming, Lim Chee; Senadeera, G. K. R.; Ekanayake, Piyasiri

2015-03-01

Possibility of use of dye extract from skin samples of a seasonal, indigenous fruit from Borneo, namely Canarium odontophyllum, in dye sensitized solar cells (DSSCs) are explored. Three main groups of flavonoid pigments are detected and these pigments exhibit different UV-vis absorption properties, and hence showing different light harvesting capabilities. When applied in DSSCs. The detected pigment constituents of the extract consist of aurone (maritimein), anthocyanidin (pelargonidin) and anthocyanidin (cyanidin derivatives). When tested in DSSC, the highest conversion efficiency of 1.43% is exhibited by cyanidin derivatives, and this is followed by conversion efficiencies of 0.51% and 0.79% for aurone and pelargonidin, respectively. It is shown that individual pigments, like cyanidin derivatives and pelargonidin, exhibit higher power conversion efficiency when compared to that of C.odontophyllum skin pigment mixture (with a conversion efficiency of only 0.68%). The results indicate a possibility of masking effects of the pigments when used as a mixture. The acidification of C.odontophyllum skin pigments with concentrated hydrochloric acid improves the conversion efficiency of the mixture from 0.68% to 0.99%. The discussion in this paper will draw data and observations from the variation in absorption and adsorption properties, the HOMO-LUMO levels, the energy band gaps and the functional group compositions of the detected flavonoids.

Influence of drying temperature on the chemical constituents of jaboticaba (Plinia Jaboticaba (Vell. Berg skin

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Ana Paula de C. Alves

2014-09-01

Full Text Available Jaboticaba is a fruit native to Brazil. Its skin represents up to 43% of the fruit and contains high levels of fiber, minerals and phenolic compounds. The use of the skin waste adds value to the fruit. However, one of the drawbacks of skin storage is the high water content, which requires drying processes to preserve the skin without leading to the loss of nutrients and antioxidants. The influence of different drying temperatures on the levels of nutrients and antioxidants was investigated. Jaboticaba (Plinia jaboticaba (Vell. Berg, genotype Sabará skins were lyophilized or dried at three temperatures (30, 45, and 60ºC, using food dryers. The skins were then ground, stored (protected from light and subjected to analysis of proximate composition, vitamin C, phytate, polyphenols, anthocyanins and antioxidant activity. The drying process had little effect on the proximate composition of the flour, presenting significant difference only for crude protein, fiber and non-nitrogenous extract. The greatest preservation of chemical constituents occurs in the lyophilized jaboticaba skins. Among the drying temperatures tested, however, the skins dried at 45 and60°C had more highly preserved nutritional substances and antioxidants.

Skin sensitization quantitative risk assessment for occupational exposure of hairdressers to hair dye ingredients.

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Goebel, Carsten; Diepgen, Thomas L; Blömeke, Brunhilde; Gaspari, Anthony A; Schnuch, Axel; Fuchs, Anne; Schlotmann, Kordula; Krasteva, Maya; Kimber, Ian

2018-06-01

Occupational exposure of hairdressers to hair dyes has been associated with the development of allergic contact dermatitis (ACD) involving the hands. p-Phenylenediamine (PPD) and toluene-2,5-diamine (PTD) have been implicated as important occupational contact allergens. To conduct a quantitative risk assessment for the induction of contact sensitization to hair dyes in hairdressers, available data from hand rinsing studies following typical occupational exposure conditions to PPD, PTD and resorcinol were assessed. By accounting for wet work, uneven exposure and inter-individual variability for professionals, daily hand exposure concentrations were derived. Secondly, daily hand exposure was compared with the sensitization induction potency of the individual hair dye defined as the No Expected Sensitization Induction Levels (NESIL). For PPD and PTD hairdresser hand exposure levels were 2.7 and 5.9 fold below the individual NESIL. In contrast, hand exposure to resorcinol was 50 fold below the NESIL. Correspondingly, the risk assessment for PPD and PTD indicates that contact sensitization may occur, when skin protection and skin care are not rigorously applied. We conclude that awareness of health risks associated with occupational exposure to hair dyes, and of the importance of adequate protective measures, should be emphasized more fully during hairdresser education and training. Copyright © 2018 Elsevier Inc. All rights reserved.

Asymptomatic skin sensitization to birch predicts later development of birch pollen allergy in adults

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Bødtger, Uffe; Poulsen, Lars K; Malling, Hans-Jørgen

2003-01-01

= 6) were followed through use of daily diary cards during 3 consecutive birch pollen seasons. At inclusion and at the 3-year follow-up visit, conjunctival and nasal challenges, intradermal late-phase reaction evaluation, and measurement of specific IgE were performed. RESULTS: Asymptomatic sensitized...... a clinical characterization of skin test-positive subjects without symptoms and to ascertain the predictive values of common allergologic tests. METHODS: Asymptomatic adults with positive skin prick test results for birch (n = 15), nonatopic control subjects (n = 25), and birch pollen-allergic patients (n...

Evaluation of selected biomarkers for the detection of chemical sensitization in human skin: a comparative study applying THP-1, MUTZ-3 and primary dendritic cells in culture.

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Hitzler, Manuel; Bergert, Antje; Luch, Andreas; Peiser, Matthias

2013-09-01

Dendritic cells (DCs) exhibit the unique capacity to induce T cell differentiation and proliferation, two processes that are crucially involved in allergic reactions. By combining the exclusive potential of DCs as the only professional antigen-presenting cells of the human body with the well known handling advantages of cell lines, cell-based alternative methods aimed at detecting chemical sensitization in vitro commonly apply DC-like cells derived from myeloid cell lines. Here, we present the new biomarkers programmed death-ligand 1 (PD-L1), DC immunoreceptor (DCIR), IL-16, and neutrophil-activating protein-2 (NAP-2), all of which have been detectable in primary human DCs upon exposure to chemical contact allergens. To evaluate the applicability of DC-like cells in the prediction of a chemical's sensitization potential, the expression of cell surface PD-L1 and DCIR was analyzed. In contrast to primary DCs, only minor subpopulations of MUTZ-3 and THP-1 cells presented PD-L1 or DCIR at their surface. After exposure to increasing concentrations of nickel and cinnamic aldehyde, the expression level of PD-L1 and DCIR revealed much stronger affected on monocyte-derived DCs (MoDCs) or Langerhans cells (MoLCs) when compared to THP-1 and MUTZ-3 cells. Applying protein profiler arrays we further identified the soluble factors NAP-2, IL-16, IL-8 and MIP-1α as sensitive biomarkers showing the capacity to discriminate sensitizing from non-sensitizing chemicals or irritants. An allergen-specific release of IL-8 and MIP-1α could be detected in the supernatants of MoDCs and MoLCs and also in MUTZ-3 and THP-1 cells, though at much lower levels. On the protein and transcriptional level, NAP-2 and IL-16 indicated sensitizers most sensitively and specifically in MoDCs. Altogether, we have proven the reciprocal regulated surface molecules PD-L1 and DCIR and the soluble factors MIP-1α, NAP-2 and IL-16 as reliable biomarkers for chemical sensitization. We further show that primary

Predicting skin sensitization potential and inter-laboratory reproducibility of a human Cell Line Activation Test (h-CLAT) in the European Cosmetics Association (COLIPA) ring trials.

Science.gov (United States)

Sakaguchi, Hitoshi; Ryan, Cindy; Ovigne, Jean-Marc; Schroeder, Klaus R; Ashikaga, Takao

2010-09-01

Regulatory policies in Europe prohibited the testing of cosmetic ingredients in animals for a number of toxicological endpoints. Currently no validated non-animal test methods exist for skin sensitization. Evaluation of changes in cell surface marker expression in dendritic cell (DC)-surrogate cell lines represents one non-animal approach. The human Cell Line Activation Test (h-CLAT) examines the level of CD86 and CD54 expression on the surface of THP-1 cells, a human monocytic leukemia cell line, following 24h of chemical exposure. To examine protocol transferability, between-lab reproducibility, and predictive capacity, the h-CLAT has been evaluated by five independent laboratories in several ring trials (RTs) coordinated by the European Cosmetics Association (COLIPA). The results of the first and second RTs demonstrated that the protocol was transferable and basically had good between-lab reproducibility and predictivity, but there were some false negative data. To improve performance, protocol and prediction model were modified. Using the modified prediction model in the first and second RT, accuracy was improved. However, about 15% of the outcomes were not correctly identified, which exposes some of the limitations of the assay. For the chemicals evaluated, the limitation may due to chemical being a weak allergen or having low solubility (ex. alpha-hexylcinnamaldehyde). The third RT evaluated the modified prediction model and satisfactory results were obtained. From the RT data, the feasibility of utilizing cell lines as surrogate DC in development of in vitro skin sensitization methods shows promise. The data also support initiating formal pre-validation of the h-CLAT in order to fully understand the capabilities and limitations of the assay. Copyright 2010 Elsevier Ltd. All rights reserved.

In vitro methods for hazard assessment of industrial chemicals – opportunities and challenges

Directory of Open Access Journals (Sweden)

Chin Lin eWong

2015-05-01

Full Text Available Allergic contact dermatitis (ACD is a delayed-type hypersensitivity immune reaction mediated by T-lymphocytes as a result of repeated exposure of an allergen primarily on skin. ACD accounts for up to 95% of occupational skin diseases (OSDs, with epoxy resins implicated as one of the most common causes of ACD. Efficient high-throughput in vitro screening for accurate identification of compounds and materials that may pose hazardous risks in the workplace is crucial. At present, the murine local lymph node assay (LLNA is the ‘method of choice’ for predicting the sensitizing potency of contact allergens. As the 3Rs principles of reduction, refinement and replacement in animal testing has gained political and economic momentum, several in vitro screening methods have been developed for identifying potential contact allergens. To date, these latter methods have been utilized primarily to assess the skin sensitizing potential of the chemical components of cosmetic products with scant research attention as to the applicability of these methods to industrial chemicals, particularly epoxy resins. Herein we review the currently utilized in vitro methods and identify the knowledge gaps with regard to assessing the generalizability of in vitro screening methods for assessing the skin sensitizing potential of industrial chemicals.

Polyvalent type IV sensitizations to multiple fragrances and a skin protection cream in a metal worker.

Science.gov (United States)

Tanko, Zita; Shab, Arna; Diepgen, Thomas Ludwig; Weisshaar, Elke

2009-06-01

Fragrances are very common in everyday products. A metalworker with chronic hand eczema and previously diagnosed type IV sensitizations to epoxy resin, balsam of Peru, fragrance mix and fragrance mix II was diagnosed with additional type IV sensitizations to geraniol, hydroxycitronellal, lilial, tree moss, oak moss absolute, citral, citronellol, farnesol, Lyral, fragrance mix II and fragrance mix (with sorbitan sesquioleate). In addition, a type IV sensitization to the skin protection cream containing geraniol and citronellol used at the workplace was detected, and deemed occupationally relevant in this case. The patient could have had contact to fragrances through private use of cosmetics and detergents. On the other hand, the fragrance-containing skin protection cream supports occupational exposure. This case report demonstrates that fragrance contact allergy has to be searched for and clarified individually, which requires a thorough history and a detailed analysis of the work place.

Chemical Characterization of Lipophilic Constituents in the Skin of Migratory Adult Sea Lamprey from the Great Lakes Region.

Directory of Open Access Journals (Sweden)

Amila A Dissanayake

Full Text Available The sea lamprey (Petromzons marinus is an invasive ectoparasite of large-bodied fishes that adversely affects the fishing industry and ecology of the Laurentian Great Lakes. Lipid content in the whole sea lamprey and muscles, liver and kidney of metamorphosing larval stages has been reported. Similarly, the fatty acid profile of the rope tissues of sexually-mature male sea lampreys has also been reported. The average body weight of a sub-adult migratory sea lamprey is 250 g, which includes 14.4% skin (36 g. Our preliminary extraction data of an adult sea lamprey skin revealed that it contained approximately 8.5% of lipophilic compounds. Lamprey skin is home to a naturally aversive compound (an alarm cue that is being developed into a repellent for use in pest management. As part of an ongoing investigation to identify the chemical structure of the sea lamprey alarm cue, we extracted the skin with water and methanol, respectively. The methanolic extract (1.55% contained exclusively lipophilic compounds and did not include the alarm cue. We chemically characterized all compounds present in the methanolic extract as cholesterol esters (CE, tri- and di-glycerides (TG and DG, cholesterol, free fatty acids (FFA and minor amounts of plasticizers. The free fatty acids fraction was composed of saturated (41.8%, monounsaturated (40.7% and polyunsaturated (17.4% fatty acids, respectively. The plasticizers characterized were phthalate and benzoate and found to be 0.95 mg and 2.54 mg, respectively, per adult sea lamprey skin. This is the first report of the chemical characterization of all the lipophilic constituents in the skin of sub-adult migratory sea lamprey. The CEs isolated and characterized from sea lamprey skin are also for the first time.

Decreased active vasodilator sensitivity in aged skin.

Science.gov (United States)

Kenney, W L; Morgan, A L; Farquhar, W B; Brooks, E M; Pierzga, J M; Derr, J A

1997-04-01

Older men and women respond to local and reflex-mediated heat stress with an attenuated increase in cutaneous vascular conductance (CVC). This study was performed to test the hypothesis that an augmented or sustained noradrenergic vasoconstriction (VC) may play a role in this age-related difference. Fifteen young (22 +/- 1 yr) and 15 older (66 +/- 1 yr) men exercised at 50% peak oxygen uptake in a 36 degrees C environment. Skin perfusion was monitored at two sites on the right forearm by laser-Doppler flowmetry: one site pretreated with bretylium tosylate (BT) to block the local release of norepinephrine and thus VC and an adjacent control site. Blockade of reflex VC was verified during whole body cooling using a water-perfused suit. CVC (perfusion divided by mean arterial pressure) at each site was reported as a percentage of the maximal CVC (%CVCmax) induced at the end of each experiment by prolonged local heating at 42 degrees C. Neither age nor BT affected the %CVCmax (75-86%) attained at high core temperatures. During the early rise phase of CVC, the %CVCmax-change in esophageal temperature (delta T(es)) curve was shifted to the right in the older men (effective delta T(es) associated with 50% CVC response for young, 0.22 +/- 0.04 and 0.39 +/- 0.04 degrees C and for older, 0.73 +/- 0.04 and 0.85 +/- 0.04 degrees C at control and BT sites, respectively). BT had no interactive effect on this age difference, suggesting a lack of involvement of the VC system in the attenuated CVC response of individuals over the age of 60 yr. Additionally, increases in skin vascular conductance were quantitatively compared by measuring increases in total forearm vascular conductance (FVC, restricted to the forearm skin under these conditions). After the initial approximately 0.2 degrees C increase in T(es), FVC was 40-50% lower in the older men (P < 0.01) for the remainder of the exercise. Decreased active vasodilator sensitivity to increasing core temperature, coupled with

Comparison of sensitivity of quantiferon-tb gold test and tuberculin skin test in active pulmonary tuberculosis

International Nuclear Information System (INIS)

Khalil, K.F.; Ambreen, A.; Butt, T.

2013-01-01

Objective: To compare the sensitivity of tuberculin skin test (TST) and quantiFERON-TB gold test (QFT-G) in active pulmonary tuberculosis. Study Design: Analytical study. Place and Duration of Study: Department of Pulmonology, Fauji Foundation Hospital, Rawalpindi, from July 2011 to January 2012. Methodology: QuantiFERON-TB gold test (QFT-G) was evaluated and compared it with tuberculin skin test (TST) in 50 cases of active pulmonary tuberculosis, in whom tuberculous infection was suspected on clinical, radiological and microbiological grounds. Sensitivity was determined against positive growth for Mycobacterium tuberculosis. Results: Out of 50 cases, 43 were females and 7 were males. The mean age was 41.84 A+- 19.03 years. Sensitivity of QFT-G was 80% while that of TST was 28%. Conclusion: QFT-G has much higher sensitivity than TST for active pulmonary tuberculosis. It is unaffected by prior BCG administration and prior exposure to atypical mycobacteria. A positive QFT-G result can be an adjunct to diagnosis in patients having clinical and radiological data compatible with pulmonary tuberculosis. (author)

GA(2)LEN skin test study II: clinical relevance of inhalant allergen sensitizations in Europe

DEFF Research Database (Denmark)

Burbach, G J; Heinzerling, L M; Edenharter, G

2009-01-01

BACKGROUND: Skin prick testing is the standard for diagnosing IgE-mediated allergies. A positive skin prick reaction, however, does not always correlate with clinical symptoms. A large database from a Global Asthma and Allergy European Network (GA(2)LEN) study with data on clinical relevance was ...... the clinical relevance of positive skin prick tests and calls for further studies, which may, ultimately, help increase the positive predictive value of allergy testing.......BACKGROUND: Skin prick testing is the standard for diagnosing IgE-mediated allergies. A positive skin prick reaction, however, does not always correlate with clinical symptoms. A large database from a Global Asthma and Allergy European Network (GA(2)LEN) study with data on clinical relevance...... was used to determine the clinical relevance of sensitizations against the 18 most frequent inhalant allergens in Europe. The study population consisted of patients referred to one of the 17 allergy centres in 14 European countries (n = 3034, median age = 33 years). The aim of the study was to assess...

Sensitivity of animals to chemical compounds links to metabolic rate.

NARCIS (Netherlands)

Baas, J.; Kooijman, S.A.L.M.

2015-01-01

Ecotoxicological studies have shown considerable variation in species sensitivity for chemical compounds, but general patterns in sensitivity are still not known. A better understanding of this sensitivity is important in the context of environmental risk assessment but also in a more general

An epidermal equivalent assay for identification and ranking potency of contact sensitizers

NARCIS (Netherlands)

Gibbs, S.; Corsini, E.; Spiekstra, S.W.; Galbiati, V.; Fuchs, H.W.; Degeorge, G.; Troese, M.; Hayden, P.; Deng, W.; Roggen, E.

2013-01-01

The purpose of this study was to explore the possibility of combining the epidermal equivalent (EE) potency assay with the assay which assesses release of interleukin-18 (IL-18) to provide a single test for identification and classification of skin sensitizing chemicals, including chemicals of low

Description and comparative study of physico-chemical parameters of the teleost fish skin mucus.

Science.gov (United States)

Guardiola, Francisco A; Cuartero, María; Del Mar Collado-González, María; Arizcún, Marta; Díaz Baños, F Guillermo; Meseguer, José; Cuesta, Alberto; Esteban, María A

2015-01-01

The study of mucosal surfaces, and in particular the fish skin and its secreted mucus, has been of great interest recently among immunologists. Measurement of the viscosity and other physico-chemical parameters (protein concentration, pH, conductivity, redox potential, osmolality and density) of the skin mucus can help to understand its biological functions. We have used five marine species of teleost: gilthead seabream (Sparus aurata L.), European sea bass (Dicentrarchus labrax L.), shi drum (Umbrina cirrosa L.), common dentex (Dentex dentex L.) and dusky grouper (Epinephelus marginatus L.), all of them with commercial interest in the aquaculture of the Mediterranean area. Mucus showed a direct shear- and temperature-dependent viscosity, with a non-Newtonian behavior, which differed however between two groups: one with higher viscosity (D. labrax, U. cirrosa, D. dentex) and the other with lower viscosity (S. aurata, E. marginatus). In addition, there was a clear interrelation between density and osmolality, as well as between density and temperature. Taking into account that high values of viscosity should improve the barrier effect against pathogens but low values of viscosity are needed for good locomotion characteristics, our results may help elucidate the relationship between physico-chemical and biological parameters of skin mucus, and disease susceptibility.

Inhibition of Neoplastic Transformation and Chemically-Induced Skin Hyperplasia in Mice by Traditional Chinese Medicinal Formula Si-Wu-Tang

Directory of Open Access Journals (Sweden)

Mandy M. Liu

2017-03-01

Full Text Available Exploring traditional medicines may lead to the development of low-cost and non-toxic cancer preventive agents. Si-Wu-Tang (SWT, comprising the combination of four herbs, Rehmanniae, Angelica, Chuanxiong, and Paeoniae, is one of the most popular traditional Chinese medicines for women’s diseases. In our previous studies, the antioxidant Nrf2 pathways were strongly induced by SWT in vitro and in vivo. Since Nrf2 activation has been associated with anticarcinogenic effects, the purpose of this study is to evaluate SWT’s activity of cancer prevention. In the Ames test, SWT demonstrated an antimutagenic activity against mutagenicity induced by the chemical carcinogen 7,12-dimethylbenz(aanthracene (DMBA. In JB6 P+ cells, a non-cancerous murine epidermal model for studying tumor promotion, SWT inhibited epidermal growth factor (EGF-induced neoplastic transformation. The luciferase reporter gene assays demonstrated that SWT suppressed EGF-induced AP-1 and TNF-α-induced NF-κB activation, which are essential factors involved in skin carcinogenesis. In a DMBA-induced skin hyperplasia assay in ‘Sensitivity to Carcinogenesis’ (SENCAR mice, both topical and oral SWT inhibited DMBA-induced epidermal hyperplasia, expression of the proliferation marker Proliferating cell nuclear antigen (PCNA, and H-ras mutations. These findings demonstrate, for the first time, that SWT prevents tumor promoter and chemical-induced carcinogenesis in vitro and in vivo, partly by inhibiting DNA damage and blocking the activation of AP-1 and NF-κB.

4D-Fingerprint Categorical QSAR Models for Skin Sensitization Based on Classification Local Lymph Node Assay Measures

Science.gov (United States)

Li, Yi; Tseng, Yufeng J.; Pan, Dahua; Liu, Jianzhong; Kern, Petra S.; Gerberick, G. Frank; Hopfinger, Anton J.

2008-01-01

Currently, the only validated methods to identify skin sensitization effects are in vivo models, such as the Local Lymph Node Assay (LLNA) and guinea pig studies. There is a tremendous need, in particular due to novel legislation, to develop animal alternatives, eg. Quantitative Structure-Activity Relationship (QSAR) models. Here, QSAR models for skin sensitization using LLNA data have been constructed. The descriptors used to generate these models are derived from the 4D-molecular similarity paradigm and are referred to as universal 4D-fingerprints. A training set of 132 structurally diverse compounds and a test set of 15 structurally diverse compounds were used in this study. The statistical methodologies used to build the models are logistic regression (LR), and partial least square coupled logistic regression (PLS-LR), which prove to be effective tools for studying skin sensitization measures expressed in the two categorical terms of sensitizer and non-sensitizer. QSAR models with low values of the Hosmer-Lemeshow goodness-of-fit statistic, χHL2, are significant and predictive. For the training set, the cross-validated prediction accuracy of the logistic regression models ranges from 77.3% to 78.0%, while that of PLS-logistic regression models ranges from 87.1% to 89.4%. For the test set, the prediction accuracy of logistic regression models ranges from 80.0%-86.7%, while that of PLS-logistic regression models ranges from 73.3%-80.0%. The QSAR models are made up of 4D-fingerprints related to aromatic atoms, hydrogen bond acceptors and negatively partially charged atoms. PMID:17226934

Absorption of radionuclide through wounded skin

International Nuclear Information System (INIS)

Kusama, Tomoko; Ogaki, Kazushi; Yoshizawa, Yasuo

1982-01-01

The translocation and absorption of 58 Co(CoCl 2 ) through a wound was investigated experimentally with mice. Physical and chemical skin damages became the objects of the investigation. Abrasion, puncture and incision were made for types of the physical damage. The chemical damage included both acid and alkaline burns. The absorptions of the radionuclide through the contaminated wounds were measured with both a 2 inches NaI(Tl) scintillation detector and an auto well gamma counter at 15,30 and 60 min after the contamination. The radionuclide was hardly absorbed through an undamaged skin. After 30 min, 20 to 40% of the radionuclide applied on the physically damaged skin was absorbed, but was not absorbed through the chemically damaged skin. The absorption rate through the physically damaged skin reached a maximum at 15 to 60 min after the contamination. The velocity of the absorption through the physically damaged skin was 100 times as much as the chemically damaged skin. The absorption rates through the physically and the chemically damaged skins were expressed by the following formulas: A=a(1-e sup(-bt)) and A=a(e sup(bt)-1), where a and b is constant, respectively. (author)

Xenobiotic-metabolizing enzymes in the skin of rat, mouse, pig, guinea pig, man, and in human skin models.

Science.gov (United States)

Oesch, F; Fabian, E; Guth, K; Landsiedel, R

2014-12-01

The exposure of the skin to medical drugs, skin care products, cosmetics, and other chemicals renders information on xenobiotic-metabolizing enzymes (XME) in the skin highly interesting. Since the use of freshly excised human skin for experimental investigations meets with ethical and practical limitations, information on XME in models comes in the focus including non-human mammalian species and in vitro skin models. This review attempts to summarize the information available in the open scientific literature on XME in the skin of human, rat, mouse, guinea pig, and pig as well as human primary skin cells, human cell lines, and reconstructed human skin models. The most salient outcome is that much more research on cutaneous XME is needed for solid metabolism-dependent efficacy and safety predictions, and the cutaneous metabolism comparisons have to be viewed with caution. Keeping this fully in mind at least with respect to some cutaneous XME, some models may tentatively be considered to approximate reasonable closeness to human skin. For dermal absorption and for skin irritation among many contributing XME, esterase activity is of special importance, which in pig skin, some human cell lines, and reconstructed skin models appears reasonably close to human skin. With respect to genotoxicity and sensitization, activating XME are not yet judgeable, but reactive metabolite-reducing XME in primary human keratinocytes and several reconstructed human skin models appear reasonably close to human skin. For a more detailed delineation and discussion of the severe limitations see the "Overview and Conclusions" section in the end of this review.

Skin-Inspired Hierarchical Polymer Architectures with Gradient Stiffness for Spacer-Free, Ultrathin, and Highly Sensitive Triboelectric Sensors.

Science.gov (United States)

Ha, Minjeong; Lim, Seongdong; Cho, Soowon; Lee, Youngoh; Na, Sangyun; Baig, Chunggi; Ko, Hyunhyub

2018-04-24

The gradient stiffness between stiff epidermis and soft dermis with interlocked microridge structures in human skin induces effective stress transmission to underlying mechanoreceptors for enhanced tactile sensing. Inspired by skin structure and function, we fabricate hierarchical nanoporous and interlocked microridge structured polymers with gradient stiffness for spacer-free, ultrathin, and highly sensitive triboelectric sensors (TESs). The skin-inspired hierarchical polymers with gradient elastic modulus enhance the compressibility and contact areal differences due to effective transmission of the external stress from stiff to soft layers, resulting in highly sensitive TESs capable of detecting human vital signs and voice. In addition, the microridges in the interlocked polymers provide an effective variation of gap distance between interlocked layers without using the bulk spacer and thus facilitate the ultrathin and flexible design of TESs that could be worn on the body and detect a variety of pressing, bending, and twisting motions even in humid and underwater environments. Our TESs exhibit the highest power density (46.7 μW/cm 2 ), pressure (0.55 V/kPa), and bending (∼0.1 V/°) sensitivities ever reported on flexible TESs. The proposed design of hierarchical polymer architectures for the flexible and wearable TESs can find numerous applications in next-generation wearable electronics.

IgE Sensitization Patterns to Commonly Consumed Foods Determined by Skin Prick Test in Korean Adults

OpenAIRE

Kim, Sung Ryeol; Park, Hye Jung; Park, Kyung Hee; Lee, Jae-Hyun; Park, Jung-Won

2016-01-01

Offending food allergens can vary with regional preferences in food consumption. In this study, we analysed sensitization rates to commonly consumed foods in Korean adults suspected of having food allergy. One hundred and thirty four subjects underwent a skin prick test (SPT) with 55 food allergens, of which 13 were made by our laboratory and the rest were commercially purchased. Of the 134 patients, 73 (54.5%) were sensitized to one or more food allergens. Sensitization to chrysalis was dete...

Determinants of skin sensitivity to solar irradiation

NARCIS (Netherlands)

Broekmans, W.; Vink, A.A.; Boelsma, E.; Klöpping-Ketelaars, W.A.A.; Tijburg, L.B.M.; Veer, van 't P.; Poppel, van G.; Kardinaal, A.F.M.

2003-01-01

Background: Acute effects of UV irradiation include UV-induced erythema. Sunlight plays an important role in the development of skin cancer. Several predictive factors of UV-induced erythema could also be predictive for skin cancer. Objective: Our objective was to quantitatively assess phenotypical

Non-allergic cutaneous reactions in airborne chemical sensitivity--a population based study

DEFF Research Database (Denmark)

Berg, Nikolaj Drimer; Linneberg, Allan; Thyssen, Jacob Pontoppidan

2011-01-01

the relationship between cutaneous reactions from patch testing and self-reported severity of chemical sensitivity to common airborne chemicals. A total of 3460 individuals participating in a general health examination, Health 2006, were patch tested with allergens from the European standard series and screened...... most severe groups of self-reported sensitivity to airborne chemicals. When adjusting for confounding, associations were weakened, and only non-allergic cutaneous reactions were significantly associated with individuals most severely affected by inhalation of airborne chemicals (odds ratio = 2.5, p = 0...

Effects of symbiotic bacteria on chemical sensitivity of Daphnia magna.

Science.gov (United States)

Manakul, Patcharaporn; Peerakietkhajorn, Saranya; Matsuura, Tomoaki; Kato, Yasuhiko; Watanabe, Hajime

2017-07-01

The crustacean zooplankton Daphnia magna has been widely used for chemical toxicity tests. Although abiotic factors have been well documented in ecotoxicological test protocols, biotic factors that may affect the sensitivity to chemical compounds remain limited. Recently, we identified symbiotic bacteria that are critical for the growth and reproduction of D. magna. The presence of symbiotic bacteria on Daphnia raised the question as to whether these bacteria have a positive or negative effect on toxicity tests. In order to evaluate the effects of symbiotic bacteria on toxicity tests, bacteria-free Daphnia were prepared, and their chemical sensitivities were compared with that of Daphnia with symbiotic bacteria based on an acute immobilization test. The Daphnia with symbiotic bacteria showed higher chemical resistance to nonylphenol, fenoxycarb, and pentachlorophenol than bacteria-free Daphnia. These results suggested potential roles of symbiotic bacteria in the chemical resistance of its host Daphnia. Copyright © 2017 Elsevier Ltd. All rights reserved.

CHEMICAL VAPOUR DEPOSITION FROM A RADIATION-SENSITIVE PRECURSOR

DEFF Research Database (Denmark)

2017-01-01

The present invention relates in one aspect to a method of depositing a thin film on a substrate by chemical vapour deposition (CVD) from a radiation-sensitive precursor substance. The method comprises the steps of: (i) placing the substrate in a reaction chamber of a CVD system; (ii) heating...... heating pulse followed by an idle period; (iii) during at least one of the idle periods, providing a pressure pulse of precursor substance inside the reaction chamber by feeding at least one precursor substance to the reaction chamber so as to establish a reaction partial pressure for thin film deposition...... is formed. According to a further aspect, the invention relates to a chemical vapour deposition (CVD) system for depositing a thin film onto a substrate using precursor substances containing at least one radiation sensitive species....

Blebbistatin, a myosin II inhibitor, suppresses Ca(2+)-induced and "sensitized"-contraction of skinned tracheal muscles from guinea pig.

Science.gov (United States)

Yumoto, Masatoshi; Watanabe, Masaru

2013-01-01

Blebbistatin, a potent inhibitor of myosin II, has inhibiting effects on Ca(2+)-induced contraction and contractile filament organization without affecting the Ca(2+)-sensitivity to the force and phosphorylation level of myosin regulatory light chain (MLC20) in skinned (cell membrane permeabilized) taenia cecum from the guinea pig (Watanabe et al., Am J Physiol Cell Physiol. 2010; 298: C1118-26). In the present study, we investigated blebbistatin effects on the contractile force of skinned tracheal muscle, in which myosin filaments organization is more labile than that in the taenia cecum. Blebbistatin at 10 μM or higher suppressed Ca(2+)-induced tension development at any given Ca(2+) concentration, but had little effects on the Ca(2+)- induced myosin light chain phosphorylation. Also blebbistatin at 10 μM and higher significantly suppressed GTP-γS-induced "sensitized" force development. Since the force inhibiting effects of blebbistatin on the skinned trachea were much stronger than those in skinned taenia cecum, blebbistatin might directly affect myosin filaments organization.

Association between atopic dermatitis and contact sensitization

DEFF Research Database (Denmark)

Hamann, Carsten R; Hamann, Dathan; Egeberg, Alexander

2017-01-01

BACKGROUND: It is unclear whether patients with atopic dermatitis (AD) have an altered prevalence or risk for contact sensitization. Increased exposure to chemicals in topical products together with impaired skin barrier function suggest a higher risk, whereas the immune profile suggests a lower...... contact dermatitis is suspected....... risk. OBJECTIVE: To perform a systematic review and meta-analysis of the association between AD and contact sensitization. METHODS: The PubMed/Medline, Embase, and Cochrane databases were searched for articles that reported on contact sensitization in individuals with and without AD. RESULTS...

Skin sensitisation: the Colipa strategy for developing and evaluating non-animal test methods for risk assessment.

Science.gov (United States)

Maxwell, Gavin; Aeby, Pierre; Ashikaga, Takao; Bessou-Touya, Sandrine; Diembeck, Walter; Gerberick, Frank; Kern, Petra; Marrec-Fairley, Monique; Ovigne, Jean-Marc; Sakaguchi, Hitoshi; Schroeder, Klaus; Tailhardat, Magali; Teissier, Silvia; Winkler, Petra

2011-01-01

Allergic contact dermatitis is a delayed-type hypersensitivity reaction induced by small reactive chemicals (haptens). Currently, the sensitising potential and potency of new chemicals is usually characterised using data generated via animal studies, such as the local lymph node assay (LLNA). There are, however, increasing public and political concerns regarding the use of animals for the testing of new chemicals. Consequently, the development of in vitro, in chemico or in silico models for predicting the sensitising potential and/or potency of new chemicals is receiving widespread interest. The Colipa Skin Tolerance task force currently collaborates with and/or funds several academic research groups to expand our understanding of the molecular and cellular events occurring during the acquisition of skin sensitisation. Knowledge gained from this research is being used to support the development and evaluation of novel alternative approaches for the identification and characterisation of skin sensitizing chemicals. At present three non-animal test methods (Direct Peptide Reactivity Assay (DPRA), Myeloid U937 Skin Sensitisation Test (MUSST) and human Cell Line Activation Test (hCLAT)) have been evaluated in Colipa interlaboratory ring trials for their potential to predict skin sensitisation potential and were recently submitted to ECVAM for formal pre-validation. Data from all three test methods will now be used to support the study and development of testing strategy approaches for skin sensitiser potency prediction. This publication represents the current viewpoint of the cosmetics industry on the feasibility of replacing the need for animal test data for informing skin sensitisation risk assessment decisions.

An epidermal equivalent assay for identification and ranking potency of contact sensitizers

Energy Technology Data Exchange (ETDEWEB)

Gibbs, Susan, E-mail: S.Gibbs@VUMC.nl [Department of Dermatology, VU University Medical Centre, Dept of Oral Cell Biology, ACTA, Amsterdam (Netherlands); Corsini, Emanuela [Laboratory of Toxicology, DiSFeB, Università degli Studi di Milano (Italy); Spiekstra, Sander W. [Department of Dermatology, VU University Medical Centre, Dept of Oral Cell Biology, ACTA, Amsterdam (Netherlands); Galbiati, Valentina [Laboratory of Toxicology, DiSFeB, Università degli Studi di Milano (Italy); Fuchs, Horst W. [CellSystems GmbH, Troisdorf (Germany); DeGeorge, George; Troese, Matthew [MB Research Labs, Spinnerstown, PA (United States); Hayden, Patrick; Deng, Wei [MatTek Corporation, Ashland, MA (United States); Roggen, Erwin [3Rs Management and Consultancy (Denmark)

2013-10-15

The purpose of this study was to explore the possibility of combining the epidermal equivalent (EE) potency assay with the assay which assesses release of interleukin-18 (IL-18) to provide a single test for identification and classification of skin sensitizing chemicals, including chemicals of low water solubility or stability. A protocol was developed using different 3D-epidermal models including in house VUMC model, epiCS® (previously EST1000™), MatTek EpiDerm™ and SkinEthic™ RHE and also the impact of different vehicles (acetone:olive oil 4:1, 1% DMSO, ethanol, water) was investigated. Following topical exposure for 24 h to 17 contact allergens and 13 non-sensitizers a robust increase in IL-18 release was observed only after exposure to contact allergens. A putative prediction model is proposed from data obtained from two laboratories yielding 95% accuracy. Correlating the in vitro EE sensitizer potency data, which assesses the chemical concentration which results in 50% cytotoxicity (EE-EC{sub 50}) with human and animal data showed a superior correlation with human DSA{sub 05} (μg/cm{sup 2}) data (Spearman r = 0.8500; P value (two-tailed) = 0.0061) compared to LLNA data (Spearman r = 0.5968; P value (two-tailed) = 0.0542). DSA{sub 05} = induction dose per skin area that produces a positive response in 5% of the tested population Also a good correlation was observed for release of IL-18 (SI-2) into culture supernatants with human DSA{sub 05} data (Spearman r = 0.8333; P value (two-tailed) = 0.0154). This easily transferable human in vitro assay appears to be very promising, but additional testing of a larger chemical set with the different EE models is required to fully evaluate the utility of this assay and to establish a definitive prediction model. - Highlights: • A potential epidermal equivalent assay to label and classify sensitizers • Il-18 release distinguishes sensitizers from non sensitizers • IL-18 release can rank sensitizer potency �

An epidermal equivalent assay for identification and ranking potency of contact sensitizers

International Nuclear Information System (INIS)

Gibbs, Susan; Corsini, Emanuela; Spiekstra, Sander W.; Galbiati, Valentina; Fuchs, Horst W.; DeGeorge, George; Troese, Matthew; Hayden, Patrick; Deng, Wei; Roggen, Erwin

2013-01-01

The purpose of this study was to explore the possibility of combining the epidermal equivalent (EE) potency assay with the assay which assesses release of interleukin-18 (IL-18) to provide a single test for identification and classification of skin sensitizing chemicals, including chemicals of low water solubility or stability. A protocol was developed using different 3D-epidermal models including in house VUMC model, epiCS® (previously EST1000™), MatTek EpiDerm™ and SkinEthic™ RHE and also the impact of different vehicles (acetone:olive oil 4:1, 1% DMSO, ethanol, water) was investigated. Following topical exposure for 24 h to 17 contact allergens and 13 non-sensitizers a robust increase in IL-18 release was observed only after exposure to contact allergens. A putative prediction model is proposed from data obtained from two laboratories yielding 95% accuracy. Correlating the in vitro EE sensitizer potency data, which assesses the chemical concentration which results in 50% cytotoxicity (EE-EC 50 ) with human and animal data showed a superior correlation with human DSA 05 (μg/cm 2 ) data (Spearman r = 0.8500; P value (two-tailed) = 0.0061) compared to LLNA data (Spearman r = 0.5968; P value (two-tailed) = 0.0542). DSA 05 = induction dose per skin area that produces a positive response in 5% of the tested population Also a good correlation was observed for release of IL-18 (SI-2) into culture supernatants with human DSA 05 data (Spearman r = 0.8333; P value (two-tailed) = 0.0154). This easily transferable human in vitro assay appears to be very promising, but additional testing of a larger chemical set with the different EE models is required to fully evaluate the utility of this assay and to establish a definitive prediction model. - Highlights: • A potential epidermal equivalent assay to label and classify sensitizers • Il-18 release distinguishes sensitizers from non sensitizers • IL-18 release can rank sensitizer potency • EC50 (chemical

Inventory of the chemicals and the exposure of the workers' skin to these at two leather factories in Indonesia

NARCIS (Netherlands)

Febriana, Sri Awalia; Jungbauer, Frank; Soebono, Hardyanto; Coenraads, Pieter-Jan

Tannery workers are exposed to hazardous chemicals. Tannery work is outsourced to newly industrialized countries (NICs) where attention into occupational health hazards is limited. In this study, we investigated the skin exposure to hazardous chemicals in tannery workers and determined the

Evaluation of a novel very high sun-protection-factor moisturizer in adults with rosacea-prone sensitive skin

Directory of Open Access Journals (Sweden)

Grivet-Seyve M

2017-06-01

Full Text Available Mathieu Grivet-Seyve,1 Francine Santoro,2 Nadège Lachmann2 1Galderma Research and Development, Sophia Antipolis, France; 2Galderma Research and Development, Egerkingen, Switzerland Background/objective: Rosacea-prone sensitive skin requires high sun-protection factor (SPF moisturizers. This study evaluated Daylong Extreme SPF 50+ lotion, a novel cream containing five ultraviolet filters, two emollients, and three skin conditioners.Subjects and methods: This was an open-label, single-center study. On day 1, before treatment, subjects answered a questionnaire on their skin conditions and sunscreen habits, and both subjects and dermatologist evaluated skin status. Subjects applied the product once daily in the morning to the face for 21 days, and after approximately 3–5 minutes they assessed tolerability and short-term cosmetic acceptability in a questionnaire and daily diary. On day 22, the dermatologist and subjects evaluated skin status for long-term tolerance and cosmetic acceptability.Results: The study enrolled 44 individuals (mean age 58.8 years, 91% female. At baseline, most subjects (39 of 44 showed erythema, and ~30% showed dryness and scaling. Dermatologists noted four cases of pustules and one case of papules. After 21 days’ treatment with the product, the dermatologist reported significantly less erythema, dryness and scaling, three cases of pustules and two cases of papules. At baseline, ~75% of subjects noted a feeling of dryness, >50% reported tension, and nearly 25% reported tickling. After using the product for 21 days, subjects reported significantly less tension, dryness, and tickling. Some subjects noted itching and burning before and after using the product. One subject noted papules during treatment. Most subjects said that the product was pleasant, did not irritate the skin or cause stinging/burning, was easy to apply, quickly absorbed, and nongreasy, improved skin moisturization, helped prevent sun-provoked facial

An elevated pro-inflammatory cytokine profile in multiple chemical sensitivity

DEFF Research Database (Denmark)

Dantoft, Thomas Meinertz; Elberling, J.; Brix, Susanne

2014-01-01

BackgroundMultiple chemical sensitivity (MCS) is a medically unexplained condition characterized by reports of recurrent unspecific symptoms attributed to exposure to low levels of common volatile chemicals. The etiology of MCS is poorly understood, but dysregulation of the immune system has been...

Use of silicon for skin and hair care: an approach of chemical forms available and efficacy.

Science.gov (United States)

Araújo, Lidiane Advincula de; Addor, Flavia; Campos, Patrícia Maria Berardo Gonçalves Maia

2016-01-01

Silicon is the second most abundant element on Earth, and the third most abundant trace element in human body. It is present in water, plant and animal sources. On the skin, it is suggested that silicon is important for optimal collagen synthesis and activation of hydroxylating enzymes, improving skin strength and elasticity. Regarding hair benefits, it was suggested that a higher silicon content in the hair results in a lower rate of hair loss and increased brightness. For these beneficial effects, there is growing interest in scientific studies evaluating the efficacy and safety of using dietary supplements containing silicon. Its use aims at increasing blood levels of this element and improving the skin and its annexes appearance. There are different forms of silicon supplements available and the most important consideration to be made in order to select the best option is related to safety and bioavailability. Silicon supplements are widely used, though there is wide variation in silicon bioavailability, ranging from values below 1% up to values close to 50%, depending on the chemical form. Therefore, the aim of this study was to evaluate the scientific literature related to the different chemical forms of silicon supplements available and the limitations and recent progress in this field. According to reported studies, among the different chemical forms available, the orthosilicic acid (OSA) presents the higher bioavailability, whereas the others forms have absorption inversely proportional to the degree of polymerization. However, clinical studies evaluating safety and efficacy are still lacking.

Local lymph node activation in rats after dermal application of the sensitizers 2,4-dinitrochlorobenzene and trimellitic anhydride

NARCIS (Netherlands)

Arts, J.H.E.; Dröge, S.C.M.; Bloksma, N.; Kuper, C.F.

1996-01-01

Five rat strains were compared for their performance in the local lymph node assay (LLNA) a promising test system for the identification of the skin-sensitizing potential of chemicals in the mouse. The contact sensitizer 2,4-dinitrochlorobenzene (DNCB) and the contact and respiratory sensitizer

Human skin volatiles: a review.

Science.gov (United States)

Dormont, Laurent; Bessière, Jean-Marie; Cohuet, Anna

2013-05-01

Odors emitted by human skin are of great interest to biologists in many fields; applications range from forensic studies to diagnostic tools, the design of perfumes and deodorants, and the ecology of blood-sucking insect vectors of human disease. Numerous studies have investigated the chemical composition of skin odors, and various sampling methods have been used for this purpose. The literature shows that the chemical profile of skin volatiles varies greatly among studies, and the use of different sampling procedures is probably responsible for some of these variations. To our knowledge, this is the first review focused on human skin volatile compounds. We detail the different sampling techniques, each with its own set of advantages and disadvantages, which have been used for the collection of skin odors from different parts of the human body. We present the main skin volatile compounds found in these studies, with particular emphasis on the most frequently studied body regions, axillae, hands, and feet. We propose future directions for promising experimental studies on odors from human skin, particularly in relation to the chemical ecology of blood-sucking insects.

Transient receptor potential ankyrin 1 activation enhances hapten sensitization in a T-helper type 2-driven fluorescein isothiocyanate-induced contact hypersensitivity mouse model

International Nuclear Information System (INIS)

Shiba, Takahiro; Tamai, Takuma; Sahara, Yurina; Kurohane, Kohta; Watanabe, Tatsuo; Imai, Yasuyuki

2012-01-01

Some chemicals contribute to the development of allergies by increasing the immunogenicity of other allergens. We have demonstrated that several phthalate esters, including dibutyl phthalate (DBP), enhance skin sensitization to fluorescein isothiocyanate (FITC) in a mouse contact hypersensitivity model, in which the T-helper type 2 (Th2) response is essential. On the other hand, some phthalate esters were found to activate transient receptor potential ankyrin 1 (TRPA1) cation channels on sensory neurons. We then found a positive correlation between the enhancing effects of several types of phthalate esters on skin sensitization to FITC and their ability to activate TRPA1. Here we examined the involvement of TRPA1 in sensitization to FITC by using TRPA1 agonists other than phthalate esters. During skin sensitization to FITC, the TRPA1 agonists (menthol, carvacrol, cinnamaldehyde and DBP) augmented the ear-swelling response as well as trafficking of FITC-presenting dendritic cells to draining lymph nodes. We confirmed that these TRPA1 agonists induced calcium influx into TRPA1-expressing Chinese hamster ovary (CHO) cells. We also found that TRPA1 antagonist HC-030031 inhibited DBP-induced calcium influx into TRPA1-expressing CHO cells. After pretreatment with this antagonist upon skin sensitization to FITC, the enhancing effect of DBP on sensitization was suppressed. These results suggest that TRPA1 activation will become a useful marker to find chemicals that facilitate sensitization in combination with other immunogenic haptens. -- Highlights: ► Role of TRPA1 activation was revealed in a mouse model of skin sensitization to FITC. ► TRPA1 agonists enhanced skin sensitization as well as dendritic cell trafficking. ► Dibutyl phthalate (DBP) has been shown to enhance skin sensitization to FITC. ► TRPA1 activation by DBP was inhibited by a selective antagonist, HC-030031. ► HC-030031 inhibited the enhancing effect of DBP on skin sensitization to FITC.

Transient receptor potential ankyrin 1 activation enhances hapten sensitization in a T-helper type 2-driven fluorescein isothiocyanate-induced contact hypersensitivity mouse model

Energy Technology Data Exchange (ETDEWEB)

Shiba, Takahiro; Tamai, Takuma; Sahara, Yurina; Kurohane, Kohta [Laboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, 52‐1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422‐8526 (Japan); Watanabe, Tatsuo [Laboratory of Food Chemistry, School of Food and Nutritional Sciences, University of Shizuoka, 52‐1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422‐8526 (Japan); Imai, Yasuyuki, E-mail: imai@u-shizuoka-ken.ac.jp [Laboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, 52‐1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422‐8526 (Japan)

2012-11-01

Some chemicals contribute to the development of allergies by increasing the immunogenicity of other allergens. We have demonstrated that several phthalate esters, including dibutyl phthalate (DBP), enhance skin sensitization to fluorescein isothiocyanate (FITC) in a mouse contact hypersensitivity model, in which the T-helper type 2 (Th2) response is essential. On the other hand, some phthalate esters were found to activate transient receptor potential ankyrin 1 (TRPA1) cation channels on sensory neurons. We then found a positive correlation between the enhancing effects of several types of phthalate esters on skin sensitization to FITC and their ability to activate TRPA1. Here we examined the involvement of TRPA1 in sensitization to FITC by using TRPA1 agonists other than phthalate esters. During skin sensitization to FITC, the TRPA1 agonists (menthol, carvacrol, cinnamaldehyde and DBP) augmented the ear-swelling response as well as trafficking of FITC-presenting dendritic cells to draining lymph nodes. We confirmed that these TRPA1 agonists induced calcium influx into TRPA1-expressing Chinese hamster ovary (CHO) cells. We also found that TRPA1 antagonist HC-030031 inhibited DBP-induced calcium influx into TRPA1-expressing CHO cells. After pretreatment with this antagonist upon skin sensitization to FITC, the enhancing effect of DBP on sensitization was suppressed. These results suggest that TRPA1 activation will become a useful marker to find chemicals that facilitate sensitization in combination with other immunogenic haptens. -- Highlights: ► Role of TRPA1 activation was revealed in a mouse model of skin sensitization to FITC. ► TRPA1 agonists enhanced skin sensitization as well as dendritic cell trafficking. ► Dibutyl phthalate (DBP) has been shown to enhance skin sensitization to FITC. ► TRPA1 activation by DBP was inhibited by a selective antagonist, HC-030031. ► HC-030031 inhibited the enhancing effect of DBP on skin sensitization to FITC.

Activation of non-sensitizing or low-sensitizing fragrance substances into potent sensitizers - prehaptens and prohaptens.

Science.gov (United States)

Karlberg, Ann-Therese; Börje, Anna; Duus Johansen, Jeanne; Lidén, Carola; Rastogi, Suresh; Roberts, David; Uter, Wolfgang; White, Ian R

2013-12-01

Experimental and clinical studies have shown that fragrance substances can act as prehaptens or prohaptens. They form allergens that are more potent than the parent substance by activation outside or in the skin via abiotic (chemical and physical factors) and/or biotic activation, thus, increasing the risk of sensitization. In the present review a series of fragrance substances with well documented abiotic and/or biotic activation are given as indicative and illustrative examples of the general problem. Commonly used fragrance substances, also found in essential oils, autoxidize on contact with air, forming potent sensitizers that can be an important source for contact allergy to fragrances and fragranced products. Some of them can act as prohaptens and be activated in the skin as well. The experimental findings are confirmed in large clinical studies. When substances with structural alerts for acting as prohaptens and/or prehaptens are identified, the possibility of generating new potent allergens should be considered. Predictive testing should include activation steps. Further experimental and clinical research regarding activation of fragrance substances is needed to increase consumer safety. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Sickness-related dysfunction in persons with self-reported multiple chemical sensitivity at four levels of severity.

Science.gov (United States)

Gibson, Pamela Reed; Vogel, Valerie M

2009-01-01

To examine quality of life outcome for persons who self-report chemical sensitivity, often referred to as multiple chemical sensitivity. Multiple chemical sensitivity is poorly understood with few providers specialising in its treatment. This lack of treatment and the ubiquity of chemicals engender severe life impacts such as job loss, financial loss, social isolation and even homelessness for persons who experience these sensitivities. Survey. We examined chemical incitants, symptoms and sickness-related behavioural dysfunction as measured by the Sickness Impact Profile in 254 persons self-identified with multiple chemical sensitivity. Chemicals rated as causing the most symptomatology in respondents were pesticide, formaldehyde, fresh paint, new carpet, diesel exhaust, perfume and air fresheners. The five highest rated symptoms in this sample were tiredness/lethargy, difficulty concentrating, muscle aches, memory difficulties and long-term fatigue. Overall mean Sickness Impact Profile score was 25.25%, showing serious impairment, with the most serious dysfunction in the categories of work (55.36%), alertness behaviour (53.45%) and recreation and pastimes (45.20%). Multiple chemical sensitivity is an important health care issue because it often includes serious dysfunction, is poorly understood by providers and poses extensive financial and treatment obstacles for those who experience it. Persons with multiple chemical sensitivity seek medical treatment in a variety of contexts and informed providers can both avoid iatrogenic harm due to medical exposures and provide any possible treatment for the chemical sensitivities. Understanding the impact of the health condition is crucial to communicate with and treat persons who experience the sensitivities.

Testing Human Skin and Respiratory Sensitizers—What Is Good Enough?

Directory of Open Access Journals (Sweden)

Anki Malmborg

2017-01-01

Full Text Available Alternative methods for accurate in vitro assessment of skin and respiratory sensitizers are urgently needed. Sensitization is a complex biological process that cannot be evaluated accurately using single events or biomarkers, since the information content is too restricted in these measurements. On the contrary, if the tremendous information content harbored in DNA/mRNA could be mined, most complex biological processes could be elucidated. Genomic technologies available today, including transcriptional profiling and next generation sequencing, have the power to decipher sensitization, when used in the right context. Thus, a genomic test platform has been developed, denoted the Genomic Allergen Rapid Detection (GARD assay. Due to the high informational content of the GARD test, accurate predictions of both the skin and respiratory sensitizing capacity of chemicals, have been demonstrated. Based on a matured dendritic cell line, acting as a human-like reporter system, information about potency has also been acquired. Consequently, multiparametric diagnostic technologies are disruptive test principles that can change the way in which the next generation of alternative methods are designed.

Elucidation of xenobiotic metabolism pathways in human skin and human skin models by proteomic profiling.

Directory of Open Access Journals (Sweden)

Sven van Eijl

Full Text Available BACKGROUND: Human skin has the capacity to metabolise foreign chemicals (xenobiotics, but knowledge of the various enzymes involved is incomplete. A broad-based unbiased proteomics approach was used to describe the profile of xenobiotic metabolising enzymes present in human skin and hence indicate principal routes of metabolism of xenobiotic compounds. Several in vitro models of human skin have been developed for the purpose of safety assessment of chemicals. The suitability of these epidermal models for studies involving biotransformation was assessed by comparing their profiles of xenobiotic metabolising enzymes with those of human skin. METHODOLOGY/PRINCIPAL FINDINGS: Label-free proteomic analysis of whole human skin (10 donors was applied and analysed using custom-built PROTSIFT software. The results showed the presence of enzymes with a capacity for the metabolism of alcohols through dehydrogenation, aldehydes through dehydrogenation and oxidation, amines through oxidation, carbonyls through reduction, epoxides and carboxylesters through hydrolysis and, of many compounds, by conjugation to glutathione. Whereas protein levels of these enzymes in skin were mostly just 4-10 fold lower than those in liver and sufficient to support metabolism, the levels of cytochrome P450 enzymes were at least 300-fold lower indicating they play no significant role. Four epidermal models of human skin had profiles very similar to one another and these overlapped substantially with that of whole skin. CONCLUSIONS/SIGNIFICANCE: The proteomics profiling approach was successful in producing a comprehensive analysis of the biotransformation characteristics of whole human skin and various in vitro skin models. The results show that skin contains a range of defined enzymes capable of metabolising different classes of chemicals. The degree of similarity of the profiles of the in vitro models indicates their suitability for epidermal toxicity testing. Overall, these

Dry skin - self-care

Science.gov (United States)

... pat skin dry then apply your moisturizer. Avoid skin care products and soaps that contain alcohol, fragrances, dyes, or other chemicals. Take short, warm baths or showers. Limit your ... gentle skin cleansers or soap with added moisturizers. Only use ...

Risk factors associated with sensitive skin and potential role of lifestyle habits: a cross-sectional study

NARCIS (Netherlands)

Falcone, D.; Richters, R.J.H.; Uzunbajakava, N.E.; Erp, P.E.J. van; Kerkhof, P.C.M. van de

2017-01-01

Sensitive skin (SS) is a widespread condition, but still not completely understood. To identify risk factors that increase the likelihood of SS, 258 women aged between 20 and 65 years old and resident in the Netherlands were surveyed by questionnaire, which included questions on sociodemographic

Relevance of Cat and Dog Sensitization by Skin Prick Testing in Childhood Eczema and Asthma.

Science.gov (United States)

Hon, Kam Lun; Tsang, Kathy Yin Ching; Pong, Nga Hin Henry; Leung, Ting Fan

2017-01-01

Household animal dander has been implicated as aeroallergen in childhood atopic diseases. Many parents seek healthcare advice if household pet keeping may be detrimental in atopic eczema (AE), allergic rhinitis and asthma. We investigated if skin sensitization by cat/dog dander was associated with disease severity and quality of life in children with AE. Demographics, skin prick test (SPT) results, disease severity (Nottingham eczema severity score NESS), Children Dermatology Life Quality Index (CDLQI), blood IgE and eosinophil counts of a cohort of AE patients were reviewed. 325 AE patients followed at a pediatric dermatology clinic were evaluated. Personal history of asthma was lowest (20%) in the dog-dander-positive-group but highest (61%) in bothcat- and-dog-dander-positive group (p=0.007). Binomial logistic regression ascertained that catdander sensitization was associated with increasing age (adjusted odds ratio [aOR], 1.056; 95% Confidence Interval [CI], 1.006 to 1.109; p=0.029), dust-mite sensitization (aOR, 4.625; 95% CI, 1.444 to 14.815; p=0.010), food-allergen sensitization (aOR, 2.330; 95% CI, 1.259 to 4.310; p=0.007) and keeping-cat-ever (aOR, 7.325; 95% CI, 1.193 to 44.971; p=0.032); whereas dogdander sensitization was associated with dust-mite sensitization (aOR, 9.091; 95% CI, 1.148 to 71.980; p=0.037), food-allergen sensitization (aOR, 3.568; 95% CI, 1.341 to 9.492; p=0.011) and keeping-dog-ever (aOR, 6.809; 95% CI, 2.179 to 21.281; p=0.001). However, neither cat nor dog sensitization were associated with asthma, allergic rhinitis, parental or sibling atopic status, disease severity or quality of life. Physicians should advise parents that there is no direct correlation between AE severity, quality of life, asthma or allergic rhinitis with cutaneous sensitization to cats or dogs. Sensitized patients especially those with concomitant asthma and severe symptoms may consider non-furry alternatives if they plan to have a pet. Highly sensitized

mHealth App for Risk Assessment of Pigmented and Nonpigmented Skin Lesions-A Study on Sensitivity and Specificity in Detecting Malignancy.

Science.gov (United States)

Thissen, Monique; Udrea, Andreea; Hacking, Michelle; von Braunmuehl, Tanja; Ruzicka, Thomas

2017-12-01

With the advent of smartphone devices, an increasing number of mHealth applications that target melanoma identification have been developed, but none addresses the general context of melanoma and nonmelanoma skin cancer identification. In this study a smartphone application using fractal and classical image analysis for the risk assessment of skin lesions is systematically evaluated to determine its sensitivity and specificity in the diagnosis of melanoma and nonmelanoma skin cancer along with actinic keratosis and Bowen's disease. In the Department of Dermatology, Catharina Hospital Eindhoven, The Netherlands, 341 melanocytic and nonmelanocytic lesions were imaged using SkinVision app; 239 underwent histopathological examination, while the rest of 102 lesions were clinically diagnosed as clearly benign and not removed. The algorithm has been calibrated using the images of the first 233 lesions. The calibrated version of the algorithm was used in a subset of 108 lesions, and the obtained results were compared with the medical findings. On the 108 cases used for evaluation the algorithm scored 80% sensitivity and 78% specificity in detecting (pre)malignant conditions. Although less accurate than the dermatologist's clinical eye, the app may offer support to other professionals who are less familiar with differentiating between benign and malignant lesions. An mHealth application for the risk assessment of skin lesions was evaluated. It adds value to diagnosis tools of its type by taking into consideration pigmented and nonpigmented lesions all together and detecting signs of malignancy with high sensitivity.

Sensitivity Comparison of the Skin Prick Test and Serum and Fecal Radio Allergosorbent Test (RAST in Diagnosis of Food Allergy in Children

Directory of Open Access Journals (Sweden)

Hamid Reza Kianifar

2016-05-01

Full Text Available Background: Diagnosis of food allergy is difficult in children. Food allergies are diagnosed using several methods that include medical histories, clinical examinations, skin prick and serum-specific immunoglobulin E (IgE tests, radio-allergosorbent test (RAST, food challenge, and supervised elimination diets. In this study we evaluated allergies to cow's milk, egg, peanut, and fish in children with suspected food allergies with skin prick tests and serum and feces RAST. Methods: Forty-one children with clinical symptoms of food allergies were enrolled in the study. Skin prick tests and serum and fecal RAST were performed and compared with challenge tests. Results: The most common sites of food allergy symptoms were gastrointestinal (82.9% and skin (48.8%. 100% of the patients responded to the challenge tests with cow’s milk, egg, peanut, and fish. 65% of the patients tested positive with the skin prick test, 12.1% tested positive with serum RAST, and 29.2% tested positive with fecal RAST. Conclusions: The skin prick test was more sensitive than serum or fecal RAST, and fecal RAST was more than twice as sensitive as serum RAST.

Full-thickness human skin explants for testing the toxicity of topically applied chemicals

International Nuclear Information System (INIS)

Nakamura, M.; Rikimaru, T.; Yano, T.; Moore, K.G.; Pula, P.J.; Schofield, B.H.; Dannenberg, A.M. Jr.

1990-01-01

This report describes a model organ-culture system for testing the toxicity of chemical substances that are topically applied to human skin. In this system, the viable keratinocytes in the full-thickness skin explants are protected by the same keratinized layer as skin remaining on the donor, and toxicity can be assessed microscopically and/or biochemically. The human skin specimens were discards from a variety of surgical procedures. They were cut into full-thickness 1.0-cm2 explants, and briefly exposed to the military vesicant sulfur mustard (SM), which was used as a model toxicant. The explants were then organ cultured in small Petri dishes for 24 h at 36 degrees C. In the 0.03-1.0% dosage range, a straight-line dose-response relationship occurred between the concentration of SM applied and the number of paranuclear vacuoles seen histologically in the epidermis. Within the same SM dosage range, there was also a proportional decrease in 14C-leucine incorporation by the explants. Thus, the number of paranuclear vacuoles reflected decreases in protein synthesis by the injured epidermal cells. The epidermis of full-thickness untreated (control) human skin explants usually remained viable for 7 d when stored at 4 degrees C in culture medium. During storage, a relatively small number of paranuclear vacuoles developed within the epidermis, but the explants were still quite satisfactory for testing SM toxicity. Incubation (for 4 or 24 h at 36 degrees C) of such control skin explants reduced (often by 50%) the small number of paranuclear vacuoles produced during 4-7 d of storage. This reduction was probably caused by autolysis of many of the vacuolated cells. Two types of paranuclear vacuoles could be identified by both light and electron microscopy: a storage type and a toxicant type. The storage type seemed to be caused by autolysis of cell components

Full-thickness human skin explants for testing the toxicity of topically applied chemicals

Energy Technology Data Exchange (ETDEWEB)

Nakamura, M.; Rikimaru, T.; Yano, T.; Moore, K.G.; Pula, P.J.; Schofield, B.H.; Dannenberg, A.M. Jr. (Johns Hopkins Univ., Baltimore, MD (USA))

1990-09-01

This report describes a model organ-culture system for testing the toxicity of chemical substances that are topically applied to human skin. In this system, the viable keratinocytes in the full-thickness skin explants are protected by the same keratinized layer as skin remaining on the donor, and toxicity can be assessed microscopically and/or biochemically. The human skin specimens were discards from a variety of surgical procedures. They were cut into full-thickness 1.0-cm2 explants, and briefly exposed to the military vesicant sulfur mustard (SM), which was used as a model toxicant. The explants were then organ cultured in small Petri dishes for 24 h at 36 degrees C. In the 0.03-1.0% dosage range, a straight-line dose-response relationship occurred between the concentration of SM applied and the number of paranuclear vacuoles seen histologically in the epidermis. Within the same SM dosage range, there was also a proportional decrease in 14C-leucine incorporation by the explants. Thus, the number of paranuclear vacuoles reflected decreases in protein synthesis by the injured epidermal cells. The epidermis of full-thickness untreated (control) human skin explants usually remained viable for 7 d when stored at 4 degrees C in culture medium. During storage, a relatively small number of paranuclear vacuoles developed within the epidermis, but the explants were still quite satisfactory for testing SM toxicity. Incubation (for 4 or 24 h at 36{degrees}C) of such control skin explants reduced (often by 50%) the small number of paranuclear vacuoles produced during 4-7 d of storage. This reduction was probably caused by autolysis of many of the vacuolated cells. Two types of paranuclear vacuoles could be identified by both light and electron microscopy: a storage type and a toxicant type. The storage type seemed to be caused by autolysis of cell components.

Sensitization to Food Additives in Patients with Allergy: A Study Based on Skin Test and Open Oral Challenge.

Science.gov (United States)

Moghtaderi, Mozhgan; Hejrati, Zinatosadat; Dehghani, Zahra; Dehghani, Faranak; Kolahi, Niloofar

2016-06-01

There has been a great increase in the consumption of various food additives in recent years. The purpose of this study was to identify the incidence of sensitization to food additives by using skin prick test in patients with allergy and to determine the concordance rate between positive skin tests and oral challenge in hypersensitivity to additives. This cross-sectional study included 125 (female 71, male 54) patients aged 2-76 years with allergy and 100 healthy individuals. Skin tests were performed in both patient and control groups with 25 fresh food additives. Among patients with allergy, 22.4% showed positive skin test at least to one of the applied materials. Skin test was negative to all tested food additives in control group. Oral food challenge was done in 28 patients with positive skin test, in whom 9 patients showed reaction to culprit (Concordance rate=32.1%). The present study suggested that about one-third of allergic patients with positive reaction to food additives showed positive oral challenge; it may be considered the potential utility of skin test to identify the role of food additives in patients with allergy.

Natural evolution of skin-test sensitivity in patients with IgE-mediated hypersensitivity to cephalosporins.

Science.gov (United States)

Romano, A; Gaeta, F; Valluzzi, R L; Zaffiro, A; Caruso, C; Quaratino, D

2014-06-01

There are studies demonstrating that skin-test sensitivity to penicillins can decrease over time and that allergic patients may lose sensitivity if the responsible compounds are avoided. With regard to subjects with IgE-mediated hypersensitivity to cephalosporins, however, such studies are lacking. We evaluated prospectively in a 5-year follow-up 72 cephalosporin-allergic patients. After the first evaluation, patients were classified into two groups according to their patterns of allergologic-test positivity: to both penicillins and cephalosporins (group A), or only to cephalosporins (group B). Skin tests and serum-specific IgE assays were repeated 1 year later and, in case of persistent positivity, 3 and 5 years after the first allergologic examination. Seven (43.7%) of the 16 subjects of group A and 38 (67.8%) of the 56 patients of group B became negative; one was lost to follow-up. Patients of group B became negative sooner and more frequently than group A subjects. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Development of an Active Topical Skin Protectant (aTSP)

Science.gov (United States)

2016-02-01

protectant as a follow-on product to Skin Exposure Reduction Paste Against Chemical Warfare Agents (SERPACWA). 15. SUBJECT TERMS decontamination , Skin...corresponding author), Chemical Warfare Agent Decontamination from Skin, In J.A. Romano Jr., B.J. Lukey, and H. Salem, eds., 2nd Edition of Chemical Warfare ...CG, and Braue, EH Jr (corresponding author), “ Chemical warfare agent decontamination from skin,” In J.A. Romano Jr., B.J. Lukey, and H. Salem

Use of silicon for skin and hair care: an approach of chemical forms available and efficacy*

Science.gov (United States)

de Araújo, Lidiane Advincula; Addor, Flavia; Campos, Patrícia Maria Berardo Gonçalves Maia

2016-01-01

Silicon is the second most abundant element on Earth, and the third most abundant trace element in human body. It is present in water, plant and animal sources. On the skin, it is suggested that silicon is important for optimal collagen synthesis and activation of hydroxylating enzymes, improving skin strength and elasticity. Regarding hair benefits, it was suggested that a higher silicon content in the hair results in a lower rate of hair loss and increased brightness. For these beneficial effects, there is growing interest in scientific studies evaluating the efficacy and safety of using dietary supplements containing silicon. Its use aims at increasing blood levels of this element and improving the skin and its annexes appearance. There are different forms of silicon supplements available and the most important consideration to be made in order to select the best option is related to safety and bioavailability. Silicon supplements are widely used, though there is wide variation in silicon bioavailability, ranging from values below 1% up to values close to 50%, depending on the chemical form. Therefore, the aim of this study was to evaluate the scientific literature related to the different chemical forms of silicon supplements available and the limitations and recent progress in this field. According to reported studies, among the different chemical forms available, the orthosilicic acid (OSA) presents the higher bioavailability, whereas the others forms have absorption inversely proportional to the degree of polymerization. However, clinical studies evaluating safety and efficacy are still lacking. PMID:27438201

Skin absorption through atopic dermatitis skin

DEFF Research Database (Denmark)

Halling-Overgaard, A-S; Kezic, S; Jakasa, I

2017-01-01

Patients with atopic dermatitis have skin barrier impairment in both lesional and non-lesional skin. They are typically exposed to emollients daily and topical anti-inflammatory medicaments intermittently, hereby increasing the risk of developing contact allergy and systemic exposed to chemicals...... ingredients found in these topical preparations. We systematically searched for studies that investigated skin absorption of various penetrants, including medicaments, in atopic dermatitis patients, but also animals with experimentally induced dermatitis. We identified 40 articles, i.e. 11 human studies...... examining model penetrants, 26 human studies examining atopic dermatitis drugs and 3 animal studies. We conclude that atopic dermatitis patients have nearly two-fold increased skin absorption when compared to healthy controls. There is a need for well-designed epidemiological and dermato...

Development of High Temperature/High Sensitivity Novel Chemical Resistive Sensor

Energy Technology Data Exchange (ETDEWEB)

Ma, Chunrui [Univ. of Texas, San Antonio, TX (United States); Enriquez, Erik [Univ. of Texas, San Antonio, TX (United States); Wang, Haibing [Univ. of Texas, San Antonio, TX (United States); Xu, Xing [Univ. of Texas, San Antonio, TX (United States); Bao, Shangyong [Univ. of Texas, San Antonio, TX (United States); Collins, Gregory [Univ. of Texas, San Antonio, TX (United States)

2013-08-13

The research has been focused to design, fabricate, and develop high temperature/high sensitivity novel multifunctional chemical sensors for the selective detection of fossil energy gases used in power and fuel systems. By systematically studying the physical properties of the LnBaCo₂O_5+d (LBCO) [Ln=Pr or La] thin-films, a new concept chemical sensor based high temperature chemical resistant change has been developed for the application for the next generation highly efficient and near zero emission power generation technologies. We also discovered that the superfast chemical dynamic behavior and an ultrafast surface exchange kinetics in the highly epitaxial LBCO thin films. Furthermore, our research indicates that hydrogen can superfast diffuse in the ordered oxygen vacancy structures in the highly epitaxial LBCO thin films, which suggest that the LBCO thin film not only can be an excellent candidate for the fabrication of high temperature ultra sensitive chemical sensors and control systems for power and fuel monitoring systems, but also can be an excellent candidate for the low temperature solid oxide fuel cell anode and cathode materials.

Nutraceuticals for Skin Care: A Comprehensive Review of Human Clinical Studies.

Science.gov (United States)

Pérez-Sánchez, Almudena; Barrajón-Catalán, Enrique; Herranz-López, María; Micol, Vicente

2018-03-24

The skin is the body's largest organ, it participates in sensitivity and offers protection against microorganisms, chemicals and ultraviolet (UV) radiation. Consequently, the skin may suffer alterations such as photo-ageing, immune dysfunction and inflammation which may significantly affect human health. Nutraceuticals represent a promising strategy for preventing, delaying, or minimising premature ageing of the skin and also to alleviate certain skin disorders. Among them, bioactive peptides and oligosaccharides, plant polyphenols, carotenoids, vitamins and polyunsaturated fatty acids are the most widely used ingredients. Supplementation with these products has shown evidence of having an effect on the signs of ageing and protection against UV radiation ageing in several human trials. In this review, the most relevant human studies on skin nutraceuticals are evaluated and the statistical resolution, biological relevance of their results, and, the trial protocols are discussed. In conclusion, quality and rigorousness of the trials must be improved to build credible scientific evidence for skin nutraceuticals and to establish a cause-effect relationship between the ingredients the beneficial effects for the skin.

Nutraceuticals for Skin Care: A Comprehensive Review of Human Clinical Studies

Directory of Open Access Journals (Sweden)

Almudena Pérez-Sánchez

2018-03-01

Full Text Available The skin is the body’s largest organ, it participates in sensitivity and offers protection against microorganisms, chemicals and ultraviolet (UV radiation. Consequently, the skin may suffer alterations such as photo-ageing, immune dysfunction and inflammation which may significantly affect human health. Nutraceuticals represent a promising strategy for preventing, delaying, or minimising premature ageing of the skin and also to alleviate certain skin disorders. Among them, bioactive peptides and oligosaccharides, plant polyphenols, carotenoids, vitamins and polyunsaturated fatty acids are the most widely used ingredients. Supplementation with these products has shown evidence of having an effect on the signs of ageing and protection against UV radiation ageing in several human trials. In this review, the most relevant human studies on skin nutraceuticals are evaluated and the statistical resolution, biological relevance of their results, and, the trial protocols are discussed. In conclusion, quality and rigorousness of the trials must be improved to build credible scientific evidence for skin nutraceuticals and to establish a cause-effect relationship between the ingredients the beneficial effects for the skin.

Nutraceuticals for Skin Care: A Comprehensive Review of Human Clinical Studies

Science.gov (United States)

Pérez-Sánchez, Almudena; Micol, Vicente

2018-01-01

The skin is the body’s largest organ, it participates in sensitivity and offers protection against microorganisms, chemicals and ultraviolet (UV) radiation. Consequently, the skin may suffer alterations such as photo-ageing, immune dysfunction and inflammation which may significantly affect human health. Nutraceuticals represent a promising strategy for preventing, delaying, or minimising premature ageing of the skin and also to alleviate certain skin disorders. Among them, bioactive peptides and oligosaccharides, plant polyphenols, carotenoids, vitamins and polyunsaturated fatty acids are the most widely used ingredients. Supplementation with these products has shown evidence of having an effect on the signs of ageing and protection against UV radiation ageing in several human trials. In this review, the most relevant human studies on skin nutraceuticals are evaluated and the statistical resolution, biological relevance of their results, and, the trial protocols are discussed. In conclusion, quality and rigorousness of the trials must be improved to build credible scientific evidence for skin nutraceuticals and to establish a cause-effect relationship between the ingredients the beneficial effects for the skin. PMID:29587342

Computer models versus reality: how well do in silico models currently predict the sensitization potential of a substance.

Science.gov (United States)

Teubner, Wera; Mehling, Anette; Schuster, Paul Xaver; Guth, Katharina; Worth, Andrew; Burton, Julien; van Ravenzwaay, Bennard; Landsiedel, Robert

2013-12-01

National legislations for the assessment of the skin sensitization potential of chemicals are increasingly based on the globally harmonized system (GHS). In this study, experimental data on 55 non-sensitizing and 45 sensitizing chemicals were evaluated according to GHS criteria and used to test the performance of computer (in silico) models for the prediction of skin sensitization. Statistic models (Vega, Case Ultra, TOPKAT), mechanistic models (Toxtree, OECD (Q)SAR toolbox, DEREK) or a hybrid model (TIMES-SS) were evaluated. Between three and nine of the substances evaluated were found in the individual training sets of various models. Mechanism based models performed better than statistical models and gave better predictivities depending on the stringency of the domain definition. Best performance was achieved by TIMES-SS, with a perfect prediction, whereby only 16% of the substances were within its reliability domain. Some models offer modules for potency; however predictions did not correlate well with the GHS sensitization subcategory derived from the experimental data. In conclusion, although mechanistic models can be used to a certain degree under well-defined conditions, at the present, the in silico models are not sufficiently accurate for broad application to predict skin sensitization potentials. Copyright © 2013 Elsevier Inc. All rights reserved.

New approach to predict photoallergic potentials of chemicals based on murine local lymph node assay.

Science.gov (United States)

Maeda, Yosuke; Hirosaki, Haruka; Yamanaka, Hidenori; Takeyoshi, Masahiro

2018-05-23

Photoallergic dermatitis, caused by pharmaceuticals and other consumer products, is a very important issue in human health. However, S10 guidelines of the International Conference on Harmonization do not recommend the existing prediction methods for photoallergy because of their low predictability in human cases. We applied local lymph node assay (LLNA), a reliable, quantitative skin sensitization prediction test, to develop a new photoallergy prediction method. This method involves a three-step approach: (1) ultraviolet (UV) absorption analysis; (2) determination of no observed adverse effect level for skin phototoxicity based on LLNA; and (3) photoallergy evaluation based on LLNA. Photoallergic potential of chemicals was evaluated by comparing lymph node cell proliferation among groups treated with chemicals with minimal effect levels of skin sensitization and skin phototoxicity under UV irradiation (UV+) or non-UV irradiation (UV-). A case showing significant difference (P < .05) in lymph node cell proliferation rates between UV- and UV+ groups was considered positive for photoallergic reaction. After testing 13 chemicals, seven human photoallergens tested positive and the other six, with no evidence of causing photoallergic dermatitis or UV absorption, tested negative. Among these chemicals, both doxycycline hydrochloride and minocycline hydrochloride were tetracycline antibiotics with different photoallergic properties, and the new method clearly distinguished between the photoallergic properties of these chemicals. These findings suggested high predictability of our method; therefore, it is promising and effective in predicting human photoallergens. Copyright © 2018 John Wiley & Sons, Ltd.

Skin Bleaching and Dermatologic Health of African and Afro-Caribbean Populations in the US: New Directions for Methodologically Rigorous, Multidisciplinary, and Culturally Sensitive Research

OpenAIRE

Benn, Emma K. T.; Alexis, Andrew; Mohamed, Nihal; Wang, Yan-Hong; Khan, Ikhlas A.; Liu, Bian

2016-01-01

Skin-bleaching practices, such as using skin creams and soaps to achieve a lighter skin tone, are common throughout the world and are triggered by cosmetic reasons that oftentimes have deep historical, economic, sociocultural, and psychosocial roots. Exposure to chemicals in the bleaching products, notably, mercury (Hg), hydroquinone, and steroids, has been associated with a variety of adverse health effects, such as Hg poisoning and exogenous ochronosis. In New York City (NYC), skin care pro...

Is Cytox 3522 (10% methylene-bis-thiocyanate) a human skin sensitizer?

DEFF Research Database (Denmark)

Andersen, Klaus Ejner; Hamann, K

1983-01-01

Methylene-bis-thiocyanate is an antimicrobial agent in Cytox 3522 (American Cyanamid Corporation) and Nalco 206 (Nalco Chemical Company). Both are wide-spectrum industrial biocides. Cytox 3522 showed a strong sensitization potential in guineau pigs using the Guinea Pig Maximization Test and the O...... and the Open Epicutaneous Test procedures. In spite of this, human sensitization has not been reported. This may be explained by several factors such as limited exposure, low-use concentration and a lack of diagnostic patch tests in selected patients....

Vehicle effects on human stratum corneum absorption and skin penetration.

Science.gov (United States)

Zhang, Alissa; Jung, Eui-Chang; Zhu, Hanjiang; Zou, Ying; Hui, Xiaoying; Maibach, Howard

2017-05-01

This study evaluated the effects of three vehicles-ethanol (EtOH), isopropyl alcohol (IPA), and isopropyl myristate (IPM)-on stratum corneum (SC) absorption and diffusion of the [ 14 C]-model compounds benzoic acid and butenafine hydrochloride to better understand the transport pathways of chemicals passing through and resident in SC. Following application of topical formulations to human dermatomed skin for 30 min, penetration flux was observed for 24 h post dosing, using an in vitro flow-through skin diffusion system. Skin absorption and penetration was compared to the chemical-SC (intact, delipidized, or SC lipid film) binding levels. A significant vehicle effect was observed for chemical skin penetration and SC absorption. IPA resulted in the greatest levels of intact SC/SC lipid absorption, skin penetration, and total skin absorption/penetration of benzoic acid, followed by IPM and EtOH, respectively. For intact SC absorption and total skin absorption/penetration of butenafine, the vehicle that demonstrated the highest level of sorption/penetration was EtOH, followed by IPA and IPM, respectively. The percent doses of butenafine that were absorbed in SC lipid film and penetrated through skin in 24 h were greatest for IPA, followed by EtOH and IPM, respectively. The vehicle effect was consistent between intact SC absorption and total chemical skin absorption and penetration, as well as SC lipid absorption and chemical penetration through skin, suggesting intercellular transport as a main pathway of skin penetration for model chemicals. These results suggest the potential to predict vehicle effects on skin permeability with simple SC absorption assays. As decontamination was applied 30 min after chemical exposure, significant vehicle effects on chemical SC partitioning and percutaneous penetration also suggest that skin decontamination efficiency is vehicle dependent, and an effective decontamination method should act on chemical solutes in the lipid domain.

Katharsis of the skin: Peeling applications and agents of chemical peelings in Greek medical textbooks of Graeco-Roman antiquity.

Science.gov (United States)

Ursin, F; Steger, F; Borelli, C

2018-04-28

Recipes for peelings date back to medical texts of old Egypt. The oldest medical papyri contain recipes for "improving beauty of the skin" and "removing wrinkles" by use of agents like salt and soda. The Egyptian Queen Cleopatra (69-30 BC) is said to have taken bathes in donkey's milk in order to improve the beauty of her skin. However, little is known about other agents and peeling applications in later Greek medical textbooks. We will discover new agents and describe ancient peeling applications. First, we will have to identify ancient Greek medical terms for the modern terms "peeling" and "chemical peeling". Second, based on the identified terms we will perform a systematic fulltext search for agents in original sources. Third, we will categorize the results into three peeling applications: (1) cleansing, (2) aesthetical improvement of the skin, and (3) therapy of dermatological diseases. We performed a full systematic keyword search with the identified Greek terms in databases of ancient Greek texts. Our keywords for peeling and chemical peeling are "smēxis" and "trīpsis". Our keywords for agents of peeling and chemical peeling are "smégmata", "rhýmmata", "kathartiká", and "trímmata". Diocles (4 th century BC) was the first one who mentioned "smēxis" and "trīpsis" as parts of daily cleansing routine. Criton (2 nd century AD) wrote about peeling applications, but any reference to the agents is lost. Antyllos (2 nd century AD) composed three lists of peeling applications including agents. Greek medical textbooks of Graeco-Roman antiquity report several peeling applications like cleansing, brightening, darkening, softening, and aesthetical improvement of the skin by use of peeling and chemical peeling, as well as therapy of dermatological diseases. There are 27 ancient agents for what is contemporarily called peeling and chemical peeling. We discovered more specific agents than hitherto known to research. This article is protected by copyright. All rights

Sensitive chemical neutron dosimetry using silver colloids

International Nuclear Information System (INIS)

Brede, O.; Boes, J.; Hoesselbarth, B.

1982-01-01

The radiation-induced formation of silver colloid was checked for its use as a sensitive dosimeter for neutron irradiation. For non-monoenergetic pulsed neutron irradiation in the Dubna IBR-30 reactor, the colloid dosimeter was found to be suitable to indicate the chemical neutron effect, i.e., to determine the sum concentration of the primary particles of water radiolysis: esub(aq)sup(-), OH and H. (author)

20170921 - An evaluation of selected (Q)SARs/expert systems for the Prediction of Skin Sensitization Potential (ASCCT)

Science.gov (United States)

Predictive testing to characterize substances for their skin sensitization potential has historically been based on animal models such as the Local Lymph Node Assay (LLNA) and the Guinea Pig Maximization Test (GPMT). In recent years, EU regulations have provided a strong incentiv...

Actively Perceiving and Responsive Soft Robots Enabled by Self-Powered, Highly Extensible, and Highly Sensitive Triboelectric Proximity- and Pressure-Sensing Skins.

Science.gov (United States)

Lai, Ying-Chih; Deng, Jianan; Liu, Ruiyuan; Hsiao, Yung-Chi; Zhang, Steven L; Peng, Wenbo; Wu, Hsing-Mei; Wang, Xingfu; Wang, Zhong Lin

2018-06-04

Robots that can move, feel, and respond like organisms will bring revolutionary impact to today's technologies. Soft robots with organism-like adaptive bodies have shown great potential in vast robot-human and robot-environment applications. Developing skin-like sensory devices allows them to naturally sense and interact with environment. Also, it would be better if the capabilities to feel can be active, like real skin. However, challenges in the complicated structures, incompatible moduli, poor stretchability and sensitivity, large driving voltage, and power dissipation hinder applicability of conventional technologies. Here, various actively perceivable and responsive soft robots are enabled by self-powered active triboelectric robotic skins (tribo-skins) that simultaneously possess excellent stretchability and excellent sensitivity in the low-pressure regime. The tribo-skins can actively sense proximity, contact, and pressure to external stimuli via self-generating electricity. The driving energy comes from a natural triboelectrification effect involving the cooperation of contact electrification and electrostatic induction. The perfect integration of the tribo-skins and soft actuators enables soft robots to perform various actively sensing and interactive tasks including actively perceiving their muscle motions, working states, textile's dampness, and even subtle human physiological signals. Moreover, the self-generating signals can drive optoelectronic devices for visual communication and be processed for diverse sophisticated uses. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Flexible polymer transistors with high pressure sensitivity for application in electronic skin and health monitoring.

Science.gov (United States)

Schwartz, Gregor; Tee, Benjamin C-K; Mei, Jianguo; Appleton, Anthony L; Kim, Do Hwan; Wang, Huiliang; Bao, Zhenan

2013-01-01

Flexible pressure sensors are essential parts of an electronic skin to allow future biomedical prostheses and robots to naturally interact with humans and the environment. Mobile biomonitoring in long-term medical diagnostics is another attractive application for these sensors. Here we report the fabrication of flexible pressure-sensitive organic thin film transistors with a maximum sensitivity of 8.4 kPa(-1), a fast response time of 15,000 cycles and a low power consumption of monitoring, which may lead to the use of flexible pressure sensors in mobile health monitoring and remote diagnostics in cardiovascular medicine.

Chemical kinetics of multiphase reactions between ozone and human skin lipids: Implications for indoor air quality and health effects.

Science.gov (United States)

Lakey, P S J; Wisthaler, A; Berkemeier, T; Mikoviny, T; Pöschl, U; Shiraiwa, M

2017-07-01

Ozone reacts with skin lipids such as squalene, generating an array of organic compounds, some of which can act as respiratory or skin irritants. Thus, it is important to quantify and predict the formation of these products under different conditions in indoor environments. We developed the kinetic multilayer model that explicitly resolves mass transport and chemical reactions at the skin and in the gas phase (KM-SUB-Skin). It can reproduce the concentrations of ozone and organic compounds in previous measurements and new experiments. This enabled the spatial and temporal concentration profiles in the skin oil and underlying skin layers to be resolved. Upon exposure to ~30 ppb ozone, the concentrations of squalene ozonolysis products in the gas phase and in the skin reach up to several ppb and on the order of ~10 mmol m -3 . Depending on various factors including the number of people, room size, and air exchange rates, concentrations of ozone can decrease substantially due to reactions with skin lipids. Ozone and dicarbonyls quickly react away in the upper layers of the skin, preventing them from penetrating deeply into the skin and hence reaching the blood. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Minimal erythema dose and minimal melanogenesis dose relate better to objectively measured skin type than to Fitzpatricks skin type

DEFF Research Database (Denmark)

Wulf, Hans Christian; Philipsen, Peter A; Ravnbak, Mette H

2010-01-01

Fitzpatrick skin type (FST I-IV) is a subjective expression of ultraviolet (UV) sensitivity based on erythema and tanning reactivity after a single exposure. Pigment protection factor (PPF) is an objective measurement of skin sensitivity in all skin types after a single exposure....

Intra-laboratory study to determine the reproducibility of LLNA:BrdU-ELISA for the prediction of the skin sensitizing potential of chemicals.

Science.gov (United States)

Chen, Wei; Xing, Caihong; Hou, Fenxia

The Local Lymph Node Assay (LLNA) has been designated as the first-choice in vivo assay for identification the skin sensitization potential of new chemicals. The LLNA:BrdU-ELISA is a validated non-radioactive modification to the LLNA. An intra-laboratory reproducibility study for the LLNA:BrdU-ELISA was conducted to demonstrate its adequate performance in our laboratory. Ten independent LLNA:BrdU-ELISAs with the preferred positive controls (PCs), i.e., 25% hexyl cinnamic aldehyde (HCA) and 25% eugenol, were conducted within a period of less than one year. In addition, different concentrations of 2,4-dinitrochlorobenzene (DNCB, an extreme sensitizer) (0.01, 0.1 and 0.3%), HCA (10, 25 and 50%) and eugenol (10, 25 and 50%), were tested to determine the EC1.6 values. Special Pathogen Free female CBA/J mice of 8-10weeks old were randomly allocated to the groups, each group having 4 mice. 25μl of AOO (vehicle, acetone: olive oil=4:1, v/v) or HCA, eugenol, DNCB at the needed concentration was applied to the dorsum of each ear of the mice, daily for 3 consecutive days. A single intraperitoneal injection of 0.5ml of BrdU solution (10mg/ml) was given on day 5. On day 6, a pair of auricular lymph nodes from each mouse was excised, and BrdU ELISA analysis was conducted. The result for each group is expressed as the mean Stimulation Index (SI). The mean of the 10 mean SIs for 25% HCA (2.58±0.95) and 25% eugenol (3.51±1.25) was not significantly different to that from the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) (i.e., the data on the formal validation study for the LLNA:BrdU-ELISA by the ICCVAM) (3.03±2.00 for 25% HCA, 6.13±6.06 for 25% eugenol) (P>0.05), with even smaller Coefficient of Variations (CV) (36.8% for 25% HCA, 35.6% for 25% eugenol) than that from the ICCVAM (66.0% for 25% HCA, 98.8% for 25% eugenol). In addition, the EC1.6 values for HCA, eugenol and DNCB (15.2, 12.5 and 0.25%, respectively) were consistent with

Respiratory and skin health among glass microfiber production workers: a cross-sectional study

Directory of Open Access Journals (Sweden)

Jaakkola Maritta S

2009-08-01

Full Text Available Abstract Background Only a few studies have investigated non-malignant respiratory effects of glass microfibers and these have provided inconsistent results. Our objective was to assess the effects of exposure to glass microfibers on respiratory and skin symptoms, asthma and lung function. Methods A cross-sectional study of 102 workers from a microfiber factory (response rate 100% and 76 office workers (73% from four factories in Thailand was conducted. They answered a questionnaire on respiratory health, occupational exposures, and lifestyle factors, and performed spirometry. Measurements of respirable dust were available from 2004 and 2005. Results Workers exposed to glass microfibers experienced increased risk of cough (adjusted OR 2.04, wheezing (adjOR 2.20, breathlessness (adjOR 4.46, nasal (adjOR 2.13 and skin symptoms (adjOR 3.89 and ever asthma (adjOR 3.51, the risks of breathlessness (95%CI 1.68–11.86 and skin symptoms (1.70–8.90 remaining statistically significant after adjustment for confounders. There was an exposure-response relation between the risk of breathlessness and skin symptoms and increasing level of microfiber exposure. Workers exposed to sensitizing chemicals, including phenol-formaldehyde resin, experienced increased risk of cough (3.43, 1.20–9.87 and nasal symptoms (3.07, 1.05–9.00. Conclusion This study provides evidence that exposure to glass microfibers increases the risk of respiratory and skin symptoms, and has an exposure-response relation with breathlessness and skin symptoms. Exposure to sensitizing chemicals increased the risk of cough and nasal symptoms. The results suggest that occupational exposure to glass microfibers is related to non-malignant adverse health effects, and that implementing exposure control measures in these industries could protect the health of employees.

Evidence and Considerations in the Application of Chemical Peels in Skin Disorders and Aesthetic Resurfacing

Science.gov (United States)

Berson, Diane S.; Cohen, Joel L.; Roberts, Wendy E.; Starker, Isaac; Wang, Beatrice

2010-01-01

Chemical peeling is a popular, relatively inexpensive, and generally safe method for treatment of some skin disorders and to refresh and rejuvenate skin. This article focuses on chemical peels and their use in routine clinical practice. Chemical peels are classified by the depth of action into superficial, medium, and deep peels. The depth of the peel is correlated with clinical changes, with the greatest change achieved by deep peels. However, the depth is also associated with longer healing times and the potential for complications. A wide variety of peels are available, utilizing various topical agents and concentrations, including a recent salicylic acid derivative, β-lipohydroxy acid, which has properties that may expand the clinical use of peels. Superficial peels, penetrating only the epidermis, can be used to enhance treatment for a variety of conditions, including acne, melasma, dyschromias, photodamage, and actinic keratoses. Medium-depth peels, penetrating to the papillary dermis, may be used for dyschromia, multiple solar keratoses, superficial scars, and pigmentary disorders. Deep peels, affecting reticular dermis, may be used for severe photoaging, deep wrinkles, or scars. Peels can be combined with other in-office facial resurfacing techniques to optimize outcomes and enhance patient satisfaction and allow clinicians to tailor the treatment to individual patient needs. Successful outcomes are based on a careful patient selection as well as appropriate use of specific peeling agents. Used properly, the chemical peel has the potential to fill an important therapeutic need in the dermatologist's and plastic surgeon's armamentarium. PMID:20725555

Changes in force and calcium sensitivity in the developing avian heart.

Science.gov (United States)

Godt, R E; Fogaça, R T; Nosek, T M

1991-11-01

The aim of this study was to characterize the development of the contractile properties of intact and chemically skinned muscle from chicken heart and to compare these characteristics with those of developing mammalian heart reported by others. Small trabeculae were dissected from left ventricles of Arbor Acre chickens between embryonic day 7 and young adulthood (7 weeks post-hatching). At all ages, increasing extracellular calcium (0.45-3.6 mM) progressively increased twitch force of electrically stimulated trabeculae. Twitch force at 1.8 mM extracellular calcium, normalized to cross-sectional area, increased to a maximum at 1 day post-hatching, remained constant through 3 weeks post-hatching, but then decreased at 7 weeks post-hatching. The maximal calcium-activated force of trabeculae chemically skinned with Triton X-100 detergent increased to a maximum 2 days before the time of hatching and was not significantly changed up to 7 weeks post-hatching. Over the ages studied, average twitch force in 1.8 mM calcium was between 26 and 66% of maximal calcium-activated force after skinning, suggesting that the contractile apparatus is not fully activated during the twitch in normal Ringer. In skinned trabeculae, the calcium sensitivity of the contractile apparatus was higher in the embryo than in the young adult. These age-dependent changes in calcium sensitivity are correlated with isoform switching in troponin T. A decrease in pH from 7.0 to 6.5 decreased the calcium sensitivity of the contractile apparatus to a greater degree in skinned trabeculae from young adult hearts than in those from embryonic hearts. This change in susceptibility to acidosis is temporally associated with isoform switching in troponin I.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemical Peels

Science.gov (United States)

... for Every Season How to Choose the Best Skin Care Products In This Section Dermatologic Surgery What is dermatologic ... for Every Season How to Choose the Best Skin Care Products Chemical Peels Uses for Chemical Peels Learn more ...

Expression of CD73 slows down migration of skin dendritic cells, affecting the sensitization phase of contact hypersensitivity reactions in mice.

Science.gov (United States)

Neuberger, A; Ring, S; Silva-Vilches, C; Schrader, J; Enk, A; Mahnke, K

2017-09-01

Application of haptens to the skin induces release of immune stimulatory ATP into the extracellular space. This "danger" signal can be converted to immunosuppressive adenosine (ADO) by the action of the ectonucleotidases CD39 and CD73, expressed by skin and immune cells. Thus, the expression and regulation of CD73 by skin derived cells may have crucial influence on the outcome of contact hypersensitivity (CHS) reactions. To investigate the role of CD73 expression during 2,4,6-trinitrochlorobenzene (TNCB) induced CHS reactions. Wild type (wt) and CD73 deficient mice were subjected to TNCB induced CHS. In the different mouse strains the resulting ear swelling reaction was recorded along with a detailed phenotypic analysis of the skin migrating subsets of dendritic cells (DC). In CD73 deficient animals the motility of DC was higher as compared to wt animals and in particular after sensitization we found increased migration of Langerin + DC from skin to draining lymph nodes (LN). In the TNCB model this led to a stronger sensitization as indicated by increased frequency of interferon-γ producing T cells in the LN and an increased ear thickness after challenge. CD73 derived ADO production slows down migration of Langerin + DC from skin to LN. This may be a crucial mechanism to avoid over boarding immune reactions against haptens. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Xenobiotica-metabolizing enzymes in the skin of rat, mouse, pig, guinea pig, man, and in human skin models.

Science.gov (United States)

Oesch, F; Fabian, E; Landsiedel, Robert

2018-06-18

Studies on the metabolic fate of medical drugs, skin care products, cosmetics and other chemicals intentionally or accidently applied to the human skin have become increasingly important in order to ascertain pharmacological effectiveness and to avoid toxicities. The use of freshly excised human skin for experimental investigations meets with ethical and practical limitations. Hence information on xenobiotic-metabolizing enzymes (XME) in the experimental systems available for pertinent studies compared with native human skin has become crucial. This review collects available information of which-taken with great caution because of the still very limited data-the most salient points are: in the skin of all animal species and skin-derived in vitro systems considered in this review cytochrome P450 (CYP)-dependent monooxygenase activities (largely responsible for initiating xenobiotica metabolism in the organ which provides most of the xenobiotica metabolism of the mammalian organism, the liver) are very low to undetectable. Quite likely other oxidative enzymes [e.g. flavin monooxygenase, COX (cooxidation by prostaglandin synthase)] will turn out to be much more important for the oxidative xenobiotic metabolism in the skin. Moreover, conjugating enzyme activities such as glutathione transferases and glucuronosyltransferases are much higher than the oxidative CYP activities. Since these conjugating enzymes are predominantly detoxifying, the skin appears to be predominantly protected against CYP-generated reactive metabolites. The following recommendations for the use of experimental animal species or human skin in vitro models may tentatively be derived from the information available to date: for dermal absorption and for skin irritation esterase activity is of special importance which in pig skin, some human cell lines and reconstructed skin models appears reasonably close to native human skin. With respect to genotoxicity and sensitization reactive

Application of rat mast cell incubates as a possible short-time test for sensitizing occupational chemicals

Energy Technology Data Exchange (ETDEWEB)

Diel, F.; Neidhart, B.; Opree, W.

1981-08-01

The direct action of sensitizing occupational chemicals (formaldehyde, phenol, phenylhydrazine, p-aminophenol) on rat mast cells was investigated by determination of histamine using HPLC separation and fluorimetric detection. It turned out that dispersed mast cells from immunized and non-immunized Wistar-rats are more sensitive than small-cut lung tissue slices. Passive cutaneous anaphylaxis was negative after a fortnight sensitizing experiment with the here described occupational chemicals. Short-time tests with rat mast cells reflect anaphylactoid response and are suitable for the screening of sensitizing chemicals.

Environment and the skin

International Nuclear Information System (INIS)

Suskind, R.R.

1990-01-01

The skin is an important organ of defense adaptation and a portal of entry for xenobiotics. It is vulnerable to physical, chemical, and biologic agents and capable of expressing responses to these agents in a variety of pathologic patterns. These patterns are characterized by morphologic and functional features which are elicited by careful examination and test procedures. Cutaneous cancer may result from exposure to nonionizing as well as ionizing radiation, to specific identifiable chemical hazards, and may be enhanced by trauma. Cutaneous hazards of chemical sources are largely found in the workplace and among consumer products, including drugs and toilet goods. Environmental skin diseases and injuries are preventable. Prior to use assessment for safety and for possible risks from exposure to an agent, product, or process is of primary importance in the prevention and control of environmental skin disease and injury

Fluorescence-based assay as a new screening tool for toxic chemicals

Science.gov (United States)

Moczko, Ewa; Mirkes, Evgeny M.; Cáceres, César; Gorban, Alexander N.; Piletsky, Sergey

2016-09-01

Our study involves development of fluorescent cell-based diagnostic assay as a new approach in high-throughput screening method. This highly sensitive optical assay operates similarly to e-noses and e-tongues which combine semi-specific sensors and multivariate data analysis for monitoring biochemical processes. The optical assay consists of a mixture of environmental-sensitive fluorescent dyes and human skin cells that generate fluorescence spectra patterns distinctive for particular physico-chemical and physiological conditions. Using chemometric techniques the optical signal is processed providing qualitative information about analytical characteristics of the samples. This integrated approach has been successfully applied (with sensitivity of 93% and specificity of 97%) in assessing whether particular chemical agents are irritating or not for human skin. It has several advantages compared with traditional biochemical or biological assays and can impact the new way of high-throughput screening and understanding cell activity. It also can provide reliable and reproducible method for assessing a risk of exposing people to different harmful substances, identification active compounds in toxicity screening and safety assessment of drugs, cosmetic or their specific ingredients.

Wavenumber selection based analysis in Raman spectroscopy improves skin cancer diagnostic specificity at high sensitivity levels (Conference Presentation)

Science.gov (United States)

Zhao, Jianhua; Zeng, Haishan; Kalia, Sunil; Lui, Harvey

2017-02-01

Background: Raman spectroscopy is a non-invasive optical technique which can measure molecular vibrational modes within tissue. A large-scale clinical study (n = 518) has demonstrated that real-time Raman spectroscopy could distinguish malignant from benign skin lesions with good diagnostic accuracy; this was validated by a follow-up independent study (n = 127). Objective: Most of the previous diagnostic algorithms have typically been based on analyzing the full band of the Raman spectra, either in the fingerprint or high wavenumber regions. Our objective in this presentation is to explore wavenumber selection based analysis in Raman spectroscopy for skin cancer diagnosis. Methods: A wavenumber selection algorithm was implemented using variably-sized wavenumber windows, which were determined by the correlation coefficient between wavenumbers. Wavenumber windows were chosen based on accumulated frequency from leave-one-out cross-validated stepwise regression or least and shrinkage selection operator (LASSO). The diagnostic algorithms were then generated from the selected wavenumber windows using multivariate statistical analyses, including principal component and general discriminant analysis (PC-GDA) and partial least squares (PLS). A total cohort of 645 confirmed lesions from 573 patients encompassing skin cancers, precancers and benign skin lesions were included. Lesion measurements were divided into training cohort (n = 518) and testing cohort (n = 127) according to the measurement time. Result: The area under the receiver operating characteristic curve (ROC) improved from 0.861-0.891 to 0.891-0.911 and the diagnostic specificity for sensitivity levels of 0.99-0.90 increased respectively from 0.17-0.65 to 0.20-0.75 by selecting specific wavenumber windows for analysis. Conclusion: Wavenumber selection based analysis in Raman spectroscopy improves skin cancer diagnostic specificity at high sensitivity levels.

Confocal laser scanning microscopy to estimate nanoparticles' human skin penetration in vitro.

Science.gov (United States)

Zou, Ying; Celli, Anna; Zhu, Hanjiang; Elmahdy, Akram; Cao, Yachao; Hui, Xiaoying; Maibach, Howard

2017-01-01

With rapid development of nanotechnology, there is increasing interest in nanoparticle (NP) application and its safety and efficacy on human skin. In this study, we utilized confocal laser scanning microscopy to estimate NP skin penetration. Three different-sized polystyrene NPs marked with red fluorescence were applied to human skin, and Calcium Green 5N was used as a counterstain. Dimethyl sulfoxide (DMSO) and ethanol were used as alternative vehicles for NPs. Tape stripping was utilized as a barrier-damaged skin model. Skin biopsies dosed with NPs were incubated at 4°C or 37°C for 24 hours and imaged using confocal laser scanning microscopy. NPs were localized in the stratum corneum (SC) and hair follicles without penetrating the epidermis/dermis. Barrier alteration with tape stripping and change in incubation temperature did not induce deeper penetration. DMSO enhanced NP SC penetration but ethanol did not. Except with DMSO vehicle, these hydrolyzed polystyrene NPs did not penetrate intact or barrier-damaged human "viable" epidermis. For further clinical relevance, in vivo human skin studies and more sensitive analytic chemical methodology are suggested.

Niacin Skin Sensitivity Is Increased in Adolescents at Ultra-High Risk for Psychosis.

Directory of Open Access Journals (Sweden)

Gregor E Berger

Full Text Available Most studies provide evidence that the skin flush response to nicotinic acid (niacin stimulation is impaired in schizophrenia. However, only little is known about niacin sensitivity in the ultra-high risk (UHR phase of psychotic disorders.We compared visual ratings of niacin sensitivity between adolescents at UHR for psychosis according to the one year transition outcome (UHR-T n = 11; UHR-NT n = 55 with healthy controls (HC n = 25 and first episode schizophrenia patients (FEP n = 25 treated with atypical antipsychotics.Contrary to our hypothesis niacin sensitivity of the entire UHR group was not attenuated, but significantly increased compared to the HC group, whereas no difference could be found between the UHR-T and UHR-NT groups. As expected, niacin sensitivity of FEP was attenuated compared to HC group. In UHR individuals niacin sensitivity was inversely correlated with omega-6 and -9 fatty acids (FA, but positively correlated with phospholipase A2 (inPLA2 activity, a marker of membrane lipid repair/remodelling.Increased niacin sensitivity in UHR states likely indicates an impaired balance of eicosanoids and omega-6/-9 FA at a membrane level. Our findings suggest that the emergence of psychosis is associated with an increased mobilisation of eicosanoids prior to the transition to psychosis possibly reflecting a "pro-inflammatory state", whereas thereafter eicosanoid mobilisation seems to be attenuated. Potential treatment implications for the UHR state should be further investigated.

Effect of detergents on the physico-chemical properties of skin stratum corneum: A two-photon excitation fluorescence microscopy study

DEFF Research Database (Denmark)

Bloksgaard, Maria; Brewer, Jonathan R.; Pashkovski, Eugene

2014-01-01

OBJECTIVE: Understanding the structural and dynamical features of skin is critical for advancing innovation in personal care and drug discovery. Synthetic detergent mixtures used in commercially available body wash products are thought to be less aggressive towards the skin barrier when compared...... to conventional detergents. The aim of this work is to comparatively characterize the effect of a mild synthetic cleanser mixture (SCM) and sodium dodecyl sulphate (SDS) on the hydration state of the intercellular lipid matrix and on proton activity of excised skin stratum corneum (SC). METHOD: Experiments were...... performed using two-photon excitation fluorescence microscopy. Fluorescent images of fluorescence reporters sensitive to proton activity and hydration of SC were obtained in excised skin and examined in presence and absence of SCM and SDS detergents. RESULTS: Hydration of the intercellular lipid matrix...

Utilization of reconstructed cultured human skin models as an alternative skin for permeation studies of chemical compounds

OpenAIRE

Kano, Satoshi; 藤堂, 浩明; 杉江, 謙一; 藤本, 英哲; 中田, 圭一; 徳留, 嘉寛; 橋本, フミ惠; 杉林, 堅次

2010-01-01

Two reconstructed human skin models, EpiskinSM and EpiDermTM, have been approved as alternative membranes for skin corrosive/irritation experiments due to their close correlation with animal skin. Such reconstructed human skin models were evaluated as alternative membranes for skin permeation experiments. Seven drugs with different lipophilicities and almost the same molecular weight were used as test penetrants. Relationships were investigated between permeability coefficients (P values) of ...

The respiratory allergen glutaraldehyde in the local lymph node assay: Sensitization by skin exposure, but not by inhalation

NARCIS (Netherlands)

Triel, J.J. van; Bree, B.W.J. van; Roberts, D.W.; Muijser, H.; Duistermaat, E.; Woutersen, R.A.; Kuper, C.F.

2011-01-01

Previously, a selection of low molecular weight contact and respiratory allergens had tested positive in both a skin and a respiratory local lymph node assay (LLNA), but formaldehyde was negative for sensitization by inhalation. To investigate whether this was due to intrinsic properties of aldehyde

Chemical-induced Vitiligo

Science.gov (United States)

Harris, John E.

2016-01-01

Synopsis Chemical-induced depigmentation of the skin has been recognized for over 75 years, first as an occupational hazard but then extending to those using household commercial products as common as hair dyes. Since their discovery, these chemicals have been used therapeutically in patients with severe vitiligo to depigment their remaining skin and improve their appearance. The importance of recognizing this phenomenon was highlighted during an outbreak of vitiligo in Japan during the summer of 2013, when over 16,000 users of a new skin lightening cosmetic cream developed skin depigmentation at the site of contact with the cream and many in remote areas as well. Depigmenting chemicals appear to be analogs of the amino acid tyrosine that disrupt melanogenesis and result in autoimmunity and melanocyte destruction. Because chemical-induced depigmentation is clinically and histologically indistinguishable from non-chemically induced vitiligo, and because these chemicals appear to induce melanocyte autoimmunity, this phenomenon should be known as “chemical-induced vitiligo”, rather than less accurate terms that have been previously used. PMID:28317525

The role of glutathione S-transferase and claudin-1 gene polymorphisms in contact sensitization

DEFF Research Database (Denmark)

Ross-Hansen, K; Linneberg, A; Johansen, J D

2013-01-01

BACKGROUND: Contact sensitization is frequent in the general population and arises from excessive or repeated skin exposure to chemicals and metals. However, little is known about its genetic susceptibility. OBJECTIVES: To determine the role of polymorphisms of glutathione S-transferase (GST) genes...

Adherence performances of pressure sensitive adhesives on a model viscoelastic synthetic film: a tool for the understanding of adhesion on the human skin.

Science.gov (United States)

Renvoise, Julien; Burlot, Delphine; Marin, Gérard; Derail, Christophe

2009-02-23

This work deals with the rheological behavior and adherence properties of pressure sensitive adhesive formulations dedicated to medical applications. We have developed a specific viscoelastic substrate which mimics adhesion on human skin to measure the adherence properties of PSAs when they are stuck on the human skin. By comparing peeling results of PSAs, dedicated to medical applications, stuck on human skin and on this viscoelastic substrate we show that this substrate, based on a blend of natural proteins, presents a better representation of the interactions occurring at the skin/adhesive interface than conventional substrates used for peel test (i.e. glass and steel).

Chemically dispersed oil is cytotoxic and genotoxic to sperm whale skin cells.

Science.gov (United States)

Wise, Catherine F; Wise, James T F; Wise, Sandra S; Wise, John Pierce

2018-06-01

Two major oil crises in United States history, the 1989 Exxon-Valdez oil spill in Alaska and the 2010 Deepwater Horizon Oil Rig explosion in the Gulf of Mexico, drew attention to the need for toxicological experiments on oil and chemically dispersed oil. We are still learning the effects these spills had on wildlife. However, little data is known about the toxicity of these substances in marine mammals. The objective of this study is to determine the toxicity of Alaskan oil, as well as chemically dispersed oil. Oil experiments were performed using the water accommodated fraction of Alaskan oil (WAF) and the chemically enhanced water accommodated fraction of Alaskan oil (CEWAF). The Alaskan WAF is not cytotoxic to sperm whale skin cells though it did induce chromosome damage; S9-mediated metabolism did not affect the cytotoxicity of WAF but did increase the levels of chromosome damage. Alaskan CEWAF is more cytotoxic and genotoxic than the WAF; S9 mediated metabolism increased both cytotoxicity and genotoxicity of CEWAF. Analysis of the PAH content of Alaskan WAF and CEWAF revealed a forty-fold increase in the total levels of PAHs in CEWAF compared to WAF. These findings show that chemically dispersed oil leads to higher levels of PAH exposure which are more toxic and likely to lead to longer and more persistent health effects. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluation of a novel very high sun-protection-factor moisturizer in adults with rosacea-prone sensitive skin.

Science.gov (United States)

Grivet-Seyve, Mathieu; Santoro, Francine; Lachmann, Nadège

2017-01-01

Rosacea-prone sensitive skin requires high sun-protection factor (SPF) moisturizers. This study evaluated Daylong Extreme SPF 50+ lotion, a novel cream containing five ultraviolet filters, two emollients, and three skin conditioners. This was an open-label, single-center study. On day 1, before treatment, subjects answered a questionnaire on their skin conditions and sunscreen habits, and both subjects and dermatologist evaluated skin status. Subjects applied the product once daily in the morning to the face for 21 days, and after approximately 3-5 minutes they assessed tolerability and short-term cosmetic acceptability in a questionnaire and daily diary. On day 22, the dermatologist and subjects evaluated skin status for long-term tolerance and cosmetic acceptability. The study enrolled 44 individuals (mean age 58.8 years, 91% female). At baseline, most subjects (39 of 44) showed erythema, and ~30% showed dryness and scaling. Dermatologists noted four cases of pustules and one case of papules. After 21 days' treatment with the product, the dermatologist reported significantly less erythema, dryness and scaling, three cases of pustules and two cases of papules. At baseline, ~75% of subjects noted a feeling of dryness, >50% reported tension, and nearly 25% reported tickling. After using the product for 21 days, subjects reported significantly less tension, dryness, and tickling. Some subjects noted itching and burning before and after using the product. One subject noted papules during treatment. Most subjects said that the product was pleasant, did not irritate the skin or cause stinging/burning, was easy to apply, quickly absorbed, and nongreasy, improved skin moisturization, helped prevent sun-provoked facial redness, did not worsen rosacea, and was easily incorporated into their skincare regimen. Half would switch to the product, and 80% of subjects would buy and recommend the product. The product was well tolerated in rosacea-prone subjects, producing objective

Skin cancer in skin of color: an update on current facts, trends, and misconceptions.

Science.gov (United States)

Battie, Claire; Gohara, Mona; Verschoore, Michèle; Roberts, Wendy

2013-02-01

For many fair-skinned individuals around the world, skin cancer is the leading malignancy. Although skin cancer comprises only 1% to 2% of all malignancies in those with darker complexions, the mortality rates in this subgroup are substantially higher when compared with their Caucasian counterparts. This discrepancy is largely as a result of delayed detection/treatment, and a false perception among patient and physician that brown skin confers complete protection against skin cancer. Recent studies show that 65% of surveyed African Americans never wore sunscreen, despite living in sunny climates, and that more than 60% of minority respondents erroneously believed that they were not at risk for skin cancer. Dark skin offers some protection from ultraviolet (UV) light. However, there is considerable heterogeneity in skin of color, a phenomenon that is accentuated by mixed heritage. Ethnicity does not confer skin type anymore. People of color do experience sunburn, and from a biological point of view, all skin types appear to be sensitive to UV-induced DNA damage, with an inverse relationship between skin color and sensitivity to UV light. Our population is changing rapidly, and within the next few decades minority populations will become the majority. It is therefore imperative to educate both physicians and patients on the perceived immunity against cutaneous malignancies, the need for sun protection, and the clinical signs of skin cancer in non-Caucasian people, so that future unnecessary mortality can be avoided.

Influence of skin cold sensation threshold in the occurrence of dental sensitivity during dental bleaching: a placebo controlled clinical trial.

Science.gov (United States)

Rahal, Vanessa; Gallinari, Marjorie de Oliveira; Barbosa, Juliana Stuginski; Martins-Junior, Reynaldo Leite; Santos, Paulo Henrique Dos; Cintra, Luciano Tavares Angelo; Briso, André Luiz Fraga

2018-01-18

This study verified the occurrence of dental sensitivity in patients submitted to a 35% hydrogen peroxide based product (Whiteness HP Maxx 35% - FGM), skin cold sensation threshold (SCST) and its influence on dental sensitivity. Sixty volunteers were divided into 4 groups (n = 15), according to SCST (low: GI and GIII, and high: GII and IV) and bleaching treatment (hydrogen peroxide: GI and GII, and placebo: GIII and GIV). SCST was determined in the inner forearm for 6 different times using a neurosensory analyzer, the TSA II (Medoc Advanced Medical Systems, Ramat Yishai, Northern District, Israel). Dental sensitivity measurements were performed 10 different times using a thermal stimulus and an intraoral device attached to TSA II, positioned in the buccal surface of the upper right central incisor. Spontaneous dental sensitivity was also determined using the Visual Analogue Scale (VAS). Data were submitted to Student's t-test and Pearson's Correlation Test (α=0.05). SCST remained the same during bleaching treatment. Distinct responses of dental sensitivity were found in patients with low and high SCST during the first and third bleaching session (p≤0.05). The teeth submitted to the bleaching treatment became more sensitive to cold than those treated with placebo. Moreover, data obtained with TSA and VAS presented moderate correlation. Bleaching treatment increased dental sensitivity and skin cold sensation threshold might represent a determining factor in this occurrence, since low and high SCST patients had different responses to the thermal stimulus in the teeth.

Mathematical Model to Predict Skin Concentration after Topical Application of Drugs

Directory of Open Access Journals (Sweden)

Hiroaki Todo

2013-12-01

Full Text Available Skin permeation experiments have been broadly done since 1970s to 1980s as an evaluation method for transdermal drug delivery systems. In topically applied drug and cosmetic formulations, skin concentration of chemical compounds is more important than their skin permeations, because primary target site of the chemical compounds is skin surface or skin tissues. Furthermore, the direct pharmacological reaction of a metabolically stable drug that binds with specific receptors of known expression levels in an organ can be determined by Hill’s equation. Nevertheless, little investigation was carried out on the test method of skin concentration after topically application of chemical compounds. Recently we investigated an estimating method of skin concentration of the chemical compounds from their skin permeation profiles. In the study, we took care of “3Rs” issues for animal experiments. We have proposed an equation which was capable to estimate animal skin concentration from permeation profile through the artificial membrane (silicone membrane and animal skin. This new approach may allow the skin concentration of a drug to be predicted using Fick’s second law of diffusion. The silicone membrane was found to be useful as an alternative membrane to animal skin for predicting skin concentration of chemical compounds, because an extremely excellent extrapolation to animal skin concentration was attained by calculation using the silicone membrane permeation data. In this chapter, we aimed to establish an accurate and convenient method for predicting the concentration profiles of drugs in the skin based on the skin permeation parameters of topically active drugs derived from steady-state skin permeation experiments.

Defense against dermal exposures is only skin deep

DEFF Research Database (Denmark)

Nielsen, Jesper Bo; Nielsen, Flemming; Sørensen, Jens Ahm

2007-01-01

study demonstrates that a limited damage to the skin significantly increases the permeability coefficient (K (p)) as well as total percutaneous penetration of chemicals, and most significantly for those compounds that due to their physicochemical characteristics (the most hydrophilic as well as the most...... compartments is affected by the physicochemical characteristics of the chemicals as well as by the integrity of the skin. This observation may have implications when evaluating the possibility of removing chemicals from the skin through different cleansing procedures following unintended dermal exposures....

Chemical stability of reactive skin decontamination lotion (RSDL®).

Science.gov (United States)

Bogan, R; Maas, H J; Zimmermann, T

2018-09-01

Reactive Skin Decontamination Lotion (RSDL ® ) is used for the decontamination of Chemical Warfare Agents and Toxic Industrial Compounds after dermal exposure. It has to be stockpiled over a long period and is handled in all climatic zones. Therefore stability is an essential matter of concern. In this work we describe a study to the chemical stability of RSDL ® as basis for an estimation of shelf life. We analysed RSDL ® for the active ingredient 2,3-butandione monoxime (diacetylmonooxime, DAM), the putative degradation product dimethylglyoxime (DMG) and unknown degradation products by means of a reversed phase high pressure liquid chromatography (HPLC). Calculations were done according to the Arrhenius equation. Based on the temperature dependent rate constants, the time span was calculated, until defined threshold values for DAM and DMG subject to specification and valid regulations were exceeded. The calculated data were compared to the ones gathered from stockpiled samples and samples exposed during foreign mission. The decline of DAM followed first order kinetics, while formation of DMG could be described by zero order kinetics. The rate constants were distinctively temperature dependent. Calculated data were in good accordance to the measured ones from stockpile and mission. Based on a specified acceptable DAM-content of 90% and a valid threshold value of 0.1% (w/w) for the degradation product DMG, RSDL ® proved to be stable for at least four years if stored at the recommended conditions of 15°C-30°C. If continuously stored at higher temperatures shelf life will decrease markedly. Therefore RSDL ® is an object for risk orientated quality monitoring during storage. Copyright © 2017 Elsevier B.V. All rights reserved.

Research on removing reservoir core water sensitivity using the method of ultrasound-chemical agent for enhanced oil recovery.

Science.gov (United States)

Wang, Zhenjun; Huang, Jiehao

2018-04-01

The phenomenon of water sensitivity often occurs in the oil reservoir core during the process of crude oil production, which seriously affects the efficiency of oil extraction. In recent years, near-well ultrasonic processing technology attaches more attention due to its safety and energy efficient. In this paper, the comparison of removing core water sensitivity by ultrasonic wave, chemical injection and ultrasound-chemical combination technique are investigated through experiments. Results show that: lower ultrasonic frequency and higher power can improve the efficiency of core water sensitivity removal; the effects of removing core water sensitivity under ultrasonic treatment get better with increase of core initial permeability; the effect of removing core water sensitivity using ultrasonic treatment won't get better over time. Ultrasonic treatment time should be controlled in a reasonable range; the effect of removing core water sensitivity using chemical agent alone is slightly better than that using ultrasonic treatment, however, chemical injection could be replaced by ultrasonic treatment for removing core water sensitivity from the viewpoint of oil reservoir protection and the sustainable development of oil field; ultrasound-chemical combination technique has the best effect for water sensitivity removal than using ultrasonic treatment or chemical injection alone. Copyright © 2017 Elsevier B.V. All rights reserved.

Is skin penetration a determining factor in skin sensitization potential and potency? Refuting the notion of a LogKow threshold for Skin Sensitization

Science.gov (United States)

Summary:Background. It is widely accepted that substances that cannot penetrate through the skin will not be sensitisers. Thresholds based on relevant physicochemical parameters such as a LogKow > 1 and a MW < 500, are assumed and widely accepted as self-evident truths. Objective...

Skin tribology: Science friction?

NARCIS (Netherlands)

van der Heide, Emile; Zeng, Xiangqiong; Masen, Marc Arthur

2013-01-01

The application of tribological knowledge is not just restricted to optimizing mechanical and chemical engineering problems. In fact, effective solutions to friction and wear related questions can be found in our everyday life. An important part is related to skin tribology, as the human skin is

Skin barrier function

DEFF Research Database (Denmark)

2016-01-01

Renowned experts present the latest knowledge Although a very fragile structure, the skin barrier is probably one of the most important organs of the body. Inward/out it is responsible for body integrity and outward/in for keeping microbes, chemicals, and allergens from penetrating the skin. Since...... the role of barrier integrity in atopic dermatitis and the relationship to filaggrin mutations was discovered a decade ago, research focus has been on the skin barrier, and numerous new publications have become available. This book is an interdisciplinary update offering a wide range of information...... on the subject. It covers new basic research on skin markers, including results on filaggrin and on methods for the assessment of the barrier function. Biological variation and aspects of skin barrier function restoration are discussed as well. Further sections are dedicated to clinical implications of skin...

Comparison of protocols for measuring cosmetic ingredient distribution in human and pig skin.

Science.gov (United States)

Gerstel, D; Jacques-Jamin, C; Schepky, A; Cubberley, R; Eilstein, J; Grégoire, S; Hewitt, N; Klaric, M; Rothe, H; Duplan, H

2016-08-01

The Cosmetics Europe Skin Bioavailability and Metabolism Task Force aims to improve the measurement and prediction of the bioavailability of topically-exposed compounds for risk assessment. Key parameters of the experimental design of the skin penetration studies were compared. Penetration studies with frozen human and pig skin were conducted in two laboratories, according to the SCCS and OECD 428 guidelines. The disposition in skin was measured 24h after finite topical doses of caffeine, resorcinol and 7-ethoxycoumarin. The bioavailability distribution in skin layers of cold and radiolabelled chemicals were comparable. Furthermore, the distribution of each chemical was comparable in human and pig skin. The protocol was reproducible across the two laboratories. There were small differences in the amount of chemical detected in the skin layers, which were attributed to differences in washing procedures and anatomical sites of the skin used. In conclusion, these studies support the use of pig skin as an alternative source of skin should the availability of human skin become a limiting factor. If radiolabelled chemicals are not available, cold chemicals can be used, provided that the influence of chemical stability, reactivity or metabolism on the experimental design and the relevance of the data obtained is considered. Copyright © 2016. Published by Elsevier Ltd.

Transfer of a two-tiered keratinocyte assay: IL-18 production by NCTC2544 to determine the skin sensitizing capacity and epidermal equivalent assay to determine sensitizer potency

DEFF Research Database (Denmark)

Teunis, Marc; Corsini, Emanuela; Smits, Mieke

2013-01-01

. The two tiered approach may offer an unique opportunity to provide an alternative method to the Local Lymph Node Assay (LLNA). These assays are both based on the use of human keratinocytes, which have been shown over the last two decades, to play a key role in all phases of skin sensitization....

Confocal laser scanning microscopy to estimate nanoparticles’ human skin penetration in vitro

Science.gov (United States)

Elmahdy, Akram; Cao, Yachao; Hui, Xiaoying; Maibach, Howard

2017-01-01

Objective With rapid development of nanotechnology, there is increasing interest in nanoparticle (NP) application and its safety and efficacy on human skin. In this study, we utilized confocal laser scanning microscopy to estimate NP skin penetration. Methods Three different-sized polystyrene NPs marked with red fluorescence were applied to human skin, and Calcium Green 5N was used as a counterstain. Dimethyl sulfoxide (DMSO) and ethanol were used as alternative vehicles for NPs. Tape stripping was utilized as a barrier-damaged skin model. Skin biopsies dosed with NPs were incubated at 4°C or 37°C for 24 hours and imaged using confocal laser scanning microscopy. Results NPs were localized in the stratum corneum (SC) and hair follicles without penetrating the epidermis/dermis. Barrier alteration with tape stripping and change in incubation temperature did not induce deeper penetration. DMSO enhanced NP SC penetration but ethanol did not. Conclusion Except with DMSO vehicle, these hydrolyzed polystyrene NPs did not penetrate intact or barrier-damaged human “viable” epidermis. For further clinical relevance, in vivo human skin studies and more sensitive analytic chemical methodology are suggested. PMID:29184403

Ethnic differences in objective and subjective skin irritation response: an international study.

Science.gov (United States)

Lee, E; Kim, S; Lee, J; Cho, S-A; Shin, K

2014-08-01

Due to global marketing in the cosmetics industry, it is important to assess ethnic population susceptibility when evaluating the safety of cosmetic products or chemicals. To investigate ethnic variations in skin irritation response to positive irritants. Clinical testing was performed in four countries on two ethnic groups - Asian and Caucasian. We performed patch tests on the subjects' back with 0.5% aqueous sodium lauryl sulfate (SLS) and 0.15% retinol prepared in 1,3-butylene glycol. Stinging tests were performed using 5% aqueous lactic acid and 0.001% (w/v) capsaicin prepared in 10% ethanol solution separately. The incidence of self-perceived skin sensitivity was similar in the two ethnic groups. However, the incidence of adverse skin reaction to cosmetics appeared significantly higher in Asian (33.0%) than in Caucasian subjects (11.3%). For standard positive irritants such as 0.5% aqueous SLS solution, Asian subjects showed significantly higher scores than Caucasian subjects. The incidence of positive reaction to the 0.15% retinol patch test tended to be higher in Asian than in Caucasian subjects. Our data also showed that neurosensitivity to 5% lactic acid and 0.001% capsaicin was higher in Asian than in Caucasian subjects. Although self-reported skin sensitivity does not appear to differ according to ethnicity, there are ethnic differences in objective and subjective skin irritation responses to several standard positive materials. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Spectrophotometer is useful for assessing vitiligo and chemical leukoderma severity by quantifying color difference with surrounding normally pigmented skin.

Science.gov (United States)

Hayashi, M; Okamura, K; Araki, Y; Suzuki, M; Tanaka, T; Abe, Y; Nakano, S; Yoshizawa, J; Hozumi, Y; Inoie, M; Suzuki, T

2018-05-01

Acquired skin hypopigmentation has many etiologies, including autoimmune melanocyte destruction, skin aging, inflammation, and chemical exposure. Distinguishing lesions from normally pigmented skin is clinically important to precisely assess disease severity. However, no gold standard assessment method has been reported. We aimed to investigate whether spectrophotometers are useful for assessing vitiligo and rhododendrol (4-(4-hydroxyphenol)-2-butanol) (Rhododenol ® )-induced leukoderma disease severity by quantifying skin color. Mexameter ® MX18 and CM-700d spectrophotometer were used for assessing vitiligo/leukoderma by measuring melanin index, L*a*b* color space, and ΔE*ab value, which represents the color difference between two subjects and is calculated by the values of L*a*b*. MX18 and CM-700d can quantitatively distinguish vitiligo/leukoderma from normally pigmented skin based on melanin index. CM-700d consistently quantified the color of vitiligo/leukoderma lesions and surrounding normally pigmented skin in L*a*b* color spaces and ΔE*ab. ΔE*ab is well correlated with melanin index and clinical appearance. ΔE*ab has been frequently used in aesthetic dentistry; however, current study is the first to use it in the measurement of skin color. ΔE*ab seems to be a useful parameter to evaluate the color contrast between vitiligo/leukoderma and surrounding normally pigmented skin and can be used to evaluate disease severity and patient's quality of life. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Assessing the sensitivity of human skin hyperspectral responses to increasing anemia severity levels

Science.gov (United States)

Baranoski, Gladimir V. G.; Dey, Ankita; Chen, Tenn F.

2015-09-01

Anemia is a prevalent medical condition that seriously affects millions of people all over the world. In many regions, not only its initial detection but also its monitoring are hindered by limited access to laboratory facilities. This situation has motivated the development of a wide range of optical devices and procedures to assist physicians in these tasks. Although noticeable progress has been achieved in this area, the search for reliable, low-cost, and risk-free solutions still continues, and the strengthening of the knowledge base about this disorder and its effects is essential for the success of these initiatives. We contribute to these efforts by closely examining the sensitivity of human skin hyperspectral responses (within and outside the visible region of the light spectrum) to reduced hemoglobin concentrations associated with increasing anemia severity levels. This investigation, which involves skin specimens with distinct biophysical and morphological characteristics, is supported by controlled in silico experiments performed using a predictive light transport model and measured data reported in the biomedical literature. We also propose a noninvasive procedure to be employed in the monitoring of this condition at the point-of-care.

Influence of skin cold sensation threshold in the occurrence of dental sensitivity during dental bleaching: a placebo controlled clinical trial

Directory of Open Access Journals (Sweden)

Vanessa Rahal

2018-01-01

Full Text Available Abstract Objective This study verified the occurrence of dental sensitivity in patients submitted to a 35% hydrogen peroxide based product (Whiteness HP Maxx 35% – FGM, skin cold sensation threshold (SCST and its influence on dental sensitivity. Material and Methods Sixty volunteers were divided into 4 groups (n = 15, according to SCST (low: GI and GIII, and high: GII and IV and bleaching treatment (hydrogen peroxide: GI and GII, and placebo: GIII and GIV. SCST was determined in the inner forearm for 6 different times using a neurosensory analyzer, the TSA II (Medoc Advanced Medical Systems, Ramat Yishai, Northern District, Israel. Dental sensitivity measurements were performed 10 different times using a thermal stimulus and an intraoral device attached to TSA II, positioned in the buccal surface of the upper right central incisor. Spontaneous dental sensitivity was also determined using the Visual Analogue Scale (VAS. Data were submitted to Student's t-test and Pearson's Correlation Test (α=0.05. SCST remained the same during bleaching treatment. Results Distinct responses of dental sensitivity were found in patients with low and high SCST during the first and third bleaching session (p≤0.05. The teeth submitted to the bleaching treatment became more sensitive to cold than those treated with placebo. Moreover, data obtained with TSA and VAS presented moderate correlation. Conclusions Bleaching treatment increased dental sensitivity and skin cold sensation threshold might represent a determining factor in this occurrence, since low and high SCST patients had different responses to the thermal stimulus in the teeth.

The critical review of methodologies and approaches to assess the inherent skin sensitization potential (skin allergies) of chemicals. Part II

DEFF Research Database (Denmark)

Thyssen, Jacob P; Giménez-Arnau, Elena; Lepoittevin, Jean-Pierre

2012-01-01

To identify specific cases, classes or specific use situations of chemicals for which 'safety thresholds' or 'safety limits' were set (in regulations, standards, in scientific research/clinical work, etc.) and critically review the scientific and methodological parameters used to set those limits....

Structure and Properties of Hydrophobic Aggregation Hydrogel with Chemical Sensitive Switch

Directory of Open Access Journals (Sweden)

Jiufang Duan

2017-01-01

Full Text Available Hydrogels with chemical sensitive switch have control release properties in special environments. A series of polyacrylamide-octadecyl methacrylate hydrogels crosslinked by N,N′-bis (acryloyl cystamine were synthesized as potential chemical sensitive system. When this hydrogel encounters dithiothreitol it can change its quality. The properties of the hydrogels were characterized by infrared spectroscopy, contact angle, and scanning electron microscopy. The water absorption of the hydrogel has the maximum value of 475%, when the content of octadecyl methacrylate is 5 wt%. The amount of weight loss was changed from 34.6% to 17.2%, as the content of octadecyl methacrylate increased from 3 wt% to 9.4 wt%. At the same time, the stress of the hydrogel decreased from 67.01% to 47.61%; the strength of the hydrogel reaches to the maximum 0.367 Mpa at 7 wt% octadecyl methacrylate. The increasing content of octadecyl methacrylate from 3 wt% to 9.4 wt% can enhance the hydrophobicity of the hydrogel; the contact angle of water to hydrogel changed from 14.10° to 19.62°. This hydrogel has the porous structure which permits loading of oils into the gel matrix. The functionalities of the hydrogel make it have more widely potential applications in chemical sensitive response materials.

Natural considerations for skin of color.

Science.gov (United States)

Baumann, Leslie; Rodriguez, David; Taylor, Susan C; Wu, Jessica

2006-12-01

Changing US demographics indicate that dermatologists will treat an increasing number of individuals of color. Early research on cutaneous anatomy and physiology was performed mostly in white populations. However, new research is elucidating similarities and differences in skin of color and white skin with regard to skin barrier, pigmentation, and sensitivity. Two of the most important issues are skin lightening and brightening. Products for use on skin of color typically should be gentle because of the proclivity of more deeply pigmented skin to develop pigmentary abnormalities in response to skin irritation or trauma. Increasing patient interest in natural remedies has been matched by research on the use of natural ingredients in dermatology. The relative gentleness of many of these products, coupled with excellent efficacy, makes natural ingredients such as soy and licorice excellent choices in the treatment of disorders such as postinflammatory hyperpigmentation (PIH) and melasma. For daily skin care, ingredients such as oatmeal and feverfew are good choices for gentle cleansing and moisturizing of dry, sensitive, or ashy skin. Sun protection is an increasing concern due to rising rates of melanoma. Several botanical products are useful in augmenting photoprotection with conventional sunscreens.

An in vitro model for detecting skin irritants: methyl green-pyronine staining of human skin explant cultures

NARCIS (Netherlands)

Jacobs, J. J. L.; Lehé, C.; Cammans, K. D. A.; Das, P. K.; Elliott, G. R.

2002-01-01

We evaluated the potential of human organotypic skin explant cultures (hOSECs) for screening skin irritants. Test chemicals were applied to the epidermis of the skin explants which were incubated for 4, 24 or 48 h in tissue culture medium. A decrease in epidermal RNA staining, visualised in frozen

Optimization of a chemical method for skinning of sardines (Sardina pilchardus during canning processing

Directory of Open Access Journals (Sweden)

Manuela Vaz Velho

2014-06-01

Full Text Available Most of sardine (Sardina pilchardus catches is used for canning purposes. The most common product presentation is a beheaded sardine with skin and bones packed in a tin can. Canned sardines can also be presented skinless and boneless. For this last type of product, after beheading and evisceration, sardines are placed in trays, cooked and then skinned by hand, one by one, and placed in the tins, a process involving high labour costs. The aim of this work was to develop a chemical process for peeling raw sardines and its subsequent application in a canning industry processing line just after the beheading and evisceration step and before cooking. Potassium hydroxide treatments (pellets a.r. 85% KOH were applied at concentrations of 2, 3 and 4% (v/v, distilled water. Frozen sardines were beheaded and eviscerated after thawing and immersed in the different potassium hydroxide solutions at 93ºC (pH respectively 13, 13 and 13.02 for 3 min and further washed with distilled water at 100°C. In this first set of experiments, fat sardines were used (average of 9.86% of fat, w/w. The best performance, with respect to skin removal, was achieved with the 2% potassium hydroxide immersion (pH 13. With this treatment the skin was totally removed after immersion. With the other tested concentrations portions of skin were always visible and in some cases changes in texture with breakdown of muscle structure and changes of colour occurred. It was decided to perform a second set of experiments using the 2% KOH treatment, but this time applied to low fat sardines (average of 4.77% of fat, w/w, following the same subsequent procedures. The results showed that the lower fat sardines are more prone to surface changes of colour and major muscle breaks than fat sardines after the potassium hydroxide treatment. In the canning industry for this type of product (skinless and boneless only fat sardines are used to assure the total removal of skin. This treatment of 2% KOH

Some Sensitivity Studies of Chemical Transport Simulated in Models of the Soil-Plant-Litter System

Energy Technology Data Exchange (ETDEWEB)

Begovich, C.L.

2002-10-28

Fifteen parameters in a set of five coupled models describing carbon, water, and chemical dynamics in the soil-plant-litter system were varied in a sensitivity analysis of model response. Results are presented for chemical distribution in the components of soil, plants, and litter along with selected responses of biomass, internal chemical transport (xylem and phloem pathways), and chemical uptake. Response and sensitivity coefficients are presented for up to 102 model outputs in an appendix. Two soil properties (chemical distribution coefficient and chemical solubility) and three plant properties (leaf chemical permeability, cuticle thickness, and root chemical conductivity) had the greatest influence on chemical transport in the soil-plant-litter system under the conditions examined. Pollutant gas uptake (SO{sub 2}) increased with change in plant properties that increased plant growth. Heavy metal dynamics in litter responded to plant properties (phloem resistance, respiration characteristics) which induced changes in the chemical cycling to the litter system. Some of the SO{sub 2} and heavy metal responses were not expected but became apparent through the modeling analysis.

Sevoflurane anaesthesia for nasal surgery in a patient with multiple chemical sensitivity.

Science.gov (United States)

Fernández Martín, M T; Álvarez López, J C

2018-01-01

Multiple chemical sensitivity syndrome is a group of complex disorders that include psychiatric disorders, chronic fatigue and/or respiratory problems. This syndrome could be triggered by specific allergens and toxins that cause neurophysiological sensitization and the appearance of the clinical symptomatology. Anaesthesia for these patients always poses a challenge for the anaesthetist, because they need to find and use drugs that do not trigger or aggravate the symptoms of the disease. Therefore, sevoflurane in these circumstances might be "the ideal anaesthetic". Performing general anaesthesia with sevoflurane as the sole anaesthetic agent, together with a series of environmental measures formed the basis for successful anaesthesia and surgery in our patient with a multiple chemical sensitivity syndrome. Copyright © 2017 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Skin entrance dose with and without lead apron in digital panoramic radiography for selected sensitive body regions.

Science.gov (United States)

Schulze, Ralf Kurt Willy; Cremers, Catrin; Karle, Heiko; de Las Heras Gala, Hugo

2017-05-01

The aim of this study was to compare the dose at skin level at five significant anatomical regions for panoramic radiography devices with and without lead apron by means of a highly sensitive dosimeter. A female RANDO-phantom was exposed in five different digital panoramic radiography systems, and the dose at skin level was assessed tenfold for each measurement region by means of a highly sensitive solid-state-dosimeter. The five measurement regions selected were the thyroid, both female breasts, the gonads, and a central region in the back of the phantom. For each panoramic machine, the measurements were performed in two modes: with and without a commercial lead apron specifically designed for panoramic radiography. Reproducibility of the measurements was expressed by absolute differences and the coefficient of variation. Values between shielded and unshielded doses were pooled for each region and compared by means of the paired Wilcoxon tests (p ≤ 0.05). Reproducibility as represented by the mean CV was 22 ± 52 % (median 2.3 %) with larger variations for small dose values. Doses at skin level ranged between 0.00 μGy at the gonads and 85.39 μGy at the unshielded thyroid (mean ± SD 15 ± 24 μGy). Except for the gonads, the dose in all the other regions was significantly lower (p < 0.001) when a lead apron was applied. Unshielded doses were between 1.02-fold (thyroid) and 112-fold (at the right breast) higher than those with lead apron shielding (mean: 14-fold ± 18-fold). Although the doses were entirely very low, we observed a significant increase in dose in the radiation-sensitive female breast region when no lead apron was used. Future discussions on shielding requirements for panoramic radiography should focus on these differences in the light of the linear non-threshold (LNT) theory which is generally adopted in medical imaging.

Role of pressure-sensitive adhesives in transdermal drug delivery systems.

Science.gov (United States)

Lobo, Shabbir; Sachdeva, Sameer; Goswami, Tarun

2016-01-01

Transdermal drug delivery systems (TDDS) are employed for the delivery of drugs across skin into the systemic circulation. Pressure-sensitive adhesive (PSA) is one of the most critical components used in a TDDS. The primary function of PSA is to help in adhesion of patch to skin, but more importantly it acts as a matrix for the drug and other excipients. Hence, apart from adhesion of the patch, PSA also affects other critical quality attributes of the TDDS such as drug delivery, flux through skin and physical and chemical stability of the finished product. This review article provides a summary of the adhesives used in various types of TDDS. In particular, this review will cover the design types of TDDS, categories of PSAs and their evaluation and regulatory aspects.

Local lymph node assay (LLNA): comparison of different protocols by testing skin-sensitizing epoxy resin system components.

Science.gov (United States)

Gamer, Armin O; Nies, Eberhard; Vohr, Hans-Werner

2008-12-01

Thirteen epoxy resin system components were tested in the LLNA with regard to their sensitizing potency. Lymph node stimulation was quantified not only by measuring the incorporation of [3H]-thymidine into the ear lymph nodes but also the counts of cells recovered from these organs. Equivalent figures were obtained with both endpoints used for the evaluation of lymph node cell proliferation if the reference stimulation indices were adjusted. When dissolved in acetone, all test substances showed skin-sensitizing potential, mainly on the boundary between "strong" and "moderate" according to common potency evaluation schemes. Replacing acetone with acetone/olive oil (4:1) as a vehicle for four selected test items, resulted in considerably lower estimated concentrations for sensitization induction. The challenges in comparing the results obtained by different LLNA variations are discussed.

Development of an in vitro skin sensitization test using human cell lines; human Cell Line Activation Test (h-CLAT). II. An inter-laboratory study of the h-CLAT.

Science.gov (United States)

Sakaguchi, H; Ashikaga, T; Miyazawa, M; Yoshida, Y; Ito, Y; Yoneyama, K; Hirota, M; Itagaki, H; Toyoda, H; Suzuki, H

2006-08-01

Recent regulatory changes have placed a major emphasis on in vitro safety testing and alternative models. In regard to skin sensitization tests, dendritic cells (DCs) derived from human peripheral blood have been considered in the development of new in vitro alternatives. Human cell lines have been also reported recently. In our previous study, we suggested that measuring CD86 and/or CD54 expression on THP-1 cells (human monocytic leukemia cell line) could be used as an in vitro skin sensitization method. An inter-laboratory study among two laboratories was undertaken in Japan in order to further develop an in vitro skin sensitization model. In the present study, we used two human cell lines: THP-1 and U-937 (human histiocytic lymphoma cell line). First we optimized our test protocol (refer to the related paper entitled "optimization of the h-CLAT protocol" within this journal) and then we did an inter-laboratory validation with nine chemicals using the optimized protocol. We measured the expression of CD86 and CD54 on the above cells using flow cytometry after a 24h and 48h exposure to six known allergens (e.g., DNCB, pPD, NiSO(4)) and three non-allergens (e.g., SLS, tween 80). For the sample test concentration, four doses (0.1x, 0.5x, 1x, and 2x of the 50% inhibitory concentration (IC(50))) were evaluated. IC(50) was calculated using MTT assay. We found that allergens/non-allergens were better predicted using THP-1 cells compared to U-937 cells following a 24 h and a 48 h exposure. We also found that the 24h treatment time tended to have a better accuracy than the 48 h treatment time for THP-1 cells. Expression of CD86 and CD54 were good predictive markers for THP-1 cells, but for U-937 cells, expression of CD86 was a better predictor than CD54, at the 24h and the 48 h treatment time. The accuracy also improved when both markers (CD86 and CD54) were used as compared with a single marker for THP-1 cells. Both laboratories gave a good prediction of allergen

Mouse Genetic Models Reveal Surprising Functions of IκB Kinase Alpha in Skin Development and Skin Carcinogenesis

Energy Technology Data Exchange (ETDEWEB)

Xia, Xiaojun [The Methodist Hospital Research Institute, Houston, TX 77030 (United States); Park, Eunmi [Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115 (United States); Fischer, Susan M. [Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX 78967 (United States); Hu, Yinling, E-mail: huy2@mail.nih.gov [Cancer and Inflammation Program, Center for Cancer Research, Frederick National Laboratory for Cancer Research, Frederick, MD 21701 (United States)

2013-02-15

Gene knockout studies unexpectedly reveal a pivotal role for IκB kinase alpha (IKKα) in mouse embryonic skin development. Skin carcinogenesis experiments show that Ikkα heterozygous mice are highly susceptible to chemical carcinogen or ultraviolet B light (UVB) induced benign and malignant skin tumors in comparison to wild-type mice. IKKα deletion mediated by keratin 5 (K5).Cre or K15.Cre in keratinocytes induces epidermal hyperplasia and spontaneous skin squamous cell carcinomas (SCCs) in Ikkα floxed mice. On the other hand, transgenic mice overexpressing IKKα in the epidermis, under the control of a truncated loricrin promoter or K5 promoter, develop normal skin and show no defects in the formation of the epidermis and other epithelial organs, and the transgenic IKKα represses chemical carcinogen or UVB induced skin carcinogenesis. Moreover, IKKα deletion mediated by a mutation, which generates a stop codon in the Ikkα gene, has been reported in a human autosomal recessive lethal syndrome. Downregulated IKKα and Ikkα mutations and deletions are found in human skin SCCs. The collective evidence not only highlights the importance of IKKα in skin development, maintaining skin homeostasis, and preventing skin carcinogenesis, but also demonstrates that mouse models are extremely valuable tools for revealing the mechanisms underlying these biological events, leading our studies from bench side to bedside.

Mouse Genetic Models Reveal Surprising Functions of IκB Kinase Alpha in Skin Development and Skin Carcinogenesis

International Nuclear Information System (INIS)

Xia, Xiaojun; Park, Eunmi; Fischer, Susan M.; Hu, Yinling

2013-01-01

Gene knockout studies unexpectedly reveal a pivotal role for IκB kinase alpha (IKKα) in mouse embryonic skin development. Skin carcinogenesis experiments show that Ikkα heterozygous mice are highly susceptible to chemical carcinogen or ultraviolet B light (UVB) induced benign and malignant skin tumors in comparison to wild-type mice. IKKα deletion mediated by keratin 5 (K5).Cre or K15.Cre in keratinocytes induces epidermal hyperplasia and spontaneous skin squamous cell carcinomas (SCCs) in Ikkα floxed mice. On the other hand, transgenic mice overexpressing IKKα in the epidermis, under the control of a truncated loricrin promoter or K5 promoter, develop normal skin and show no defects in the formation of the epidermis and other epithelial organs, and the transgenic IKKα represses chemical carcinogen or UVB induced skin carcinogenesis. Moreover, IKKα deletion mediated by a mutation, which generates a stop codon in the Ikkα gene, has been reported in a human autosomal recessive lethal syndrome. Downregulated IKKα and Ikkα mutations and deletions are found in human skin SCCs. The collective evidence not only highlights the importance of IKKα in skin development, maintaining skin homeostasis, and preventing skin carcinogenesis, but also demonstrates that mouse models are extremely valuable tools for revealing the mechanisms underlying these biological events, leading our studies from bench side to bedside

Chemosensory perception, symptoms and autonomic responses during chemical exposure in multiple chemical sensitivity

DEFF Research Database (Denmark)

Andersson, Linus; Claeson, Anna Sara; Dantoft, Thomas Meinertz

2016-01-01

Purpose: Multiple chemical sensitivity (MCS) is a prevalent medically unexplained symptom characterized by symptom reactions to everyday chemical exposure below hygienic thresholds. The aim of this study was to investigate the expressions of hyper-reactivity in MCS during whole-body exposure to low...... concentrations of the odorant n-butanol. Methods: We exposed 18 participants with MCS and 18 non-ill controls to a low concentration of the odorant n-butanol using an exposure chamber. The first 10 min constituted blank exposure, after which the n-butanol concentration increased and reached a plateau at 11.5 mg....../m3. Results: MCS participants, compared with controls, reported greater perceived odor intensities, more unpleasantness to the exposure and increasing symptoms over time. MCS participants also expressed higher pulse rate and lower pulse rate variability than controls did. No group differences were...

Skin Sensitive Difference of Human Body Sections under Clothing--Multiple Analysis of Skin Surface Temperature Changes

Institute of Scientific and Technical Information of China (English)

李俊; 吴海燕; 张渭源

2003-01-01

A new researching method on clothing comfort perception is developed.By it the skin surface temperature changes and subjective psychological perception of human body sections stimulated by the same cold stimulation are studied.With the multiple comparison analysis method the changing laws of skin temperature of main human body sections is obtained.

IgE Sensitization Patterns to Commonly Consumed Foods Determined by Skin Prick Test in Korean Adults.

Science.gov (United States)

Kim, Sung Ryeol; Park, Hye Jung; Park, Kyung Hee; Lee, Jae-Hyun; Park, Jung-Won

2016-08-01

Offending food allergens can vary with regional preferences in food consumption. In this study, we analysed sensitization rates to commonly consumed foods in Korean adults suspected of having food allergy. One hundred and thirty four subjects underwent a skin prick test (SPT) with 55 food allergens, of which 13 were made by our laboratory and the rest were commercially purchased. Of the 134 patients, 73 (54.5%) were sensitized to one or more food allergens. Sensitization to chrysalis was detected most frequently, at a rate of 25.4%. Sensitization rates to other food allergens were as follows: maize grain (13.4%), shrimp (11.9%), almond (11.1%), wheat flour (8.2%), lobster (8.2%), buckwheat (8.2%), mackerel (5.2%), pollack (5.2%), halibut (4.5%), peanut (4.5%), anchovy (4.4%), squid (3.7%), saury (3.0%), common eel (3.0%), yellow corvina (3.0%), hairtail (2.2%), octopus (2.2%), and others. In addition to well-known food allergens, sensitivity to mackerel, chrysalis, pollack, and halibut, which are popular foods in Korea, was observed at high rates in Korean adults. We suggest that the SPT panel for food allergy in Korea should include these allergens.

IgE Sensitization Patterns to Commonly Consumed Foods Determined by Skin Prick Test in Korean Adults

Science.gov (United States)

2016-01-01

Offending food allergens can vary with regional preferences in food consumption. In this study, we analysed sensitization rates to commonly consumed foods in Korean adults suspected of having food allergy. One hundred and thirty four subjects underwent a skin prick test (SPT) with 55 food allergens, of which 13 were made by our laboratory and the rest were commercially purchased. Of the 134 patients, 73 (54.5%) were sensitized to one or more food allergens. Sensitization to chrysalis was detected most frequently, at a rate of 25.4%. Sensitization rates to other food allergens were as follows: maize grain (13.4%), shrimp (11.9%), almond (11.1%), wheat flour (8.2%), lobster (8.2%), buckwheat (8.2%), mackerel (5.2%), pollack (5.2%), halibut (4.5%), peanut (4.5%), anchovy (4.4%), squid (3.7%), saury (3.0%), common eel (3.0%), yellow corvina (3.0%), hairtail (2.2%), octopus (2.2%), and others. In addition to well-known food allergens, sensitivity to mackerel, chrysalis, pollack, and halibut, which are popular foods in Korea, was observed at high rates in Korean adults. We suggest that the SPT panel for food allergy in Korea should include these allergens. PMID:27478328

Skin contamination - prevention and decontaminating

International Nuclear Information System (INIS)

Henning, K.

2001-01-01

A detailed examination is made of the structure of human skin. Measures were drawn up to prevent skin contamination in nuclear installations as well as contaminated skin was decontaminated from the personnel. By systematically applying these measures a significant level of success was achieved in preventing contamination in nuclear installations. Cases where more far-reaching chemical methods had to be used were kept to a minimum. (R.P.)

In vivo observation of age-related structural changes of dermal collagen in human facial skin using collagen-sensitive second harmonic generation microscope equipped with 1250-nm mode-locked Cr:Forsterite laser

Science.gov (United States)

Yasui, Takeshi; Yonetsu, Makoto; Tanaka, Ryosuke; Tanaka, Yuji; Fukushima, Shu-ichiro; Yamashita, Toyonobu; Ogura, Yuki; Hirao, Tetsuji; Murota, Hiroyuki; Araki, Tsutomu

2013-03-01

In vivo visualization of human skin aging is demonstrated using a Cr:Forsterite (Cr:F) laser-based, collagen-sensitive second harmonic generation (SHG) microscope. The deep penetration into human skin, as well as the specific sensitivity to collagen molecules, achieved by this microscope enables us to clearly visualize age-related structural changes of collagen fiber in the reticular dermis. Here we investigated intrinsic aging and/or photoaging in the male facial skin. Young subjects show dense distributions of thin collagen fibers, whereas elderly subjects show coarse distributions of thick collagen fibers. Furthermore, a comparison of SHG images between young and elderly subjects with and without a recent life history of excessive sun exposure show that a combination of photoaging with intrinsic aging significantly accelerates skin aging. We also perform image analysis based on two-dimensional Fourier transformation of the SHG images and extracted an aging parameter for human skin. The in vivo collagen-sensitive SHG microscope will be a powerful tool in fields such as cosmeceutical sciences and anti-aging dermatology.

Improvements in skin-testing technique.

Science.gov (United States)

Carr, Warner W

2006-01-01

Allergy skin testing is the primary modality used in the diagnosis of allergic diseases and guides development of treatment and avoidance plans. The goal of the Allergist is to skin test the appropriate population with a device and technique that minimizes pain while maximizing sensitivity and specificity. The debate involving the use of intradermal versus skin-prick testing in the diagnosis of aeroallergy has been long lasting. Past and present medical literature will be reviewed, establishing the lack of diagnostic use of intradermal testing in the setting of aeroallergy. New skin devices continue to be developed with a trend toward production of multidevices. Performance characteristics of various skin test devices will be reviewed with an emphasis on sensitivity, specificity, and variability of skin-prick testing devices. Significant statistical differences exist between all devices tested and reported in the literature. Whether these statistical differences equate to clinical differences is not known. With this review the practicing allergist should carefully evaluate multiple different devices and choose a device that suits their practice needs. In addition, allergists must ensure that technicians are sufficiently trained on the correct use of their device and should conduct continuing education to ensure that proper skin testing techniques are being used in their practice. Finally, the use of skin testing in pediatrics will be reviewed with a focus on safety. Care should be taken when skin testing infants < or = 6 months of age, especially in the setting of eczema and a family history of atopy.

Chemical burn or reaction

Science.gov (United States)

Chemicals that touch skin can lead to a reaction on the skin, throughout the body, or both. ... leave the person alone and watch carefully for reactions affecting the entire body. Note: If a chemical gets into the eyes, the eyes should be ...

Cows Milk-Dependent Exercise- Induced Anaphylaxis under the Condition of a Premenstrual or Ovulatory Phase Following Skin Sensitization

Directory of Open Access Journals (Sweden)

Toshinori Bito

2008-01-01

Discussion: The symptoms against cows milk began when she took baths with bath salts containing cows milk as its main ingredient for one year at the age 15 years. Sensitization to cows milk through eczematous skin is indicated from this history. Hormonal change during a premenstrual or ovulatory phase is also an important factor for the development of FDEIA in this case.

Elastin hydrolysate derived from fish enhances proliferation of human skin fibroblasts and elastin synthesis in human skin fibroblasts and improves the skin conditions.

Science.gov (United States)

Shiratsuchi, Eri; Nakaba, Misako; Yamada, Michio

2016-03-30

Recent studies have shown that certain peptides significantly improve skin conditions, such as skin elasticity and the moisture content of the skin of healthy woman. This study aimed to investigate the effects of elastin hydrolysate on human skin. Proliferation and elastin synthesis were evaluated in human skin fibroblasts exposed to elastin hydrolysate and proryl-glycine (Pro-Gly), which is present in human blood after elastin hydrolysate ingestion. We also performed an ingestion test with elastin hydrolysate in humans and evaluated skin condition. Elastin hydrolysate and Pro-Gly enhanced the proliferation of fibroblasts and elastin synthesis. Maximal proliferation response was observed at 25 ng mL(-1) Pro-Gly. Ingestion of elastin hydrolysate improved skin condition, such as elasticity, number of wrinkles, and blood flow. Elasticity improved by 4% in the elastin hydrolysate group compared with 2% in the placebo group. Therefore, elastin hydrolysate activates human skin fibroblasts and has beneficial effects on skin conditions. © 2015 Society of Chemical Industry.

GABA and GABA-Alanine from the Red Microalgae Rhodosorus marinus Exhibit a Significant Neuro-Soothing Activity through Inhibition of Neuro-Inflammation Mediators and Positive Regulation of TRPV1-Related Skin Sensitization

Science.gov (United States)

Scandolera, Amandine; Hubert, Jane; Humeau, Anne; Lambert, Carole; De Bizemont, Audrey; Winkel, Chris; Kaouas, Abdelmajid; Renault, Jean-Hugues; Reynaud, Romain

2018-01-01

The aim of the present study was to investigate the neuro-soothing activity of a water-soluble hydrolysate obtained from the red microalgae Rhodosorus marinus Geitler (Stylonemataceae). Transcriptomic analysis performed on ≈100 genes related to skin biological functions firstly revealed that the crude Rhodosorus marinus extract was able to significantly negatively modulate specific genes involved in pro-inflammation (interleukin 1α encoding gene, IL1A) and pain detection related to tissue inflammation (nerve growth factor NGF and its receptor NGFR). An in vitro model of normal human keratinocytes was then used to evaluate the ability of the Rhodosorus marinus extract to control the release of neuro-inflammation mediators under phorbol myristate acetate (PMA)-induced inflammatory conditions. The extract incorporated at 1% and 3% significantly inhibited the release of IL-1α and NGF secretion. These results were confirmed in a co-culture system of reconstructed human epithelium and normal human epidermal keratinocytes on which a cream formulated with the Rhodosorus marinus extract at 1% and 3% was topically applied after systemic induction of neuro-inflammation. Finally, an in vitro model of normal human astrocytes was developed for the evaluation of transient receptor potential vanilloid 1 (TRPV1) receptor modulation, mimicking pain sensing related to neuro-inflammation as observed in sensitive skins. Treatment with the Rhodosorus marinus extract at 1% and 3% significantly decreased PMA-mediated TRPV1 over-expression. In parallel with these biological experiments, the crude Rhodosorus marinus extract was fractionated by centrifugal partition chromatography (CPC) and chemically profiled by a recently developed 13C NMR-based dereplication method. The CPC-generated fractions as well as pure metabolites were tested again in vitro in an attempt to identify the biologically active constituents involved in the neuro-soothing activity of the Rhodosorus marinus extract

GABA and GABA-Alanine from the Red Microalgae Rhodosorus marinus Exhibit a Significant Neuro-Soothing Activity through Inhibition of Neuro-Inflammation Mediators and Positive Regulation of TRPV1-Related Skin Sensitization

Directory of Open Access Journals (Sweden)

Amandine Scandolera

2018-03-01

Full Text Available The aim of the present study was to investigate the neuro-soothing activity of a water-soluble hydrolysate obtained from the red microalgae Rhodosorus marinus Geitler (Stylonemataceae. Transcriptomic analysis performed on ≈100 genes related to skin biological functions firstly revealed that the crude Rhodosorus marinus extract was able to significantly negatively modulate specific genes involved in pro-inflammation (interleukin 1α encoding gene, IL1A and pain detection related to tissue inflammation (nerve growth factor NGF and its receptor NGFR. An in vitro model of normal human keratinocytes was then used to evaluate the ability of the Rhodosorus marinus extract to control the release of neuro-inflammation mediators under phorbol myristate acetate (PMA-induced inflammatory conditions. The extract incorporated at 1% and 3% significantly inhibited the release of IL-1α and NGF secretion. These results were confirmed in a co-culture system of reconstructed human epithelium and normal human epidermal keratinocytes on which a cream formulated with the Rhodosorus marinus extract at 1% and 3% was topically applied after systemic induction of neuro-inflammation. Finally, an in vitro model of normal human astrocytes was developed for the evaluation of transient receptor potential vanilloid 1 (TRPV1 receptor modulation, mimicking pain sensing related to neuro-inflammation as observed in sensitive skins. Treatment with the Rhodosorus marinus extract at 1% and 3% significantly decreased PMA-mediated TRPV1 over-expression. In parallel with these biological experiments, the crude Rhodosorus marinus extract was fractionated by centrifugal partition chromatography (CPC and chemically profiled by a recently developed 13C NMR-based dereplication method. The CPC-generated fractions as well as pure metabolites were tested again in vitro in an attempt to identify the biologically active constituents involved in the neuro-soothing activity of the Rhodosorus

Comet assay in reconstructed 3D human epidermal skin models—investigation of intra- and inter-laboratory reproducibility with coded chemicals

Science.gov (United States)

Pfuhler, Stefan

2013-01-01

Reconstructed 3D human epidermal skin models are being used increasingly for safety testing of chemicals. Based on EpiDerm™ tissues, an assay was developed in which the tissues were topically exposed to test chemicals for 3h followed by cell isolation and assessment of DNA damage using the comet assay. Inter-laboratory reproducibility of the 3D skin comet assay was initially demonstrated using two model genotoxic carcinogens, methyl methane sulfonate (MMS) and 4-nitroquinoline-n-oxide, and the results showed good concordance among three different laboratories and with in vivo data. In Phase 2 of the project, intra- and inter-laboratory reproducibility was investigated with five coded compounds with different genotoxicity liability tested at three different laboratories. For the genotoxic carcinogens MMS and N-ethyl-N-nitrosourea, all laboratories reported a dose-related and statistically significant increase (P 30% cell loss), and the overall response was comparable in all laboratories despite some differences in doses tested. The results of the collaborative study for the coded compounds were generally reproducible among the laboratories involved and intra-laboratory reproducibility was also good. These data indicate that the comet assay in EpiDerm™ skin models is a promising model for the safety assessment of compounds with a dermal route of exposure. PMID:24150594

Skin decontamination: principles and perspectives.

Science.gov (United States)

Chan, Heidi P; Zhai, Hongbo; Hui, Xiaoying; Maibach, Howard I

2013-11-01

Skin decontamination is the primary intervention needed in chemical, biological and radiological exposures, involving immediate removal of the contaminant from the skin performed in the most efficient way. The most readily available decontamination system on a practical basis is washing with soap and water or water only. Timely use of flushing with copious amounts of water may physically remove the contaminant. However, this traditional method may not be completely effective, and contaminants left on the skin after traditional washing procedures can have toxic consequences. This article focuses on the principles and practices of skin decontamination.

Macrophage migration inhibitory factor triggers chemotaxis of CD74+CXCR2+ NKT cells in chemically induced IFN-γ-mediated skin inflammation.

Science.gov (United States)

Hsieh, Chia-Yuan; Chen, Chia-Ling; Lin, Yee-Shin; Yeh, Trai-Ming; Tsai, Tsung-Ting; Hong, Ming-Yuan; Lin, Chiou-Feng

2014-10-01

IFN-γ mediates chemically induced skin inflammation; however, the mechanism by which IFN-γ-producing cells are recruited to the sites of inflammation remains undefined. Secretion of macrophage migration inhibitory factor (MIF), a proinflammatory cytokine, from damaged cells may promote immune cell recruitment. We hypothesized that MIF triggers an initial step in the chemotaxis of IFN-γ-producing cells in chemically induced skin inflammation. Using acute and chronic models of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation in mouse ears, MIF expression was examined, and its role in this process was investigated pharmacologically. The cell populations targeted by MIF, their receptor expression patterns, and the effects of MIF on cell migration were examined. TPA directly caused cytotoxicity accompanied by MIF release in mouse ear epidermal keratinocytes, as well as in human keratinocytic HaCaT cells. Treatment with the MIF antagonist (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester considerably attenuated TPA-induced ear swelling, leukocyte infiltration, epidermal cell proliferation, and dermal angiogenesis. Inhibition of MIF greatly diminished the dermal infiltration of IFN-γ(+) NKT cells, whereas the addition of exogenous TPA and MIF to NKT cells promoted their IFN-γ production and migration, respectively. MIF specifically triggered the chemotaxis of NKT cells via CD74 and CXCR2, and the resulting depletion of NKT cells abolished TPA-induced skin inflammation. In TPA-induced skin inflammation, MIF is released from damaged keratinocytes and then triggers the chemotaxis of CD74(+)CXCR2(+) NKT cells for IFN-γ production. Copyright © 2014 by The American Association of Immunologists, Inc.

The identification of a sensitizing component used in the manufacturing of an ink ribbon

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Anderson, Stacey E.; Tapp, Loren; Durgam, Srinivas; Meade, B. Jean; Jackson, Laurel G.; Cohen, David E.

2015-01-01

Skin diseases including dermatitis constitute ≈ 30% of all occupational illnesses, with a high incidence in the printing industry. An outbreak of contact dermatitis among employees at an ink ribbon manufacturing plant was investigated by scientists from the National Institute for Occupational Safety and Health (NIOSH). Employees in the process areas of the plant were exposed to numerous chemicals and many had experienced skin rashes, especially after the introduction of a new ink ribbon product. To identify the causative agent(s) of the occupational dermatitis, the murine local lymph node assay (LLNA) was used to identify the potential of the chemicals used in the manufacture of the ink ribbon to induce allergic contact dermatitis. Follow-up patch testing with the suspected allergens was conducted on exposed employees. Polyvinyl butyral, a chemical component used in the manufacture of the ink ribbon in question and other products, tested positive in the LLNA, with an EC3 of 3.6%, which identifies it as a potential sensitizer; however, no employees tested positive to this chemical during skin patch testing. This finding has implications beyond those described in this report because of occupational exposure to polyvinyl butyral outside of the printing industry. PMID:22375946

Influence of skin cold sensation threshold in the occurrence of dental sensitivity during dental bleaching: a placebo controlled clinical trial

OpenAIRE

Vanessa Rahal; Marjorie de Oliveira Gallinari; Juliana Stuginski Barbosa; Reynaldo Leite Martins-Junior; Paulo Henrique dos Santos; Luciano Tavares Angelo Cintra; André Luiz Fraga Briso

2018-01-01

Abstract Objective This study verified the occurrence of dental sensitivity in patients submitted to a 35% hydrogen peroxide based product (Whiteness HP Maxx 35% – FGM), skin cold sensation threshold (SCST) and its influence on dental sensitivity. Material and Methods Sixty volunteers were divided into 4 groups (n = 15), according to SCST (low: GI and GIII, and high: GII and IV) and bleaching treatment (hydrogen peroxide: GI and GII, and placebo: GIII and GIV). SCST was determined in the in...

Investigating Motivations for Women's Skin Bleaching in Tanzania

Science.gov (United States)

Lewis, Kelly M.; Robkin, Navit; Gaska, Karie; Njoki, Lillian Carol

2011-01-01

Why do many African women continue to use damaging skin-bleaching cosmetics that contain dangerous chemicals (e.g., mercury) that may increase their rates of infertility, skin cancer, and serious skin/brain/kidney disease? To address this question, our study investigated motivations driving the preservation of skin-bleaching practices in Tanzania.…

The measurement of skin impedance for the diagnosis of skin cancer

International Nuclear Information System (INIS)

Menzies, S.; Crook, B.; McCarthy, W.

1996-01-01

Full text: In vivo skin impedance measurements have been reported to be diagnostic in differentiating benign from malignant skin tumours (Kiss G et al. Borgyogy Vener Szle 45: 164,1969; Melczer N. In: Cancer of the Skin. Saunders Co. Philadelphia, 1976, pp293-313). However, in contrast to non-melanoma skin cancer, only, a small sample of malignant melanomas were reported in these previous studies. We performed skin impedance measurements on a larger sample of melanomas in order to assess the potential use of such instrumentation for clinical diagnosis. The diagnostic method described by Kiss and Horvath was reproduced with only minor modifications. Low voltage impedance measurements at 1600 Hz were taken over each lesion and on nearby surrounding normal skin. Filter paper (4mm diameter) soaked in 0.1 M KCl was used at the skin-probe interface. A minimum of 2 skin and 1 lesion measurements were taken. All lesions were taken from relatively hairless sites and were non abraded or ulcerated. With the exception of 6 seborrhoeic keratoses all lesions were excised for histological diagnosis. The lesions tested were 27 invasive melanomas, 3 in situ melanomas, 27 basal cell carcinomas (BCC), 70 benign melanocytic lesions, 19 seborrhoeic keratoses, 5 Bowens disease (in situ SCC), 1 squamous cell carcinoma (SCC) and 25 other benign lesions. Results were interpreted as previously (Melczer) by the quotient of skin impedance / lesion impedance > 1.5 indicating malignancy. Analysis of total melanocytic lesions gave a sensitivity of 44% and specificity of 83% for the diagnosis of invasive melanoma (p < 0.05). Fifty two percent of BCCs were positively diagnosed. Analysis of all benign versus all invasive malignancy gave a sensitivity of 47% and specificity of 77% for the diagnosis of invasive malignancy (p < 0.01). While impedance measurements at 1600 Hz provide a statistically significant differentiation of melanoma versus non-melanoma and invasive malignancy versus benign lesions

Skin subtype categorization based on a new questionnaire for Korean women.

Science.gov (United States)

Park, Byeong Jin; Kim, Jeong Eun; Ko, JooYeon; Kim, Myoung Shin; Park, Eun Joo; Lee, Ga Young; Lee, Jong Hee; Na, Jung Im; Chang, Sung Eun

2018-03-02

Several terms have been used to characterize skin types. However, these are not based on evident dermatologic definitions, which usually include subjective and psychological properties. The objective of this study is to establish a new practical questionnaire to classify skin subtypes in Korean women to establish treatment and skin care guidance. Eight experts developed consensus statements about skin types and created a questionnaire. The content was categorized into four major subtypes: dry or non-dry; oily or nonoily; sensitive or nonsensitive; and pigmented or nonpigmented. A total of 512 patients completed the questionnaire. Correlations with age, skin Fitzpatrick's phototypes, and dermatologic comorbidities were analyzed. Korean women commonly have oily skin but complain of dryness after cleansing. They are especially sensitive to skin care products and prone to developing pigmentary lesions. There was a trend in the proportion of dry skin subtype that increased as pigmented skin increased and oily skin decreased with advanced age. The proportion of sensitive skin was higher in patients with dermatologic comorbidities. The proportion of the pigmented skin was higher in darker Fitzpatrick skin phototypes. This is the first questionnaire established for Korean women to classify practical skin subtypes and may provide a basis for treating various skin conditions.

Chemical Peeling with a Modified Phenol Formula for the Treatment of Facial Freckles on Asian Skin.

Science.gov (United States)

Sun, Hua-Feng; Lu, Hai-Shan; Sun, Le-Qi; Ping, Wei-Dong; Mao, Dong-Sheng; Li, Dan

2018-04-01

Chemical peeling is an efficient method for the treatment of pigment disorders. For freckles, medium-depth to deep peeling using a phenol solution is one of the most effective chemical peels, and modifications of facial skin can be observed up to 20 years after peeling. However, applying phenol to the skin may cause serious side effects. Phenol peeling has been rarely used in Asia due to its tendency to cause permanent pigmentary changes and hypertrophic scars. In total, 896 Chinese inpatients with facial freckles were enrolled in this study. The phenol formula was modified with crystalline phenol, dyclonine, camphor, anhydrous alcohol and glycerin and adjusted to a concentration of 73.6-90.0%. The entire peeling treatment was divided into two procedures performed separately on 2 days. All patients exhibited 26% or greater improvement, and 99.66% of patients exhibited 51% or greater improvement (good and excellent). Scarring and systemic complications were not observed in any patient. The modified phenol formula is very effective and safe for the treatment of facial freckles in Asian patients. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A national population study of the prevalence of multiple chemical sensitivity.

Science.gov (United States)

Caress, Stanley M; Steinemann, Anne C

2004-06-01

The authors conducted a telephone survey of 1054 randomly selected individuals within the continental United States to determine the prevalence of chemical hypersensitivity and the medical diagnosis of multiple chemical sensitivity (MCS) in the American population. The etiology and symptomatology of MCS also were investigated. Results produced a 95% confidence level and a +/-3% margin of error. The authors found that 11.2% of Americans reported an unusual hypersensitivity to common chemical products such as perfume, fresh paint, pesticides, and other petrochemical-based substances, and 2.5% reported they had been medically diagnosed with MCS. Additionally, 31.1% of those sampled reported adverse reactions to fragranced products, and 17.6% experienced breathing difficulties and other health problems when exposed to air fresheners. Although chemical hypersensitivity was more common in women, it affected individuals in all demographic groups studied.

Quantitative Genome-Wide Analysis of Yeast Deletion Strain Sensitivities to Oxidative and Chemical Stress

Directory of Open Access Journals (Sweden)

Stanley Fields

2006-03-01

Full Text Available Understanding the actions of drugs and toxins in a cell is of critical importance to medicine, yet many of the molecular events involved in chemical resistance are relatively uncharacterized. In order to identify the cellular processes and pathways targeted by chemicals, we took advantage of the haploid Saccharomyces cerevisiae deletion strains (Winzeler et al., 1999. Although ~4800 of the strains are viable, the loss of a gene in a pathway affected by a drug can lead to a synthetic lethal effect in which the combination of a deletion and a normally sublethal dose of a chemical results in loss of viability. WE carried out genome-wide screens to determine quantitative sensitivities of the deletion set to four chemicals: hydrogen peroxide, menadione, ibuprofen and mefloquine. Hydrogen peroxide and menadione induce oxidative stress in the cell, whereas ibuprofen and mefloquine are toxic to yeast by unknown mechanisms. Here we report the sensitivities of 659 deletion strains that are sensitive to one or more of these four compounds, including 163 multichemicalsensitive strains, 394 strains specific to hydrogen peroxide and/or menadione, 47 specific to ibuprofen and 55 specific to mefloquine.We correlate these results with data from other large-scale studies to yield novel insights into cellular function.

Chemical peels for melasma in dark-skinned patients

Directory of Open Access Journals (Sweden)

Rashmi Sarkar

2012-01-01

Full Text Available Melasma is a common disorder of hyperpigmentation, which has a severe impact on the quality of life. Inspite of tremendous research, the treatment remains frustrating both to the patient and the treating physician. Dark skin types (Fitzpatrick types IV to VI are especially difficult to treat owing to the increased risk of post-inflammatory hyperpigmentation (PIH. The treatment ranges from a variety of easily applied topical therapies to agents like lasers and chemical peels. Peels are a well-known modality of treatment for melasma, having shown promising results in many clinical trials. However, in darker races, the choice of the peeling agent becomes relatively limited; so, there is the need for priming agents and additional maintenance peels. Although a number of new agents have come up, there is little published evidence supporting their use in day-to -day practice. The traditional glycolic peels prove to be the best both in terms of safety as well as efficacy. Lactic acid peels being relatively inexpensive and having shown equally good results in a few studies, definitely need further experimentation. We also recommend the use of a new peeling agent, the easy phytic solution, which does not require neutralisation unlike the traditional alpha-hydroxy peels. The choice of peeling agent, the peel concentration as well as the frequency and duration of peels are all important to achieve optimum results.

High Sensitivity, Low Power Nano Sensors and Devices for Chemical Sensing

Science.gov (United States)

Li, Jing; Powell, Dan; Getty, Stephanie; Lu, Yi-Jiang

2004-01-01

The chemical sensor market has been projected to grow to better than $40 billion dollars worldwide within the next 10 years. Some of the primary motivations to develop nanostructured chemical sensors are monitoring and control of environmental pollution; improved diagnostics for consumption; improvement in measurement precision and accuracy; and improved detection limits for Homeland security, battlefield environments, and process and quality control of industrial applications. In each of these applications, there is demand for sensitivity, selectivity and stability of environmental and biohazard detection and capture beyond what is currently commercially available. Nanotechnology offers the ability to work at the molecular level, atom by atom, to create large structures with fundamentally new molecular organization. It is essentially concerned with materials, devices, and systems whose structures and components exhibit novel and significantly improved physical, chemical and biological properties, phenomena, and process control due to their nanoscale size. One such nanotechnology-enabled chemical sensor has been developed at NASA Ames leveraging nanostructures, such as single walled carbon nanotubes (SWNTs) and metal oxide nanobelts or nanowires, as a sensing medium bridging a pair of interdigitated electrodes (IDE) realized through a silicon-based microfabrication and micromachining technique. The DE fingers are fabricated on a silicon substrate using standard photolithography and thin film metallization techniques. It is noteworthy that the fabrication techniques employed are not confined to the silicon substrate. Through spin casting and careful substrate selection (i.e. clothing, glass, polymer, etc.), additional degrees of freedom can be exploited to enhance sensitivity or to conform to unique applications. Both in-situ growth of nanostructured materials and casting of nanostructured dispersions were used to produce analogous chemical sensing devices.

Reduction of Salmonella on chicken meat and chicken skin by combined or sequential application of lytic bacteriophage with chemical antimicrobials.

Science.gov (United States)

Sukumaran, Anuraj T; Nannapaneni, Rama; Kiess, Aaron; Sharma, Chander Shekhar

2015-08-17

The effectiveness of recently approved Salmonella lytic bacteriophage preparation (SalmoFresh™) in reducing Salmonella in vitro and on chicken breast fillets was examined in combination with lauric arginate (LAE) or cetylpyridinium chloride (CPC). In another experiment, a sequential spray application of this bacteriophage (phage) solution on Salmonella inoculated chicken skin after a 20s dip in chemical antimicrobials (LAE, CPC, peracetic acid, or chlorine) was also examined in reducing Salmonella counts on chicken skin. The application of phage in combination with CPC or LAE reduced S. Typhimurium, S. Heidelberg, and S. Enteritidis up to 5 log units in vitro at 4 °C. On chicken breast fillets, phage in combination with CPC or LAE resulted in significant (p<0.05) reductions of Salmonella ranging from 0.5 to 1.3 log CFU/g as compared to control up to 7 days of refrigerated storage. When phage was applied sequentially with chemical antimicrobials, all the treatments resulted in significant reductions of Salmonella. The application of chlorine (30 ppm) and PAA (400 ppm) followed by phage spray (10(9)PFU/ml) resulted in highest Salmonella reductions of 1.6-1.7 and 2.2-2.5l og CFU/cm(2), respectively. In conclusion, the surface applications of phage in combination with LAE or CPC significantly reduced Salmonella counts on chicken breast fillets. However, higher reductions in Salmonella counts were achieved on chicken skin by the sequential application of chemical antimicrobials followed by phage spray. The sequential application of chlorine, PAA, and phage can provide additional hurdles to reduce Salmonella on fresh poultry carcasses or cut up parts. Copyright © 2015 Elsevier B.V. All rights reserved.

Windows of sensitivity to toxic chemicals in the motor effects development.

Science.gov (United States)

Ingber, Susan Z; Pohl, Hana R

2016-02-01

Many chemicals currently used are known to elicit nervous system effects. In addition, approximately 2000 new chemicals introduced annually have not yet undergone neurotoxicity testing. This review concentrated on motor development effects associated with exposure to environmental neurotoxicants to help identify critical windows of exposure and begin to assess data needs based on a subset of chemicals thoroughly reviewed by the Agency for Toxic Substances and Disease Registry (ATSDR) in Toxicological Profiles and Addenda. Multiple windows of sensitivity were identified that differed based on the maturity level of the neurological system at the time of exposure, as well as dose and exposure duration. Similar but distinct windows were found for both motor activity (GD 8-17 [rats], GD 12-14 and PND 3-10 [mice]) and motor function performance (insufficient data for rats, GD 12-17 [mice]). Identifying specific windows of sensitivity in animal studies was hampered by study designs oriented towards detection of neurotoxicity that occurred at any time throughout the developmental process. In conclusion, while this investigation identified some critical exposure windows for motor development effects, it demonstrates a need for more acute duration exposure studies based on neurodevelopmental windows, particularly during the exposure periods identified in this review. Published by Elsevier Inc.

Chemical applicability domain of the Local Lymph Node Assay (LLNA) for skin sensitisation potency. Part 2. The biological variability of the murine Local Lymph Node Assay (LLNA) for skin sensitisation.

Science.gov (United States)

Roberts, David W; Api, Anne Marie; Aptula, Aynur O

2016-10-01

The Local Lymph Node Assay (LLNA) is the most common in vivo regulatory toxicology test for skin sensitisation, quantifying potency as the EC3, the concentration of chemical giving a threefold increase in thymidine uptake in the local lymph node. Existing LLNA data can, along with clinical data, provide useful comparator information on the potency of sensitisers. Understanding of the biological variability of data from LLNA studies is important for those developing non-animal based risk assessment approaches for skin allergy. Here an existing set of 94 EC3 values for 12 chemicals, all tested at least three times in the same vehicle have been analysed by calculating standard deviations (SD) for logEC3 values. The SDs range from 0.08 to 0.22. The overall SD for the 94 logEC3 values is 0.147. Thus the 95% confidence limits (2xSD) for LLNA EC3 values are within a factor of 2, comparable to those for physico-chemical measurements such as partition coefficients and solubility. The residual SDs of Quantitative Mechanistic Models (QMMs) based on physical organic chemistry parameters are similar to the overall SD of the LLNA, indicating that QMMs of this type are unlikely to be bettered for predictive accuracy. Copyright © 2016 Elsevier Inc. All rights reserved.

Metabolic and redox barriers in the skin exposed to drugs and xenobiotics.

Science.gov (United States)

Korkina, Liudmila

2016-01-01

Growing exposure of human skin to environmental and occupational hazards, to numerous skin care/beauty products, and to topical drugs led to a biomedical concern regarding sustainability of cutaneous chemical defence that is essential for protection against intoxication. Since skin is the largest extra-hepatic drug/xenobiotic metabolising organ where redox-dependent metabolic pathways prevail, in this review, publications on metabolic processes leading to redox imbalance (oxidative stress) and its autocrine/endocrine impact to cutaneous drug/xenobiotic metabolism were scrutinised. Chemical and photo-chemical skin barriers contain metabolic and redox compartments: their protective and homeostatic functions. The review will examine the striking similarity of adaptive responses to exogenous chemical/photo-chemical stressors and endogenous toxins in cutaneous metabolic and redox system; the role(s) of xenobiotics/drugs and phase II enzymes in the endogenous antioxidant defence and maintenance of redox balance; redox regulation of interactions between metabolic and inflammatory responses in skin cells; skin diseases sharing metabolic and redox problems (contact dermatitis, lupus erythematosus, and vitiligo) Due to exceptional the redox dependence of cutaneous metabolic pathways and interaction of redox active metabolites/exogenous antioxidants with drug/xenobiotic metabolism, metabolic tests of topical xenobiotics/drugs should be combined with appropriate redox analyses and performed on 3D human skin models.

Anchoring molecular mechanisms to the adverse outcome pathway for skin sensitization: Analysis of existing data

NARCIS (Netherlands)

Veen, J.W. van der; Soeteman-Hernández, L.G.; Ezendam, J.; Stierum, R.; Kuper, F.C.; Loveren, H. van

2014-01-01

Allergic contact dermatitis (ACD) is a hypersensitivity immune response induced by small protein-reactive chemicals. Currently, the murine local lymph node assay (LLNA) provides hazard identification and quantitative estimation of sensitizing potency. Given the complexity of ACD, a single

On-Skin Interaction Using Body Landmarks

DEFF Research Database (Denmark)

Steimle, Juergen; Bergstrom-Lehtovirta, Joanna; Weigel, Martin

2017-01-01

The human skin is a promising surface for input to computing devices but differs fundamentally from existing touch-sensitive devices. The authors propose the use of skin landmarks, which offer unique tactile and visual cues, to enhance body-based user interfaces....

Main approaches for delivering antioxidant vitamins through the skin to prevent skin ageing.

Science.gov (United States)

Gašperlin, Mirjana; Gosenca, Mirjam

2011-07-01

One of the major contributions to skin photoageing and diseases is oxidative stress, caused by UV radiation inducing reactive oxygen and nitrogen species. Successful prophylaxis and therapy would necessitate control of the oxidant/antioxidant balance at the affected site, which can be achieved through the external supply of endogenous antioxidants. This review discusses possible strategies for dermal delivery of the antioxidant vitamins E and C, as oral supplementation has proved insufficient. These antioxidants have low skin bioavailability, owing to their poor solubility, inefficient skin permeability, or instability during storage. These drawbacks can be overcome by various approaches, such as chemical modification of the vitamins and the use of new colloidal drug delivery systems. New knowledge is included about the importance of: enhancing the endogenous skin antioxidant defense through external supply; the balance between various skin antioxidants; factors that can improve the skin bioavailability of antioxidants; and new delivery systems, such as microemulsions, used to deliver vitamins C and E into the skin simultaneously. A promising strategy for enhancing skin protection from oxidative stress is to support the endogenous antioxidant system, with antioxidants containing products that are normally present in the skin.

Chemical kinetic functional sensitivity analysis: Elementary sensitivities

International Nuclear Information System (INIS)

Demiralp, M.; Rabitz, H.

1981-01-01

Sensitivity analysis is considered for kinetics problems defined in the space--time domain. This extends an earlier temporal Green's function method to handle calculations of elementary functional sensitivities deltau/sub i//deltaα/sub j/ where u/sub i/ is the ith species concentration and α/sub j/ is the jth system parameter. The system parameters include rate constants, diffusion coefficients, initial conditions, boundary conditions, or any other well-defined variables in the kinetic equations. These parameters are generally considered to be functions of position and/or time. Derivation of the governing equations for the sensitivities and the Green's funciton are presented. The physical interpretation of the Green's function and sensitivities is given along with a discussion of the relation of this work to earlier research