Assessment Of Skin Irritation Research Articles

Anti-inflammatory efficacy and skin irritation study of Cleome gynandra extract: an animal model and pre-clinical evaluation

Cleome gynandra, a kind of medicinal herb which has strong antioxidant properties has been traditionally used for treating various ailments including skin inflammatory diseases. To date, the anti-inflammatory efficacy of C. gynandra based cream has not been reported. The aim of the study was to evaluate the anti-inflammatory activities of C. gynandra leaf extract cream using an in vivo arachidonic acid-induced ear edema in the rat model. The expression of genes related to rat ear inflammation was measured to evaluate the topical anti-inflammatory activity of C. gynandra cream. The toxicity effect of C. gynandra cream was determined through a skin irritation test in rats and human cumulative skin irritation assessment. Data collected evidently showed a significantly higher (p<0.05) percentage of recovery rate (70.21±5.14%) in rats treated with C. gynandra cream when compared to the negative control (27.43±4.75%) and basal cream (55.8±4.61%), indicating that C. gynandra cream effectively reduced inflammation symptoms in rat ear edema model study. The expressions of all pro-inflammatory cytokines and acute inflammatory-related genes were significantly down-regulated in C. gynandra cream-treated group than untreated group (negative control). The dermatological safety aspect of C. gynandra cream was confirmed by human cumulative skin irritation assessment with the average cumulative irritation index of 0.046, indicating a non-irritating effect. The overall findings demonstrated that C. gynandra cream has great potential to be applied for treating skin-related inflammatory diseases.

Skin irritation assessment and potential mechanism of Capparis spinosa L. fruits

Ethnopharmacological relevanceIn China, Capparis spinosa L. fruits (CSF) are often used topically in Uyghur folk medicine in treating rheumatic diseases with remarkable efficacy. However, it has noticed severe skin irritation after a short time application with high dose of CSF, which limited long-term clinical use. To date, there is almost no research related to skin irritation of CSF.Aim of the study: This study was intended to perform the first systematic assessment of morphological and histological changes in skin after stimulation with CSF. Furthermore, potential irritant components in CSF and related mechanisms were explored by in vitro transdermal techniques, network pharmacology, molecular docking, and experimental validation. Materials and methodsSkin changes after single and multiple stimulations with CSF were observed and subjected to skin irritation response scoring, irritation strength assessment, and histopathological analysis. In addition, in vitro transdermal technology, liquid chromatography-mass spectrometry (LC-MS) method, network pharmacology, molecular docking, and experimental validation were used to further exploit underlying skin irritant components and possible mechanisms of action. ResultsCSF induced significant morphological (erythema and edema) and histological (epidermal thickening and inflammatory infiltration) changes in skin of mice, which were similar to the clinical presentation of irritation contact dermatitis (ICD). The ethyl acetate fraction of CSF (CFEAF) was the main source of CSF-induced skin irritation. Kaempferol, flazin, and gallic acid were potential major irritant compounds. Moreover, CFEAF, kaempferol, flazin, and gallic acid could increase the levels of pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α), intercellular adhesion molecule-1 (ICAM-1), and interleukin-17A (IL-17A) to promote skin inflammation. The potential mechanism of CSF-induced skin irritation may be activation of the nuclear factor kappa-B (NF-κB) signaling pathway, including phosphorylation of NF-κB p65 (p65) and nuclear factor-kappa B inhibitor alpha (IκBα). ConclusionKaempferol, flazin, and gallic acid are potential skin irritant components from CSF. Altogether, they induce skin irritation responses through promoting the release of the inflammatory factors TNF-α and ICAM-1, as well as activating the NF-κB signaling pathway. In addition, IL-17A may be an important pro-inflammatory factor in skin irritation.

Stacked ensemble learning on HaCaT cytotoxicity for skin irritation prediction: A case study on dipterocarpol

Skin irritation is an adverse effect associated with various substances, including chemicals, drugs, or natural products. Dipterocarpol, extracted from Dipterocarpus alatus, contains several skin benefits notably anticancer, wound healing, and antibacterial properties. However, the skin irritation of dipterocarpol remains unassessed. Quantitative structure-activity relationship (QSAR) is a recommended tool for toxicity assessment involving less time, money, and animal testing to access unavailable acute toxicity data. Therefore, our study aimed to develop a highly accurate machine learning-based QSAR model for predicting skin irritation. We utilized a stacked ensemble learning model with 1064 chemicals. We also adhered to the recommendations from the OECD for QSAR validation. Subsequently, we used the proposed model to explore the cytotoxicity of dipterocarpol on keratinocytes. Our findings indicate that the model displayed promising statistical quality in terms of accuracy, precision, and recall in both 10-fold cross-validation and test datasets. Moreover, the model predicted that dipterocarpol does not have skin irritation, which was confirmed by the cell-based assay. In conclusion, our proposed model can be applied for the risk assessment of skin irritation in untested compounds that fall within its applicability domain. The web application of this model is available at https://qsarlabs.com/#stackhacat.

Synthesis and Preliminary Characterization of Polyurethane Matrices Used as a Drug Carrier for Bromelain

Bromelain, a natural substance sourced from pineapples, was found effective in various colds, in preventing heart attack and respectively in excess weight. On the other hand, it is well-known that pineapples juice increases the gastric acidity and respectively the people with hemophilia, internal bleeding must also be very careful in consuming this fruit. The objectives of this study were to obtain and to characterize a drug delivery system used for the transmembrane transfer of bromelain. The samples based on polyurethane matrices with and respectively without bromelain were synthesized and characterized by measurements of pH, encapsulation efficacy, cumulative drug release in a degradative media and in simulated gastric acid, electron microscopy and by modern techniques such as Zetasizer, cytotoxicity assay, and various non-invasive skin irritation assessment. The results indicate the obtaining of polyurethane matrices with mean sizes between 322-342 nm and neutral pH, that have a medium stability against the clusters formation tendency and a medium drug release rate. The non-irritative potential and the results on their cytotoxicity are important evidences that can be used for the further clinical trials of the polyurethane carriers.

In vitro assessment of skin irritation and corrosion properties of graphene-related materials on a 3D epidermis.

The increasing use of graphene-related materials (GRMs) in many technological applications, ranging from electronics to biomedicine, needs a careful evaluation of their impact on human health. Skin contact can be considered one of the most relevant exposure routes to GRMs. Hence, this study is focused on two main adverse outcomes at the skin level, irritation and corrosion, assessed following two specific Test Guidelines (TGs) defined by the Organization for Economic Co-operation and Development (OECD) (439 and 431, respectively) that use an in vitro 3D reconstructed human epidermis (RhE) model. After the evaluation of their suitability to test a large panel of powdered GRMs, it was found that the latter were not irritants or corrosive. Only GRMs prepared with irritant surfactants, not sufficiently removed, reduced RhE viability at levels lower than those predicting skin irritation (≤50%, after 42 min exposure followed by 42 h recovery), but not at levels lower than those predicting corrosion (<50%, after 3 min exposure or <15% after 1 h exposure). As an additional readout, a hierarchical clustering analysis on a panel of inflammatory mediators (interleukins: IL-1α, IL-1β, IL-6, and IL-18; tumor necrosis factor-α and prostaglandin E2) released by RhE exposed to these materials supported the lack of irritant and pro-inflammatory properties. Overall, these results demonstrate that both TGs are useful in assessing GRMs for their irritant or corrosion potential, and that the tested materials did not cause these adverse effects at the skin level. Only GRMs prepared using toxic surfactants, not adequately removed, turned out to be skin irritants.

Preclinical safety of tetrahydrocurcumin loaded lipidic nanoparticles incorporated into tacrolimus ointment: In vitro and in vivo evaluation

Preclinical safety and proof of concept studies for a topical ointment comprising of concentrated tetrahydrocurcumin loaded lipidic nanoparticles (THC-LNs) and tacrolimus ointment (TTO) is proposed in the present investigation. The skin irritation potential and acute dermal toxicity were performed in rats in compliance with the Organization for Economic Cooperation and Development (OECD) guidelines (402, 404 and 410) while the cytotoxic potential was performed in HaCaT cells. Finally, in vivo evaluation was performed in Imiquimod mice model of psoriasis. In primary skin irritation assessment, TTO formulation, marketed formulation (Tacroz® Forte), THC-LNs, and blank LNs were topically applied on intact skin sites in rats while another group served as a negative control group for 72 h. TTO did not induce any adverse reactions. Repeated 28 days dermal toxicity followed by biochemical and histopathological assessment showed negligible alternations and skin lesions. THC-LNs revealed negligible cytotoxic potential in HaCaT cells. TTO showed significantly high anti-psoriatic activity in comparison to marketed ointment. This was also confirmed via histopathological evaluation. Based on these findings, it can be ascertained that TTO showed minimal toxicity and has ample potential for further clinical analysis. The above studies affirm the potential of TTO as an alternative for psoriasis.

In Silico Models for Skin Sensitization and Irritation.

The assessment of skin irritation, and in particular of skin sensitization, has undergone an evolution process over the last years, pushing forward to new heights of quality and innovation. Public and commercial in silico tools have been developed for skin sensitization and irritation, introducing the possibility to simplify the evaluation process and the development of topical products within the dogma of the computational methods, representing the new doctrine in the field of risk assessment.The possibility of using in silico methods is particularly appealing and advantageous due to their high speed and low-cost results.The most widespread and popular topical products are represented by cosmetics. The European Regulation 1223/2009 on cosmetic products represents a paradigm shift for the safety assessment of cosmetics transitioning from a classical toxicological approach based on animal testing, towards a completely novel strategy, where the use of animals for toxicity testing is completely banned. In this context sustainable alternatives to animal testing need to be developed, especially for skin sensitization and irritation, two critical and fundamental endpoints for the assessment of cosmetics.The Quantitative Risk Assessment (QRA) methodology and the risk assessment using New Approach Methodologies (NAM) represent new frontiers to further improve the risk assessment process for these endpoints, in particular for skin sensitization.In this chapter we present an overview of the already existing models for skin sensitization and irritation. Some examples are presented here to illustratetools and platforms used for the evaluation of chemicals.

Assessment of Skin Irritation and Sensitisation Effects by Topical Pterostilbene

Pterostilbene has dermal medicinal benefits such as anti-inflammatory, antioxidative effects and photoprotective properties against UVB radiation. The purpose of this study was to evaluate the dermal toxicity of pterostilbene via skin irritation and sensitisation. A skin irritation test was done according to the Organization Economic Co-operation and Development 404 guideline with the scoring of irritation based on erythema and oedema in 5 albino rabbits were observed up to 14 days. The sensitisation test using the Buehler Test in accordance with the ISO 10993-10 guideline was used to study the sensitisation effect of pterostilbene on the skin surface of albino guinea pigs. According to the primary dermal irritation index (PDII), the positive control group was classified with severe irritation (scorings of 7.71). No irritation was observed for the negative control and the 5% pterostilbene treated groups. But, a slight irritation reaction with PDII scorings of 0.86 was observed in the 10% pterostilbene treated group. The sensitisation study indicated that pterostilbene did not produce any sensitisation signs, thus classified as a non-sensitiser agent according to the Magnusson &amp; Kligman classification. Pterostilbene-treated skin also did not indicate any signs of irritation and sensitisation. In conclusion, pterostilbene did not cause dermal toxicity upon application on the skin.

Formulation and Evaluation of Gel Based Herbal Hand Wash Using Extracts of Argemone Mexicana

The primary purpose of developing an herbal hand wash with a gel basis is to promote "personal hygiene." Hand hygiene is a requirement and one of the most critical processes in the preparation of meals, food service, and house and other day care facilities. On the market, antibacterial hand wash is composed of alcohol-based cleaning products, which have a number of disadvantages. An effort was made to develop a gel-based herbal hand wash utilising Argemone Mexicana extracts to avoid the adverse effects of synthetic hand wash preparations such as itching, dryness, irritation, and dermatitis. The antibacterial activity of the prepared gel hand wash toward E. coli, S. aureus, and P. aeruginosa was determined using the Agar plate diffusion technique. Physical and chemical characteristics such as pH, Viscosity, Foam height, Foam retention, Anti-Microbial Activity, Skin irritation assessment, and other parameters were used to evaluate herbal hand wash, and the results were found to be within normal ranges with minimum to no adverse effects.

Tailored Limonene-Based Nanosized Microemulsion: Formulation, Physicochemical Characterization and In Vivo Skin Irritation Assessment.

Purpose: Microemulsion (ME) achieved progressing consequences on both the research and industry levels due to their distinctive properties. ME based-limonene system is considered as a surrogate to the traditional microemulsion composed of conventional oils. Thus, a novel microemulsion based on D-limonene and Gelucire® 44/12 had been designed and evaluated with assessing the factors affecting its physicochemical characteristics and in vivo skin irritation. Methods: The impact of microemulsion components and ratios on the isotropic region of the pseudo-ternary phase diagram was investigated. The optimal formula was evaluated in terms of percentage transmittance, average globule size, size distribution, zeta potential, microscopical morphology, stability under different storage conditions and its effect on the mice ear skin.Results: The results demonstrated that Labrasol® and Labrafil® M 1944 CS had been selected as surfactant and co-surfactant, respectively, due to their emulsifying abilities. The largest isotropic area in the pseudo-ternary phase diagram was at a weight ratio of 4:1 for Labrasol® and Labrafil® M 1944 CS. The optimized microemulsion with 25% w/w of the lipid phase and 58.3% w/w of the aqueous phase displayed an optical transparency of 96.5±0.88 %, average globule size of 125±0.123 nm, polydispersity index of 0.272±0.009, zeta potential of -18.9± 2.79 mV with rounded globules morphology and high stability. The in vivo skin irritation and the histopathological evaluation of microemulsion elucidated its safety profile when applied on the skin. Conclusion: The formulated microemulsion is a prospective aid for an essential oil to minimize its volatility, enhance its stability, and mask its dermal irritant.

Evaluation of toxicity profiles of rare earth elements salts (lanthanides)

The presented study aims to extend the knowledge of toxicological profile of rare earth elements salts (REEs). The basal toxicity test performed comprised assessment of cytotoxicity (3T3 Balb/c Neutral Red Uptake Test) that allows for calculation of LD50 (rats) on the basis of the concentration which leads to a 50% reduction in cell growth (IC50). Environmental toxicity was addressed by the Tubifex tubifex (T.t.) express test. The in vitro skin irritation (OECD TG 439) and skin corrosion tests (OECD TG 431) utilizing the 3D in vitro reconstructed human epidermal model EpiDerm (MatTek IVSL, SK) were used for assessment of skin irritation and corrosion potential hazard of REEs. Mutagenic effects were determined using the bacterial reverse mutation assay (Ames Test) on 5 Salmonella typhimurium strains with and without metabolic activation (OECD TG 471). Endocrine disruption was evaluated by means of a yeast-based assay YES/YAS (Xenometrix, CH). Skin sensitization was assessed using the LuSens assay, based on a genetically modified human keratinocyte cell line (OECD TG 442D). The tested REEs have no potential of mutagenicity or skin sensitization, exhibit very weak endocrine disruption potential and only exceptional local irritation/corrosion effects for thulium (III) chloride anhydrous, but have acute and chronic toxic effects on the aquatic environment.

In vitro skin irritation assessment using EpiDerm™: applicability for updating toxicity information of oxybenzone and N,N-diethyl-m-toluamide

A skin irritation test using in vitro reconstructed human epidermis (RhE) models was established for hazard identification of irritant chemicals in accordance with UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS) category. In this study, EpiDerm™ was used to assess skin irritation by oxybenzone and N,N-diethyl-m-toluamide (DEET), which are widely used sunscreen and insect repellent components, respectively. EpiDerm™ was applied with oxybenzone and DEET, combined and sequentially with each single dose. Epidermal morphology and differentiation/proliferation were examined microscopically. Oxybenzone and sequential administration groups were determined as nonirritant with cell viability >50% and the morphology was comparable to the human epidermis. Contrastingly, the DEET and coadministration groups exhibited cell viability <50% and poor epidermal morphology. Interleukin (IL)-1α release from substance-treated EpiDerm™ increased inversely to cell viability, suggesting the pro-inflammatory reaction was initiated by DEET. CK-10, E-cadherin, Ki-67, laminin, and ceramide were identified as relevant markers to assess oxybenzone- or DEET-induced epidermal injury. In conclusion, these results may indicate to be aware of the possible skin irritation by indiscriminate use of oxybenzone and DEET without animal testing.

Solution Properties of Alkyl β‐D‐Maltosides

AbstractAlkyl β‐D‐maltosides are an important class of sugar‐based nonionic surfactants and have been widely studied. Nevertheless, it is still necessary to investigate further their amphiphilic structure‐surface property relationships. In this article, we reported a series of properties of synthetic alkyl β‐D‐maltosides (6a–6i, n = 6–18) including their hydrophilic–lipophilic balance (HLB) number, water solubility, hygroscopicity, moisture‐retention capacity, foaming ability, surface tension, thermotropic phase behavior, and skin irritation. Their HLB number and water solubility decreased with increasing alkyl chain length. Hexyl β‐D‐maltoside exhibited the strongest hygroscopicity and moisture‐retention capacity. Decyl β‐D‐maltoside and dodecyl β‐D‐maltoside possessed excellent foaming power and foaming stability. Furthermore, the critical micelle concentration (CMC) of alkyl β‐D‐maltoside (6a–6g, n = 6–14) and their surface tension at CMC decreased with increasing alkyl chain length. At last, alkyl β‐D‐maltosides (6a–6g) should be considered as safe surfactants by the skin irritation assessment.

Round robin study to evaluate the reconstructed human epidermis (RhE) model as an in vitro skin irritation test for detection of irritant activity in medical device extracts

Assessment of skin irritation is an essential component of the safety evaluation of medical devices. OECD Test Guideline 439 describes the use of reconstructed human epidermis (RhE) as an in vitro test system for classification of skin irritation by neat chemicals. An international round robin study was conducted to evaluate the RhE method for determination of skin irritant potential of medical device extracts. Four irritant polymers and three non-irritant controls were obtained or developed that had demonstrated their suitability to act as positive or negative test samples. The RhE tissues (EpiDerm™ and SkinEthic™ RHE) were dosed with 100 μL aliquots of either saline or sesame oil extract. Incubation times were 18 h (EpiDerm™) and 24 h (SkinEthic™ RHE). Cell viability reduction > 50% was indicative of skin irritation. Both the EpiDerm™ and SkinEthic™ RHE tissues were able to correctly identify virtually all of the irritant polymer samples either in the saline, sesame oil or both solvent extracts. Our results indicate that RhE tissue models can detect the presence of strong skin irritants at low levels in dilute medical device polymer extracts. Therefore, these models may be suitable replacements for the rabbit skin irritation test to support the biological evaluation of medical devices.

Comparative assessment of local tolerance of alcohols commonly used in alcohol-based hand rubs for hand hygiene

Hand hygiene plays a key role in nosocomial infection prevention. To achieve users' adherence, products' dermal tolerance is essential. We aimed at making a comparative assessment of skin irritation and phototoxicity of the 3 alcohols commonly used in alcohol-based hand rubs (Ethanol, Propan-2-ol, Propan-1-ol) at 60, 70, 80 or 85% w/w in water or with co-formulates (hydrating, emollient and skin protective agents). In vitro validated OECD methods 439 and 432 were used. For irritation, EpiSkin™ Small Model was the chosen Reconstructed Human Epidermis (RhE). For phototoxicity, co-formulates alone or in mixture with and without alcohol were tested using BALB/c 3T3 cell cultures. Whilst Ethanol and Propan-2-ol could not be differentiated and displayed good skin tolerance profiles, Propan-1-ol based products lead to significant viability impairments of RhE at 60, 70 or 80% and at 60% in the presence of co-formulates. However, these results could not be reproduced in another RhE model. Taking also into account bibliographic data on Propan-1-ol, this suggests that our results are probably related to a lack of specificity of the used RhE. Therefore, it can be relevant in case of significant results to use two different RhE models before performing any classification and/or performing any complementary tests.

화장품 소재로서 후박 에틸아세테이트 분획물의 미백활성에 관한 효과

천연물인 후박(Magnolia obovata Bark, M. obovata Bark)을 에탄올 추출 및 농축하여 에틸아세테이트 층으로 분획한 분획물이 피부에 안전하고 효과적인 미백 활성을 확인함으로써 미백 화장품 원료 소재로서 가능성을 확인하였다. 후박의 에탄올 농축물을 에틸아세테이트 분획하여 유효물질 honokiol을 HPLC로 정량하였다. 후박 에틸아세테이트 분획물에 대한 in vitro 미백활성 결과, 농도 의존적으로 세포 외 멜라닌 분비를 감소시켜 <TEX>$IC_{50}=11.05{\mu}g/mL$</TEX>임을 확인하였다. 또한 세포에 독성을 가지지 않는 최대농도인 <TEX>$12.5{\mu}g/mL$</TEX> 처리 시 최대 약 60%의 멜라닌 분비 억제로 세포 외로 분비되는 멜라닌의 양을 효과적으로 억제함을 확인할 수 있었다. 또한 <TEX>${\alpha}-MSH$</TEX> (50 nM) 처리한 그룹과 비교하여 <TEX>$IC_{50}=10.85{\mu}g/mL$</TEX>로 우수한 세포 내 멜라닌 생성억제 효과를 보였으며 세포에 자극이 되지 않는 최대농도인 <TEX>$12.5{\mu}g/mL$</TEX> 처리 시 최대 약 59%의 멜라닌 생성 억제를 확인하여 세포 외 멜라닌 분비 뿐만 아니라 세포 내에 존재하는 멜라닌의 양 또한 효과적으로 억제함을 확인할 수 있었다. 양성대조군으로 사용된 <TEX>${\alpha}-arbutin$</TEX>의 경우, <TEX>$IC_{50}=59.99{\mu}g/mL$</TEX>로 후박 에틸아세테이트 분획물이 양성대조군 <TEX>${\alpha}-arbutin$</TEX>과 비교하여 우수한 세포 내 멜라닌 생성 억제 효과를 가짐을 확인하였다. 임상연구의 경우, 후박 에틸아세테이트 분획물을 적용한 화장품 크림은 (주)대한피부과학연구소(KDRI) 윤리위원회의 IRB 승인(KDRI-IRB-1536) 후 반복 첩포를 통한 인체 누적첩포시험을 진행하여 무감작 물질로 확인하였다. 또한 후박 에틸아세테이트 분획물을 적용한 화장품 크림은 대조군 대비 국소적 미백효과와 신뢰성 있는 피부 안전성을 보여주었다. 최종적으로 후박 에틸아세테이트 분획물이 안전하고 효과적인 미백효과를 가지는 화장품 소재로 충분한 이용 가능성이 있음을 확인하였다. EtOAc fractions of Magnolia obovata (M. obovata) Bark extracts were studied for the potential ingredient as a safe and effective whitening cosmetic material. The concentration of active substances honokiol was determined by HPLC. In vitro, the fractions reduced the extracellular and intracellular melanin contents in B16F10 cells in dose dependently and inhibited extracellular melanin secretion (<TEX>$IC_{50}=11.05{\mu}g/mL$</TEX>). The <TEX>$12.5{\mu}g/mL$</TEX> treatment of maximum concentration effectively inhibited up to about 60% to the amount of extracullular melanin. Also, the <TEX>$12.5{\mu}g/mL$</TEX> treatment of maximum concentration effectively inhibited up to about 59% to the amount of intracullular melanin (<TEX>$IC_{50}=10.85{\mu}g/mL$</TEX>). The <TEX>$IC_{50}$</TEX> value of <TEX>${\alpha}-arbutin$</TEX> used as a positive control was <TEX>$59.99{\mu}g/mL$</TEX>. So, EtOAc fractions of M. obovata Bark extracts showed whitening effect when compared with the non-treatment group. In case of in vivo study, Cosmetic cream with EtOAc fractions of M. obovata Bark extracts was approved by Ethics committee of KDRI (IRB number: KDRI-IRB-1537). As a result in progress for skin sensitization as well as assessment of skin irritation through repeated patch test, skin allergens was identified as non sensitizing agents. Also, cosmetic cream with EtOAc fractions of M. obovata Bark extracts showed significant topical whitening effect and reliable skin safety when compared with the non-treatment group. In conclusion, EtOAc fractions of M. obovata Bark extracts may be a useful cosmetic ingredient for effective skin whitening.

In vitro skin irritation assessment becomes a reality in China using a reconstructed human epidermis test method

The in vitro EpiSkin™ test method was validated in 2007 by the European Union Reference Laboratory for alternatives to animal testing (EURL ECVAM) as a full replacement method for the Draize acute skin irritation test and adopted in the OECD Test Guideline 439 in 2009. Based on the EpiSkin™ technology, the production of a reconstructed epidermis model has been established and standardized in China. The evaluation of the in vitro skin irritation test method using this EpiSkin™ model produced in China was performed on a set of 45 chemicals. Good predictive capacity was obtained with 94% (n=17) for sensitivity, 75% (n=28) for specificity and 82% for accuracy. The accuracy of the included 20 OECD reference chemicals also met the OECD acceptance criteria, indicating that this testing method based on the EpiSkin™ model produced in China can be used as a stand-alone test method to predict skin irritation. The availability and validity of in vitro epidermis model and testing method are of great significance for extending the applications of non-animal alternative testing methods in China.

Evaluation of skin irritation in rats using simultaneous laser Doppler flowmetry and oxygenation monitoring

The possibility of assessment of skin irritation in rats with the use of simultaneous laser Doppler flowmetry (LDF) and oxygenation monitoring was investigated. The study was designed according to ISO 10993-10 using formaldehyde as a model irritant. 4-Hour application of 1 % formaldehyde induced significant local increase in skin microcirculation for the first 2 days by a factor of up to 2.4, whereas tissue oxygenation increased in much lower extent. The microcirculation was significantly inhibited by 10 % formaldehyde following treatment and then it gradually increased for 24 and 48 h of recovery period. The results correlated with visual evaluation of skin edema and erythema in treated zones. LDF/oxygenation signals provide early information on skin irritation and damage in rat model. The technique is valuable for preclinical/toxicological studies of chemical substances and medical materials.

An integrated testing strategy for in vitro skin corrosion and irritation assessment using SkinEthic™ Reconstructed Human Epidermis

The SkinEthic™ Reconstructed Human Epidermis (RHE) method has been formally adopted for the regulatory assessment of skin irritation (OECD TG 439) and corrosion (OECD TG 431). Recently, the OECD adopted an Integrated Approach on Testing and Assessment (IATA) for skin corrosion and skin irritation (OECD GD 203), which provides guidance on the integration of existing and new information in a modular approach for classification and labelling. The present study aimed to evaluate the use of the SkinEthic™ RHE model within the proposed OECD IATA. Data on 86 substances were integrated in a bottom-up and top-down testing strategy to assess their capacity for EU CLP and UN GHS classifications. For EU CLP, strategies showed an accuracy of 84.8% to discriminate non-classified from classified substances, 94.4% to discriminate corrosive from non-corrosive substances, and 68.5% to discriminate the four (sub)-categories. For UN GHS, strategies showed an accuracy of 89.5% to discriminate non-classified from classified substances, 93.4% to discriminate corrosive from non-corrosive substances, and 74.2% to discriminate four GHS (sub)-categories (excluding Category 3). In conclusion, the integration of SkinEthic™ RHE irritation and corrosion data in a bottom-up and top-down testing strategy allows the classification of substances according to EU CLP and UN GHS.

Assessment of Skin Irritation Caused by S-(-)-10,11-Dihydroxyfarnesoic Acid Methyl Ester, a Metabolite of Beauveria bassiana CS1029

Assessment of Skin Irritation Caused by S-(-)-10,11-Dihydroxyfarnesoic Acid Methyl Ester, a Metabolite of Beauveria bassiana CS1029