Surfactants are amphiphilic substances that induce surface tension reduction, washing, and emulsification and are used for various purposes. Recently, biosurfactants manufactured from renewable resources and with high biocompatibility have gained increasing attention. Sophorolipid (SL), a type of biosurfactant derived from Starmerella bombicola, possesses detergency and emulsification properties, making it suitable for household and personal care applications. However, there are limited toxicological data on SLs. In this study, we conducted cytotoxicity and skin-irritation tests using SLs, revealing that cytotoxicity and skin irritation induced by SLs were extremely low (logIC 50 = 4.76 mg/L) and equivalent to those of solvents and oils used in personal care products.

With the growing importance of alternative test methods that implement the 3Rs principles (Reduction, Refinement and Replacement) and the global importance of biological safety assessment data for medical devices is increasing. We have developed and optimized the \'KeraSkin™ Skin Irritation Test (KeraSkin™ SIT) for medical device\' for regulatory application in biological evaluation according to ISO 10993-23. We conducted a round robin study to optimize and evaluate the performance of KeraSkin™ SIT for medical devices using KeraSkin™ Reconstructed Human Epidermis (RhE), which is developed and manufactured in Korea. This round robin study was performed to assess the transferability, reproducibility (within and between laboratories) and predictive capacity in 1 lead laboratory and 3 participating laboratories based on OECD Guidance Document 34. The predictive capacity, the results showed 83.3 % of sensitivity, 100 % of specificity and 91.6 % of accuracy. In conclusion, the results demonstrate that \'KeraSkin™ SIT for medical device\' provides a robust test method for detecting irritant activity of medical device extracts and can be utilized for identifying low levels of potent irritants in medical device extracts. Therefore, it fulfills the requirements to be included as a \'me-too\' test method to EpiDerm™ and SkinEthic™ skin irritation test in ISO 10993-23.

After EU ban on animal testing for cosmetics in 2013, there has been an increasing global interest in alternatives test methods. To development for alternatives test method, we need to get the toxic data about in vitro and in vivo of chemicals. However, database sometimes provide limited in vivo and in vitro data on chemicals. Further, the data generated using the OECD TG439 (in vitro skin irritation) are scattered in difference databases, and it is not easy to navigate through them. Therefore, we complied \'Reference Chemical Database System for Skin Irritation Alternative Test (RCDS-Skin Irritation)\' to allow easy, one-stop access to test chemical information. We established the systematic RCDS-Skin Irritation by collecting physiochemical properties, CAS number, human data, and in vivo (OECD TG404) data from overseas chemicals database including European Chemicals Agency (ECHA) etc., and in vitro data using Reconstructed human Epidermis (RhE) (OECD TG439). As a result, we developed the RCDS-Skin Irritation that contains information on 149 chemicals including the data we generated by performing tests using EpiDerm™ SIT, SkinEthic™ RHE and KeraSkin™ SIT. Therefore, the RCDS-Skin Irritation established based on our study will provide insight for safety assessment of chemicals and for development of alternative test methods.

Toxicological assessment of chemicals is crucial for safeguarding human health and the environment. However, traditional animal experiments are associated with ethical, technical, and predictive limitations in assessing the toxicity of chemicals to the skin. With the recent development of bioengineering and tissue engineering, three-dimensional (3D) skin models have been commonly used as an alternative for toxicological studies. The skin consists of the subcutaneous, dermis, and epidermis. All these layers have crucial functions such as physical and biological protection and thermoregulation. The epidermis is the shallowest layer protecting against external substances and media. Because the skin is the first contact point for many substances, this organ is very significant for assessing local toxicity following skin exposure. According to the classification of the United Nations Global Harmonized System, skin irritation is a major potentially hazardous characteristic of chemicals, and this characteristic must be accurately assessed and classified for enhancing chemical safety management and preventing and reducing chemical accidents. This review discusses the research progress of 3D skin models and introduces their application in assessing chemical skin irritation.

Skin corrosion testing is integral to evaluating the potential harm posed by chemicals, impacting regulatory decisions on safety, transportation, and labeling. Traditional animal testing methods are giving way to in vitro alternatives, such as reconstructed human epidermis (RhE) models, aligning with evolving ethical standards. This study evaluates the QileX-RhE test system\'s performance for chemical subcategorization within the OECD TG 431 framework. Results demonstrate its ability to differentiate subcategories, accurately predicting 83% of UN GHS Category 1A and 73% of UN GHS Category 1B/1C chemicals with 100% sensitivity in corrosive prediction. Additionally, this study provides a comprehensive assessment of the test method\'s performance by employing nuanced parameters such as positive predictive value (PPV), negative predictive value (NPV), post-test odds and likelihood rations, offering valuable insights into the applicability and effectiveness of the QileX-RhE test method.

Despite the wide application of graphene-based materials, the information of the toxicity associated to some specific derivatives such as aminated graphene oxide is scarce. Likewise, most of these studies analyse the pristine materials, while the available data regarding the harmful effects of degraded forms is very limited. In this work, the toxicity of graphene oxide (GO), aminated graphene oxide (GO-NH2), and their respective degraded forms (dGO and dGO-NH2) obtained after being submitted to high-intensity sonication was evaluated applying in vitro assays in different models of human exposure. Viability and ROS assays were performed on A549 and HT29 cells, while their skin irritation potential was tested on a reconstructed human epidermis model. The obtained results showed that GO-NH2 and dGO-NH2 substantially decrease cell viability in the lung and gastrointestinal models, being this reduction slightly higher in the cells exposed to the degraded forms. In contrast, this parameter was not affected by GO and dGO which, conversely, showed the ability to induce higher levels of ROS than the pristine and degraded aminated forms. Furthermore, none of the materials is skin irritant. Altogether, these results provide new insights about the potential harmful effects of the selected graphene-based nanomaterials in comparison with their degraded counterparts.

The skin is a potential route of exposure to antimicrobial cleaning products (ACP). Skin irritation, reversible damage to the skin, is an endpoint for protecting consumers and operators accidently exposed to these complex mixtures. To assess skin irritation of 24 ACP formulations, a new protocol was developed and adapted from OECD Test Guideline No. 439 with EpiDerm™ (epidermis model) replaced by Phenion® FT (full thickness tissue, including epidermis and dermis) as the test system. A full thickness tissue was utilized to provide a more human in vivo-like model. Formulations were applied to Phenion® FT and cell viability measured by MTT reduction after a 15-min exposure and 42 h post exposure period. A prediction model was applied, and results compared with in vivo rabbit skin irritation data. Concordance between in vivo and in vitro was demonstrated to be suitable (i.e., sensitivity 78%, specificity 83%, and accuracy 79%) using this modified OECD Test Guideline No. 439 method with a 70% cell viability selected as the most reasonable cut off for discriminating non-irritants (EPA Class IV). These results were considered suitable to develop a draft IATA i.e., with any ACP formulation identified as EPA Category IV in this test. The method will be further refined to distinguish irritant categories.

In the development and optimization of dermatological products, In Vitro Permeation Testing (IVPT) is pivotal for controlled study of skin penetration. To enhance standardization and replicate human skin properties reconstructed human skin and synthetic membranes are explored as alternatives. Strat-M® is a membrane designed to mimic the multi-layered structure of human skin for IVPT. For instance, in Strat-M®, the steady-state fluxes (JSS) of resorcinol in formulations free of permeation enhancers were found to be 41 ± 5 µg/cm2·h for the aqueous solution, 42 ± 6 µg/cm2·h for the hydrogel, and 40 ± 6 µg/cm2·h for the oil-in-water emulsion. These results were closer to excised human skin (5 ± 3, 9 ± 2, 13 ± 6 µg/cm2·h) and surpassed the performance of EpiSkin® RHE (138 ± 5, 142 ± 6, and 162 ± 11 µg/cm2·h). While mass spectrometry and Raman microscopy demonstrated the qualitative molecular similarity of EpiSkin® RHE to human skin, it was the porous and hydrophobic polymer nature of Strat-M® that more faithfully reproduced the skin\'s diffusion-limiting barrier. Further validation through similarity factor analysis (∼80-85%) underscored Strat-M®\'s significance as a reliable substitute for human skin, offering a promising approach to enhance realism and reproducibility in dermatological product development.

For years, the strive for in vitro methods for toxicological assessment suitable to replace animal studies gained progressive importance. OECD Test Guideline (TG) 431 was implemented in 2004, allowing to circumvent animal testing according to OECD TG 404 while reliably predicting skin corrosion potential of many substances and products. However, non-animal assays often show protocol-dependent limitations, that complicate or even prevent the testing of several groups of substances. In this study, the suitability of the OECD TG 431 for assessment of the skin corrosion potential of known acidic, thus often skin corrosive or irritating acrylic and methacrylic acid-based adhesives and monomers, was investigated. The commercially available Phenion® Open Source Reconstructed Epidermis (OS-REp) model, developed at Henkel & Co. KGaA, was used. The EpiDerm™ prediction model was considered most applicable to the Phenion® OS-REp model. All Proficiency Substances listed in OECD TG 431, amongst them six acids, were correctly classified and subcategorized as Skin Corr. 1 A or 1B/C corrosives. The OS-REp model was shown to be suitable for the assessment of skin corrosion potential in accordance with OECD TG 431. However, our results also indicate that acrylic and methacrylic monomer-based adhesives might fall outside the applicability domain of this guideline.

Here we investigate the suitability of in vitro models to assess the skin and eye irritation potential of six microbial strains. Acute skin irritation was tested according to the unmodified and modified OECD test guideline (OECD TG) 439, while acute eye irritation was examined using the OECD TG 491 and 492. The OECD TG 439 guideline, modified to introduce 8-10 μg/mL of streptomycin during the recovery phase and use of test items containing 100% microbial product instead of finished formulae, was found to be suitable for skin irritation evaluation. On the other hand, the OECD TG 491 procedure was the most appropriate for evaluating eye irritation. None of the six microbial strains, namely, Lactiplantibacillus plantarum (IMI 507026, IMI 507027, IMI 507028), Lacticaseibacillus rhamnosus (IMI 507023), and Pediococcus pentosaceus (IMI 507024, IMI 507025), tested in this study caused skin or eye irritation under the study condition.