Chemical-induced allergies at workplace represent a significant occupational health issue. These substances must be properly identified as sensitizers. In previous studies, an original model using mouse bone marrow-derived dendritic cells (BMDC) was developed for this purpose.

The aim of this study was to evaluate the predictive capacity of the BMDC model with a large panel of sensitizers (including pre- and pro-haptens) and non-sensitizers.

The readout from the BMDC model is based on expression levels of six phenotypic markers measured by flow cytometry.

The results indicate that 29 of the 37 non-sensitizers, and 81 of the 86 sensitizers were correctly classified compared to the Local Lymph Node Assay (LLNA). Statistical analysis revealed the BMDC model to have a sensitivity of 94%, a specificity of 78%, and an accuracy of 89%. The EC2 (Effective Concentration) values calculated with this model allow sensitizers to be categorized into four classes: extreme, strong, moderate and weak.

These excellent predictive performances show that the BMDC model discriminates between sensitizers and non-sensitizers with outstanding precision equal to or better than existing validated alternative models. Moreover, this model allows to predict sensitization potency of chemicals. The BMDC test could therefore be proposed as an additional tool to assess the sensitizing potential and potency of chemicals.

Topical and transdermal treatments have been dramatically growing recently and it is crucial to consider skin sensitization during the drug discovery and development process for these administration routes. Various tests, including animal and non-animal approaches, have been devised to assess the potential for skin sensitization. Furthermore, numerous in silico models have been created, providing swift and cost-effective alternatives to traditional methods such as in vivo, in vitro, and in chemico methods for categorizing compounds. In this study, a quantitative structure-activity relationship (QSAR) model was developed using the innovative hierarchical support vector regression (HSVR) scheme. The aim was to quantitatively predict the potential for skin sensitization by analyzing the percent of cysteine depletion in Direct Peptide Reactivity Assay (DPRA). The results demonstrated accurate, consistent, and robust predictions in the training set, test set, and outlier set. Consequently, this model can be employed to estimate skin sensitization potential of novel or virtual compounds.

Bisphenol (BP-)A is a chemical used in Europe to produce polycarbonate plastics and epoxy resin or as colour developer in thermal paper. Due to its toxicity, BPA presence was restricted by European regulations. Therefore, substitute chemicals are replacing BPA.

To assess the allergenic sensitizing potential of 27 substitutes to BPA used in the industry.

The expression of two costimulatory molecules and six cytokines were analysed by flow cytometry in mouse bone marrow-derived dendritic cells (BMDCs) exposed to the chemicals.

All substances except one induced overexpression of at least one receptor and were thus identified as having allergenic sensitizing potential. Based on the BMDC model, they were classified as extreme (1 out of 27), strong (20 out of 27) and moderate (5 out of 27) sensitizers. BPA was classified as a moderate sensitizer and BPF was the only substitute classified as a non-sensitizer. The more potent substitutes induced more than 2-fold secretion of CCL3, CCL4 and/or CCL5 by dendritic cells.

Most of the BPA substitutes tested in this study have an allergenic sensitizing potential; 24 of them being more potent than BPA itself. Only BPE, BPF and 2,4-BPS appeared to be weaker sensitizers than BPA.

Skin direct contact with chemical or physical substances is predisposed to allergic contact dermatitis (ACD), producing various allergic reactions, namely rash, blister, or itchy, in the contacted skin area. ACD can be triggered by various extremely complicated adverse outcome pathways (AOPs) remains to be causal for biosafety warrant. As such, commercial products such as ointments or cosmetics can fulfill the topically safe requirements in animal and non-animal models including allergy. Europe, nevertheless, has banned animal tests for the safety evaluations of cosmetic ingredients since 2013, followed by other countries. A variety of non-animal in vitro tests addressing different key events of the AOP, the direct peptide reactivity assay (DPRA), KeratinoSens™, LuSens and human cell line activation test h-CLAT and U-SENS™ have been developed and were adopted in OECD test guideline to identify the skin sensitizers. Other methods, such as the SENS-IS are not yet fully validated and regulatorily accepted. A broad spectrum of in silico models, alternatively, to predict skin sensitization have emerged based on various animal and non-animal data using assorted modeling schemes. In this article, we extensively summarize a number of skin sensitization predictive models that can be used in the biopharmaceutics and cosmeceuticals industries as well as their future perspectives, and the underlined challenges are also discussed.

Gliadins are major wheat allergens. Their treatment by acid or enzymatic hydrolysis has been shown to modify their allergenic potential. As the interaction of food proteins with dendritic cells (DCs) is a key event in allergic sensitization, we wished to investigate whether deamidation and enzymatic hydrolysis influence gliadin processing by DC and to examine the capacity of gliadins to activate DCs. We compared the uptake and degradation of native and modified gliadins by DCs using mouse bone marrow-derived DCs. We also analyzed the effects of these interactions on the phenotypes of DCs and T helper (Th) lymphocytes. Modifying gliadins induced a change in physicochemical properties (molecular weight, hydrophobicity, and sequence) and also in the peptide size. These alterations in turn led to increased uptake and intracellular degradation of the proteins by DCs. Native gliadins (NGs) (100 μg/mL), but not modified gliadins, increased the frequency of DC expressing CD80 (15.41 ± 2.36% vs 6.81 ± 1.10%, p < 0.001), CCR7 (28.53 ± 8.17% vs 17.88 ± 2.53%, p < 0.001), CXCR4 (70.14 ± 4.63% vs 42.82 ± 1.96%, p < 0.001), and CCR7-dependent migration (2.46 ± 1.45 vs 1.00 ± 0.22, p < 0.01) compared with NGs. This was accompanied by Th lymphocyte activation (30.37 ± 3.87% vs 21.53 ± 3.14%, p < 0.1) and proliferation (16.39 ± 3.97% vs 9.31 ± 2.80%, p > 0.1). Moreover, hydrolysis decreases the peptide size and induces an increase in gliadin uptake and degradation. Deamidation and extensive enzymatic hydrolysis of gliadins modify their interaction with DCs, leading to alteration of their immunostimulatory capacity. These findings demonstrate the strong relationship between the biochemical characteristics of proteins and immune cell interactions.