Applicability of the DPRA on mixture testing: challenges and opportunities.

The in chemico direct peptide reactivity assay (DPRA) is validated to assess protein reactivity of chemical compounds, relating to the molecular initiating event of skin sensitization induction. According to OECD TG 442C, the DPRA is technically applicable to test multi-constituent substances and mixtures of known composition, even though limited experimental data are publicly available. First, we assessed the DPRA's predictive capability for individual substances, but at concentrations other than the recommended 100 mM, i.e., based on the LLNA EC3 concentration (Experiment A). Next, the applicability of the DPRA to test unknown mixtures was assessed (Experiment B). Here, the complexity of unknown mixtures was reduced to mixtures containing either two known skin sensitizers with varying potencies, or a combination of a skin sensitizer with a non-skin sensitizer, or multiple non-sensitizers. Experiments A and B revealed that one extremely potent sensitizer (oxazolone) was incorrectly classified as a non-sensitizer when tested at its low EC3 concentration of 0.4 mM instead of the suggested molar excess conditions of 100 mM (Experiments A). For binary mixtures tested in experiments B, the DPRA was able to distinguish all skin sensitizers and the strongest skin sensitizer in the mixture was determinant for the overall peptide depletion of a sensitizer. In conclusion, we confirmed that the DPRA test method can be used efficiently for well-known characterized mixtures. However, when deviating from the recommended testing concentration of 100 mM, caution should be taken in case of negative results, limiting the DPRA's applicability for mixtures of unknown composition.

Quantitative risk assessment of allergens leaching from menstrual hygiene products.

Allergic contact dermatitis (ACD) often associated with the topical use of perfumed products, remains one of the most common chronic skin disorders in Western countries. Since labelling of scented menstrual hygiene products (MHPs) is not mandatory, women might be unknowingly exposed to allergens. Given that vaginal mucosae lack the vital barrier function of the skin, skin allergens can easily penetrate and become systemically available and hence women may experience adverse effects in the anogenital region. The aim of this study was therefore to investigate whether women using scented MHPs are at risk of sensitization and hence developing ACD. Hereto, a Quantitative Risk Assessment (QRA) is performed on four well-known skin sensitizing chemicals (α-isomethyl ionone, benzyl salicylate, hexyl cinnamaldehyde and heliotropine) that were previously found leaching from five different scented MHPs including tampons and sanitary pads. The amounts of heliotropine, leached by one of the investigated tampons, exceeded acceptable exposure levels determined with the QRA and could induce sensitization. In addition, although no sensitization is expected for the other three compounds, an allergenic reaction might be provoked in women who are already sensitized. Labelling of allergens on scented MHPs would therefore help consumers to prevent adverse effects linked to ACD.

Evaluating micellar liquid chromatographic methods on octadecyl particle-based and monolithic columns to predict the skin permeation of drug and cosmetic molecules.

A micellar liquid chromatographic method was developed to assist in the modeling of the skin permeability of pharmaceutical and cosmetic compounds. The composition of the mobile phase was determined by means of a two-factor central composite design, after which it was tested on both a particle-based and monolithic column. The latter provided the opportunity to increase the flow rate from 1 to 8 mL/min without reaching too high backpressures. The micellar conditions allowed analyzing a large test set of compounds with diverse characteristics with just one mobile-phase composition. The obtained experimental chromatographic descriptors besides two sets of theoretical molecular descriptors were used to model the skin permeability coefficient log Kp, applying multiple linear regression and partial least squares regression approaches. The micellar method on the monolithic column provided useful models with similar or even slightly better performance parameters than the method on the particle-based column. Furthermore, a much faster analysis can be achieved when applying a flow rate of 8 mL/min, making the micellar monolithic method ideal to estimate skin permeability.

Sensitizing fragrances in absorbent hygiene products.

BACKGROUND: Allergenic fragrances are present in a wide range of products but they are not regulated in all industries to the same extent. In Europe, absorbent hygiene products (AHPs) are only covered by the general product safety directive and therefore fragrances can be used freely, whereas in cosmetics and toys the use of these ingredients is regulated. METHOD: An analytical method was developed to evaluate the presence of 24 sensitizing fragrances in AHPs. This method allows simultaneous identification and quantification and was validated using the total error approach with an acceptance value of ±15%. RESULTS: The validated method was applied to evaluate 10 scented AHPs consisting of four tampons, three panty liners, and three sanitary pads. Eight allergenic fragrances were identified in these products and five products contained at least one allergen above 10 µg/g. CONCLUSION: The presence of these allergens is not communicated to the consumer. This is, however, a strict requirement in other industries (eg, cosmetics, toys) to ensure adequate consumer protection. Knowing that the exposed area is more susceptible to allergens and irritants, the presence of these allergens should be disclosed.