The activity of methacrylate esters in skin sensitisation test methods II. A review of complementary and additional analyses

• Published in: Regulatory toxicology and pharmacology 2021-02, Vol.119, p.104821, Article 104821
• Main Author: Kimber, Ian
• Format: Article
• Language: English
• Subjects: Direct peptide reactivity assay (DPRA); In vitro assays; Local lymph node assay; Methacrylates; Predictive test methods; QSAR; Risk assessment; Skin sensitisation
• ISSN: 0273-2300; 1096-0295
• DOI: 10.1016/j.yrtph.2020.104821

Allergic contact dermatitis is an important occupational health issue, and there is a need to identify accurately those chemicals that have the potential to induce skin sensitisation. Hazard identification was performed initially using animal (guinea pig and mouse) models. More recently, as a result of the drive towards non-animal methods, alternative in vitro and in silico approaches have been developed. Some of these new in vitro methods have been formally validated and have been assigned OECD Test Guideline status. The performance of some of these recently developed in vitro methods, and of 2 quantitative structure-activity relationships (QSAR) approaches, with a series of methacrylate esters has been reviewed and reported previously. In this article that first review has been extended further with additional data and complementary analyses. Results obtained using in vitro methods (Direct Peptide Reactivity Assay, DPRA; ARE-Nrf2 luciferase test methods, KeratinoSens and LuSens; Epidermal Sensitisation Assay, EpiSensA; human Cell Line Activation Test, h-CLAT, and the myeloid U937 Skin Sensitisation test, U-SENS), and 2 QSAR approaches (DEREK™-nexus and TIMES-SS), with 11 methacrylate esters and methacrylic acid are reported here, and compared with existing data from the guinea pig maximisation test and the local lymph node assay. With this series of chemicals it was found that some in vitro tests (DPRA and ARE-Nrf2 luciferase) performed well in comparison with animal test results and available human skin sensitisation data. Other in vitro tests (EpiSensA and h-CLAT) proved rather more problematic. Results with DEREK™-nexus and TIMES-SS failed to reflect accurately the skin sensitisation potential of the methacrylate esters. The implications for assessment of skin sensitising activity are discussed. •Non-animal methods for skin sensitisation hazard identification are considered.•Their performance with a series of methacrylate esters has been determined.•Comparisons have been made with the mouse LLNA and GPMT.•DPRA and ARE-Nrf2 luciferase performed well in comparison with animal tests.•EpiSensA, h-CLAT DEREK™-nexus and TIMES-SS performed less well.