The activity of methacrylate esters in skin sensitisation test methods: A review

Skin sensitisation associated with allergic contact dermatitis is an important occupational and environmental disease. The identification of skin sensitisation hazards was traditionally performed using animal tests; originally guinea pig assays and subsequently the murine local lymph node assay (LLNA). More recently there has, for a variety of reasons, been an increased interest in, and requirement for, non-animal assays. There are now available both validated in vitro assays and a variety of approaches based on consideration of quantitative structure-activity relationships (QSAR). With the increased availability and use of non-animal alternatives for skin sensitisation testing there is a continuing need to monitor the performance of these approaches using series of chemicals that do not normally form part of validation exercises. Here we report studies conducted with 11 methacrylate esters and methacrylic acid in which results obtained with 3 validated in vitro tests for which there are OECD guidelines (the Direct Peptide Reactivity Assay, DPRA; ARE-Nrf2 luciferase test methods, and - with some chemicals - a dendritic cell activation test, the myeloid U937 Skin Sensitisation test [U-SENS] assay) have been compared with QSAR approaches (DEREK and TIMES-SS), and with LLNA and guinea pig maximisation test (GPMT) data. The conclusions drawn from these data are that - with this series of chemicals at least - there is a strong correlation between the results of animal tests and the in vitro assays considered, but not with either DEREK or TIMES-SS.