Interpretation of murine local lymph node assay (LLNA) data for skin sensitization: Overload effects, danger signals and chemistry-based read-across

摘要: Abstract There is a large body of information on testing chemicals for skin sensitization in the murine local lymph node assay (LLNA), which potency quantified by EC3 value, derived from dose-response data. This finds use risk assessment and regulatory classification, also assessing performance non-animal methods. However, some LLNA results are not straightforward to interpret, cases published values questionable. These usually arise where dose–response does show monotonic increasing pattern but bell-shaped, or shows decrease response with dose over whole range tested. By analogy long-recognised phenomenon guinea pig sensitization, this referred as overload effect. Here mechanistic rationale presented explain effect, at same time production danger signals even when sensitizer non-irritant. Some illustrative examples effect can lead misinterpretation results, chemistry-based read-across applied reinterpret