Extrapolating local lymph node assay EC3 values to estimate relative sensitizing potency.
ABSTRACT The assessment of the potency of a skin sensitizing chemical is a key starting point for its subsequent risk assessment/management. The Local Lymph Node Assay can provide information on the relative skin sensitizing potency of contact allergens by interpolation from the dose response curve the concentration of a chemical required to elicit a threshold positive response (EC3 value). However, interpolation requires that the dose response curve have at least one stimulation index (SI) value above and one SI value below the threshold value of 3. For instances where all test concentrations result in SI values above 3, there was a need to develop a method that would permit estimation of EC3 values. This has been achieved by log-linear extrapolation using the two lowest test concentrations from the dose response curve. Before applying this approach, it is important that data quality is assessed. The dose response must include concentrations on the linear portion of the curve and, ideally, the SI induced by the lowest dose should approach 3. Judicious use of this approach for extrapolating EC3 values can provide information on a likely potency classification for use in risk assessment and may avoid the need for repeat animal testing.