Strategies for identifying false positive responses in predictive skin sensitization tests.

It is important that predictive toxicological test methods are selective for their intended endpoint and that their limitations are understood and acknowledged. The local lymph node assay (LLNA) is a relatively new predictive test for skin sensitization potential that can replace traditional guinea pig tests and offers significant scientific and animal welfare advantages. However, there has been some concern that certain irritant materials may yield false positive results, although it must be emphasized that false positives also occur in guinea pig methods. Consequently, we have examined the performance in the LLNA of a range of skin irritants, from varying chemical classes and covering a range of irritation potency. The results presented here demonstrate clearly that the majority of skin irritants are negative in the LLNA. These results are reviewed in the context of the occurrence of false positive reactions in the guinea pig maximization test and the strategies for dealing with such results are discussed. The need for careful scientific evaluation of the results in all predictive tests for sensitization is thus emphasized. In terms of specificity, the LLNA has been more fully evaluated than other predictive test methods and is at least as accurate. In terms of animal welfare, objectivity, reproducibility and reliability it is superior to other methods. In summary, all predictive skin sensitization test results should be evaluated in a scientifically rigorous manner and the additional data provided herein further support the adoption of the LLNA as a complete replacement for the traditional guinea pig methods.