STRATEGIES FOR IDENTIFYING FALSE-POSITIVE RESPONSES IN PREDICTIVE SKIN SENSITIZATION TESTS

It is important that predictive toxicological test methods are selecti ve for their intended endpoint and that their limitations are understo od 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 an imal welfare advantages. However, there has been some concern that cer tain irritant materials may yield false positive results, although it must be emphasized that false positives also occur in guinea pig metho ds. Consequently, we have examined the performance in the LLNA of a ra nge of skin irritants, from varying chemical classes and covering a ra nge of irritation potency. The results presented here demonstrate clea rly that the majority of skin irritants are negative in the LLNA. Thes e results are reviewed in the context of the occurrence of false posit ive reactions in the guinea pig maximization test and the strategies f or dealing with such results are discussed. The need for careful scien tific evaluation of the results in all predictive tests for sensitizat ion is thus emphasized. In terms of specificity, the LLNA has been mor e fully evaluated than other predictive test methods and is at least a s accurate. In terms of animal welfare, objectivity, reproducibility a nd reliability it is superior to other methods. In summary, all predic tive skin sensitization test results should be evaluated in a scientif ically rigorous manner and the additional data provided herein further support the adoption of the LLNA as a complete replacement for the tr aditional guinea pig methods. (C) 1998 Elsevier Science Ltd. All right s reserved.