ICCVAM evaluation of the murine local lymph node assay. Data analyses completed by the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods.
To evaluate the reliability of the murine local lymph node assay (LLNA), a test for allergic contact dermatitis activity, the inter- and intralaboratory consistency statistics (h and k, respectively) were calculated for validation studies testing multiple chemicals. The analysis indicated the absence of excessive variability in the dose calculated to induce a threefold or greater increase in the stimulation index (SI). To assess the appropriateness of using an SI of 3 as the decision criteria for identifying a sensitizing compound, LLNA results based on SI values of 2.0, 2.5, 3.0, 3.5, and 4.0 were compared with guinea pig or human results. The results supported the use of an SI of 3 as the decision criteria. Assay performance was determined by comparing LLNA results to results obtained for guinea pigs or humans. The accuracy of the LLNA was 89% when compared with results from the guinea pig maximization test (GPMT)/Buehler assay (BA). The performance of the LLNA and the GPMT/BA was similar when each was compared to human maximization test results plus substances included as human patch test allergens. The LLNA offered advantages over the GPMT in respect to both the time required to conduct the test and the assay cost.
Haneke
K E
KE
National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods, National Institute of Environmental Health Sciences, MD EC-17, Research Triangle Park, NC 27709, USA.
Tice
R R
RR
Carson
B L
BL
Margolin
B H
BH
Stokes
W S
WS
D000827:Animal Welfare; D000818:Animals; D017449:Dermatitis, Allergic Contact / Q000175:diagnosis / Q000191:economics / Q000209:etiology*; D004781:Environmental Exposure / Q000191:economics / Q000706:statistics & numerical data; D006077:Government Agencies / Q000191:economics / Q000706:statistics & numerical data; D019983:Guideline Adherence; D017408:Guidelines as Topic / Q000592:standards; D006168:Guinea Pigs; D006801:Humans; D007373:Interinstitutional Relations; D023441:Local Lymph Node Assay; D008198:Lymph Nodes / Q000187:drug effects; D051379:Mice; D009930:Organic Chemicals / Q000032:analysis / Q000633:toxicity*; D010380:Peer Review / Q000379:methods / Q000592:standards; D015203:Reproducibility of Results; D018570:Risk Assessment / Q000191:economics / Q000706:statistics & numerical data; D012680:Sensitivity and Specificity; D018675:Toxicity Tests / Q000191:economics / Q000379:methods / Q000706:statistics & numerical data*; D014481:United States
D009930:Organic Chemicals