PMID- 18593646 OWN - NLM STAT- MEDLINE DCOM- 20081028 LR - 20191210 IS - 1873-488X (Electronic) IS - 1056-8719 (Linking) VI - 58 IP - 1 DP - 2008 Jul-Aug TI - Interlaboratory validation of the modified murine local lymph node assay based on adenosine triphosphate measurement. PG - 11-26 LID - 10.1016/j.vascn.2008.05.001 [doi] AB - INTRODUCTION: The murine local lymph node assay (LLNA) is a well-established alternative to the guinea pig maximization test (GPMT) or Buehler test (BT) for the assessment of the skin sensitizing ability of drugs and chemicals. Daicel Chemical Industries Ltd. has developed a modified LLNA based on the adenosine triphosphate (ATP) content (LLNA-DA). We conducted 2 interlaboratory validation studies to evaluate the reliability and relevance of LLNA-DA. METHODS: The experiment involved 17 laboratories, wherein 14 chemicals were examined under blinded conditions. In the first study, 3 chemicals were examined in 10 laboratories and the remaining 9 were examined in 3 laboratories. In the second study, 1 chemical was examined in 7 laboratories and the remaining 4 chemicals were examined in 4 laboratories. The data were expressed as the ATP content for each chemical-treated group, and the stimulation index (SI) for each chemical-treated group was determined as the increase in the ATP content relative to the concurrent vehicle control group. An SI of 3 was set as the cut-off value for exhibiting skin sensitization activity. RESULTS: The results of the first study obtained in the experiments conducted for the 3 chemicals that were examined in all the 10 laboratories and for 5 of the remaining 9 chemicals were sufficiently consistent with small variations in their SI values. The sensitivity, specificity, and accuracy of LLNA-DA against those of GPMT/BT were 7/8 (87.5%), 3/3 (100%), and 10/11 (90.9%), respectively. In the second study, all the 5 chemicals studied demonstrated acceptably small interlaboratory variations. DISCUSSION: In the first study, a large variation was observed for 2 chemicals; in the second study, this variation was small. It was attributed to the application of dimethylsulfoxide as the solvent for the metallic salts. In conclusion, these 2 studies provide good evidence for the reliability of the LLNA-DA. FAU - Omori, Takashi AU - Omori T AD - Kyoto University School of Public Health, Japan. omori@pbh.med.kyoto-u.ac.jp FAU - Idehara, Kenji AU - Idehara K FAU - Kojima, Hajime AU - Kojima H FAU - Sozu, Takashi AU - Sozu T FAU - Arima, Kazunori AU - Arima K FAU - Goto, Hirohiko AU - Goto H FAU - Hanada, Tomohiko AU - Hanada T FAU - Ikarashi, Yoshiaki AU - Ikarashi Y FAU - Inoda, Taketo AU - Inoda T FAU - Kanazawa, Yukiko AU - Kanazawa Y FAU - Kosaka, Tadashi AU - Kosaka T FAU - Maki, Eiji AU - Maki E FAU - Morimoto, Takashi AU - Morimoto T FAU - Shinoda, Shinsuke AU - Shinoda S FAU - Shinoda, Naoki AU - Shinoda N FAU - Takeyoshi, Masahiro AU - Takeyoshi M FAU - Tanaka, Masashi AU - Tanaka M FAU - Uratani, Mamoru AU - Uratani M FAU - Usami, Masahito AU - Usami M FAU - Yamanaka, Atsushi AU - Yamanaka A FAU - Yoneda, Tomofumi AU - Yoneda T FAU - Yoshimura, Isao AU - Yoshimura I FAU - Yuasa, Atsuko AU - Yuasa A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Validation Study DEP - 20080521 PL - United States TA - J Pharmacol Toxicol Methods JT - Journal of pharmacological and toxicological methods JID - 9206091 RN - 0 (Irritants) RN - 0 (Solvents) RN - 8L70Q75FXE (Adenosine Triphosphate) SB - IM MH - Adenosine Triphosphate/metabolism MH - Animals MH - Dermatitis, Allergic Contact/diagnosis/*etiology MH - Female MH - Irritants/*toxicity MH - *Local Lymph Node Assay MH - Mice MH - Mice, Inbred CBA MH - Reproducibility of Results MH - Solvents/chemistry MH - Toxicity Tests/methods EDAT- 2008/07/03 09:00 MHDA- 2008/10/29 09:00 CRDT- 2008/07/03 09:00 PHST- 2008/03/27 00:00 [received] PHST- 2008/05/07 00:00 [accepted] PHST- 2008/07/03 09:00 [pubmed] PHST- 2008/10/29 09:00 [medline] PHST- 2008/07/03 09:00 [entrez] AID - S1056-8719(08)00028-2 [pii] AID - 10.1016/j.vascn.2008.05.001 [doi] PST - ppublish SO - J Pharmacol Toxicol Methods. 2008 Jul-Aug;58(1):11-26. doi: 10.1016/j.vascn.2008.05.001. Epub 2008 May 21.