PMID- 10513674 OWN - NLM STAT- MEDLINE DCOM- 19991029 LR - 20190921 IS - 0260-437X (Print) IS - 0260-437X (Linking) VI - 19 IP - 5 DP - 1999 Sep-Oct TI - Local lymph node assay: use in hazard and risk assessment. PG - 299-306 AB - The murine local lymph node assay (LLNA) was developed as an alternative method for the identification of chemicals that have the ability to cause skin sensitization and allergic contact dermatitis. The assay now has been evaluated extensively in the context of both national and international inter-laboratory collaborative trials and has been the subject of detailed comparisons with guinea pig test methods and human skin sensitization data. On the basis of these evaluations the LLNA has been endorsed recently by the US Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) as a stand-alone method for skin sensitization testing. The assay offers a number of important benefits compared with conventional guinea pig test methods, among these being provision of an objective and quantitative endpoint. Moreover, the LLNA provides advantages in the context of animal welfare; compared with guinea pig tests, fewer animals are required and these animals are subject to less trauma. It is important now that the validation status of the LLNA is recognized and the method applied widely so that these advantages may be realized. Hazard identification represents only the first step in the risk assessment process. A full toxicological evaluation of skin sensitization activity requires an understanding of relative potency. Guinea pig methods do not lend themselves readily to assessment of potency, and interest recently has focused on the utility of the LLNA for this purpose. Contained within this review article are brief descriptions of the history of the LLNA and the immunobiological basis for the method, together with detailed accounts of the conduct and interpretation of the assay. Procedural modifications to, and alternative endpoints for, the LLNA are considered also. Finally, the current regulatory status of the LLNA is summarized and the application of the method for the purposes of defining relative potency and developing risk assessments is reviewed. FAU - Dearman, R J AU - Dearman RJ AD - Astra Zeneca Central Toxicology Laboratory, Macclesfield, Cheshire, UK. Rebecca.Dearman@CTL.Zeneca.com FAU - Basketter, D A AU - Basketter DA FAU - Kimber, I AU - Kimber I LA - eng PT - Journal Article PT - Review PL - England TA - J Appl Toxicol JT - Journal of applied toxicology : JAT JID - 8109495 RN - 0 (Allergens) RN - 0 (Hazardous Substances) SB - IM MH - Allergens/*toxicity MH - Animals MH - Dermatitis, Allergic Contact/*etiology MH - Hazardous Substances/toxicity MH - Humans MH - Lymph Nodes/*drug effects/pathology MH - Mice MH - Risk Assessment/methods RF - 83 EDAT- 1999/10/08 09:00 MHDA- 2000/06/20 09:00 CRDT- 1999/10/08 09:00 PHST- 1999/10/08 09:00 [pubmed] PHST- 2000/06/20 09:00 [medline] PHST- 1999/10/08 09:00 [entrez] AID - 10.1002/(SICI)1099-1263(199909/10)19:5<299::AID-JAT591>3.0.CO;2-C [pii] AID - 10.1002/(sici)1099-1263(199909/10)19:5<299::aid-jat591>3.0.co;2-c [doi] PST - ppublish SO - J Appl Toxicol. 1999 Sep-Oct;19(5):299-306. doi: 10.1002/(sici)1099-1263(199909/10)19:5<299::aid-jat591>3.0.co;2-c.