PMID- 12581276 OWN - NLM STAT- MEDLINE DCOM- 20030520 LR - 20190721 IS - 0105-1873 (Print) IS - 0105-1873 (Linking) VI - 47 IP - 6 DP - 2002 Dec TI - The local lymph node assay: past, present and future. PG - 315-28 AB - The local lymph node assay (LLNA) was developed originally as a method for the identification of chemicals that have the potential to cause skin sensitization and allergic contact dermatitis. The assay is based on an understanding that the acquisition of contact sensitization is associated with, and dependent upon, the stimulation by chemical allergens of lymphocyte proliferative responses in skin-draining lymph nodes. Those chemicals that provoke a defined level of lymph node cell (LNC) proliferation (a 3-fold or greater increase compared with concurrent vehicle controls) are classified as skin sensitizers. Following its original inception and development, the LLNA was the subject of both national and international interlaboratory collaborative trials, and of very detailed comparisons with other test methods and with human skin sensitization data. The assay has now been validated fully as a stand-alone test for the purposes of hazard identification. In recent years, there has been a growing interest also in the use of the LLNA to assess the potency of contact allergens and in risk assessment. There is reason to believe that the extent of skin sensitization achieved is associated with the vigour of LNC proliferation induced in draining nodes. Given this relationship, the relative potency of skin sensitizing chemicals is measured in the LLNA by derivation of an EC3 value, this being the concentration of chemical required to provoke a 3-fold increase in the proliferation of LNC compared with controls. Experience to date indicates that relative potency as determined using this approach correlates closely with what is known of the activity of skin sensitizing chemicals in humans. In this article, we review the development, evaluation and validation of the LLNA for the purposes of hazard identification, and the more recent application of the method for evaluation of potency in the context of risk assessment. In addition, we consider what new applications and modifications are currently being investigated. FAU - Kimber, Ian AU - Kimber I AD - Syngenta Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, UK. ian.kimber@syngenta.com FAU - Dearman, R J AU - Dearman RJ FAU - Basketter, D A AU - Basketter DA FAU - Ryan, C A AU - Ryan CA FAU - Gerberick, G F AU - Gerberick GF LA - eng PT - Journal Article PT - Review PL - England TA - Contact Dermatitis JT - Contact dermatitis JID - 7604950 RN - 0 (Allergens) SB - IM MH - Allergens/pharmacology MH - Animals MH - Dermatitis, Allergic Contact/diagnosis MH - Humans MH - *Local Lymph Node Assay MH - Reproducibility of Results MH - Risk Assessment MH - Skin/*drug effects RF - 127 EDAT- 2003/02/13 04:00 MHDA- 2003/05/21 05:00 CRDT- 2003/02/13 04:00 PHST- 2003/02/13 04:00 [pubmed] PHST- 2003/05/21 05:00 [medline] PHST- 2003/02/13 04:00 [entrez] AID - cod470601 [pii] AID - 10.1034/j.1600-0536.2002.470601.x [doi] PST - ppublish SO - Contact Dermatitis. 2002 Dec;47(6):315-28. doi: 10.1034/j.1600-0536.2002.470601.x.