Encyclopedia of Immunotoxicology

2016 Edition
| Editors: Hans-Werner Vohr

Local Lymph Node Assay (IMDS), Modifications

  • Peter Ulrich
  • Hans-Werner Vohr
Reference work entry
DOI: https://doi.org/10.1007/978-3-642-54596-2_899


In 1998, after a decade of scientific evaluation and extensive interlaboratory validation, the local lymph node assay (see  Local Lymph Node Assay) was peer reviewed and was, in principle, endorsed as a stand-alone test by an independent panel of experts on behalf of the US Interagency Co-ordinating Committee on the Validation of Alternative Methods (ICCVAM) in 1999. However, improvements were suggested by the peer review panel concerning the discrimination of contact allergenic from irritation potential. Some irritating and phototoxic compounds were shown to cause a false-positive response, since they induced a vigorous cell proliferation in the ear-draining lymph nodes (Scholes et al. 1992) or a marked LN hyperplasia (Homey et al. 1998; Ulrich et al. 1998). The occurrence of false-positive results is an obvious consequence of the tight physiological connection between inflammatory tissue processes and specific immune reactions, with the latter being more vigorous, when...

This is a preview of subscription content, log in to check access.


  1. ECETOC (2003) Contact sensitization: classification according to potency. European centre for ecotoxicity and toxicology of chemicals, BrusselsGoogle Scholar
  2. Ehling G, Hecht M, Heusener A, Huesler J, Gamer AO, van Loveren H, Maurer T, Riecke K, Ullmann L, Ulrich P, Vandebriel R, Vohr H-W (2005) An European inter-laboratory validation of alternative endpoints of the murine local lymph node assay. 1st round (and 2nd round). Toxicology 212:60–68PubMedCrossRefGoogle Scholar
  3. Gamer AO, Nies E, Vohr HW (2008) Local lymph node assay (LLNA): comparison of different protocols by testing skin-sensitizing epoxy resin system components. Reg Tox Pharmacol 52:290–298CrossRefGoogle Scholar
  4. Gerberick GF, Cruse LW, Ryan CA (1999) Local lymph node assay: differentiating allergic and irritant responses using flow cytometry. Methods 19:48–55PubMedCrossRefGoogle Scholar
  5. Homey B, von Schilling C, Blumel J et al (1998) An integrated model for the differentiation of chemical-induced allergic and irritant skin reactions. Toxicol Appl Pharmacol 153:83–94PubMedCrossRefGoogle Scholar
  6. Kaplan DH, Igyarto BZ, Gaspari AA (2012) Early immune events in the induction of allergic contact dermatitis. Nat Rev Immunol 12:114PubMedCentralPubMedGoogle Scholar
  7. Scholes EW, Basketter DA, Lovell WW, Sarll AE, Pendlington RU (1992) The identification of photoallergic potential in the local lymph node assay. Photodermatol Photoimmunol Photomed 8:249–254Google Scholar
  8. Ulrich P, Vohr HW (2012) Utilization of irritation data in local lymphnode assay. In: Zhai H, Wilhelm KP, Maibach H (eds) Marzulli and Maibach’s dermatotoxicology, 8th edn. Informa Healthcare, LondonGoogle Scholar
  9. Ulrich P, Homey B, Vohr HW (1998) A modified murine local lymph node assay for the differentiation of contact photoallergy from phototoxicity by analysis of cytokine expression in skin-draining lymph node cells. Toxicology 125:149–168PubMedCrossRefGoogle Scholar
  10. Ulrich P, Streich J, Suter W (2001) Intra-laboratory validation of alternative endpoints in the murine local lymph node assay for the identification of contact allergic potential: primary ear skin irritation and ear-draining lymph node hyperplasia induced by topical chemicals. Arch Toxicol 74:733–744PubMedCrossRefGoogle Scholar
  11. Vohr HW, Ahr HJ (2005) Sensitivity of the LLNA. Archiv Toxicol 79:721–728CrossRefGoogle Scholar
  12. Vohr HW, Blumel J, Blotz A, Homey B, Ahr HJ (2000) An intra-laboratory validation of the integrated model for the differentiation of skin reactions (IMDS): discrimination between (photo)allergic and (photo)irritant reactions in mice. Arch Toxicol 73(10–11):501–509PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Novartis Pharma AG (NIBR), PCS - Biologics SafetyBaselSwitzerland
  2. 2.Bayer HealthCare, Bayer Pharma AGWuppertalGermany