The regulatory use of the Local Lymph Node Assay for the notification of new chemicals in Europe

Regulatory Toxicology and Pharmacology

Volumn 60, Issue 3, 2011, Pages 300-307

  Angers Loustau, Alexandre ^a   Tosti, Luca ^a   Casati, Silvia ^a  

^a JOINT RESEARCH CENTRE   (Italy)

Author keywords

Local Lymph Node Assay; New Chemicals Database; Reduced Local Lymph Node Assay; Skin sensitisation

Indexed keywords

ACCURACY; ARTICLE; CHEMICAL LABELING; CONTROLLED STUDY; EXPERIMENTAL GUINEA PIG; FEMALE; HUMAN; INTERMETHOD COMPARISON; LOCAL LYMPH NODE ASSAY; MALE; MOUSE; NONHUMAN; PRACTICE GUIDELINE; PRIORITY JOURNAL; PROCESS DEVELOPMENT; REFERENCE DATABASE; RISK ASSESSMENT; SCREENING TEST; SKIN SENSITIZATION; VALIDATION PROCESS;

ANIMALS; DATA MINING; DATABASES, FACTUAL; DERMATITIS, ALLERGIC CONTACT; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG APPROVAL; DRUG EVALUATION, PRECLINICAL; EUROPEAN UNION; FEMALE; IMMUNIZATION; IRRITANTS; LOCAL LYMPH NODE ASSAY; MICE; MICE, INBRED CBA; SKIN;

ANIMALIA;

EID: 79960115226     PISSN: 02732300     EISSN: 10960295     Source Type: Journal    
DOI: 10.1016/j.yrtph.2011.04.006     Document Type: Article

References (28)

1. Ahuja V., Platzek T., Fink H., Sonnenburg A., Stahlmann R. Study of the sensitising potential of various textile dyes using a biphasic murine local lymph node assay. Arch. Toxicol. 2010, 709:18.
2. Anon Globally harmonised system of classification and labelling of chemicals (GHS). Part 3: Health and environmental hazards 2003, United Nations Organisation, New York, NY, USA, and Geneva, Switzerland, pp. 151-158.
3. Anzai T., Ullmann L.G., Hayashi D., Satoh T., Kumazawa T., Sato K. Effects of strain differences and vehicles on results of local lymph node assays. Exp. Anim. 2010, 59(2):245-249.
4. Balls M., Hellsten E. Statement on the validity of the local lymph node assay for skin sensitisation testing. ECVAM Joint Research Centre, European Commission, Ispra. ATLA 2000, 28:366-367.
5. Basketter D.A., Gerberick G.F., Kimber I. Skin sensitisation, vehicle effects and the local lymph node assay. Food Chem. Toxicol. 2001, 39(6):621-627.
6. Basketter D.A., Andersen K.E., Lidén C., van Loveren H., Boman A., Kimber I., Alanko K., Berggren E. Evaluation of the skin sensitising potency of chemicals using existing methods and considerations of relevance for elicitation. Contact Dermat. 2005, 52:39-43.
7. Basketter D.A., Kimber I. Predictive test for irritants and allergens and their use in quantitative risk assessment. Contact Dermatitis 2006, 179-188. Springer Verlag, Heidelberg. 4th ed. P.J. Frosch, T. Menné, J.P. Lepoittevin (Eds.).
8. Basketter D.A., Dearman R.J., Kimber I., Gerberick G.F., Ryan C.A. The impact of LLNA group size on the identification and potency classification of skin sensitizers: a review of published data. Cutan. Ocul. Toxicol. 2009, 28(1):19-22.
9. Buehler E.V. Delayed contact hypersensitivity in the guinea pig. Arch. Dermatol. 1965, 91:171-177.
10. Cockshott A., Evans P., Gerberick G.F., Betts C.J., Dearman R.J., Kimber I., Basketter D.A. Use and abuse of the local lymph node assay: a regulatory perspective. Hum. Exp. Toxicol. 2006, 25:387-394.
11. ESAC (2007), Statement on the Reduced Local Lymph Node Assay (rLLNA), European Commission Directorate General, Joint Research Centre, Institute for Health and Consumer Protection, European Centre for the Validation of Alternative Methods, April 2007. Available at: (accessed 22 October 2010). http://ecvam.jrc.it/ft_doc/ESAC26_statement_rLLNA_20070525-1.pdf.
12. Eskes C., Cole T., Hoffmann S., Worth A., Cockshott A., Gerner I., Zuang V. The ECVAM international validation study on in vitro test for acute skin irritation: selection of test chemicals. ATLA 2007, 35:603-619.
13. European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC), 1999. Brussels. Document No.46 - Potency Values from the Local Lymph Node Assay: Application to Classification, Labelling and Risk Assessment.
14. Garcia C., Ball N., Cagen S., Carrillo J.C., Certa H., Eigler D., Esch H., Graham C., Haux C., Kreiling R., Mehling A. Comparative testing for the identification of skin-sensitizing potentials of nonionic sugar lipid surfactants. Regul. Toxicol. Pharmacol. 2010, 58(2):301-307.
15. Gerberick G.F., Ryan C.A., Dearman R.J., Kimber I. Local lymph node assay (LLNA) for detection of sensitization capacity of chemicals. Methods 2007, 41(1):54-60.
16. Haseman J.K., Strickland J., Allen D., Salicru E., Paris M., Tice R.R., Stokes W.S. Safety assessment of allergic contact dermatitis hazards: An analysis supporting reduced animal use for the murine local lymph node assay. Regul. Toxicol. Pharmacol. 2011 Feb, 59(1):191-196.
17. Jowsey I.R., Clapp C.J., Safford B., Gibbons B.T., Basketter D.A. The impact of vehicle on the relative potency of skin-sensitizing chemicals in the local lymph node assay. Cutan. Ocul. Toxicol. 2008, 27(2):67-75.
18. Kimber I., Hilton J., Dearman R.J., Gerberick G.F., Ryan C.A., Basketter D.A., Scholes E.W., Ladics G.S., Loveless S.E., House R.V., et al. An international evaluation of the murine local lymph node assay and comparison of modified procedures. Toxicology 1995, 103(1):63-73.
19. Kimber I., Dearman R.J., Betts C.J., Gerberick G.F., Ryan C.A., Kern P.S., Patlewicz G.Y., Basketter D.A. The local lymph node assay and skin sensitisation: a cut-down screen to reduce animal requirements. Contact Dermat. 2006, 54:181-185.
20. Loveless S.E., Ladics G.S., Gerberick G.F., Ryan C.A., Basketter D.A., Scholes E.W., House R.V., Hilton J., Dearman R.J., Kimber I. Further evaluation of the local lymph node assay in the final phase of an international collaborative trial. Toxicology 1996, 108(1-2):141-152.
21. Loveless S.E., Api A.M., Crevel R.W., Debruyne E., Gamer A., Jowsey I.R., Kern P., Kimber I., Lea L., Lloyd P., Mehmood Z., Steiling W., Veenstra G., Woolhiser M., Hennes C. Potency values from the local lymph node assay: application to classification, labelling and risk assessment. Regul. Toxicol. Pharmacol. 2010, 56(1):54-66.
22. Magnusson B., Kligman A.M. Allergic contact dermatitis in the guinea pig: Identification of contact allergens 1970, Charles C. Thomas, Springfield, IL, USA, p. 141.
23. NIH, 1999. The Murine Local Lymph Node Assay. The Results of an Independent Peer Review Evaluation Coordinated By the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and the National Toxicology Program Center for the Evaluation of Alternative Toxicological Methods (NICEATM). NIH Publication No. 99-4494, p. 211. Research Triangle Park, NC, USA.
24. OECD OECD Guideline for the Testing of Chemicals No. 402: Acute Dermal Toxicity 1992, Organisation for Economic Cooperation and Development, Paris, France.
25. OECD OECD Guideline for the Testing of Chemicals No. 429: Skin Sensitisation: Local Lymph Node Assay 2002, Organisation for Economic Cooperation and Development, Paris, France.
26. OECD OECD Guideline for the Testing of Chemicals No. 429: Skin Sensitisation: Local Lymph Node Assay (updated) 2010, Organisation for Economic Cooperation and Development, Paris, France.
27. van der Jagt, K., Munn, S., Tørsløv, J. and de Bruijn, J., 2004. Alternative approaches can reduce the use of test animals un-der reach. Addendum to the report: Assessment of additional testing needs under REACH Effects of (Q)SARS, risk based testing and voluntary industry initiatives. JRC Report EUR 21405 EN; (accessed 22 October 2010). http://ecb.jrc.ec.europa.eu/documents/REACH/PUBLICATIONS/Reducing_the_use_of_testanimalsunderREACHIHCPreport.pdf.
28. van Loveren H., Cockshott A., Gebel T., Gundert-Remy U., de Jong W.H., Matheson J., McGarry H., Musset L., Selgrade M.K., Vickers C. Skin sensitisation in chemical risk assessment: report of a WHO/IPCS international workshop focusing on dose 692 response assessment. Regul. Toxicol. Pharmacol. 2008, 50:155-199.