An Evaluation of Performance Standards and Non-radioactive Endpoints for the Local Lymph Node Assay

Anon. (2002). OECD Guideline for the Testing of Chemicals No. 429: Skin Sensitisation: Local Lymph Node Assay, 7pp. Paris, France: Organisation for Economic Cooperation and Development.

Anon. (2003). Globally Harmonised System of Classification and Labelling of Chemicals (GHS). Part 3: Health and Environmental Hazards, pp. 151–158. New York, NY, USA, and Geneva, Switzerland: United Nations Organisation.

Anon. (1967). Council Directive 67/548/EEC on the approximation of the laws, regulations and administrative provisions relating to the classification, packaging and labelling of dangerous substances. Official Journal of the European Communities 196, 1–98.

Anon. (1999). Directive 1999/45/EC of the European Parliament and of the Council of 31 May 1999 concerning the approximation of the laws, regulation and administrative provisions of the Member States relating to the classification, packaging and labelling of dangerous preparations. Official Journal of the European Communities L200, 1–68.

Anon. (2006). Regulation No 1907/2006 of the European Parliament and of the Council of 18 December 2006 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), establishing a European Chemicals Agency, amending Directive 1999/45/EC and repealing Council Regulation (EEC) No 793/93 and Commission Regulation (EC) No 1488/94 as well as Council Directive 76/769/EEC and Commission Directives 91/155/EEC, 93/67/EEC, 93/105/EC and 2000/21/EC. Official Journal of the European Union L396, 1–849.

Magnusson B. & Kligman A.M. (1970). Allergic Contact Dermatitis in the Guinea Pig: Identification of Contact Allergens, 141pp. Springfield, IL, USA: Charles C. Thomas.

Buehler E.V. (1965). Delayed contact hypersensitivity in the guinea pig. Archives of Dermatology 91, 171–177.

Kimber I. & Basketter D.A. (1992). The murine local lymph node assay; collaborative studies and new directions: A commentary. Food & Chemical Toxicology 30, 165–169.

Anon. (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, 211pp. Research Triangle Park, NC, USA: NIEHS.

Balls M. & Hellsten E. (2000). Statement on the validity of the local lymph node assay for skin sensitisation testing. ATLA 28, 366–367.

Gerberick G.F. , Ryan C.A. , Kimber I. , Dearman R.J. , Lea L.J. & Basketter D.A. (2000). Local lymph node assay validation assessment for regulatory purposes. American Journal of Contact Dermatitis 11, 3–18.

Dean J.H. , Twerdok L.E. , Tice R.R. , Sailstad D.M. , Hattan D.G. & Stokes W.S. (2001). ICCVAM evaluation of the murine local lymph node assay. II. Conclusions and recommendations of an independent scientific peer review panel. Regulatory Toxicology & Pharmacology 34, 258–273.

Wahlberg J.E. & Boman A. (1985). Guinea pig maximization test. In Contact allergy predictive tests in guinea pigs: Current Problems in Dermatology (ed. Maibach H.I. & Andersen K.E. ), pp 59–106. New York, NY, USA: S. Karger.

Cronin M.T.D. & Basketter D.A. (1994). Multivariate QSAR analysis of a skin sensitisation database. SAR & QSAR in Environmental Research 2, 159–179.

Basketter D.A. & Gerberick G.F. (1996). Interlaboratory evaluation of the Buehler test. Contact Dermatitis 35, 146–151.

Anon. (2001). Commission Directive 2001/59/EC of 6 August 2001 adapting to technical progress for the 28th time Council Directive 67/548/EEC on the approximation of laws, regulations and administrative provisions relating to the classification, packaging and labelling of dangerous substances. Official Journal of the European Union L225, 1–333.

Basketter D.A. , Andersen K.E. , Lidén C. , van Loveren H. , Boman A. , Kimber I. , Alanko K. & Berggren E. (2005). Evaluation of the skin sensitising potency of chemicals using existing methods and considerations of relevance for elicitation. Contact Dermatitis 52, 39–43.

Kimber I. , Basketter D.A. , Butler M. , Gamer A. , Garrigue J.L. , Newsome C. , Steiling W. & Vohr H-W. (2003). Classification of allergens according to potency: proposals. Food & Chemical Toxicology 41, 1799–1809.

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. (2008). Skin sensitization in chemical risk assessment: report of a WHO–IPCS international workshop focusing on dose-response assessment. Regulatory Toxicology & Pharmacology 50, 155–199.

Basketter D.A. , Gerberick F. & Kimber I. (2007). The local lymph node assay and the assessment of relative potency: status of validation. Contact Dermatitis 57, 70–75.

Felter S.P. , Ryan C.A. , Basketter D.A. , Gilmour N.J. & Gerberick G.F. (2003). Application of the risk assessment paradigm to the induction of allergic contact dermatitis. Regulatory Toxicology & Pharmacology 37, 1–10.

Api A.M. , Basketter D.A. , Cadby P.A. , Cano M-F. , Ellis G. , Gerberick G.F. , Griem P. , McNamee P.M. , Ryan C.A. & Safford B. (2008). Dermal sensitisation quantitative risk assessment (QRA) for fragrance ingredients. Regulatory Toxicology & Pharmacology, in press.

Balls M. (1997). Defined structural and performance criteria would facilitate the validation and acceptance of alternative test procedures. ATLA 25, 483–484.

ICCVAM (2003). ICCVAM Guidelines for the Nomination and Submission of New, Revised, and Alternative Test Methods. NIH Publication No. 03-4508. Research Triangle Park, NC, USA: NIEHS. Available at: http://iccvam.niehs.nih.gov/docs/guidelines/subguide.htm (Accessed 30.01.08).

Stokes W.S. , Schechtman L.M. , Rispin A. , Gupta K. , Hamernik K. , Tice R. & Wind M. (2006). The use of test method performance standards to streamline the validation process. ALTEX 23 Special Issue, 342–345.

Anon. (2005). Guidance Document on the Validation and International Acceptance of New or Updated Test Methods for Hazard Assessment. OECD Series on Testing and Assessment No. 34, 96pp. Paris, France: Organisation for Economic Cooperation and Development.

Anon. (2004). ICCVAM Recommended Performance Standards for In Vitro Test Methods for Skin Corrosion. NIH Publication No. 04-4510. Research Triangle Park, NC, USA: NIEHS. Available at: http://iccvam.niehs.nih.gov/docs/docs.htm#invitro (Accessed 30.01.08).

Anon. (2004). OECD Guideline for the Testing of Chemicals No. 431: In Vitro Skin Corrosion: Human Skin Model Test, 8pp. Paris, France: Organisation for Economic Cooperation and Development.

ECVAM (2007). Performance Standards for Applying Human Skin Models to In Vitro Skin Irritation Testing, 13pp. Available, under Downloads of Study Documents, at: http://ecvam.jrc.it/index.htm (Accessed 12.12.07).

Kimber I. , Dearman R.J. , Scholes E.W. & Basketter D.A. (1994). The local lymph node assay: developments and applications. Toxicology 93, 13–31.

Kimber I. , Dearman R.J. , Basketter D.A. , Ryan C.A. & Gerberick G.F. (2002). The local lymph node assay: past, present and future. Contact Dermatitis 47, 315–328.

Basketter D.A. , Gerberick G.F. & Kimber I. (2007). The local lymph node assay: current position in regulatory classification of skin sensitizing chemicals. Cutaneous & Ocular Toxicology 26, 293–301.

Ehling G. , Hecht M. , Heuser A. , Huesler J. , Gamer A.O. , 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. First round. Toxicology 212, 60–68.

Ehling G. , Hecht M. , Heuser A. , Huesler J. , Gamer A.O. , 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. Second round. Toxicology 212, 69–79.

Sikorski E.E. , Gerberick G.F. , Ryan C.A. , Miller C.M. & Ridder G.M. (1996). Phenotypic analysis of lymphocyte subpopulations in lymph nodes draining the ear following exposure to contact allergens and irritants. Fundamental & Applied Toxicology 34, 25–35.

Gerberick G.F. , Cruse L.W. , Miller C.M. , Sikorski E.E. & Ridder G.M. (1997). Selective modulation of T cell memory markers CD62L and CD44 on murine lymph node cells following allergen and irritant treatment. Toxicology & Applied Pharmacology 146, 1–10.

Gerberick G.F. , Cruse L.W. , Ryan C.A. , Hulette B.C. , Chaney J.G. , Skinner R.A. , Dearman R.J. & Kimber I. (2002). Use of a B cell marker to discriminate between allergens and irritants in the local lymph node assay. Toxicological Sciences 68, 420–428.

Hariya T. , Hatao M. & Ichikawa H. (1999). Development of a non-radioactive endpoint in a modified local lymph node assay. Food & Chemical Toxicology 37, 87–93.

Dearman R.J. , Hope J.C. , Hopkins S.J. , Debicki R.J. & Kimber I. (1993). Interleukin 6 (IL-6) production by lymph node cells: an alternative endpoint for the murine local lymph node assay. Toxicological Methods 4, 268–278.

Dearman R.J. , Hilton J. , Basketter D.A. & Kimber I. (1999). Cytokine endpoints for the local lymph node assay: consideration of interferon-γ and interleukin 12. Journal of Applied Toxicology 19, 149–155.

Takeyoshi M. , Yamasaki K. , Yakabe Y. , Takatsuki M. & Kimber I. (2001). Development of non-radio isotopic endpoint of murine local lymph node assay, based on 5-bromo-2'-deoxyuridine (BrdU) incorporation. Toxicology Letters 119, 203–208.

Takeyoshi M. , Sawaki M. , Yamasaki K. & Kimber I. (2003). Assessment of statistical analysis in non-radioisotopic local lymph node assay (non-RI-LLNA) with alpha-hexylcinnamic aldehyde as an example. Toxicology 30, 259–263.

Takeyoshi M. , Iida K. , Shiraishi K. & Hoshuyama S. (2005). Novel approach for classifying chemicals according to skin sensitizing potency by non-radioisotopic modification of the local lymph node assay. Journal of Applied Toxicology 25, 129–134.

Ladics G.S. , Smith C. , Heaps K.L. & Loveless S.E. (1995). Comparison of ¹²⁵I-iododeoxyuridine (¹²⁵IUdR) and [³H]-thymidine ([³H]TdR) for assessing proliferation in the mouse local lymph node assay. Toxicological Methods 5, 143–152.

Van Och F.M.M. , Slob W. , de Jong W. , Vanderbriel R.J. & van Loveren H. (2000). A quantitative method for assessing the sensitizing potency of low molecular weight chemicals using a local lymph node assay: employment of a regression method that includes determination of uncertainty factors. Toxicology 146, 49–59.

ICCVAM (2007). Draft ICCVAM Performance Standards For The Murine Local Lymph Node Assay: Methods For Assessing Lymphocyte Proliferation (September 7, 2007). Research Triangle Park, NC, USA: NIEHS. Available at: http://iccvam.niehs.nih.gov/docs/immunotox_docs/llna/LLNAPerfStd12Sep07FD.pdf (Accessed 20.02.08).

Hartung T. , Bremer S. , Casati S. , Coecke S. , Corvi R. , Fortaner S. , Halder M. , Hoffmann S. , Janusch-Roi A. , Prieto P. , Scott S. , Worth A. & Zuang V. (2004). A modular approach to the ECVAM principles on test validity. ATLA 32, 467–472.

Ishizaka A. , Tono-oka T. & Matsumoto S. (1984). Evaluation of the proliferative response of lymphocytes by measurement of intracellular ATP. Journal of Immunological Methods 72, 127–132.

Dexter S.J. , Camara M. , Davies M. & Shakesheff K.M. (2003). Development of a bioluminescent ATP assay to quantify mammalian and bacterial cell number from a mixed population. Biomaterials 24, 27–34.

Yamashita K. , Idehara K. , Fukuda N. , Yamagishi G. & Kawada N. (2005). Development of a modified local lymph node assay using ATP measurement as an endpoint. AATEX 11, 136–144.

Idehara K. , Yamagishi G. , Yamashita K. & Ito M. (2008). Characterization and evaluation of a modified local lymph node assay using ATP as a non-radio isotopic endpoint. Journal of Pharmacological & Toxicological Methods, in press.

Takeyoshi M. , Minobe Y. & Takatsuki M. (2007). Promising endpoint and assay performance of non-radioisotopic local lymph node assay based on BrdU incorporation. Abstract T5-7-4, Abstracts for the 6th World Congress on Alternatives and Animal Use in Life Sciences, Tokyo, Japan. p. 75. Available at: http://www.ech.co.jp/wc6 (Accessed 25.08.07).

Vohr H.W. , Bluemel J. , Blotz A. , Homey B. & Ahr H.J. (2000). An intra-laboratory validation of the integrated model for the differentiation of skin reactions (IMDS): discrimination between (photo) allergic and (photo) irritant skin reactions in mice. Archives of Toxicology 73, 501–509.

Gerberick G.F. , Ryan C.A. , Kern P.S. , Schlatter H. , Dearman R.J. , Kimber I. , Patlewicz G.Y. & Basketter D.A. (2005). Compilation of historical local lymph node data for the evaluation of skin sensitization alternatives. Dermatitis 16, 157–202.

Basketter D.A. , Lea L.J. , Dickens A. , Briggs D. , Pate I. , Dearman R.J. & Kimber I. (1999). A comparison of statistical approaches to the derivation of EC3 values from local lymph node assay dose responses. Journal of Applied Toxicology 19, 261–266.

Ryan C.A. , Gerberick G.F. , Cruse L.W. , Basketter D.A. , Lea L. , Blaikie L. , Dearman R.J. , Warbrick E.V. & Kimber I. (2000). Activity of human contact allergens in the murine local lymph node assay. Contact Dermatitis 43, 95–102.

Dearman R.J. , Betts C.J. , Farr C. , McLaughlin J. , Berdasco N. , Wiench K. & Kimber I. (2007). Comparative analysis of skin sensitization potency of acrylates (methyl acrylate, ethyl acrylate, butyl acrylate and ethylhexyl acrylate) using the local lymph node assay. Contact Dermatitis 57, 242–247.

Warbrick E.V. , Dearman R.J. , Ashby J. , Schmezer P. & Kimber I. (2001). Preliminary assessment of the skin sensitizing activity of selected rodent carcinogens using the local lymph node assay. Toxicology 163, 63–69.

Basketter D.A. & Scholes E.W. (1992). Comparison of the local lymph node assay with the guinea-pig maximization test for the detection of a range of contact allergens. Food & Chemical Toxicology 30, 65–69.

Haneke K.E. , Tice R.R. , Carson B.L. , Margolin B.H. & Stokes W.S. (2001). ICCVAM evaluation of the murine local lymph node assay. III. Data analyses completed by the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods. Regulatory Toxicology & Pharmacology 34, 274–286.