Many chemicals are known to be, or have been implicated as, contact allergens, and allergic contact dermatitis is an important occupational and environmental health issue. It is the responsibility of toxicologists to identify those chemicals that have the potential to induce skin sensitisation, and to assess the conditions under which there will exist a risk to human health. This article describes progress that has been made in the development of new approaches to the toxicological evaluation of skin sensitisation, and the benefits to animal welfare that such developments have already produced, and are likely to produce in the future. In this context, the local lymph node assay is described with regard to hazard identification and risk assessment, and possible strategies for the development of in vitro approaches to safety assessment are discussed.
RingJ., KramerU., SchaferT., & BehrendtH. (2001). Why are allergies increasing?Current Opinion in Immunology13, 701–708.
2.
KimberI., & DearmanR.J. (2002). Approaches to assessment of the allergenic potential of novel proteins in food from genetically modified crops. Toxicological Sciences68, 4–8.
3.
BasketterD.A., GerberickG.F., KimberI., & WillisC. (1999). Toxicology of Contact Dermatitis. Allergy, Irritancy and Urticaria, 180 pp. Chichester, UK: John Wiley & Sons.
4.
KimberI., & DearmanR.J. (1997). Toxicology of Chemical Respiratory Hypersensitivity, 172 pp. London, UK: Taylor & Francis.
5.
KimberI., CumberbatchM., DearmanR.J., BhushanM., & GriffithsC.E.M. (2000). Cytokines and chemokines in the initiation and regulation of epidermal Langerhans cell mobilization. British Journal of Dermatology142, 401–412.
MagnussonB., & KligmanA.M. (1970). Allergic Contact Dermatitis in the Guinea Pig, 180 pp. Springfield, IL, USA: Charles C. Thomas.
8.
BuehlerE.V. (1965). Delayed contact hypersensitivity in the guinea pig. Archives of Dermatology91, 171–177.
9.
KimberI., & BasketterD.A. (1992). The murine local lymph node assay: a commentary on collaborative trials and new directions. Food and Chemical Toxicology30, 165–169
10.
KimberI., DearmanR.J., ScholesE.W., & BasketterD.A. (1994). The local lymph node assay: developments and applications. Toxicology93, 13–31.
11.
DearmanR.J., BasketterD.A., & KimberI. (1999). Local lymph node assay: use in hazard and risk assessment. Journal of Applied Toxicology19, 299–306.
12.
KimberI., DearmanR.J., BasketterD.A., RyanC. A., & GerberickG.F. (2003). The local lymph node assay: past, present and future. Contact Dermatitis, in press.
13.
BasketterD.A., GerberickG.F., KimberI., & LovelessS.E. (1996). The local lymph node assay: a viable alternative to currently accepted skin sensitisation tests. Food and Chemical Toxicology34, 986–997.
14.
National Institutes of Health (1999). The Murine Local Lymph Node Assay: A Test Method for Assessing the Allergic Contact Dermatitis Potential of Chemicals/Compounds. NIH Publication No. 99–4494. 211 pp. Research Triangle Park, NC, USA: NIEHS.
15.
DeanJ.H., TwerdokL.E., TiceR.R., SailstadD. M., HattanD.G., & StokesW.S. (2001). ICCVAM evaluation of the murine local lymph node assay. II. Conclusions and recommendations of an independent scientific peer review panel. Regulatory Toxicology and Pharmacology34, 258–273.
16.
ECVAM (2000). Statement on the validity of the local lymph node assay for skin sensitisation testing. ATLA28, 366–367.
17.
KimberI., & BasketterD.A. (1997). Contact sensitization: a new approach to risk assessment. Human and Ecological Risk Assessment3, 385–395.
KimberI., & DearmanR.J. (1991). Investigation of lymph node cell proliferation as a possible immunological correlate of contact sensitising potential. Food and Chemical Toxicology29, 125–129.
20.
KimberI., GerberickG.F., & BasketterD.A. (1999). Thresholds in contact sensitization: theoretical and practical applications. Food and Chemical Toxicology37, 553–560.
21.
BasketterD.A., BlaikieL., DearmanR.J., KimberI., RyanC.A., GerberickG.F., HarveyP., EvansP., WhiteI.R., & RycroftR.J.G. (2000). Use of the local lymph node assay for the estimation of relative contact allergic potency. Contact Dermatitis42, 344–348.
22.
GerberickG.F., RobinsonM.K., RyanC.A., DearmanR.J., KimberI., BasketterD.A., WrightZ., & MarksJ.G. (2001). Contact allergenic potency: correlation of human and local lymph node assay data. American Journal of Contact Dermatitis12, 156–161.
23.
KimberI., PichowskiJ.S., BasketterD.A., & DearmanR.J. (1999). Immune responses to contact allergens: novel approaches to hazard evaluation. Toxicology Letters106, 237–246.
24.
KimberI., PichowskiJ.S., BettsC.J., CumberbatchM., BasketterD.A., & DearmanR.J. (2001). Alternative approaches to the identification and characterization of chemical allergens. Toxicology in Vitro15, 307–312.
25.
RyanC.A., HuletteB.C., & GerberickG.F. (2001). Approaches for the development of cell-based in vitro methods for contact sensitization. Toxicology in Vitro15, 43–55.
26.
EnkA.H., & KatzS.I. (1992). Early molecular events in the induction phase of contact sensitivity. Proceedings of the National Academy of Sciences USA89, 1398–1402.
27.
SallustoF., & LanzavecchiaA. (1994). Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/ macrophage colony stimulating factor plus interleukin-4 and is down-regulated by tumor necrosis factor α. Journal of Experimental Medicine179, 1109–1118.
28.
ReutterK., JagerD., DegwertJ., & HoppeU. (1997). In vitro model for contact sensitization. II. Induction of IL-1β m RNA in human blood-derived dendritic cells by contact sensitizers. Toxicology in Vitro11, 619–626.
29.
PichowskiJ.S., CumberbatchM., DearmanR.J., BasketterD.A., & KimberI. (2000). investigation of induced changes in interleukin 1β mRNA expression by cultured human dendritic cells as an in vitro approach to skin sensitization testing. Toxicology in Vitro14, 351–360.
30.
PichowskiJ.S., CumberbatchM., DearmanR.J., BasketterD.A., & KimberI. (2001). Allergen-induced changes in interleukin 1β (IL-1β) mRNA expression by human blood-derived dendritic cells: inter-individual differences and relevance for sensitization testing. Journal of Applied Toxicology21, 115–121.
31.
PennieW.D., TugwoodJ.D., OliverG.J.A., & KimberI. (2000). The principles and practice of toxicogenomics: applications and opportunities. Toxicological Sciences54, 277–283.
32.
OrphanidesG., PennieW.D., MoffatG.J., & KimberI. (2001). Toxicogenomics: theoretical and practical applications. Comments on Toxicology7, 333–346.
33.
PennieW.D., & KimberI. (2002). Toxicogenomics: transcript profiling and potential application to chemical allergy. Toxicology in Vitro16, 319–326.
34.
BarrattM.D., BasketterD.A., ChamberlainM., AdamsG.D., & LangowskiJ.J. (1994). An expert system rulebase for identifying contact allergens. Toxicology in Vitro8, 1053–1060.
35.
RobertsD.W., & BasketterD.A. (1997). Further evaluation of the quantitative structure–activity relationship for skin-sensitizing alkyl transfer agents. Contact Dermatitis37, 107–112.
36.
RobertsD.W., YorkM., & BasketterD.A. (1999). Structure–activity relationships in the murine local lymph node assay for skin sensitization: α,β-di-ketones. Contact Dermatitis41, 14–17.
37.
ZinkeS., GernerI., & SchledeE. (2002). Evaluation of a rule base for identifying contact allergens by using a regulatory database: comparison of data on chemicals notified in the European Union with “structural alerts” used in the DEREK expert system. ATLA30, 285–298.
38.
KimberI., & DearmanR.J. (1997). Cell and molecular biology of chemical allergy. Clinical Reviews in Allergy and Immunology15, 145–168.
39.
DearmanR.J., SmithS., BasketterD.A., & KimberI. (1997). Classification of chemical allergens according to cytokine secretion profiles induced in mice. Journal of Applied Toxicology17, 53–62.
40.
DearmanR., & KimberI. (2001). Cytokine fingerprinting and hazard assessment of chemical respiratory allergy. Journal of Applied Toxicology21, 153–163.
