PMID- 10439340 OWN - NLM STAT- MEDLINE DCOM- 19990928 LR - 20190921 IS - 0260-437X (Print) IS - 0260-437X (Linking) VI - 19 IP - 4 DP - 1999 Jul-Aug TI - A comparison of statistical approaches to the derivation of EC3 values from local lymph node assay dose responses. PG - 261-6 AB - Effective risk assessment and management of allergic contact dermatitis require three key factors: adequate hazard identification, measurement of the relative potency of identified hazards and an understanding of the nature, extent and duration of exposure. Suitable methods for hazard identification, such as the murine local lymph node assay (LLNA) and the guinea-pig maximization test, are well established and conditions of human exposure normally can be well anticipated. Thus, the need is for a robust and quantitative method for the estimation of relative skin sensitizing potency. One possible approach is via the analysis of LLNA dose-response data. In the LLNA, contact allergens are defined currently as those chemicals that cause a threefold or greater increase in lymph node cell proliferative activity compared with concurrent vehicle-treated controls. It is possible to estimate the concentration of a sensitizer required to generate a threefold stimulation of proliferation in draining lymph nodes; such a concentration is known as the EC3 value. Using a variety of statistical approaches to derive EC3 values from LLNA dose-response data for 10 chemicals, it has been demonstrated that simple linear interpolation between the values either side of the threefold stimulation index provides a robust assessment of the EC3 value without the need for recourse to more sophisticated statistical techniques. Provided that the appropriate concentrations of test chemical have been selected, EC3 values obtained in this way are reproducible both within and between laboratories and form the basis for examination of the utility of this approach for the estimation of relative skin sensitizing potency. FAU - Basketter, D A AU - Basketter DA AD - Safety and Environmental Assurance Centre, Unilever Research, Sharnbrook, UK. FAU - Lea, L J AU - Lea LJ FAU - Dickens, A AU - Dickens A FAU - Briggs, D AU - Briggs D FAU - Pate, I AU - Pate I FAU - Dearman, R J AU - Dearman RJ FAU - Kimber, I AU - Kimber I LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Appl Toxicol JT - Journal of applied toxicology : JAT JID - 8109495 RN - 0 (Allergens) SB - IM MH - Allergens/*toxicity MH - Animals MH - *Data Interpretation, Statistical MH - Dose-Response Relationship, Drug MH - Linear Models MH - Lymph Nodes/*drug effects/metabolism/pathology MH - Lymphocyte Activation/*drug effects MH - Mice MH - Mice, Inbred CBA MH - *Models, Statistical MH - Predictive Value of Tests MH - Toxicity Tests EDAT- 1999/08/10 10:00 MHDA- 2000/06/20 09:00 CRDT- 1999/08/10 10:00 PHST- 1999/08/10 10:00 [pubmed] PHST- 2000/06/20 09:00 [medline] PHST- 1999/08/10 10:00 [entrez] AID - 10.1002/(SICI)1099-1263(199907/08)19:4<261::AID-JAT572>3.0.CO;2-5 [pii] AID - 10.1002/(sici)1099-1263(199907/08)19:4<261::aid-jat572>3.0.co;2-5 [doi] PST - ppublish SO - J Appl Toxicol. 1999 Jul-Aug;19(4):261-6. doi: 10.1002/(sici)1099-1263(199907/08)19:4<261::aid-jat572>3.0.co;2-5.