PMID- 12062936 OWN - NLM STAT- MEDLINE DCOM- 20020807 LR - 20190819 IS - 0300-483X (Print) IS - 0300-483X (Linking) VI - 176 IP - 1-2 DP - 2002 Jul 1 TI - Determination of the sensitising activity of the rubber contact sensitisers TMTD, ZDMC, MBT and DEA in a modified local lymph node assay and the effect of sodium dodecyl sulfate pretreatment on local lymph node responses. PG - 123-34 AB - A modified local lymph node assay (LLNA) was used to determine the sensitising activity of four chemicals used for the production of natural rubber latex products. Tetramethylthiuramdisulfide (TMTD), 2-mercaptobenzothiazole (MBT) and zincdimethyldithiocarbamate (ZDMC), three moderate human sensitisers, and diethylamine (DEA) a known human sensitiser, were epicutaneously administered on the ear and the proliferating activity in the draining (auricular) lymph node (LN) was determined by ex vivo (3)H-thymidine incorporation. Consistent results were obtained for TMTD and ZDMC with stimulation indices (SI) above 3, identifying these compounds as sensitiser, while for DEA and MBT inconsistent results were obtained. For all parameters determined such as LN weight, LN cell number, cell proliferation per 2 x 10(6) cells, and cell proliferation per LN statistical significant increases were observed. The SI, expressed as cellular proliferation per LN or per animal (left and right LN combined), was the most sensitive parameter with an optimum at day 5 after start of treatment.Furthermore, we investigated whether the use of sodium dodecyl sulfate (SDS) was able to enhance weak responses in the LLNA. SDS treatment with dosages of 10% and higher resulted in a SI above 3, while a dosage of 1% SDS showed no activity. Pretreatment with 1% SDS 1 h before application of the rubber chemicals enhanced the responses to these chemicals consistently, identifying also DEA and MBT as sensitisers. Our results indicate that SDS had synergistic activity on the LN responses of the administered rubber chemicals in the LLNA. For the moderately responding sensitisers TMTD and ZDMC both IFN-gamma and IL-4 production was observed. For the weakly responding sensitisers DEA and MBT both IFN-gamma and IL-4 cytokine production was only observed after pretreatment of the animals with 10% SDS. For 10% and 20% SDS, inducing approximately a SI of 20 in the LLNA, no induction of cytokines was observed. FAU - De Jong, Wim H AU - De Jong WH AD - Laboratory for Pathology and Immunobiology, National Institute of Public Health and the Environment, P.O. Box 1, 3720 BA, Bilthoven, The Netherlands. w.de.jong@rivm.nl FAU - Tentij, Marlies AU - Tentij M FAU - Spiekstra, Sander W AU - Spiekstra SW FAU - Vandebriel, Rob J AU - Vandebriel RJ FAU - Van Loveren, Henk AU - Van Loveren H LA - eng PT - Journal Article PL - Ireland TA - Toxicology JT - Toxicology JID - 0361055 RN - 0 (Allergens) RN - 0 (Benzothiazoles) RN - 0 (Diethylamines) RN - 0 (Surface-Active Agents) RN - 0 (Thiazoles) RN - 0D771IS0FH (Thiram) RN - 207137-56-2 (Interleukin-4) RN - 368GB5141J (Sodium Dodecyl Sulfate) RN - 5RLR54Z22K (captax) RN - 73D8UA974J (Ziram) RN - 82115-62-6 (Interferon-gamma) RN - 9006-04-6 (Rubber) RN - B035PIS86W (diethylamine) SB - IM MH - Allergens/*toxicity MH - Animals MH - Benzothiazoles MH - Cell Division/drug effects MH - Cells, Cultured MH - Diethylamines/toxicity MH - Dose-Response Relationship, Drug MH - Drug Synergism MH - Female MH - Interferon-gamma/metabolism MH - Interleukin-4/metabolism MH - Latex Hypersensitivity/*etiology MH - *Local Lymph Node Assay MH - Lymph Nodes/cytology/*drug effects/metabolism MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Rubber/chemistry MH - Sodium Dodecyl Sulfate/*pharmacology MH - Surface-Active Agents/*pharmacology MH - Thiazoles/toxicity MH - Thiram/toxicity MH - Ziram/toxicity EDAT- 2002/06/14 10:00 MHDA- 2002/08/08 10:01 CRDT- 2002/06/14 10:00 PHST- 2002/06/14 10:00 [pubmed] PHST- 2002/08/08 10:01 [medline] PHST- 2002/06/14 10:00 [entrez] AID - S0300483X02001312 [pii] AID - 10.1016/s0300-483x(02)00131-2 [doi] PST - ppublish SO - Toxicology. 2002 Jul 1;176(1-2):123-34. doi: 10.1016/s0300-483x(02)00131-2.