Ranking of allergenic potency of rubber chemicals in a modified local lymph node assay

W.H. de Jong*, F.M.M. van Och, C.F. den Hartog Jager, S.W. Spiekstra, W. Slob, R.J. Vandebriel, H. van Loveren

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Ranking of allergenic potency of rubber chemicals in a modified local lymph node assay.

De Jong WH, Van Och FM, Den Hartog Jager CF, Spiekstra SW, Slob W, Vandebriel RJ, Van Loveren H.

Laboratory for Pathology and Immunobiology, National Institute for Public Health and the Environment, RIVM, P.O.Box 1, 3720 BA Bilthoven, The Netherlands. w.de.jong@rivm.nl

A modified local lymph node assay (LLNA) with ex vivo tritium thymidine (3H-TdR) labeling of the proliferating lymph node cells was used for determination of the allergenic potency of chemicals used in the production of rubber for latex medical gloves. Fifteen chemicals known to induce contact hypersensitivity reactions in man, including various thiuram, carbamate, and benzothiazole compounds, and one amine were tested. The EC3 (effective concentration inducing a 3-fold increase in proliferation of lymph node cells [Stimulation Index, SI = 3]) was calculated with nonlinear regression analysis, including a bootstrap method for determination of the 5-95% confidence interval of the EC3 value. This procedure identified 14 out of the 15 chemicals tested as sensitizers, while for one chemical, ZDBC, no EC3 could be calculated due to low responses and a lack of a dose-response relationship in the data obtained. The ranking order of the chemicals with increasing EC3 values (and thus decreasing allergenic potency) was found to be in the following order: ZDEC < TMTD < TETD < ZPC < ZDMC < MBTS < PTD < TMTM < MBT < MBI < PTT < ZMBT < TBTD < DEA < ZDBC. Our results indicate that the chemicals of choice for use in the production of natural rubber latex products would be for the thiuram compounds, TBTD; for the carbamates, ZDBC; and for the benzothiazoles, ZMBT. However, one has to be aware that besides potency, the total amount of residual chemical present in the final product is also important for allergy induction
Original languageEnglish
Pages (from-to)226-232
Number of pages7
JournalToxicological Sciences
Issue number2
Publication statusPublished - 1 Jan 2002

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