Ranking of Allergenic Potency of Rubber Chemicals in a Modified Local Lymph Node Assay

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 hyper...

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Bibliographic Details
Published in:Toxicological sciences 2002-04, Vol.66 (2), p.226-232
Main Authors: De Jong, Wim H., Van Och, François M. M., Den Hartog Jager, Constance F., Spiekstra, Sander W., Slob, W., Vandebriel, Rob J., Van Loveren, Henk
Format: Article
Language:English
Subjects:
Administration, Cutaneous
Allergens - classification
Allergens - toxicity
allergy
Animals
Biological and medical sciences
chemicals
Dose-Response Relationship, Drug
Female
General aspects
Immunopathology
latex
Latex Hypersensitivity - etiology
LLNA
Local Lymph Node Assay
Lymph Nodes - drug effects
Lymph Nodes - pathology
Medical sciences
Mice
Mice, Inbred BALB C
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Summary: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.
ISSN:1096-6080
1096-0929
1096-0929
DOI:10.1093/toxsci/66.2.226