A COMBINED MURINE LOCAL LYMPH NODE AND IRRITANCY ASSAY TO PREDICT SENSITIZATION AND IRRITANCY POTENTIAL OF CHEMICALS

Author： Woolhiser Michael R. Hayes Benjamin B. Meade B. Jean

ISSN： 1537-6524

Source： Toxicology Mechanisms and Methods, Vol.8, Iss.4, 1998-09, pp. : 245-256

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Abstract

In an effort to establish a single, rapid screening procedure for the sensitization and irritancy potential of new chemicals, the parameters of a murine Local Lymph Node Assay and a mouse ear swelling irritancy assay were combined. To validate this assay, a range of chemical irritants and sensitizers were evaluated for their ability to elicit responses in B6C3F1 female mice. Chemicals were administered for four consecutive days to the dorsal and ventral surfaces of each ear. An increasein ear thickness served to predict irritancy, while [3H]thymidine uptake by cervical draining lymph nodes suggested sensitization. All chemicals known to be potent chemical sensitizers (oxazolone, 2,4-dinitrofluorobenzene, toluene diisocyanate) produced a marked lymph node cell proliferation in this assay. Animals exposed to irritating agents (sodium lauryl sulfate, croton oil, tetradecane, nonanoic acid, and benzalkonium chloride) experienced a significant increase in ear swelling. In addition, these irritating agents elicited lowlevel lymphocyteproliferation.In cases wherechemicals areconsidered tobeboth potent sensitizers and irritants (2,4-dinitrofluorobenzene, toluene diisocyanate, and benzalkonium chloride), robust increases in [3H]thymidine incorporation and ear swelling were demonstrated. Results were dose-responsive for all chemicals tested. The combined LLNA/ear swelling assay appears to be a reliable predictor of sensitization and irritancy potential, since it identified the activity of all eight chemicals tested. The advantages of this approach include a further reduction in the number of animals and time required to screen chemicals for both irritancy and/or sensitization potential. Although this assay does not have the capacity to discriminate between nonspecific lymph node proliferation and weak sensitizing ability of strong irritants, the information gained by the irritation component of the assay provides additional information when evaluating the significance of low-level lymphocyte proliferation in the LLNA. With further validation this assay could be useful as a common screening tool in the research and development of new chemical products.