A REAPPRAISAL OF THE SKIN-SENSITIZING ACTIVITY OF 2,4-DINITROTHIOCYANOBENZENE

A debate continues regarding the immunological properties of 2,4-dinit rothiocyanobenzene (DNTB). In some investigations this chemical was sh own not to cause skin sensitization when applied topically but to indu ce instead hyporesponsiveness or immunological tolerance. In other stu dies DNTB was found to cause skin sensitization, but not tolerance. Ho wever, this chemical continues to be used to discriminate between the properties of skin sensitizing and non-sensitizing chemicals. This stu dy demonstrates that topical exposure of mice to DNTB induces skin sen sitization in mice and that this is associated with the accumulation o f dendritic cells in draining lymph nodes and the stimulation of lymph node cell proliferation; the latter responses being of equivalent mag nitude to those stimulated by 2,4-dinitrochlorobenzene (DNCB), a chemi cal known to cause contact sensitization. Moreover, exposure of mice t o DNTB, as with exposure to DNCB, resulted in the development of a cyt okine secretion pattern by draining lymph node cells (LNC) characteris tic of contact allergens. Thus, DNTB and DNCB each induced the product ion by LNC of high levels of interferon-gamma, but little or no interl eukin 4 or interleukin 10. Finally, DNTB was shown in the guinea pig m aximization test to behave as an extreme skin sensitizer. These result s confirm that DNTB should not be regarded as a universal tolerogen an d that it possesses a significant potential to induce contact sensitiz ation. The use of this chemical as a presumptive non-sensitizer and/or tolerogen for the evaluation of the selectivity of new predictive tes t methods for the identification of contact allergens is therefore con sidered to be inappropriate. (C) 1997 Elsevier Science Ltd.