Evaluation of the potential for dermal exposure to 3-Amino-5-mercapto-1,2,4-triazole (AMT) to induce pulmonary hyperreactivity.
Abstract
3-Amino-5-mercapto-1,2,4-triazole (AMT) is an intermediate in the production of the herbicide DE498. Little toxicological information is available for either compound. These studies were conducted, using BALB/c female mice, to evaluate the potential of AMT to cause allergic sensitization and induce pulmonary hyper-reactivity following dermal exposure. Using the Local Lymph Node assay, AMT was identified as a sensitizer at concentrations of 15% and greater. AMT was negative for contact sensitization in the Mouse Ear Swelling Test. Phenotypic analysis of draining lymph node cells following 4 days of dermal exposure demonstrated an increase in B220 + cells at all concentrations of AMT tested and a significant increase in IgE + /B220 + cells in the 25% dose group. In sub-chronic dermal exposure (5 days a week for 11 weeks) studies, 4 of 5 animals exposed to 25% AMT had elevated levels of total serum IgE and 2 of the 5 experienced airway hyperreactivity upon methacholine challenge. Cytokine modulation in draining lymph node cells was determined by RNase Protection Assay. Upregulation of cytokines associated with TH2 responses and mast cell growth and differentiation (IL-4, 5, 10, 13, and 9) was observed. These studies suggest that AMT is a sensitizer with the potential to induce pulmonary reactivity.
