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Evaluation of the dermal sensitization potential of 3-amino-5-mercapto-1,2,4-triazole and n-(2,6-difluorophenyl)-5-methyl)1,2,4) triazolo-(1,5a)-pyrimidine-2-sulfonamide.

Klink-KJ; Meade-BJ
Toxicologist 2001 Mar; 60(1):171-172
3-Amino-5-mercapto-l,2,4-triawle (AMT) is an intermediate used in the production of the herbicide. N-(2,6-Difluorophenyl)-5-methyl)1,2,4) triazolo-(l,5a)pyrimidine-2-sulfonamide (DE498), and has been listed by the EPA as a chemical needing further toxicity testing. These studies focus on evaluating the immunomodulatory effects of AMT and DE498 using a murine model. Female BALB/c mice (N=5-8 per group) were used for all studies. Initial evaluation of irritancy/sensitizing potential was accomplished using a modified Local Lymph Node Assay (LLNA) with a 3 day dosing scheme. The Mouse Ear Swelling Test (MEST) was used to further evaluate contact hypersensitivity potential and the IgE inducing potential was assessed by measurement of total serum IgE levels and phenotypic analysis of IgE+/ B220+ cells in the draining lymph nodes. Airway hyperreactivity following chemical exposure was evaluated by methacholine challenge using whole body plethysmography. No signs of systemic toxicity or irritancy were observed with either chemical at concentrations up to 25% AMT and 40% DE498. DE498 was negative in the LLNA. A dose dependent increase in lymphocyte proliferation was observed following exposure to AMT, reaching a 3-fold increase over control at a concentration of 25%. An increase in B220+ cells was observed at all concentrations of AMT tested while only the 25% dose group exhibited a significant increase in IgE+/B220+ cells. AMT was negative in the MEST at concentrations up to 25%. Following dermal exposure 5 days a week for 28 days, 2 of 5 animals exposed to 25% AMT demonstrated elevated levels of total serum IgE and an increase in airway hyperreactivity upon methacholine challenge. These studies indicate that DE498 does not induce sensitization following dermal exposure, however AMT was identified as a sensitizer and has the potential to induce airway hyperreactivity.
Herbicides; Models; Laboratory-animals; Animals; Animal-studies; Lymph-nodes; Ear-disorders; Lymphocytes; Exposure-assessment; Exposure-levels; Methacholines; Sensitization
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The Toxicologist. Society of Toxicology 40th Annual Meeting, March 25-29, 2001, San Francisco, California