Range-Finding Report on the Immunotoxicity of Disulfoton in Female B6C3F1 Mice (CAS No. 298-04-4)
Report Date: August 2009
The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of the NTP or the U.S. Government.
Disulfoton, O,O-diethyl S-[2-(ethylthio)ethyl] phosphorodithioate, is a selective, systemic organophosphate insecticide and acaricide that is effective against multiple insects. It is often used to control a variety of insects, including aphids, spider mites, and coffee leaf miners. Disulfoton products are used on a wide variety of food and nonfood crops, with the highest use on cotton and wheat. Disulfoton inhibits the breakdown of acetylcholine by cholinesterase, and cholinergic muscarinic receptors have been identified on immune cells, including lymphocytes.
Disulfoton was nominated to the NTP for toxicological evaluation and was selected for immunotoxicity studies by the project officer. Thus, the purpose of these studies was to determine the potential effects of DST on the immune system.
The study reported herein is an initial range-finding study conducted in female B6C3F1 mice. The animals were exposed daily for 28 days by oral gavage. The in-life phase of the study was conducted between 20, Apr. 05 and 25, Jul. 07. DST was prepared weekly as a solution in corn oil.
Female B6C3F1 mice were administered DST at doses of 0.01, 0.05, 0.1, 0.5 and 1 mg/kg/day for 28 days. Overall, exposure to DST had no effects on body weight. Organ weights were not affected with the exception of absolute spleen weight in Study 1, which had a maximum increase of 19%. This effect was not reproduced in a second study (Study 3) where no significant effect was observed in either absolute or relative spleen weight.
The percent weight (% body weight) of spleen was not significantly altered, suggesting that the changes in Study 1 were related to body weight. Although there were sporadic changes in the number of erythrocytes, concentration of hemoglobin and hematocrit, these alterations in hematological parameters were not dose responsive in nature and would not be considered biologically significant.
Seven functional assays including the spleen immunoglobulin M antibody-forming cell response to sheep red blood cells, anti-sRBC IgM antibody response, anti-Keyhole Limpet Hemocyanin IgM antibody response, spleen cell proliferative response to anti-CD3 stimulation, natural killer cell activity assay, spleen mixed leukocyte response and cytotoxic T cell activity assay were conducted. There were no biologically meaningful changes associated with any of the assays. Additionally, flow cytometric analyses were undertaken to determine the number and percentages of leukocytes in the spleen. As with the functional assays, there were no significant changes observed in any of the cell types.
In conclusion, oral exposure to disulfoton by gavage produced minimal toxicological and immunological effects in female B6C3F1 mice when administered daily for 28 days at doses up to and including 1 mg/kg,