Subacute toxicity of ethylenebisisothiocyanate sulfide in the laboratory rat

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Abstract
Ethylenebisisothiocyanate sulfide (EBIS) was administered in the diet to groups of rats at 0, 1, 10, 100 and 1000 ppm for up to 90 days. The rats receiving EBIS at 1000 ppm demonstrated a toxic response within 8-14 days, reflected as a reversible paralysis of the hind legs. If left on the 1000 ppm diet, the animals soon died. When removed from the diet, the animals recovered, only to become ataxic on further dietary exposure at the high level. No histologic lesion could be identified in either H and E- or luxol fast blue-stained sections of brain, spinal cord or peripheral nerves from the paralyzed animals. The ability to reverse the paralysis by removing the animals from the test diet coupled with the lack of histologically observable lesions suggests a biochemical (reversible) rather than somatic lesion. Ingestion of 1000 ppm EBIS for 7 days resulted in measurable changes in thyroid function. Total serum thyroxine levels were markedly decreased, as was iodide uptake by the thyroid. Ingestion of EBIS at dietary levels of 100, 10, 1 and 0 ppm for 90 days produced no observable adverse effect. Growth, as seen by body weight increases, diet consumption, and thyroid function, was normal. No EBIS-related lesions were detected during the histopathologic evaluation of major tissues and organs taken from rats fed 100 ppm EBIS or control diets. In this 90 day dietary study with EBIS, no effects were noted at a level of 100 ppm in the diet, equivalent to an average intake ranging from 67 mg/kg body wt at wk 1 to 31 mg/kg body wt at wk 12. [EBIS is an autoxidation product of ethylenebisdithiocarbamic acid fungicides and may exist as a residue in and on food crops.].