Subacute toxicity in rats of orally administered fenitrothion alone and in a selected formulation

Young adult male and female Sprague-Dawley rats received 1.0, 5.0, 10.0, or 20.0 mg/kg body wt of technical fenitrothion ( O,O-dimethyl O-(4-nitro- m-tolyl)phosphorothioate) in ethanol:propylene glycol (25:75) in the absence or presence of 1.5% ( v v ) of each of Atlox 3409F (emulsifier) and Dowanol TPM (cosolvent) by daily gavage for 30 consecutive days. At 7, 14, 21, and 30 days of treatment, five randomly selected rats from each treatment group were killed; tissues (liver, kidney, brain, spinal cord, and distal sciatic nerve) were preserved for morphological examination. The effects of treatment were assessed by measuring changes in blood plasma pseudocholinesterase (ψChE), erythrocytic and brain acetylcholinesterase (AChE), and hepatic and renal nonspecific carboxylesterase (CE) as well as routine hematology and serum biochemistry. At 8, 30, 60, and 90 days after treatment, five animals of each group were killed to assess the reversibility of any observed biochemical, physiological, or histopathological effects. No changes in the routine hematological and serum biochemical parameters or in tissue morphology were observed which could be related either to the vehicle, emulsifier(s)-cosolvent, or to a dose-dependent effect of fenitrothion. A dose-dependent inhibition of the tissue esterases was observed at doses above 1.0 mg fenitrothion/kg body wt. Recovery of esteratic activity from the treatment was rapid except for those rats receiving the largest dose; however, within 2 months after treatment, the activities of all treated rats were comparable to control activities. The emulsifier (Atlox 3409F) and the cosolvent (Dowanol TPM), at concentrations routinely employed in aerial spraying formulations, did not substantially enhance or reduce the toxicity of fenitrothion.