An assessment of the neurotoxic potential of fenitrothion in the hen.

The potential of single, toxic doses of fenitrothion (O,O-dimethyl O-(4-nitro-m-tolyl)phosphorothioate) to elicit delayed neurotoxicity in the adult White Leghorn hen was compared to the effects produced following similar treatment with the known neurotoxin, tri-o-tolyl phosphate (TOTP). Hens (2.0-2.5 kg body wt) received single oral doses of fenitrothion (500 mg/kg) or TOTP (500 mg/kg), the resulting toxicity being assessed by measuring biochemical (brain and spinal cord acetylcholinesterase (AChE) and neurotoxic esterase (NTE), physiological (motor function) and morphological (cross- and longitudinally-sectioned and stained preparations) parameters of the brains, spinal cords and sciatic nerves of groups (n = 5) of hens at 24 h, 7, 14, 28, 42 and 56 days post-treatment. At 24 h after treatment, fenitrothion caused a marked inhibition of neuronal AChE while TOTP had no effect. In contrast, TOTP caused a significant inhibition of NTE whereas fenitrothion was without effect. At 7 days after treatment, the NTE was still significantly reduced in TOTP-treated hens but normal levels of activity were detected at 14 days post-treatment. No alternation in NTE activity was found in any fenitrothion-treated hens. A characteristic, central-peripheral, distal axonopathy was observed following treatment with TOTP, mild signs appeared 7-14 days post-treatment and increased in severity up to 28 days after treatment, concomitant with morphological changes primarily in the sciatic nerves and spinal cords. Minimal morphological changes were elicited by fenitrothion at this dosage, the tissues appearing no different than those seen in vehicle-treated control hens. The results demonstrated that fenitrothion was distinctly different from TOTP in the biochemical, physiological and morphological effects produced in acutely treated hens and that fenitrothion could not be considered to be neuropathic in the classical manner of TOTP.