PHARMACOKINETICS AND NEUROTOXICITY OF DIPTEREX IN HENS A COMRARATIVE STUDY OF ADMINISTRATION METHODS

Abstract

We compared the tissue concentration of dipterex and the inhibition of the neuropathy target esterase (NTE) activity among groups of hens (n = 8 each) which were intravenously (IV), subcutaneously (SC) or orally (PO) administered the insecticide dipterex. The tissue concentrations of dipterex in the SC group were higher than those in the IV and PO groups. When dosed subcutaneously, the tissue concentration of dipterex was high in the brain, spinal cord and muscle at 3 hr after dosing and then concentrated in the spinal cord and muscle for the subsequent 3 hr. When dosed intravenously or orally, dipterex was evenly dispersed in various tissues. All hens treated with dipterex showed acute neurotoxic signs within 15 min after dosing. The hend dosed intravenously recovered from this acute poisoning within 3 hr, and the hens dosed orally recovered within 6 hr, while the hens dosed subcutaneously redovered within 24 hr after dosing. One hen in the SC group exhibited acute neurological sequelae following the acute poisoning. In addition, the loss of body weight was the largest in the SC group (157 ± 49 g), moderate in the IV group (133 ± 91 g), small in the PO group (96 ± 54 g) and the smallest in the PMSF (phenylmethanesulfonyl fluoride, which was dosed to promote delayed neuropathy) grourp (80 ± 49g). In the untreated hens, the activity of NTE in both the cerebrum and cerebellum was higher than that in the midbrain (p < 0.01). There was no difference in NTE activity between the cerebrum and cerebellum. In both the cerebrum and midbrain, the inhibition of NTE activity in the PO group was less than that in the IV and SC groups, and no difference was found between the IV and SC groups. In the cerebellum, the inhibition of NTE activity in the SC group was larger than that in the IV and PO groups. These results indicate that the SC dosing of dipterex results in a stronger neurotoxicity compared to IV and PO dosing. However it was difficult to induce the clinical signs of delayed neuropathy with any administration of dipterex in hens, even when the promotion of delayed neurotoxicity of dipterex was attempted with PMSF or double doses of dipterex itself.