The repeated
intravenous injections (RIVInj) of 5 mg/kg/day
leptophos [O-(4-bromo-2, 5-dichlorophenyl) O-methyl phenylphosphonothioate] for 3 consecutive days caused delayed
ataxia in 4 out of 9 hens (44.4%). And one out of 9 hens (11.1%) given RIVInj of 3 mg/kg
leptophos for 5 days was affected with
ataxia. Twenty hens, however, which received a single
intravenous injection (SIVInj) of 15 mg/kg
leptophos did not exhibit any delayed neuropathic signs at all. Thus, delayed neurotoxicity was increased by the subdividing RIVInj of the critical dose which was shown in the SIVInj of
leptophos. The
leptophos concentration in plasma and liver decreased very rapidly after finish of either SIVInj or RIVInj. Although no significant differences were observed in the
biological half life of
leptophos in plasma by different dosages, the mean level of
leptophos decreased significantly with frequency of
injections. On the contrary, the evident accumulation of
leptophos was observed in only sciatic nerve with RIVInj. Leg muscle maintained relatively high level of
leptophos after the last injection. These results suggest that
leptophos seems to transfer from blood to affinitive tissues such as sciatic nerve or leg muscles and to accumulate there easily in initial stage after repeated iv
injections, and that this causes the enhancement of neuropathy with repeated administrations of divided critical dose of
leptophos in both iv and
oral administration.