FUNCTIONAL AND HISTOLOGIC EVIDENCE OF NEUROPATHY IN CHICKS FOLLOWING IN OVO TREATMENT WITH ORGANOPHOSPHORUS COMPOUNDS (EMBRYO, TOCP)

This study was designed to examine the vulnerability of the embryonic nervous system to damage from neurotoxic organophosphorus compounds. The chick embryo was the test organism. Eggs were injected into the albumen on incubation day 14 with either triorthocresyl phosphate (TOCP) or leptophos, compounds that cause organophosphate-induced delayed neuropathy (OPIDN) in man and chickens. Neuropathy was evaluated after hatching by examining motor function and tissue morphology.; A neuropathy that resembled severe OPIDN in hens was produced using both compounds, at doses that caused high embryo mortality. Survivors were severely ataxic from hatching until the study was ended at 3 weeks post-hatching. Nerve fiber degeneration and muscle atrophy were present in the legs. A lower dose that did not increase mortality caused a neuropathy that was not grossly evident but was detected using quantitative measures of gait and perching ability and measures of leg nerve and muscle morphology. These chicks walked with a short stride and with their feet directed more openly than controls, alterations consistent with leg weakness. Ability to perch without visual orientation was also impaired. TOCP-treated chicks had a distal motor neuropathy consistent with OPIDN: impeded muscle fiber growth indicating muscle denervation and subsequent hypertrophy of fibers indicating a compensatory response by remaining fibers. Denervation was also evident by excessive terminal branching of motor axons, a response by remaining axons to innervate denervated muscle fibers. Some recovery occurred by 25 days after hatching, seen as a reduction in excess axonal branches and the return of muscle fibers toward control size. The functional motor impairment did not diminish.; This is the first report of neuropathy in the embryo of any species caused by treatment with neurotoxic organophosphates. The doses that caused severe embryo neuropathy produce a comparable condition given orally to hens. Embryo vulnerability contrasts with the resistance of juveniles of all species tested, including chicks treated after hatching. The chick embryo is proposed to be uniquely suited for testing embryo sensitivity to delayed neuropathy and it may also be useful as a test for OPIDN.