Peripheral nerve damage in chicks following treatment with organophosphorus compounds in ovo

Chick embryos were treated with tri-o-cresyl phosphate (TOCP) or leptophos, organophosphorus compounds that cause delayed neurotoxicity. Embryos received either TOCP (62 or 250 microliter/kg egg) or leptophos (125 to 750 mg/kg egg) Day 14 of incubation and were examined after hatching for nerve damage. The high doses caused high embryo mortality. Chicks which survived the high doses were grossly ataxic from hatching until the study was ended at 3 weeks posthatching. On Posthatching Day 2, many degenerating nerve fibers were observed in the profundus/superficialis peroneus nerve in chicks surviving the high doses. TOCP-treated chicks were followed in detail for neuromuscular changes. Twenty days after hatching there were fewer large nerve fibers in the distal ischiadic nerve compared with controls and the largest nerve fibers were absent in the peroneus profundus nerve. Consistent with the evidence of denervation there was increased terminal branching of motor axons in femoral (sartorius) and tibial (external gastrocnemius and peroneus longus) leg muscles. The leg nerves of chicks treated with the low dose of TOCP did not show either an excessive number of degenerating nerve fibers or a detectable loss of large nerve fibers. However, terminal branching of motor axons was increased in the external gastrocnemius and peroneus longus muscles of 5- and 15-day-old chicks, followed by recovery by Day 25. The evidence is interpreted as a distal axonopathy in chicks treated with TOCP during late embryonic development.