The effect of tri-ortho-cresyl phosphate on the development of organophosphate-induced delayed neurotoxicity in immature chickens and modulation by selected hormones and hormone antagonists

The reason for the insusceptibility of young animals to organophosphorus-induced delayed neurotoxicity (OPIDN) remains to be elucidated. The present study was undertaken to determine the influence of age-related changes in hormone concentrations on the development of OPIDN in the domestic chicken. In the first experiment it was demonstrated that a relatively fast growing broiler-breed of chicken developed OPIDN when dosed with a single oral dose (500 mg/kg body weight) of tri-o-cresyl phosphate (TOCP) at 6 weeks of age while a slower growing layer-breed was not susceptible until 12 weeks of age. The serum growth hormone and testosterone profiles indicated the growth hormone concentrations began to decline in both breeds approximately 3 weeks before they became susceptible to OPIDN and that testosterone concentrations in the broiler-breed birds increased significantly from 1 to 9 weeks of age, while testosterone concentrations in the layer-breed birds remained relatively constant. In the second experiment, testosterone and estradiol were administered to broiler-breed cockerels from 6 through 10 weeks of age to interfere with sexual development and the organophosphorus delayed neurotoxin TOCP was administered in a single oral dose of 500 mg/kg body weight at 7 weeks of age. One of 5 birds in the testosterone/TOCP group and 2 of 5 birds in the estradiol/TOCP group developed OPIDN as opposed to 5 of 5 birds in the TOCP group. This suggested that interference with sexual development via administration of testosterone or estradiol protected the bird against development of OPIDN.; The administration of the synthetic corticoid dexamethasone had no effect on the development of OPIDN in young broiler-breed chickens nor did thiouracil which has been demonstrated to cause a decrease in circulating growth hormone concentrations.