Effect of route of administration on the development of organophosphate-induced delayed neurotoxicity in 4-week-old chicks.
The poor absorption of organophosphate delayed neurotoxins through the gastrointestinal tract has been suggested as a reason why young chickens are not susceptible to organophosphate-induced delayed neurotoxicity (OPIDN). In the present study, 4-wk-old White Leghorn chickens were administered a single dose of 500 mg tri-o-tolyl phosphate (TOTP)/kg body weight or 100 mg o-tolyl saligenin phosphate (TSP)/kg body weight via the oral, intramuscular, or intraperitoneal route. In addition, TOTP TSP were administered intravenously at 250 and 50 mg/kg body weight, respectively. Forty-eight hours after dosing, half the birds in each group were killed for subsequent determination of whole-brain and sciatic nerve neurotoxic esterase (NTE) activity while the remaining 5 birds per group were observed daily from d 7 through d 21 for development of OPIDN clinical signs. TOTP administered by the 4 routes generally resulted in whole-brain and sciatic nerve NTE inhibition in excess of 85%. TSP given via the different routes resulted in 75-84% inhibition of whole-brain NTE activity and 66-79% inhibition of sciatic nerve NTE activity. No birds displayed clinical signs typical of OPIDN during the 21-d test. Thus, the resistance of the young chicken to the delayed effects of organophosphate compounds is due to factors other than the poor absorption of the compound through the gastrointestinal tract or the inability of the bird to convert TOTP to its neuroactive metabolite, TSP.
Olson
B A
BA
Department of Animal Science, Michigan State University, East Lansing 48824.
Bursian
S J
SJ
D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000187:drug effects*; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D002645:Chickens; D003408:Cresols / Q000633:toxicity*; D007273:Injections, Intramuscular; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D009943:Organophosphorus Compounds / Q000633:toxicity*; D010525:Peripheral Nerves / Q000187:drug effects*; D012584:Sciatic Nerve / Q000187:drug effects; D014317:Tritolyl Phosphates / Q000008:administration & dosage / Q000633:toxicity*
D003408:Cresols; D009943:Organophosphorus Compounds; D014317:Tritolyl Phosphates; C000516:2-(2-cresyl)-4H-1-3-2-benzodioxaphosphorin-2-oxide; D002265:Carboxylic Ester Hydrolases; C021859:neurotoxic esterase; C025541:tri-o-cresyl phosphate