Delayed neurotoxic effects of bis (1-methylethyl) phosphorofluoridate (DFP) in the European ferret: a possible mammalian model for organophosphorus-induced delayed neurotoxicity.
This study examined the effects of the organophosphorus delayed neurotoxicant bis (1-methylethyl) phosphorofluoridate (DFP) on the central nervous system of the European ferret. Animals received subcutaneous injections of either 2 or 4 mg DFP/kg b.w. The extent of neuropathology was determined by the Fink-Heimer method, the activities of neuropathy target esterase (NTE) and cholinesterase (ChE) by enzyme assay methods, and the severity of clinical signs by a graded scale. In ferrets injected with 4 mg DFP/kg b.w., dense axonal and terminal degeneration were noted at 21 and 28 days post-DFP in the gracile, inferior vestibular, and lateral reticular nuclei, medial and dorsal accessory nuclei of the inferior olive, and in cerebellar folia I-IV. Degeneration was also noted in laminae VI-VII throughout most of the spinal cord and in the ventral motor nucleus at the level of the cervical enlargement. Both NTE and ChE activities were maximally inhibited at 6 hr post-dosing. NTE activity returned to control levels by 4 days while ChE activities reached control levels at 21 days. Clinical signs at 21 and 28 days post-DFP ranged from slight hindlimb weakness to severe ataxia or hindlimb paralysis. Less severe degeneration and clinical signs were noted in the animals exposed to 2 mg DFP/kg b.w. These findings indicate that the European ferret may be a model species for assessing the effects of organophosphorus delayed neurotoxicants.
Tanaka
D
D
Department of Anatomy, Michigan State University, East Lansing 48824.
Bursian
S J
SJ
Lehning
E J
EJ
Aulerich
R J
RJ
D000818:Animals; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D002490:Central Nervous System / Q000187:drug effects*; D002531:Cerebellum / Q000187:drug effects; D002802:Cholinesterases / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005289:Ferrets; D007531:Isoflurophate / Q000633:toxicity*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects; D009943:Organophosphorus Compounds / Q000633:toxicity*; D016622:Silver Staining / Q000379:methods; D013116:Spinal Cord / Q000187:drug effects; D013997:Time Factors
D009943:Organophosphorus Compounds; D007531:Isoflurophate; D002265:Carboxylic Ester Hydrolases; C021859:neurotoxic esterase; D002802:Cholinesterases