Acute toxicity of cyclohexylmethylphosphonofluoridate (CMPF) in rhesus monkeys: serum biochemical and hematologic changes.
Changes in serum biochemical and hematological parameters were studied in 20 male rhesus monkeys following acute poisoning by the organophosphate nerve agent cyclohexylmethylphosphonofluoridate (CMPF or GF). Animals were challenged with 5 x LD50 GF (233 micrograms/kg, IM) following pretreatment with pyridostigmine (0.3-0.7 mg/kg per 24 h) and treated with atropine (0.4 mg/kg, IM) and either 2-PAM (25.7 mg/kg, IM) or H16 (37.8 mg/kg, IM) at the onset of clinical signs or at 1 min after exposure. Muscle fasciculations, tremors, or convulsions occurred in 19 of 20 animals. Serum biochemical and hematologic parameters were analyzed 2 days and 7 days after exposure and compared to pre-exposure baseline values. Significant increases in creatine kinase (CK), lactate dehydrogenase (LD), aspartate transaminase (AST), alanine transaminase (ALT) and potassium ion (K+), associated with damage to striated muscle and metabolic acidosis, occurred in both oxime-treated groups 2 days after exposure. Total protein, albumin, red blood cell (RBC) count, hemoglobin concentration (Hb) and hematocrit (Hct), were decreased in both oxime-treated groups at 7 days. The results demonstrate that animals exposed to a single high dose of GF and treated with standard therapy exhibit changes in serum biochemical and hematological indices directly and indirectly associated with their clinical presentations.
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000931:Antidotes / Q000008:administration & dosage / Q000494:pharmacology; D001219:Aspartate Aminotransferases / Q000097:blood; D001285:Atropine / Q000008:administration & dosage / Q000494:pharmacology; D015415:Biomarkers / Q000097:blood; D002619:Chemical Warfare Agents / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D002801:Cholinesterase Reactivators / Q000008:administration & dosage / Q000494:pharmacology; D003402:Creatine Kinase / Q000097:blood; D007273:Injections, Intramuscular; D007770:L-Lactate Dehydrogenase / Q000097:blood; D007928:Lethal Dose 50; D008253:Macaca mulatta; D008297:Male; D009943:Organophosphorus Compounds / Q000633:toxicity*; D010091:Oximes; D011188:Potassium / Q000097:blood; D011220:Pralidoxime Compounds / Q000008:administration & dosage / Q000494:pharmacology; D011726:Pyridinium Compounds / Q000008:administration & dosage / Q000494:pharmacology; D011729:Pyridostigmine Bromide / Q000008:administration & dosage / Q000494:pharmacology; D012640:Seizures / Q000139:chemically induced
D000931:Antidotes; D015415:Biomarkers; D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D009943:Organophosphorus Compounds; D010091:Oximes; D011220:Pralidoxime Compounds; D011726:Pyridinium Compounds; D001285:Atropine; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D003402:Creatine Kinase; C022870:asoxime chloride; D011729:Pyridostigmine Bromide; C028797:pralidoxime; D011188:Potassium; C053914:cyclohexyl methylphosphonofluoridate