title: Acute toxicity of cyclohexylmethylphosphonofluoridate (CMPF) in rhesus monkeys: serum biochemical and hematologic changes.
abstract: 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.
mesh_terms: 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
chemical_list: 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