into three categories, based upon its actions in different parts of the nervous system. Muscarinic receptors that respond to acetylcholine are found in smooth muscles, the heart and exocrine glands. The muscarinic symptoms of cholinergic poisoning are therefore tightness in the chest, wheezing due to bronchoconstriction, bradycardia, miosis, increased salivation, lacrimation and sweating and increased peristalsis, which leads to nausea, vomiting and diarrhea. Nicotinic receptors responding to acetylcholine can be found in skeletal muscle and the autonomic ganglia. The nicotinic symptoms of cholinergic poisoning are therefore fatigue, involuntary twitching, muscular weakness, hypertension and hyperglycemia. Symptoms of accumulation of acetylcholine in the central nervous system are diverse and include tension, anxiety, ataxia, convulsions, depression of the respiratory and circulatory centers and coma. Acute toxicity The acute toxicity of chlorfenvinphos varies widely between species. Oral LD50 values range from 9.6–39 mg/kg in rats to >12,000 mg/kg in dogs. Though no direct data on the acute toxicity in humans is available, an in vitro study of the detoxification of chlorfenvinphos has shown that human liver enzymes were almost as effective as those of rabbits, who have an oral LD50 of 412-4,700 mg/kg., Long-term toxicity Prolonged exposure to chlorfenvinphos has been observed to decrease plasma and erythrocyte cholinesterase activity in humans. No significant genotoxicity, carcinogenicity or teratogenicity has been reported. On the basis of a NOAEL of 0.05 mg/kg observed in rats, an acceptable daily intake for humans of 0.0005 mg/kg has been established. Biomarkers Biomarkers of exposure Traces of unchanged chlorfenvinphos and its polar metabolites can be detected in animals, which have been exposed to chlorfenvinphos. These small amounts can be used to prove that chlorfenvinphos exposure has occurred and the method of analysis is non-invasive. Another method to assess chlorfenvinphos exposure is to measure the activity of cholinesterases in the blood. Two pools of cholinesterases exist in the blood: acetylcholinesterase in erythrocytes and pseudocholinesterase in plasma. The acetylcholinesterase in erythrocytes is identical to the acetylcholinesterase found in neuromuscular tissue. The function of plasma pseudocholinesterase is unknown, but its activity is considered to be a more sensitive biomarker for organophosphate exposure than erythrocyte cholinesterase activity. The inhibition of the individual cholinesterases or the inhibition of their combined activity can be used as a marker of exposure. However, cholinesterase inhibition is caused by all anticholinesterase compounds and is therefore not a specific biomarker for chlorfenvinphos. In addition, the activity of cholinesterases in the blood