Cholinesterase carbamate insecticides

Diagnosis of organophosphate poisoning (including methyl parathion) can be confirmed by evaluation of serum (plasma) cholinesterase and erythrocyte cholinesterase. However, cholinesterase inhibition is not specific for organophosphates. For example, carbamate insecticides also result in cholinesterase inhibition, which is usually transitory. Erythrocyte cholinesterase measurement is a specific test for... 

The inhibition of brain cholinesterase is a biomarker assay for organophosphorous (OP) and carbamate insecticides (Chapter 10, Section 10.2.4). OPs inhibit the enzyme by forming covalent bonds with a serine residue at the active center. Inhibition is, at best, slowly reversible. The degree of toxic effect depends upon the extent of cholinesterase inhibition caused by one or more OP and/or carbamate insecticides. In the case of OPs administered to vertebrates, a typical scenario is as follows sublethal symptoms begin to appear at 40-50% inhibition of cholinesterase, lethal toxicity above 70% inhibition. 

Carbamates are used as insecticides, nematocides, fungicides, and herbicides the toxicity of carbamate insecticides is similar to that of OP compounds and is based on the inhibition of ACHE. Also, carbamate metabolites may inhibit ACHE but are usually weaker inhibitors than the unchanged compound. Cholinesterase inhibition caused by carbamates is labile, of short duration, and rapidly reversible in fact, the half-life of the inhibited enzymes ranges between some minutes and 2 to 3 hours for RBC-ACHE and is on the order of some minutes for PCHE. Accumulation of cholinesterase activity on repeated exposures, as observed with OP compounds, does not occur with... 

Occupational exposure to carbamate insecticides may be monitored by measuring RBC-ACHE and/or PCHE. However, given the low cholinesterase inhibition levels and the short time duration of this effect, ACHE inhibition can generally be used as a biomarker of exposure only when exposure levels are high. Three sequential samples are recommended to establish an individual baseline before exposure. In exposed workers, blood sampling and analysis should be carried out soon after the end of exposure (WHO, 1986). 

Enzymatic techniques have also been employed in the analysis of these compounds. The toxicity of carbamate insecticides is due to the inhibition of the enzyme acetylcholine esterase, so the determination of these compounds can be achieved by enzyme inhibition (2,83,119), bioassay (118,167), or enzyme-linked immunosorbent assay (ELISA) (168-171). In the detection of carbamates by fluorimetric enzyme inhibition, the effluent from a reversed-phase chromatographic column was incubated with cholinesterase, which was introduced via a postcolumn reagent delivery pump. Then, the resulting partially inhibited cholinesterase was reacted with N-methyl indoyl acetate to produce a fluorophore and a reduction in the baseline fluorescence (172). 

The coupling of HPLC with a cholinesterase-inhibition AutoAnalyzer for the determination of organophosphate and carbamate insecticides has much potential for the routine screening of residues of these compounds [58]. 

Toxicity Bendiocarb is moderately toxic if it is ingested or absorbed through the skin. Skin absorption is the most likely route of exposure. It is a mild irritant to the skin and eyes.4 Like other carbamate insecticides, bendiocarb is a reversible inhibitor of cholinesterase, an essential nervous system enzyme. Symptoms of bendiocarb poisoning include weakness, blurred vision, headache, nausea, abdominal cramps, chest discomfort, constriction of pupils, sweating, muscle tremors, and decreased pulse. 

Table I. Cholinesterase-Inhibitive Effects" of Several Organophosphate and Carbamate Insecticides...

Unlike the nonspecific effects and uncommon occurrence of direct mortality observed in wildlife exposed to chlorinated hydrocarbon pesticides, several studies have documented direct mortality from exposure to OP and carbamate insecticides. The method by which the OPs and carbamate insecticides affect wildlife is quite different from the method by which the chlorinated hydrocarbon insecticides effect wildlife. The OPs and carbamates inhibit cholinesterase, primarily acetylcholinesterase (AChE), which is an enzyme that functions in the breakdown of the neurotransmitter acetylcholine. Acetylcholine functions in the transmission of nerve impulses. Therefore, when AChE is inhibited by an OP or carbamate insecticide, it can no longer breakdown acetylcholine and there is continued transmission of nerve impulses that eventually leads to nerve and muscle exhaustion. The respiratory muscles are a critical muscle group that is affected, often leading to respiratory paralysis as the immediate cause of death. A major difference in the mode of action between OPs and carbamates is that the inhibition of AChE by OPs is, from a biological standpoint, irreversible, while the inhibition from exposure to carbamates is reversible in a biologically relevant time frame. There... 

Agents that cause these symptoms include organo-phosphate and carbamate insecticides (cholinesterase inhibitors),pilocarpine, physostigmine, and certain species of mushrooms that contain muscarine. 

The ability of PBO in synergize cholinesterase-inhibiting insecticides has often been ignored when the mode of action of PBO is discussed. Moore field (I95KJ presented detailed data on this subject and showed that both aromatic and heterocyclic carbamates can be potentiated with PBO. A graphical presentation of data is reproduced in Fig. 19.3 on the effect of adding PBO to iwo carbamate insecticides to control house flics. This is of particular interest in that application was only made to female flies by individual measured drops - much more precise and relevant to effective control than spray applications to Hies of both sexes. This was a classic demonstration of the powerful synergistic action of PRO... 

Oxamyl has a high acute toxicity displaying the typical effects of carbamate insecticides, e.g. rapid onset of cholinesterase inhibition followed by rapid recovery. Symptoms of acute intoxication in animals included tremors, salivation, lacrimation, bulging eyes, and muscular twitching. The oral LD50 for oxamyl in the rat is the range of 5 to 15 mg/kg. 

Carbamates generally act quickly. They are strongly toxic to a wide range of insect pests, but have a weak effect on the red spider mite. Some of them exhibit systemic characteristics. The duration of their action varies considerably. In a similar manner to the phosporic acid esters discussed later, they exert their action by paralysing the cholinesterase enzyme. During this process, the carbamate part of the molecule is attached to the esteratic site, and the aromatic part to the anionic site of the cholinesterase enzyme. As the distance between the esteratic and anionic sites is SO nm in the cholinesterase molecule, carbamate insecticides will be most efficient if the distance between the two groups to be bound to the two sites of the enzyme is also 50 nm. (Metcalf and Fukuto, 1965 1967 Fukuto et ai, 1967). 

Moderately toxic herbicide exhibited low to moderate toxicity in experimental animals when administered by oral, intraperitoneal, intravenous, and subcutaneous routes skin absorption is slow cholinesterase inhibitor in human ingestion can cause carbamate poisoning, which can be lethal when taken in large amount probable lethal oral dose in adult human estimated to be larger than other carbamate insecticides within the range... 

A. May potentiate agents metabolized by the cholinesterase enzyme (eg, depolarizing neuromuscular blocking agents—succinylcholine, cocaine, esmolol), cholinesterase inhibitors (eg, organophosphate and carbamate insecticides), and other cholinergic agents (eg, pilocarpine). 

A. Oximes are used to treat poisoning caused by cholinesterase inhibitor insecticides and nerve agents, ie, organophosphates, mixtures of organophospho-ms and carbamate insecticides, or pure carbamate insecticide intoxication with nicotinic-associated symptoms. Because of its low toxicity, possible ineffectiveness if treatment is delayed until after the cholinesterase enzyme has aged, ability to reverse nicotinic as well as muscarinic effects, and ability to reduce atropine requirements, pralidoxime should be used early and empirically for suspected cholinesterase inhibitor poisoning. 

The mechanism by which pesticides exert their toxic effects on mammals has been characterized for only a few groups of compounds [17,18]. For example, the mechanism for organophosphorus and carbamate insecticides involves inhibition of cholinesterase also, nitrophenols and higher chlorinated phenols are inhibitors for oxidative phosphorylation [10]. Fat-soluble substances (e.g., organochlorines such as DDT, HCH, and other persistent substances) accumulate in the body and, when stored in fatty tissues, cannot be... 

Organophosphate and carbamate insecticides, %vhich inhibit cholinesterase... 

Cholinesterase inhibitors (e.g., organophosphate and carbamate insecticides). Long-term inhibition of cholinesterase activity produces cataracts in humans and monkeys. 

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