INDEX Cholinesterases

It frequently invalidates the measurement of blood cholinesterase activity as a diagnostic index of poisoning. 

The Committee examined five organophosphate pesticides (acephate, chlorpyrifos, dimethoate, disulfoton, and ethion), which are all cholinesterase inhibitors and may be present as residues in fruits and vegetables. Chlorpyrifos was used as the index compound. The TEF was defined as the ratio of the NOAEL or LOAEL for each pesticide to the NOAEL or LOAEL for chlorpyrifos. TEFs based on LOAELs were used when a NOAEL could mot be established for two of the compounds. 

The UK Pesticide Safety Directorate (PSD) has decided to use the TEF approach for assessment of combined risk from exposure to mixtures of acetyl cholinesterase inhibitors (organophosphate (OP) compounds and carbamates) (PSD 1999). Despite clear differences in the action of carbamates and OP compounds, the index compounds selected for all acetyl cholinesterase inhibitors were either aldicarb (carbamate) or chlorpyrifos (OP). The POD for determining relative potency was predetermined as the dose level that produced 20% inhibition of red blood cell cholinesterase in a 90-day dietary study in rats. 

The understandable correlation among careless technique, absenteeism, cholinesterase inhibition, and elevated average urinary PNP levels suggested that the latter was a highly reliable biological index of chronic parathion exposure and one that could ultimately predict chronic parathion toxicity. 

According to inpatient records from St Luke s Hospital, the most common laboratory finding related to sarin toxicity was a decrease in plasma cholinesterase (ChE) levels in 74% of patients. In patients with more severe toxicity, plasma ChE levels tended to be lower, but a more accurate indication of ChE inhibition is measurement of erythrocyte ChE, as erythrocyte ChE (AChE) is considered true ChE and plasma ChE is pseudo ChE . However, erythrocyte ChE is not routinely measured, whereas plasma ChE is included in many clinical chemistry panels thus, it can be used as a simple index for ChE activity. In both the Matsumoto and Tokyo subway sarin attacks, plasma ChE served as a useful index of sarin exposure. In 92% of hospitalized patients, plasma ChE levels returned to normal on the following day. In addition, inpatient records from... 

A new installment in the interesting story of the selective effect of haloxon (VI) on helminth cholinesterase appeared recently. It had been shown earlier that the phosphorylated enzyme i.e., bis-(dichloroethoxy)-phosphoryl cholinesterase, which arises from interaction of haloxon with a cholinesterase of sheep, dephosphorylates rapidly compared to the corresponding phosphorylated enzyme which formed from haloxon and cholinesterase from Haemonchus contortus The higher therapeutic index of haloxon relative to older organophos-phate anthelmintics was attributed to this observed biochemical difference between host and parasite. 

In spite of the drastic fall of cholinesterase activity in many cases of cancer, the reduction does not come early enough or with sufficient regularity to serve for cancer detection. One possible exception can be the diagnostic distinction between tumor- or gallstone-produced biliary obstruction (FI, K35, W25). The monitoring of cholinesterase activity in cancer patients, however can serve as a sensitive index of a patient s state and prognosis. 

There is generally a fall in plasma cholinesterase activity after burn injury (P15, V6, V8). There is a clear-cut relationship between the severity of the injury, as expressed by the burn index, and the lowest measured cholinesterase activity if that is expressed in terms of percentage of the patient s normal values (V6). Particularly in severely burned patients, there may be a very sharp fall of esterase activity within one day that is, in a shorter time than can be accounted for by the normal catabolism of the enzyme. The initial drop therefore seems to indicate a dilution effect,... 

Properties Colorless clear vise, liq. mild odor sol. in most org. soivs., 95% ethanol, acetone, DMSO, ketones, chlorinated hydrocarbons sol. < 1 mg/ml in water insol. in aliphatic hydrocarbons m.w. 430.91 dens. 1.508 g/cm (22.2 C) vapor pressure 10.3 mm Hg (25 C) f.p. 27 C b.p. 236-237 C (5 mm) flash pt. 252 C ref. index 1.5022 Toxicology LD50 (oral, rat) 1850 mg/kg, (skin, rabbit) > 23,700 mg/kg mod. toxic by ing. may cause irritation of skin, respiratory tract cholinesterase inhibitor may cause tremors, convulsions, irritability, hypermotility, diarrhea, enzyme inhibition, change in blood/tissue levels, changes in liver/kidney wt questionable carcinogen experimental teratogen and reproductive effects mutagenic data ... 

Czolkos et al. Cellobiose dehydrogenase, soybean peroxidase, tyrosinase, horseradish peroxidase, butyryl cholinesterase and acetyl cholinesterase Voltammetric Toxicity index Chemical oxygen demand Biochemical oxygen demand Wastewater [59]... 

PbB has long been used as the standard index of dose in estimating dose-effect and dose-response relationships. Some would argue that it is perhaps less valid than certain other measurements which reflect in quantitative fashion the bioavailable fraction of PbB, much as erythrocyte cholinesterase inhibition reflects the toxic impact of exposure to organophosphate insecticides. Indeed, it has been reported that inhibition of erythrocyte membrane Na, K-ATPase activity is better correlated with lead toxicity than erythrocyte lead concentration (Raghavan ei al, 1981). This was attributed to the fact that the subjects had variable concentrations of a low molecular weight lead binding protein which influenced the bioavailable fraction of PbB. It is possible that EP reflects bioavailable lead in a similar fashion. 

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