Plasma cholinesterase activity

Individuals with hereditary low plasma cholinesterase levels (Kalow 1956 Lehman and Ryan 1956) and those with paroxysmal nocturnal hemoglobinuria, which is related to abnormally low levels of erythrocyte acetylcholinesterase (Auditore and Hartmann 1959), would have increased susceptibility to the effects of anticholinesterase agents such as methyl parathion. Repeated measurements of plasma cholinesterase activity (in the absence of organophosphate exposure) can be used to identify individuals with genetically determined low plasma cholinesterase. 

Brock A. 1991. Inter and intraindividual variations in plasma cholinesterase activity and substance concentration in employees of an organophosphorus insecticide factory. Br J Ind Med 48 562-567. 

Howard JK, East NJ, Chaney JL. 1978. Plasma cholinesterase activity in early pregnancy. Arch Environ Health September/October 277-278. 

Venkataraman BV, Niyer GY, Narayanan R, et al. 1990. Er34hrocyte and plasma cholinesterase activity in normal pregnancy. Indian J Physiol Pharmacol 34 26-28. 

Although this study (Hart 1980) did not identify an effect level, the NOAEL is below the LOEL found in all studies examining the toxicity of diisopropyl methylphosphonate. The LOEL for diisopropyl methylphosphonate is 262 mg/kg/day for male mink and 330 mg/kg/day for female mink (Bucci et al. 1997), doses at which statistically significant decreases in plasma cholinesterase (butyrylcholinesterase) but not RBC cholinesterase (acetylcholinesterase) activity were observed (Bucci et al. 1997). In general, a decrease in plasma cholinesterase activity is considered to be a marker of exposure rather than a marker of adverse effect, while a decrease in RBC acetylcholinesterase activity is a neurological effect thought to parallel the inhibition of brain acetylcholinesterase activity and is thus considered an adverse effect. Diisopropyl methylphosphonate was not found to inhibit red blood cell cholinesterase at doses at which plasma cholinesterase was significantly inhibited. No effects were observed in males at 45 mg/kg/day (Bucci et al. 1997) or at 63 mg/kg/day (Bucci et al. 1994), and no effects were observed in females at 82 mg/kg/day (Bucci et al. 1994), or at 57 mg/kg/day (Bucci et al. 1997). 

Hoffman RS, Henry GC, Howland MA, et al. 1992. Association between life-threatening cocaine toxicity and plasma cholinesterase activity. Ann Emerg Med 21 248-253... 

Based on the data from controlled human studies, the NOEL for plasma cholinesterase inhibition for a single dose of chlorpyrifos is between 0.1 and 0.5 mg/kg bw/day, and the more conservative 0.1 mg/kg bw/day (100 pg/kg bw/day) is used in this assessment as the acute NOEL for chlorpyrifos. The repeated dose NOEL in humans is 0.03 mg/kg bw/day (30 pg/kg bw/day), based on plasma cholinesterase activity, and this is the basis for the establishment of the reference dose of 0.003 mg/kg bw/day (3 pg/kg bw/day) used by the EPA in assessing dietary risk to chlorpyrifos. For the work described here, both NOELs are used as bases for assessing risks to persons who have the potential for non-dietary exposure to chlorpyrifos. For exposures that are infrequent or of short duration, the 100 pg/kg bw/day NOEL is assumed to be the more appropriate value, and the lower 30 pg/kg bw/day will be used in those situations in which exposure may be considered to be more frequent. ... 

The results from using the Student s f-test for a distributional analysis are presented in Table 4. These results indicate the probability of a given worker in the listed scenario exceeding the NOEL of the toxicity endpoint. The probability of exceeding the LOEL and of thus experiencing a depression of plasma cholinesterase activity is not given (except for chronic exposure scenarios in the "100 ug/kg bw/day" column). Hence, even these probabilities may be considered to be conservative and not fully representative of the probability of a worker actually experiencing a toxic effect. 

Blood specimens of approximately 5 mL were collected on two separate days during the week preceding the study. Additional blood specimens of approximately 5 mL each were collected approximately 24 and 48 hr after the start of the study. These blood specimens were drawn and assayed for plasma cholinesterase activity by personnel from the Michigan Division Medical Department of The Dow Chemical Company. 

Solar-Rodriguez, F., M-P. Miguez-Santiyan, A. Reja-Sanchez, V. Roncero-Cordero, and J.-P. Garcia-Cambero. 1998. Recovery of brain acetylcholinesterase and plasma cholinesterase activities in quail (Cotumix cotumix) after chlorpyrifos administration and effect of prahdoxime treatment. Environ. Toxicol. Chem. 17 1835-1839. 

A comprehensive approach to a states response to a chemical terrorism includes having a plan not only for the crisis and consequence management phases of the incident, but also for all elements required for complete resolution of the event. This may include the necessity to definitively establish whether chemical agents were used, to provide supporting evidence to confirm other analyses, or to provide the forensic proof required to support a criminal prosecution. The collection and analysis of biomedical samples - blood, urine or other tissue from affected humans or animals - is one of the means for providing such information. Although current capabilities such as urinary thiodyglycol excretion or plasma cholinesterase activity can be performed, there is scope for far more sensitive and specific assessments that overcome the limitations of these approaches. 

Table 6.3 Brain MChR Binding and Brain and Plasma Cholinesterase Activities in Rainbow Trout (Oncorhynchus mykiss) Exposed to Sample Extracts and Controls. Reprinted from Petty et al. (2000), copyright (2000) reproduced with permission from Elsevier...

In 2-yr feeding trials, NOELs based on blood plasma cholinesterase activity for rats and dogs were 30 and 10 pg/kg daily, respectively (Worthing and Hance, 1991). 

The only undesirable effects observed during these studies were signs and complaints of lodlnlsm by the subjects given 2-PAM 1 and decreases in red-cell and plasma cholinesterase activities of about 20% in the subjects given 111. Less of 111 was excreted in the urine (3% during 24 h) than of the monoquaternary compounds (27% in 14 h). 

Owls did not avoid famphur-poisoned Coturnix, fed normally, and did not lose weight. By the tenth day, plasma-cholinesterase activities in owls were depressed 45-81%, and brain cholinesterase activities were depressed 32-73%... 

Mivacurium is a mixture of three stereoisomers, the two short-acting cis-trans and trans-trans isomers comprising about 94% of the mixture. Both have very short half-lives of about 2 minutes, while the much less potent c/s-c/s isomer has about one-tenth the neuromuscular blocking potency of the other two isomers. The c/s-c/s isomer undergoes some renal excretion as well as being broken down by plasma cholinesterase with a half-life of about 50 minutes (Table 6.4). The short-acting isomers are broken down almost entirely by plasma cholinesterase with a high rate of clearance and a short duration of action. The duration of action of mivacurium is increased when there is a reduction in plasma cholinesterase activity as in patients with marked renal and hepatic disease. The same is true for elderly patients. 

In in vitro studies, phosphine decreased red blood cell or plasma cholinesterase activity, and similar effects were seen in vivo in workers using phosphine fumigant (Potter et al. 

Phenelzine, a monoamine oxidase inhibitor, has been reported to cause significant prolongation of suxamethonium paralysis due to depressed plasma cholinesterase levels (to about 10% of normal). Recovery of plasma cholinesterase activity took 2 weeks (13). 

Dorandeu, F., Foquin, A., Briot, R., Delacour, C., Denis, J., Alonso, A., Froment, M.T., Renault, F., Lallement, G., Masson, P. (2008). An unexpected plasma cholinesterase activity rebound after challenge with a high dose of the nerve agent VX. Toxicology 248 151-7. 

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