Review of the U.S. Army's Health Risk Assessments for Oral Exposure to Six Chemical-Warfare Agents (1999) / Chapter Skim
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G: Inhibition of Cholinesterases and an Evaluation of the Methods Used to Measure Cholinesterase Activity
G: Inhibition of Cholinesterases and an Evaluation of the Methods Used to Measure Cholinesterase Activity
Pages 295-304
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From page 295... ...
One CaE, known as neuropathy target esterase (NTE) , is an enzyme associated with organophosphateinduced delayed neuropathy (OPIDN)
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From page 296... ...
AChE activity also occurs in the serum of developing mammals and birds, decreasing to adult levels after birth (Smucker and Wilson 19901. Together with AChEs, BuChEs are also found at synapses, motor end plates, and muscle fibers.
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From page 297... ...
Many of the physiological effects of anti-ChEs are attributable to excess neurotransmitter ACh (Taylor 1996~. The precise symptoms and the time course depend on the chemicals and the localization of the receptors affected.
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From page 298... ...
Prolonged muscle weakness and muscle damage might last several weeks or longer after exposure to high concentrations of some OPs, including methyl parathion, fenthion, and dimethoate. These experimental observations might correspond to the proximal muscle weakness that sometimes develops in individuals after an organophosphate pesticide-induced cholinergic crisis.
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From page 299... ...
GA, GB, AND GD STUDIES In its evaluation of the critical studies of GA, GB, and GD, the subcommittee noted that ChE assay kits and instructions developed for humans appeared to be applied without question to studies of experimental animals. Validation of such applications has not been done, and, therefore, ChE measurements reported in the critical studies of GA (Bucci et al.
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From page 300... ...
Moreover, the studies were conducted with a substrate concentration of acety~thiocholine of 5.4 mM and a pH of 7.2, which have been shown to reduce human blood-AChE activity by approximately 40% (Wilson et al.
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From page 301... ...
TABLE G-3 Effect of a Constant Blank on Acetylcholinesterase Activity Dose 0-ACT 20-ACT 30-ACT 40-ACT %-20 °/O-30 °/O-40 1 100 120 130 140 100 100 100 2 90 110 120 130 92 92 93 3 70 90 100 110 75 77 79 4 40 60 70 80 50 54 57 5 25 45 55 65 38 42 46 6 8 28 38 48 23 29 34 7 5 25 35 45 21 27 32 8 3 23 33 43 19 26 31 SLOPE -15.5 -15.5 -15.5 -15.5 -13.0 -11.9 -11.1 INTCPT 112.5 132.5 142.5 152.5 110.6 109.4 109.0 CORR -0.969 -0.969 -0.969 -0.969 -0.970 -0.968 -0.967 The effect of a constant high blank, such as that occuring with the thiol oxidase activity of rodent red blood cells, is illustrated above. Arbitrary units of blank activity 0, 20,30, and 40 are added to a 100-unit enzyme activity.
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From page 302... ...
No corrections were made for the high AChE concentrations in plasma. At best, subtraction of the plasma values presumably yielded an estimated activity of the total AChE activity in the blood, whether it was from RBCs, serum, or platelets.
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From page 303... ...
Rat RBCs contain high third oxidase activity and low AChE activity, which can result in large errors in calculating percentage of inhibition if uncorrected. There was no indication that such corrections were made in the assays used in the critical studies of GA, GB, and GD.
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From page 304... ...
Another reason is that methods that subtracted plasma activities from whole-blood activities avoided the problem of plasma-AChE activities, so long as the relative changes in total AChE activity were not affected. However, the problem of high thio!
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