Cholinesterases population studies

Neurologic signs did not occur over a 30-day period in male prisoner volunteers in California who ingested daily doses of methyl parathion ranging from 1.0 to 19 mg. There were no uniform changes in plasma or erythrocyte cholinesterase levels at any of these doses (Rider et al. 1969). By increasing concentrations of methyl parathion administered to the same experimental population and using the same protocol, a dose that inhibited cholinesterase values was established. These additional studies were published nearly 20 years ago in abstract form only therefore, they are not discussed in this section. 

The major action resulting from human exposure to diazinon is the inhibition of cholinesterase activity (refer to Section 2.4 for discussion). Two pools of cholinesterases are present in human blood acetylcholinesterase in erythrocytes and serum cholinesterase (sometimes referred to as pseudocholinesterase or butyrlcholinesterase) in plasma. Acetylcholinesterase, present in human erythrocytes, is identical to the enzyme present in neural tissue (the target of diazinon action) while serum cholinesterase has no known physiological function. Inhibition of both forms of cholinesterase have been associated with exposure to diazinon in humans and animals (Coye et al. 1987 Edson and Noakes 1960 Soliman et al. 1982). Inhibition of erythrocyte, serum, or whole blood cholinesterase may be used as a marker of exposure to diazinon. However, cholinesterase inhibition is a common action of anticholinesterase compounds such as organophosphates (which include diazinon) and carbamates. In addition, a wide variation in normal cholinesterase values exists in the general population, and there are no studies which report a quantitative... 

In Section III, we review studies on persistent effects of exposure to cholinesterase inhibitors. The human epidemiological literature is examined for evidence that persistent behavioral effects of exposure can be measured in populations with histories of acute poisoning and/or chronic ongoing exposure. We then review behavioral data from animal models designed to characterize the behavioral changes caused by experimental treatments with cholinesterase-inhibiting pesticides and identify similarities with the literature on human.s exposed occupationally to these compounds. 

The comparative cholinesterase studies, as described, provide infonnation on adverse outcomes (cholinesterase inhibition) following cither acute or repeated exposures in populations at various life stages. In a review of cumulative risk assessment procedures for the OP pesticides (EPA, 2(K)2b), acute and/or repeated dose comparative cholinestera.se data in rats were available for a limited number of OP pesticides. These data raised uncertainties regarding the adequacy of adult risk potency factors to be protective of potential age-dependent. sensitivity to cholinestera.se inhibition and of potential adverse neurodevelopmental outcomes that arc a result of the inhibition t)f cholinesterase. As a re,sull, a thrcc-fold database uncertainty factor was applied in the cumulative risk calculation for those chemicals that did not have comparative cholinesterase data twailable for evaluation. This... 

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