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Determining a threshold sub-acute dose leading to minimal physiological alterations following prolonged exposure to the nerve agent VX in rats

Overview of attention for article published in Archives of Toxicology, November 2017
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Title
Determining a threshold sub-acute dose leading to minimal physiological alterations following prolonged exposure to the nerve agent VX in rats
Published in
Archives of Toxicology, November 2017
DOI 10.1007/s00204-017-2108-5
Pubmed ID
Authors

E. Bloch-Shilderman, I. Rabinovitz, I. Egoz, G. Yacov, N. Allon, U. Nili

Abstract

VX, a potent inhibitor of cholinesterase (ChE), is considered as one of the most toxic, persistent and least volatile nerve agents. VX is absorbed in various environmental surfaces and is gradually released long after its initial dispersal. Its toxicity is mainly caused by disrupting central and peripheral cholinergic nervous system activity, leading to potential long-term detrimental effects on health. The primary objective of the present study was to assess the threshold VX dose leading to minimal physiological alterations following prolonged VX exposure. Characterization of such a threshold is crucial for dealing with unresolved operative dilemmas such as when it is safe enough to resettle a population that has been evacuated from a VX-contaminated area. Rats, continuously exposed to various doses of VX (0.225-45 µg/kg/day) for 4 weeks via implanted mini-osmotic pumps, showed a dose-dependent and continuous decrease in ChE activity in whole blood, brain and muscles, ranging between 20 and 100%. Exposure to 13.5 µg/kg/day led to a stable low ChE activity level (~ 20%), accompanied by transient and negligible electrocorticogram spectral power transformations, especially in the theta and alpha brain wave frequencies, and a significant decrease in total brain M2 receptor density. These changes were neither accompanied by observable signs of intoxication nor by changes in motor function, circadian rhythm or TSPO level (a reliable marker of brain damage). Following exposure to lower doses of 2.25 and 0.225 µg/kg/day, the only change measured was a reduction in ChE activity of 60 and 20%, respectively. Based on these results, we delineate ChE inhibition as the physiological measure most susceptible to alterations following prolonged VX exposure, and determine for the first time the threshold sub-acute VX dose for minimal physiological effects (up to 20% reduction in ChE activity) in the rat as 0.225 µg/kg/day.

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Geographical breakdown

Country Count As %
Unknown 8 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 3 38%
Professor > Associate Professor 1 13%
Researcher 1 13%
Student > Bachelor 1 13%
Unknown 2 25%
Readers by discipline Count As %
Chemistry 2 25%
Nursing and Health Professions 1 13%
Biochemistry, Genetics and Molecular Biology 1 13%
Psychology 1 13%
Computer Science 1 13%
Other 0 0%
Unknown 2 25%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 12 November 2017.
All research outputs
#20,451,991
of 23,007,887 outputs
Outputs from Archives of Toxicology
#2,380
of 2,652 outputs
Outputs of similar age
#286,068
of 328,166 outputs
Outputs of similar age from Archives of Toxicology
#29
of 35 outputs
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