Toxicity cholinergic

Erythrocyte cholinesterase levels were monitored in two men exposed dermally to methyl parathion after entering a cotton field that had been sprayed with this pesticide (Nemec et al. 1968). The field was entered on two separate occasions twice within 2 hours after an ultra-low-volume spraying and a third time within 24 hours after spraying. Dermal methyl parathion residues 2 hours after spraying were 2-10 mg on the arms dermal residues 24 hours after spraying were 0.16-0.35 mg on the arms. The exposed individuals did not have signs of cholinergic toxicity, but erythrocyte cholinesterase levels after the third exposure were 60-65% of preexposure levels. 

The MRL is based on a NOAEL of 0.5 mg/m3 for decreased acetylcholinesterase activity in rats exposed to disulfoton 4 hours/day for 5 days in a study by Thyssen (1978). The NOAEL was adjusted for intermittent exposure, converted to a human equivalent concentration, and divided by an uncertainty factor of 30 (3 for extrapolation from animals to humans and 10 for human variability). Inhibition of erythrocyte cholinesterase activity and unspecified behavioral disorders were observed at 1.8 mg/m, and unspecified signs of cholinergic toxicity were observed at 9.8 mg/m. Similar effects were observed in rats or mice exposed to higher concentrations for shorter duMtions (Doull 1957 Thyssen 1978). The NOAEL value of 0.5 mg/m is supported by another study, in which no significant decrease in the activity of brain, serum, or submaxillary gland cholinesterase was found in rats exposed to 0.14-0.7 mg/m for 1 hour/day for 5-10 days (DuBois and Kinoshita 1971). Mild depression of erythrocyte cholinesterase activity was reported in workers exposed by the inhalation and dermal routes (Wolfe et al. 1978). 

The toxicity of diazinon may be affected by other substances. Some chemicals may increase the toxicity of diazinon in an additive manner. Anticholinesterase organophosphates and carbamates would be expected to act in an additive manner with diazinon with respect to its potential to induce cholinergic toxicity. 

Conventional nerve agents, such as sarin and soman, are OP compounds of pentavalent phosphorus that are well known as threats in the context of warfare and terrorism (Sidell and Borak, 1992). These substances produce acute cholinergic toxicity and death via inhibition of acetylcholinesterase (AChE) in the central and peripheral nervous systems (Marrs et al, 1996). 

In conhast to conventional nerve agents, DN agents produce permanent neurological dysfunction in the form of OPIDN rather than cholinergic toxicity and death (Richardson, 2005). Like conventional nerve agents, DN agents are OP compounds of pentavalent phosphorus that are readily synthesized, but they are designed to inactivate... 

Thus, when the RIP>1, the compound is a more potent inhibitor of AChE than NTE, and cholinergic toxicity would be expected to predominate over OPIDN. In fact, when the RIP >1, the dose required to produce OPIDN tends to be greater than the median lethal dose (LD50) for the compound (Kropp and Richardson, 2003 Richardson, 1992). 

One herb, the calabar bea, actually causes cholinergic toxicity (as seen with pesticide overdoses) due to the physostigmine content in the ripe seeds. This toxicity includes bradycardia and hypotension, potentially leading to cardiac and respiratory arrest. ... 

Cholingeric Calabar bean Physostigma venenosum Physostigmine in ripe seeds Cholinergic toxicity Chewing seeds releases more physostigimine... 

Calabar bean Physostigma venenosum Cholinergic toxicity... 

Azinphos-methyl requires bioactivation for its action. The parent compound is activated to the potent oxon by microsomal mixed-function oxidase enzymes, which in turn elicits toxicity by inhibiting acetylcholinesterase in synapse and neuromuscular junctions. AChE inhibition leads to overstimulation of cholinergic receptors on postsynaptic neurons, muscle cells, and/or end-organs and consequent signs and symptoms of cholinergic toxicity. 

While prolonged exposures to carbofuran could lead to typical signs of cholinergic toxicity, recovery from cholinergic signs is rapid and residual chronic toxicity is not likely regardless of exposure. 

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