The health effects associated with<unk>  are a result of excess acetylcholine (ACh) present at different nerves and receptors in the body because acetylcholinesterase is blocked. Accumulation of ACh at motor nerves causes overstimulation of nicotinic expression at the neuromuscular junction. When there is an accumulation of ACh at autonomic ganglia synapses this causes overstimulation of muscarinic expression in the parasympathetic nervous system.<unk> s irreversibly and non-competitively inhibit acetylcholinesterase, causing poisoning by phosphorylating the serine hydroxyl residue on AChE, which inactivates AChE. AChE is critical for nerve function, so the inhibition of this enzyme, which causes acetylcholine accumulation, results in muscle overstimulation. This causes disturbances across the cholinergic synapses and can only be reactivated very slowly, if at all. Paraoxonase (PON1) is a key enzyme involved in OP toxicity and has been found to be critical in determining an organism's sensitivity to OP exposure. PON1 can inactivate some OPs through hydrolysis. PON1 hydrolyzes the active metabolites in several OP insecticides such as chlorpyrifos oxon, and diazoxon, as well as, nerve agents such as soman, sarin, and VX. PON1 hydrolyzes the metabolites, not the parent compounds of insectides. The presence of PON1 polymorphisms causes there to be different enzyme levels and catalytic efficiency of this esterase, which in turn suggests that different individuals may be more susceptible to the toxic effect of OP exposure. Higher levels of PON1 plasma hydrolytic activity provide a greater degree of protection against OP pesticides. Rats injected with purified PON1 from rabbit serum were more resistant to acute cholinergic activity than the control rats. PON1 knockouts in mice are found to be more sensitive to the toxicity of pesticides, like chlorpyrifos. Animal experiments indicate that while PON1 plays a significant role in regulating the toxicity of OPs its degree of protection given depends on the compound (i.e. Chlorpyrifos oxon or diazoxon). The catalytic efficiency with which PON1 can degrade toxic OPs determines the degree of protection that PON1 can provide for organism. The higher the concentration of PON1 the better the protection provided. PON1 activity is much lower in neonates, so neonates are more sensitive to OP exposure. In 2006, reports up to a 13-fold variation was seen in PON1 levels in adults, as well as, specifically regarding sensitivity to diazoxon, a variation up to 26 and 14-fold was reported in a group of newborns and Latino mothers. This wide range in variability of enzyme levels determining a human's sensitivity to various OPs is being researched further.
Organophosphate poisoning
Carbamate poisoning
Salicylate poisoning
Myasthenia gravis
Strychnine poisoning
Sulfuric acid poisoning
Tin poisoning
Chlorine gas poisoning