Organophosphates 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 organisms 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).
However, for fast initial screening, determining AChE and BuChE activity in the blood are the most widely used procedures for confirming a diagnosis of OP poisoning. The most widely used portable testing device is the Test-mate ChE field test,: 13  which can be used to determine levels of Red Blood Cells (RBC), AChE and plasma (pseudo) cholinesterase (PChE) in the blood in about four minutes. This test has been shown to be just as effective as a regular laboratory test and because of this, the portable ChE field test is frequently used by people who work with pesticides on a daily basis. Treatment
Current antidotes for OP poisoning consist of a pretreatment with carbamates to protect AChE from inhibition by OP compounds and post-exposure treatments with anti-cholinergic drugs. Anti-cholinergic drugs work to counteract the effects of excess acetylcholine and reactivate AChE. Atropine can be used as an antidote in conjunction with pralidoxime or other pyridinium oximes (such as trimedoxime or obidoxime), though the use of "-oximes" has been found to be of no benefit, or to be possibly harmful, in at least two meta-analyses. Atropine is a muscarinic antagonist, and thus blocks the action of acetylcholine peripherally. These antidotes are effective at preventing lethality from OP poisoning, but current treatment lack the ability to prevent post-exposure incapacitation, performance deficits, or permanent brain damage.