Standard treatments for OP poisoning are ineffective for OPIDP. COPIND occurs without cholinergic symptoms and is independent of AChE inhibition. COPIND appears with a delay and is long lasting. Symptoms associated with COPIND include cognitive deficit, mood changes, autonomic dysfunction, peripheral neuropathy, and extrapyramidal symptoms. The underlying mechanisms of COPIND have not been determined, but it is hypothesized that withdrawal of OP pesticides after chronic exposure or acute exposure could be a factor. Pregnancy
Evidence of exposure to OP pesticides during gestation and early postnatal period have been linked to neurodevelopmental effects in animals, specifically rats. Animals exposed in utero to chlorpyrifos exhibited decreased balance, poorer cliff avoidance, decreased locomotion, delays in maze performance, and increased gait abnormalities. Early gestation is believed to be a critical time period for the neurodevelopmental effects of pesticides. OPs affect the cholinergic system of fetuses, so exposure to chlorpyrifos during critical periods of brain development potentially could cause cellular, synaptic, and neurobehavioral abnormalities in animals. In rats exposed to methylparathion, studies found reduced AChE activity in all brain regions and subtle alterations in behaviors such as locomotor activity and impaired cage emergence. Organophosphates as whole have been linked to decreases in the length of limbs, head circumference, and slower rates of postnatal weight gain in mice. Cancer
The International Agency for Research on Cancer (IARC) found that organophosphate exposure may increase cancer risk. Tetrachlorvinphos and parathion were classified as "possibly carcinogenic", malathion, and diazinon. Cause
OP pesticide exposure occurs through inhalation, ingestion and dermal contact.
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).