Organophosphates accumulated exposure

Urine catecholamines may also serve as biomarkers of disulfoton exposure. No human data are available to support this, but limited animal data provide some evidence of this. Disulfoton exposure caused a 173% and 313% increase in urinary noradrenaline and adrenaline levels in female rats, respectively, within 72 hours of exposure (Brzezinski 1969). The major metabolite of catecholamine metabolism, HMMA, was also detected in the urine from rats given acute doses of disulfoton (Wysocka-Paruszewska 1971). Because organophosphates other than disulfoton can cause an accumulation of acetylcholine at nerve synapses, these chemical compounds may also cause a release of catecholamines from the adrenals and the nervous system. In addition, increased blood and urine catecholamines can be associated with overstimulation of the adrenal medulla and/or the sympathetic neurons by excitement/stress or sympathomimetic drugs, and other chemical compounds such as reserpine, carbon tetrachloride, carbon disulfide, DDT, and monoamine oxidase inhibitors (MAO) inhibitors (Brzezinski 1969). For these reasons, a change in catecholamine levels is not a specific indicator of disulfoton exposure. 

Organophosphates illustrate several points. First, repeated exposure can be a problem not only because of accumulation of the substance (as can occur with other substances such as aspirin) but also because of accumulation of the effect, if it is irreversible. Therefore the dose-time relationship is important as weU as the dose-response relationship. Secondly, understanding the mechanism allows effective detection and treatment thirdly, other factors such as decomposition and exposure to other chemicals can have a large impact on toxicity and finally the dose is crucial, and it would seem, at least from the information available at present, that OPs can be used safely if they are used sparingly and carefully. 

Cholinesterase inhibition may persist for a period of days to weeks. Therefore, repeated exposure to azamethiphos over a period of time may result in the accumulation of enzyme inhibition and onset of acute toxicity. Azamethiphos does not appear to be capable of eliciting organophosphate-induced delayed neuropathy. Likewise, azamethiphos does not appear to be carcinogenic. 

Cholinesterase inhibition can sometimes persist for weeks thus, repeated exposures to small amounts of this material may result in accumulation of acetylcholinesterase inhibition with possible sudden-onset acute toxicity. Chlorpyrifos may be capable of causing organophosphate-induced delayed neurotoxicity in humans a massive overdose resulted in signs characteristic of delayed neurotoxicity. Animal studies generally indicate, however, that doses several times higher than the LD50 would be required to initiate delayed neurotoxicity. 

Organophosphorus compounds (OPC) cause two major toxic effects. The first is the well-known acute toxicity initiated by inhibition of acetylcholinesterase (AChE) with subsequent accumulation of acetylcholine at nerve endings. The second effect is organophosphate-induced delayed polyneuropathy (OPIDP) (ataxia and paralysis appearing 2-3 weeks after exposure) associated with inhibi-... 

Toxic substances can interfere with normal neurotransmission in a variety of ways, ether directly or indirectly, and cause various central effects. For example, cholinesterase inhibitors such as the organophosphate insecticides cause accumulation of excess acetylcholine. The accumulation of this neurotransmitter in the CNS in humans after exposure to toxic insecticides leads to anxiety, restlessness, insomnia, convulsions, slurred speech and central depression of the respiratory and circulatory centres. 

Phthalates as well as organophosphates seem to be accumulated in the hrnnan body as they have been detected in human body fat. Butyl benzyl phthalate amoimted to 0.19 pg/g (= mg/kg) in human adipose tissue in the US. In a series of studies trialkyl-, triha-loalkyl-, and triaryl phosphates were analyzed in human adipose tissue. " Although there was no history of exposure to organophosphates, TDCPP and TBEP were detected at levels of 0.5-110 pg/kg and 4.0-26.8 pg/kg, respectively. TCEP, however could not be detected. TBEP and TDCPP were also the only organophosphates detected in adipose tissue obtained from human cadavers from 6 Ontario municipalities in the Great Lakes Basin area. TBEP levels ranged from 25 to 483 pg/kg TDCPP from 1.5 to 22 pg/kg, respectively. " ... 

Organophosphates and their family of conqmunds are potent neurotoxins that share structural similarities to chemical warfare agents such as sarin, soman and VX. Organophosphates are cholinesterase inhibitors and exposure to OP compounds leads to increased neurotransmitter accumulation. Classical synq)toms of OP exposure include salivation, lacrimination, urination and defecation. E q)osure to OP con )ounds can cause Ettigue, dizziness, vomiting, paralysis and even death (2). 

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