Organophosphates biomarkers

Following exposure of humans to organophosphates, but not specifically methyl parathion, restoration of plasma cholinesterase occurs more rapidly than does restoration of erythrocyte cholinesterase (Grob et al. 1950 Midtling et al. 1985). These findings are supported by studies of methyl parathion in animals. Erythrocyte cholinesterase levels are representative of acetylcholinesterase levels in the nervous system, and, therefore, may be a more accurate biomarker of the neurological effects of chronic low level exposure of humans to methyl parathion (Midtling et al. 1985 NIOSH 1976). 

Organophosphate Ester Hydraulic Fluids. Interpretation of the biomarkers of exposure to organophosphate ester hydraulic fluids is complicated by the diversity of composition among the hydraulic fluids in this class. Erythrocyte acetylcholinesterase activity is a good biomarker of exposure to certain organophosphates (e.g., insecticides), but results are inconsistent with organophosphate components of... 

Organophosphate Ester Hydraulic Fluids. The biomarkers of effects after exposure to organophosphate ester hydraulic fluids are well established in cases of delayed neuropathy (clinical signs of peripheral neuropathy). Further study would be helpful to determine whether certain effects (such as diarrhea after oral exposure) are due to direct action of the toxic agent on the target organ or to inhibition of acetylcholinesterase at the acetylcholine nerve receptor site on the organ. 

Table 4 Other Biomarkers Used in Biological Monitoring of Human Exposure to Organophosphates...

A combination of neurological signs is usually a biomarker of organophosphate exposure. Neurological signs such as pupil miosis, muscular tremors, and increased salivation have been observed in humans accidentally exposed to disulfoton (Yashiki et al. 1990) and in animals given disulfoton (Schwab et al. 1981). 

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. 

Wessels, D., D.B. Barr, and P. Mendola. 2003. Use of biomarkers to indicate exposure of children to organophosphate pesticides Implications for a longitudinal study of children s environmental health. Environ. Health Perspect. 111(16) 1939-1946. 

In a study of biomarkers of exposure to organophosphate insecticides, the urine of 6- and 7-year-old Italian children was analyzed for dimethyl- and diethyl- phosphates, thiophosphates, and dithiophosphates, such as the examples shown in Figure 18.11. Levels of these metabolites were found to correlate well with insecticide applications inside or outside the homes where the children... 

Figure 18.11 Examples of dimethyl- and diethyl- organophosphate, organothiophosphate, and organodithio-phosphate esters that can be measured in urine as biomarkers of exposure to various organophosphate ester insecticides.

Costa LG, Cole TB, Vitalone A, Furlong CE (2005) Measurement of paraoxonase (PON1) status as a potential biomarker of susceptibility to organophosphate toxicity. Clin Chim Acta, 352 37-47. 

Devi, K.P., Pandian, S.K., and Kumar, N.S.S., Cholinesterase activity in clam Meretrix casta Possible biomarker for organophosphate pesticide pollution, Bull. Environ. Contain. Toxicol., 74, 250, 2005. 

The LOAELadj (0.054 mg/kg per day) used by ORNL for derivation of the RfD for GB was based on the lowest dose that caused a significant depression in RBC AChE activity in rats (Bucci and Parker 1992). The subcommittee notes that ChE inhibition is typically considered a biomarker of exposure to organophosphate agents rather than an adverse effect. However, it is generally agreed that inhibition of ChE contributes... 

Whyatt RM, Barr DB. Measurement of organophosphate metabolites in postpartum meconium as a potential biomarker of prenatal exposure a validation study. Environ Health Perspect 2001 109 417-20. 

Elimination products such as hydrolyzed organophosphate or covalently bound organophos-phate are the biomarkers of choice for detection of exposure, since the persistence of the intact nerve agents, although sufficiently long to interfere with therapeutic measures, is too short for this... 

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