Organophosphates metabolites

C.P. Weisskopf and J.N. Seiber, New approaches to the analysis of organophosphate metabolites in the urine of field workers, in ACS Symposium Series Biological Monitoring for Pesticide Exposure Measurement, Estimation, and Risk Reduction, eds. R.G.M. Wang, C.A. Franklin, R.C. Honeycutt, and J.C. Reinert, American Chemical Society, Washington, DC, pp. 206-214 (1989). 

Richter ED, Kowalski M, Leventhal A, et al. 1992. Illness and excretion of organophosphate metabolites four months after household pest extermination. Arch Environ Health 47(2) 135-138. 

Richter, E.D., M. Kowalski, A. Leventhal, F. Grauer, J. Marzouk, S. Brenner, I. Shkolnik, S. Lerman, H. Zahavi, A. Bashari, A. Peretz, H. Kaplanski, N. Gruener and P. Ben Ishai (1992). Illness and Excretion of Organophosphate Metabolites Four Months after Household Pest Extermination, Arch. Environ. Health, 47, 135-138. 

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. 

Weisskopf CP, Seiber JN. New approaches to analysis of organophosphate metabolites in the urine of fields workers. ACS Symp Ser 1989 382 206-14. 

Organophosphate flame retardants and plasticisers Perfluorinated compounds Pharmaceuticals and personal care products Polar pesticides and their degradation/transformation products Surfactants and their metabolites... 

Davies JE, Peterson JC. 1997. Surveillance of occupational, accidental, and incidental exposure to organophosphate pesticides using urine alkyl phosphate and phenolic metabolite measurements. Aim NY Acad Sci 837 257-268. 

Pre-exposure to the organophosphate diazinon at exposures half the LC50 values increased the LC50 value by a factor of about five for guppy (Poecilia reticulata), but had no effect on the value for zebra fish (Brachydanio rerio). This was consistent with the observation that during pre-exposure of guppy there was a marked inhibition in the synthesis of the toxic metabolites diazoxon and pyrimidinol, whereas this did not occur with zebra fish in which the toxicity was mediated primarily by the parent compound (Keizer et al. 1993). 

Diisopropyl methylphosphonate is an organophosphate compound that was first produced in the United States as a by-product of the manufacture of the nerve gas isopropyl methylphosphonofluoridate (GB, or Sarin) (ATSDR 1996 EPA 1989 Robson 1977, 1981). It is not a nerve gas and is not a metabolite or degradation product (Roberts et al. 1995). Diisopropyl methylphosphonate constitutes approximately 2-3% of the crude GB product, but it is neither a metabolite nor a degradation product of GB (EPA 1989 Rosenblatt et al. 1975b). Diisopropyl methylphosphonate is not normally produced except for its use in research. One method of producing diisopropyl methylphosphonate is to combine triisopropyl phosphite and methyl iodide. The mixture is then boiled, refluxed, and distilled, yielding diisopropyl methylphosphonate and isopropyl iodide (Ford-Moore and Perry 1951). Diisopropyl methylphosphonate may also be prepared from sodium isopropyl methylphosphonate by a reaction at 270° C, but a portion of the resulting diisopropyl methylphosphonate is converted to trimethylphosphine oxide at this temperature (EPA 1989). 

Studies with rats and chickens given oral doses of TOCP and tn-/ ara-cresyl phosphate provide more definitive evidence that, following absorption, organophosphate esters in hydraulic fluids (or their metabolites) may be widely distributed among tissues with a preferential distribution to fatty tissues, the liver, and the kidneys (Abou-Donia et al. 1990a, 1990b Kurebayashi et al. 1985 Somkuti and Abou-Donia 1990 Suwita and Abou-Donia 1990). 

A study with a dog exposed to an occluded dermal dose of TOCP labeled with radioactive phosphorus provides limited evidence that organophosphate esters in hydraulic fluids may be widely distributed after dermal absorption (Hodge and Sterner 1943). Similar widespread distribution of radioactivity among tissues was observed in male cats after dermal exposure to [uniformly labeled 14C-phenyl]TOCP (Nomeir and Abou-Donia 1986). Tissues and fluids with the highest concentrations of radioactivity in these studies included the bile, gall bladder, urinary bladder, liver, kidney, and fat, thus suggesting that TOCP and metabolites are somewhat preferentially distributed to these tissues. 

Studies directly examining the metabolism of organophosphate ester hydraulic fluids in animals are limited. One study identified metabolites in ether extracts of bile obtained from rabbits given single,... 

Studies with rats treated orally with triaryl or trialkyl phosphate esters (which may be found in organophosphate ester hydraulic fluids) indicate that these compounds and their metabolites are readily excreted in the urine, bile, feces and, to a limited extent, in expired air (Kurebayashi et al. 1985 Somkuti and Abou-Donia 1990a Suzuki et al. 1984a Yang et al. 1990). Urinary excretion of metabolites appears to be the predominant elimination route in rats for tri-ort/zo-cresyl phosphate and tri-para-cresyl phosphate, but biliary excretion of parent material and metabolites is also important (Kurebayashi et al. 1985 NTP... 

Organophosphate Ester Hydraulic Fluid. Analyses of blood or urine for the presence of organophosphates or their metabolites can be valuable in confirming exposure to organophosphate ester hydraulic fluids however, sample collections must be completed during or shortly after exposure unless exposure levels are very high. Urinary excretion of metabolites can be completed within a few days of exposure, depending on the level of exposure. 

Chemicals degraded by WRF include pesticides such as organochlorines DDT and its very toxic metabolite DDE [8, 9] and organophosphate pesticides such as chlorpyrifos, fonofos and terbufos [10] polychlorinated biphenyls (PCBs) of different degrees of chlorine substitution [11-13], some even to mineralization [14, 15] diverse polycyclic aromatic hydrocarbons (PAHs) in liquid media and from contaminated soils or in complex mixtures such as creosote [16-18] components of munition wastes including TNT and its metabolites DNT [19-23], nitroglycerin [24] and RDX [25]. 

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. 

---