Organophosphorus compounds. See

The Friedel-Crafts reaction in the presence of anhydrous aluminum trichloride is one of the best methods for the manufacture of aromatic organophosphorus compounds see Eqs. (101) and (102) ... 

Methods for Determining Biomarkers of Exposure and Effect. Section 2.6.1 reported on biomarkers used to identify or quantify exposure to diazinon. Some methods for the detection of the parent compound in biological samples were described above. The parent chemical is quickly metabolized so the determination of metabolites can also serve as biomarkers of exposure. The most specific biomarkers will be those metabolites related to 2-isopropyl-6-methyl-4-hydroxypyrimidine. A method for this compound and 2-(r-hydroxy-l -methyl)-ethyl-6-methyl-4-hydroxypyrimidine in dog urine has been described by Lawrence and Iverson (1975) with reported sensitivities in the sub-ppm range. Other metabolites most commonly detected are 0,0-diethylphosphate and 0,0-diethylphosphorothioate, although these compounds are not specific for diazinon as they also arise from other diethylphosphates and phosphorothioates (Drevenkar et al. 1993 Kudzin et al. 1991 Mount 1984 Reid and Watts 1981 Vasilic et al. 1993). Another less specific marker of exposure is erythrocyte acetyl cholinesterase, an enzyme inhibited by insecticidal organophosphorus compounds (see Chapter 2). Methods for the diazinon-specific hydroxypyrimidines should be updated and validated for human samples. Rapid, simple, and specific methods should be sought to make assays readily available to the clinician. Studies that relate the exposure concentration of diazinon to the concentrations of these specific biomarkers in blood or urine would provide a basis for the interpretation of such biomarker data. 

It is known that human exposure to organophosphorus compounds can result in a variety of acute toxic effects. These arise primarily as a result of the inhibition of acetylcholinesterase. Signs of acute toxicity are due to effects on the central nervous system (anxiety, ataxia, hypotension), to muscarinic effects (wheezing, cough, rhinitis) and to nicotinic effects (muscle weakness, mydriasis and tachycardia). Other acute effects include chest tightness, abdominal cramps, confusion and convulsions. With some organophosphorus compounds, a specific syndrome may develop. This is delayed peripheral neuropathy or OP-induced delayed neuropathy (OPIDN). (For a more detailed discussion on the toxicity of organophosphorus compounds see Chapter 10.)... 

Organophosphorus Derivatives. Neopentyl glycol treated with pyridine and phosphorus trichloride in anhydrous dioxane yields the cycHc hydrogen phosphite, 5,5-dimethyl-l,3-dioxaphosphorinane 2-oxide (2) (32,33). Compounds of this type maybe useful as flameproofing plasticizers, stabilizers, synthetic lubricants, oil additives, pesticides, or intermediates for the preparation of other organophosphoms compounds (see Flame retardants Phosphorus compounds). 

Diphenylphosphinic acid [1707-03-5] M 218.2, m 194-195 , pK 1.72. Recrystd from 95% EtOH and dried under vacuum at room temperature, [see Kosolapoff Organophosphorus Compounds J Wiley, NY, 1950 Kosolapoff and Maier Organic Phosphorus Compounds Wiley-Interscience, NY, 1972-1976.]... 

Phosphatases are numerous and important enzymes (see also Chapt. 2). They are classified as phosphoric monoester hydrolases (phosphatases, EC 3.1.3), phosphoric diester hydrolases (phosphodiesterases, EC 3.1.4), triphosphoric monoester hydrolases (EC 3.1.5), diphosphoric monoester hydrolases (pyrophosphatases, EC 3.1.7), and phosphoric triester hydrolases (EC 3.1.8) [21] [63]. Most of these enzymes have a narrow substrate specificity restricted to endogenous compounds. However, some of these enzymes are active toward xenobiotic organophosphorus compounds, e.g., alkaline phosphatase (EC 3.1.3.1), acid phosphatase (EC 3.1.3.2), aryldialkylphosphatase (para-oxonase (PON1), EC 3.1.8.1) and diisopropyl-fluorophosphatase (tabunase, somanase, EC 3.1.8.2) [64 - 70]. However, such a classification is far from definitive and will evolve with further biochemical findings. Thus, a good correlation has been found in human blood samples between somanase and sarinase activities on the one hand, and paraoxonase (PON1) type Q isozyme concentrations on the other [71]. 

Phosphinates are a class of organophosphorus compounds, the metabolism of which has received less attention than that of phosphates (see above) or phosphorothioates and P-halidc compounds (see below). Many phosphinates are rapid but transient inhibitors of acetylcholinesterase and carboxyl-esterases. And like organophosphates and phosphonates, phosphinates are substrates of arylesterases (EC 3.1.1.2). This is exemplified by 4-nitrophen-yl ethyl(phenyl)phosphinate (9.62), whose (-)-enantiomer was hydrolyzed by rabbit serum arylesterase almost 10 times faster than the (+)-enantiomer [133],... 

Irreversible inhibition in an organism usually results in a toxic effect. Examples of this type of inhibitor are the organophosphorus compounds that interfere with acetylcholinesterase (see Box 7.26). The organophosphorus derivative reacts with the enzyme in the normal way, but the phosphory-lated intermediate produced is resistant to normal hydrolysis and is not released from the enzyme. 

Two examples of toxicity, where the target is known, are carbon monoxide, which interacts specifically with hemoglobin, and cyanide, which interacts specifically with the enzyme cytochrome a3 of the electron transport chain (see chap. 7). The toxic effects of these two compounds are a direct result of these interactions and, it is assumed, depend on the number of molecules of the toxic compound bound to the receptors. However, the final toxic effects involve cellular damage and death and also depend on other factors. Other examples where specific receptors are known to be involved in the mediation of toxic effects are microsomal enzyme inducers, organophosphorus compounds, and peroxisomal proliferators (see chaps. 5-7). 

With irreversible interactions, however, a single interaction will theoretically be sufficient. Furthermore, continuous or repeated exposure allows a cumulative effect dependent on the turnover of the toxin-receptor complex. An example of this is afforded by the organophosphorus compounds, which inhibit cholinesterase enzymes (see Aldridge (7) and chap. 7). 

With a molecular emission cavity flame detector, relying on measurement of the 526 nm emission of HPO (see Section II.C.l and III.B.3.b), nanogram amounts of phosphates or organophosphorus compounds can be assessed in automated systems160,348. Determination of m, the time elapsed between sample ignition and maximum emission, allows the resolution of ternary or more complex mixtures of insecticides. Dicrotophos, dimethoate, malathion and parathion mixed in aqueous solution were separated and identified in nanograms per millilitre concentrations348. 

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