Parathion recovery studies

Daly, IW. 1989. A 13-week subchronic toxicity study of methyl parathion in dogs via the diet followed by a one-month recovery period. Stilwell, KS Mobay Corporation. 

Standardized procedures were adopted with regard to sample preparation, recovery of toxicant, and chemical assay. In order to determine the nature and magnitude of penetrated residues, it was necessary to disassociate all extra-surface residues. The techniques originally developed to effect this separation and which were used in most of the DDT penetration studies have been described by Gunther 11). Certain modifications which have been developed subsequently in connection with the parathion studies are described in detail below since this phase of penetration studies assumes singular importance (see also 14). 

Another product of esterase cleavage is p-nitrophenol (PNP), which is generated in the human body by the degradation of parathion, parathion-methyl and parathion-ethyl. Some methods for the determination of PNP in urine are summarized in Table 9.5. PNP can, for example, be determined in the urine of occupationally exposed subjects by means of GC-ECD. Sample preparation involves acid hydrolysis, extraction with diethyl ether, derivatization with diazoethane and purification on silica gel columns. The LOD was 20 pg L with a recovery of 85-98%. This method has also been used in a study on selected pesticide residues and metabolites in urine from a survey of the US general population.In the context of another survey study, a more complicated technique to detect PNP in urine has recently been used by Hill et involving GC-MS-MS with positive chemical ionization after derivatization with l-chloro-3-iodopropane. The authors also used this method for the determination of the metabolite TCP and 10 other analytes in urine.Sample preparation involved hydrolysis with p-glucuronidase, several extraction steps using different solvents and purification by SPE (silica gel column). The LOD was 1 pg L with an inter-assay RSD... 

Recovery of phosphinylated acetylcholinesterase was also greatly enhanced in our studies of methyl parathion-resistant tobacco budworm larvae (Figure 5). Phosphinylated acetylcholinesterase recovery can be measured without the complication of "aging" which occurs with phosphorylated enzyme (Figure 6). Activity was totally inhibited with 4-nitrophenyl methyl(phenyl)phosphinate. Excess inhibitor was removed by solid phase extraction and recovering activity at 30°C was monitored in aliquots. We have confirmed this insensitivity with individual heads of adults from these strains and we are investigating inheritance of this trait. 

It. should also be noted that some studies have shown improvements in learning associated with exposure to cholinesterase inhibitors. These effects in rats were either transient during exposure or observed at low doses or after recovery the compounds studied include parathion (water maze Evens et al., 1998), chlorfenvinpho.s (active avoidance Socko et al., 1999), and aldicarb (passive avoidance and water maze Palumbo et al., 2001). These observations probably reflect the memory-enhancing properties of low levels of cholinergic stimulation, the basis for the therapeutic use of some cholinesterase inhibitors in the treatment of Alzheimer s dementia. 

The mass balance approach was used to develop an in vivo animal model for skin penetration of topically applied dmgs in hairless rats (Simonsen et al., 2002). Two dmgs, C-sahcylic acid and C-butyl salicylate were topically applied for the assessment of the model. Rapid and differentiated percutaneous absorption of both compounds was indicated by urinary excretion data. Total mass balance on the applied radioactivity was performed, and 90% recovery was achieved. Carver and Riviere (1989) conducted an extensive mass balance study with " C-labeled xeno-biotics after topical and intravenous administration to pigs. These authors reported that dermal absorption of C-benzoic acid, caffeine, malathion, parathion, progesterone, and testosterone was 25.7, 11.8, 5.2, 6.7, 16.2, and 8.8%, respectively, following topical administration to pigs. 

The effect of a topically applied dose of parathion, carbaryl, and thiodicarb on red blood cell cholinesterase activity in the rat was reviewed along with pharmacokinectic data developed on their percutaneous absorption. Parathion and thiodicarb inhibited 50% of the red cell cholinesterase activity at dose levels of 3.2 and 33 mg/kg of bw, while no inhibition was detected with carbaryl at dose levels as high as 417 mg/kg of w. Parathion and carbaryl were absorbed at 0.33 and 0.18 ug/hr/cm, while thiodicarb was absorbed at rates varying from 0.27 to 0.042 ug/hr/cm of skin. Skin loss and plasma elimination data were used to calculate the values. The topically applied pesticides slowly penetrated skin and were available for absorption into blood and redistribution to other tissues. Recovery data suggested that evaporative losses occurred during the course of the 5-day study. The pesticides may be removed from skin by washing, thus reducing the amount available for absorption. 

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