Organophosphates development

Since the problems with DDT, organochlorine insecticides have largely been replaced by organophosphates. Early organophosphates developed in... 

In 1916, calcium arsenate [7778-44-1] dusted by airplane was used to control the boU weevil however, throughout many developments in effective insecticides, such as organophosphates, the boU weevils became resistant to poisons that were formerly effective (see Insectcontroltechnology). 

Developmental Effects. Adverse effects of methyl parathion on hirman fetal development have not been reported. Based on studies in animals, such effects appear to be possible if pregnant women were exposed during the first trimester to high concentrations of methyl parathion that resulted in significant depression of cholinesterase levels, particularly if concomitant signs and symptoms of organophosphate intoxication occur. Such an exposure scenario may occur with occupational exposure, exposure in homes or offices illegally sprayed with methyl parathion, or accidental exposure to methyl parathion, but is less likely as a result of low-level exposure. 

Mice that were exposed dermally to residues of methyl parathion in emulsifiable concentrate on foliage, and were muzzled to prevent oral intake, developed inhibition of plasma cholinesterase and erythrocyte cholinesterase after two 10-hour exposures (Skinner and Kilgore 1982b). For the organophosphate pesticides tested in this study, cholinergic signs generally were seen in mice with cholinesterase inhibition >50% results for this end point were not broken down by pesticide. 

A recent method, still in development, for determining total 4-nitrophenol in the urine of persons exposed to methyl parathion is based on solid phase microextraction (SPME) and GC/MS previously, the method has been used in the analysis of food and environmental samples (Guidotti et al. 1999). The method uses a solid phase microextraction fiber, is inserted into the urine sample that has been hydrolyzed with HCl at 50° C prior to mixing with distilled water and NaCl and then stirred (1,000 rpm). The fiber is left in the liquid for 30 minutes until a partitioning equilibrium is achieved, and then placed into the GC injector port to desorb. The method shows promise for use in determining exposures at low doses, as it is very sensitive. There is a need for additional development of this method, as the measurement of acetylcholinesterase, the enzyme inhibited by exposure to organophosphates such as methyl parathion, is not an effective indicator of low-dose exposures. 

Organophosphates, such as methyl parathion, are known to inhibit cholinesterase activity. A method has been developed to measure the extent of this inhibition and relate it to organophosphate exposure (EPA 1980d Nabb and Whitfield 1967). In this EPA-recommended method, blood is separated into plasma and red blood cell fractions. The fractions are treated with saline solution, brought to pH 8 with sodium hydroxide, and dosed with acetylcholine perchlorate. The ensuing acetic acid releasing enzyme reaction... 

Murphy SD. 1982. Toxicity of hepatic metabolism of organophosphate insecticides in developing rats. In Hunt VR, Smith MK, Worth D, eds. Banbury report, Vol. II. Environmental factors in hiunan growth and development symposium, November 1-4, 1981. Cold Spring Harbor, NY Cold Spring Harbor Laboratory, 125-136. 

CoMSIA (comparative molecular similarity index analysis) is a recent development from CoMFA and does not suffer from the alignment problem. It has been used to model hERG potassium channel inhibition by drugs [59] and the toxicity of phenylsulfonyl carboxylates [60], organophosphates [61], and polybrominated diphenyl ethers [62], with results comparable to those from CoMFA. 

Previously, we have shown that functional secretion of OPH molecules into the periplasmic space induced about 2.8-fold higher specific whole cell OPH activity [10]. From the detail reaction kinetic studies in this work, we showed that this periplasmic space-secretion strategy provided much improved bioconversion capability and efficiency ( 1.8-fold) for Paraoxon as a model organophosphate compound. From these results, we confirmed that Tat-driven periplasmic secretion of OPH can be successfully employed to develop a whole cell biocatalysis system with notable enhanced bioconversion efficiency and capability for environmental toxic organophosphates. 

Chohnesterase-inhibiting pesticides (e g., organophosphate and carbamate pesticides) are detected by dipping the developed chromatogram in a solution of the enzyme chohnesterase followed by incubation for a short period. Then the plate is dipped in a substrate solution, e.g., 1-naphthyl acetate/fast blue salt B. In the presence of the active enzyme, 1-naphthyl acetate is hydrolyzed to 1-naphthol and acetic acid, and the 1-naphthol is coupled with fast blue salt B to form a violet-blue azo dye. The enzyme is inhibited by the pesticide zones, so the enzyme-substrate reaction does not occur pesticides are, therefore, detected as colorless zones on a violet-blue background [36]. 

In order to select the fresh fruits and vegetables for the OPMBS, each task force member company provided a list of commodities that the company considered to be the most important for its organophosphate products. A matrix was developed based upon a crop group strategy and the importance of commodities in the diet of infants and children. Thirteen fresh fruits and vegetables were eventually selected for inclusion in this study. 

The development of class-selective antibodies is another approach to multi-analyte analysis. The analyst may design haptens that will generate antibodies that recognize an epitope common to several compounds, as explained above for the analysis of pyrethroids by measuring PBA. Other examples of class-selective immunoassays that have been developed are mercapturates," glucuronides, pyrethroids, organophosphate insecticides, and benzoylphenylurea insecticides." ... 

Intermediate-duration oral exposure to Durad 110 produced deaths in chickens associated with the delayed development of neuropathy at dosage levels of 4,000 mg/kg/day in a 28-day study and 90 mg/kg/day in a 90-day study (FMC 1986). At 100 mg/kg/day over a 13-week period, 2 of 12 male and 1 of 12 female rats died with exposure to tri- -butyl phosphate (Healy et al. 1995). Dietary administration of Pydraul 90E for 90 days providing daily doses of 50 mg/kg/day produced no chemical-related deaths in rats (Monsanto 1979). An organophosphate ester hydraulic fluid designated MIL-H-83306 also caused death in 4 of 4 rats exposed by gavage to 1,000 mg/kg over a 26-day period (Mattie et al. 1993). 

Acute exposure to certain organophosphate esters produces a slowly developing neuropathy in humans, OPIDN, that is functionally characterized by initial weakness and subsequent ataxia and paralysis in the lower limbs (8-14 days or longer, following exposure) (Ecobichon 1991 Johnson 1975 Murphy 1986). 

No NOAELs or LOAELs were identified for toxic effects in humans after inhalation exposure to organophosphate ester hydraulic fluids. Reliable NOAELs and LOAELs for acute inhalation exposure are restricted to 4-hour NOAELs for systemic effects in rats exposed to Fyrquel 220 or Durad MP280 and 4-hour LOAELs for mild lethargy in rats exposed to Durad MP280 and Fyrquel 220 (Gaworski et al. 1986). The study identifying these NOAEL and LOAEL values did not measure cholinesterase inhibition, did not allow sufficient follow-up time for the development of delayed neurotoxic effects, and used a... 

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