Esterase-inhibiting photo-oxidation products from the organophosphorus insecticide pyrimithate

Pyrimithate (2-dimethylamino-6-methylpyrimidin-4-yl diethyl phosphorothio-nate) decomposes when exposed to u.v. light in the presence of air to a complex mixture of products, some of which inhibit esterases directly or indirectly. Separation of the mixture by thin-layer and liquid chromatography gave five pure components in sufficient quantity for spectroscopic identification. A sixth was tentatively identified. The structures ( II-VII ) show that oxidative attack occurs at the dimethylamino group and at the sulphur atom.     

The relationship of esterases to organophosphorus insecticide tolerance in mosquitofish

The levels of peripheral acetylcholinesterase and carboxylesterases and their organophosphate sensitivities were studied in two populations of mosquitofish (Gambusia affinis). One population, highly resistant to organochlorine insecticides, demonstrated a low tolerance to parathion and methyl parathion. The organochlorine resistant fish possessed higher levels of both peripheral acetylcholinesterase and carboxylesterases. The sensitivities of these esterases to organophosphate inhibition were the same in both populations. The esterases were more sensitive to paraoxon than to methyl paraoxon. Carboxylesterases were far more sensitive to organophosphate inhibition than was acetylcholinesterase. Carboxylesterases, by their higher affinity for the organophosphates, may serve to protect acetylcholinesterase from inhibition.     

The effects of small applications of an organophosphorus poison,fenthion on the weaver-bird Quelea quelea

Experiments were carried out in East Africa to determine the effects of single-drop applications of the avicide Queletox (active ingredient fenthion) on the Red-billed Quelea Q. quelea, an important agricultural pest. Birds treated with relatively large amounts of Queletox died within a few hours, as expected. Most of those receiving the smallest lethal doses died 12 to 48 h after treatment. From their terminal fat and muscle condition it was concluded that they died of starvation, despite their apparently healthy appearance following treatment and the easy availability of suitable food. LD₅₀'s of 80 and 220 mg/kg were obtained for Queletox applied to the feathers of the back in drops of varying sizes or concentrations, the amount of solvent having an important effect on the toxicity. The possibility is raised of reducing the amounts of Queletox used in control operations against the birds, making them safer and cheaper.     

Neurophysiological alterations in Caenorhabditis elegans exposed to dichlorvos,an organophosphorus insecticide

AChE inhibition is widely regarded as a good biomarker of exposure to organophosphorus insecticides (OPIs), suggesting increase in the cholinergic transmission and consequent accumulation of acetylcholine in the organism. This might lead to behavioral changes and create widespread disturbances in the normal physiology of an organism. In the present study we have employed the model organism Caenorhabditis elegans to evaluate the biochemical and behavioral alterations induced by dichlorvos, a well known OPI. Exposure of worms to dichlorvos (at sublethal concentrations: 5, 50, 100, 150 and 200 μM) induced a concentration and time dependent AChE inhibition, and accumulation of acetylcholine. Further, we also observed cessation in feeding (by 72%), shutting of pharyngeal pumping, inhibition of egg laying (34–55%), contraction of nose (45%) and significant paralysis (50%) after 4 h of exposure. Significant correlation was observed between biochemical effects and behavioral parameters clearly suggesting the implications of sublethal concentrations of dichlorvos on non-target invertebrate organism such as C. elegans. These data further suggest that assessment of subtle neurophysiological parameters may serve as useful indicators of OPI exposure.     

Amelioratory effect of vitamin E on organophosphorus insecticide diazinon-induced oxidative stress in mice liver

Considering that the involvement of reactive oxygen species (ROS) has been implicated in the toxicity of organophosphate insecticides (OPIs), the aim of this study was to investigate the ameliorative properties of vitamin E (vitE) against the subchronic effect of diazinon (DZN) on oxidative damage markers such as lipid peroxidation (LPO) and the antioxidant defense system (ADS) in the liver of male MFI albino mice. The groups were intraperitoneally (i.p) administered with either vehicle or vitE (100 mg/kg body weight) or ¼ LD₅₀ of DZN (16.25 mg/kg b.w.) or ½ LD₅₀ of DZN; 32.5 mg/kg b.w) or ¼ LD₅₀-DZN + vitE or ½ LD₅₀ + vitE every consecutive day for 14 days. Hepatic damage markers analysis revealed that alanine transferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) were significantly decreased in both DZN doses. Also, the significantly increased levels of biomarkers of oxidative stress as LPO and protein carbonyl (PC) and the decreased antioxidant defenses like reduced glutathione (GSH), and free radical scavenger enzymes viz., catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione reductase (GSH-Rx) were noted in DZN-treated groups as compared to control group. Distinctly lower levels of GSH and increased levels of LPO, along with alterations in endogenous antioxidant enzymes were evident in hepatic toxicity of DZN which is dose-dependent. Hepatic specific marker enzymes were restored to normalcy in mice supplemented with vitE following treatment with DZN which otherwise was decreased in the DZN-treated mice. The results show that co-treatment of vitE with DZN prevents or diminishes the oxidative stress of DZN-treated mice and may act as a putative protective agent against DZN-induced liver tissue injury.     

Evaluation of inexpensive thin-layer chromatographic procedures for the estimation of some organophosphorus and carbamate insecticide residues in fruit and vegetables

Modified versions of previously published procedures for the extraction and clean-up of some organophosphorus insecticide residues in fruits and vegetables are described, and their usefulness in combination with selected thin-layer chromatographic procedures is experimentally assessed for several pesticides in apples, oranges, tomatoes, carrots and peas. A simple extraction procedure for insecticidal carbamates is similarly evaluated for carbaryl and propoxur residues in apples, carrots and peas. Semi-quantitative estimation, by visual comparison with standards, is shown to be possible in many cases at residue levels as low as 0.4 mg kg^?1, and the combined procedures should be useful in the screening of fruits or vegetables for compliance with maximum residue limits.     

The effects of salinity and temperature on the in vitro metabolism of the organophosphorus insecticide fenitrothion by the blue crab,Callinectes sapidus

The in vitro metabolism of fenitrothion [O,O-dimethyl-O-(3-methyl-4-nitrophenyl)phosphorothioate] by subcellular fractions prepared from the hepatopancrease of blue crabs, Callinectes sapidus, which had been acclimated to either 22°C, 34‰ (parts per thousand); 22°C, 17‰; or 17°C, 34‰ seawater was investigated. In the microsomal fraction, fenitrothion was metabolized to fenitrooxon and 3-methyl-4-nitrophenol. Fenitrothion was metabolized to desmethyl fenitrothion in the cytosolic fraction. The rates of formation of the detoxification products, 3-methyl-4-nitrophenol and desmethyl fenitrothion, were greater in subcellular fractions prepared from crabs which had been acclimated to the lower salinity seawater. The rate of formation of the more toxic metabolite fenitrooxon was greater in the microsomal fraction prepared from crabs which had been acclimated to higher salinity water. All three of these metabolites were formed at considerably faster rates in subcellular fractions from crabs acclimated to and incubated at 22 than at 17°C. These results suggest that enzyme activity contributes to the increased in vivo toxicity of fenitrothion to blue crabs at elevated salinities and temperatures. Also, the observed differences in the rate of formation of the oxon have a greater effect on toxicity than differences in the rate of formation of 3-methyl-4-nitrophenol and desmethyl fenitrothion.     

Persistence of fenthion residues in olive oil

The level of fenthion residues was followed for up to one year in olive oil samples. The concentration of the parent compound decreased slowly following a double-phase first-order decay model, both in the freezer and laboratory, while the total concentration (parent compound and its sulfoxide) remained unchanged. Storage, therefore, cannot be used as a decontamination technique for oil containing higher than the toxicologically acceptable residues of this compound.     

Time-controlled cholinesterase reactions as a means of measuring water-soluble residues of organophosphorus insecticide spray deposits on plant surfaces

Ellman's method of cholinesterase assay which is often used for residue analysis of organophosphorus insecticides has been modified by adding the protein denaturant, sodium dodecyl sulphate, to control the duration of the reaction. In doing so, the reaction time can be standardised to facilitate the measurement in a field laboratory of residues of water-soluble organophosphates, particularly on plant surfaces that have been subjected to sprays. Thirty samples can be analysed in 1 h by timing each step of the procedure for a series of 30 reaction tubes at 1-min intervals from the incubation of the enzyme with the insecticide to the final addition of the sodium dodecyl sulphate. Results from a series of aerial spray trials are presented and discussed briefly as an example of a field application of the method.     

Fonofos residues in an organic soil and vegetable crops following treatment of the soil with the insecticide

Fonofos (O-ethyl S-phenyl ethylphosphonodithioate) was applied to an organic soil as band treatment at the rates of 1.12 and 2.24 kg/ha. The persistence of the insecticide and its translocation into onions and two rotation crops (lettuces and carrots) was studied under field conditions. Proportionally more residues persisted in the soil from the higher rate of application. In autumn, 4 months after soil treatment, about 40-48 % of the initially recovered levels of fonofos remained in soil. However, the amount of fonofos present at the harvest time, during the second growing season was only 16–26% of the insecticide concentration found in spring. Onions harvested 4 months after application of fonofos had no detectable residue (> 0.005 mg/kg) whereas lettuces and carrots grown in the following year contained fonofos in various amounts. At the lower rate of application the insecticide residues in lettuces and carrots were < 0.005 and 0.025 mg/kg, respectively, and those from the higher application rate were 0.012 and 0.036 mg/kg. About 72–80% of the residue could be removed by peeling the carrots. No residue of the oxygen analogue, O-ethyl S-phenyl ethylphos-phonothioate (I) was detected in any soil or crop samples.     

Toxic effects of novel organophosphorus insecticide (RPR-V) on certain biochemical parameters of euryhaline fish, Oreochromis mossambicus

The euryhaline fish, Oreochromis mossambicus was exposed to sub-lethal concentration (0.017 mg L⁻¹) of a novel phosphorothionate, 2-butenoic acid-3-(diethoxy phosphinothionyl) ethyl ester (RPR-V) for 30 days and allowed to recover for 7 days. Important biomarker enzymes were assayed in plasma, brain, gill, liver, kidney, and muscle during exposure tenures of day-3, -7, -15, -30, and also at 7 days (withdrawal) after stopping treatment. Acetylcholinesterase (AChE) activities of brain, gill, and muscle were strongly inhibited by 67, 75, and 66%, respectively, on day-30. Exposure (time) dependent increases in alanine aminotransferase (ALAT), and aspartate aminotransferase (ASAT), acid phosphatase (AcP), and alkaline phosphatase (AkP), activities in plasma and kidney; AcP and AkP activities in gill were noticed. However, significant decrease in ALAT, ASAT, AcP, and AkP activities in liver was observed. The depletion of glycogen was observed in liver, brain, and gill tissues, an indication of typical stress related response of the fish with pesticide. A significant increase in lactate dehydrogenase (LDH) activity in gill and brain was observed and decreased in liver and muscle, indicating tissue damage and muscular harm. Depletion of glutathione (GSH) was observed in the above tissues, there by enhancing the lipid peroxidation resulting in cell damage. The induction in hepatic glutathione-S-transferase (GST) levels indicates the protection against the toxicity of xenobiotic-induced lipid peroxidation. There was a significant recovery in all the above biochemical parameters, in all the tissues of fish after a recovery period of 7 days. These results revealed that RPR-V affects the intermediary metabolism of O. mossambicus and the increase of biomarker enzymes in plasma, might be due to the necrosis of liver.     

Hormonal responses and tolerance to cold of female quail following parathion ingestion

Thirty-week-old female bobwhite quail (Colinus virgininus), maintained at 26 ± 1°C, were provided diets containing 0,25, or 100 ppm parathion ad libitum. After 10 days, birds were exposed to mild cold (6 ± 1°C) for 4, 8, 12, 24, or 48 hr. Brain acetylcholinesterase activity was inhibited in a dose-dependent manner in birds receiving 25 and 100 ppm parathion. Body weight, egg production, and plasma luteinizing hormone and progesterone concentrations were reduced in birds receiving 100 ppm parathion compared with other groups. Cold exposure did not alter plasma corticosterone levels in the 0- and 25-ppm parathion groups, but a two- to fivefold elevation of plasma corticosterone was observed in birds fed 100 ppm parathion. These findings indicate that (i) short-term ingestion of parathion can impair reproduction possibly by altering gonadotropin or steroid secretion, and (ii) tolerance to cold may be reduced following ingestion of this organophosphate.     

Determination of trichlorfon and fenthion residues in animals of different species

Original results of analyses of residues of trichlorfon and fenthion and its metabolites following application of commercial products to cattle, sheep and pigs, together with results taken from the literature are compared. Despite the use of higher dose rates of trichlorfon, residues are lower than those of fenthion after dermal application. On the other hand, the residues of trichlorfon that occur in the animals following oral application briefly approach the theoretical maximum level in the tissues. The results are discussed in relation to the physical and chemical properties of the pesticides and their metabolites.     

Phototransformation of the insecticide hydramethylnon in aqueous systems

Sunlight irradiation of hydramethylnon in aqueous media of different pH values resulted in 80-94% transformation within 10h. The rate of disappearance of the insecticide was affected marginally by the initial pH of the reaction medium. After 10 h irradiation, eight photoproducts were formed. Three products were isolated as pure crystalline substances and the structures of two of these (I & III) were characterised by mass and NMR spectroscopy. The reaction mechanisms involved in the formation of photoproducts are discussed.     

Dermal pharmacokinetics of the insecticide furathiocarb in rats

The pharmacokinetics of furathiocarb were studied in vivo in male Sprague-Dawley rats following dermal treatment. HPLC and post-column derivatization were used for the analysis of furathiocarb and its metabolites (carbofuran, 3-hydroxycarbofuran and 3-ketocarbofuran). Carbofuran and 3-hydroxycarbofuran were detected in plasma and urine rather than furathiocarb. 3-Ketocarbofuran, another potential metabolite, was not observed in any sample. The concentration of carbofuran was higher than that of 3-hydroxycarbofuran in plasma, but the reverse was the case in urine. The corresponding area under the plasma concentration-time curve, Tmax, and Cmax values of carbofuran and 3-hydroxycarbofuran for 1500 mg kg-1 doses were 2.4-8.0 mg equiv hml-1, 12 h and 0.1-0.4 mg equiv ml-1, respectively. T1/2 was calculated only for 3-hydroxycarbofuran (28 h). Two metabolites were excreted in a dose-dependent manner without saturation.     

新型高效杀虫剂茚虫威毒理学研究进展

新型噁二嗪类杀虫剂茚虫威对鳞翅目昆虫具有卓越的杀虫活性。神经毒理学研究表明,茚虫威在昆虫体内活化为N 去甲氧羰基代谢物（DCJW）,并作用于失活态钠离子通道,破坏神经冲动传递。近年来对茚虫威的研究表明,昆虫具有对茚虫威产生高水平抗性的风险。     

Photodegradation of the carbamate insecticide ethiofencarb

In order to study the photoreactivity and possible photodegradation pathways of ethiofencarb (2-ethylthiomethylphenyl methylcarbamate) on plant surfaces, model experiments in the presence of cyclohexane, cyclohexene methylcarbamate)onand iso-propanol were performed. Both artificial light (λ > 280 nm) and natural sunlight were used. Half-lives of the ethiofencarb photodegradation were in the order cyclohexane < isopropanol < cyclohexene and ranged from 75 min to more than 20 h. Depending on the solvent and the light source chosen, different photo-products were obtained. When ethiofencarb was irradiated in the presence of cyclohexane, photo-oxidation to the corresponding sulfoxide was the main degradation pathway, followed by a cyclization reaction. In the case of isopropanol as model solvent, numerous photoproducts were detected as a result of photo-oxidation, hydrolysis and the addition to ethiofencarb of the solvent molecule.     

The novel pyridazine pyrazolecarboxamide insecticide dimpropyridaz inhibits chordotonal organ function upstream of TRPV channels

The cover image is based on the Research Article The novel pyridazine pyrazolecarboxamide insecticide dimpropyridaz inhibits chordotonal organ function upstream of TRPV channels by Christian Spalthoff et al., https://doi.org/10.1002/ps.7352

     

Hydrolysis of the pyrethroid insecticide fenpropathrin in aqueous media

The hydrolysis of [¹⁴C] fenpropathrin ( I ) [(RS)-α-cyano-3-phenoxybenzyl 2,2,3,3-tetramethylcyclopropanecarboxylate] was studied in buffer solutions at pH 1.9–10.4, and in natural river and sea water at 25, 40, 55 and 65°C under laboratory conditions. The hydrolysis of I proceeded predominantly through neutral (pH independent) and base-catalysed processes in the regions below pH 3.9 and above pH 7.0, respectively, whereas both reactions occurred between pH 3.9 and 7.0. The rates of hydrolysis of I in buffer solutions were similar to those in one sample of river and one sample of sea water. If this obtains generally, it may be expected that the half-life of I in natural waters, normally within the range pH 5–9, will range from 1.54 to 1080 days at 40°C, 11.3 to 8520 days at 25°C and, by extrapolation of the data obtained in buffer solutions, 106 to 83 000 days at 10°C. The rate constants for hydrolysis of I in aqueous media can be expressed by: Where log k_N = 9.60–(5.56 × 10³ T^?1) and log k_B = 7.32–(2.56 × 10³ T^?1). The calculated rate constants were in good accord with the observed values in buffer solutions. Cleavage of the ester linkage was more rapid than hydration of the cyano group at any pH and temperature tested.