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1.
O,O,S-Trimethyl phosphorothioate (OOS), a contaminant of technical formulations of some organophosphorus pesticides, was found to be immunotoxic at subtoxic doses in female C57Bl/6 mice. Mice treated orally with acute doses of 10 mg/kg OOS show no overt toxic signs such as weight loss or malaise. In addition, the levels of serum cholinesterase was not decreased. Histopathologic investigation demonstrated no alterations in liver, lung, kidney, heart, skin, brain, spleen, or gut. The LD50 for delayed toxicity was approximately 35 mg/kg. Despite the lack of general toxic changes at doses of 5–10 mg/kg OOS, specific immunotoxic changes were found. The humoral or cell-mediated immune response of splenocytes from mice treated with 10 mg/kg OOS to in vivo immunization was diminished with respect to control animals. Responses were measured in ex vivo assays. Cytotoxic T-lymphocyte (CTL) responses were assessed by alloimmunization with the tumor P815 followed by a 51Cr release assay done ex vivo with splenic lymphocytes. Humoral responses were assessed by immunization with sheep red blood cells followed by a Jerne plaque assay to determine anti-sheep red blood cell antibody. Both cellular and humoral responses could be stimulated in vitro using cells from OOS-pretreated, primed animals, thus indicating that no permanent cellular elterations had occurred.  相似文献   

2.
Oral administration of O,O,S-trimethyl phosphorothioate (OOS), an impurity in several technical organophosphorus insecticides, causes delayed toxicity in rats with death occurring up to 28 days after the treatment. The oral LD50 was determined to be 60 mg/kg. The effect of a single nonlethal dose of OOS (20 mg/kg) on in vivo protein synthesis in different organs was determined by measurement of the incorporation of [14C]leucine at 6 hr to 28 days after treatment. As early as 6 hr after OOS treatment the incorporation of [14C]leucine into the liver, lung, thymus, kidney, and spleen was elevated and remained elevated for up to 7 days. With the exception of the lung, organ weights were significantly decreased during the same time period. On Day 28 after treatment, the amount of [14C]leucine incorporation had decreased to the control level in all of the organs studied. Treatment with OOS at 20 mg/kg caused a significant increase in hematocrit on Days 3,5, and 7, and as early as 6 hr after treatment at 60 mg/kg. The clinical biochemistry of plasma indicated that there was no significant change from control values in the glutamic pyruvic transaminase, glutamic oxalic transaminase, lactate dehydrogenase, or alkaline phosphatase activities with the 20 mg/kg dose. The analysis of the intermediary metabolites indicated that the redox state of cytosol was more reduced on Day 5, whereas that of mitochondria was not affected by OOS. Data obtained at selected times after oral administration of a 60 mg/kg dose of OOS and that obtained from animals starved for 3 days are also discussed.  相似文献   

3.
The in vivo metabolism of [14CH3S]- and [14CH3O]O,O,S-trimethyl phosphorothioate (OOS) was followed in rats after oral administration of threshold or LD50 toxic doses of 20 or 60 mg/kg. Similar metabolic studies were conducted with coadministration of 1% O,O,O-trimethyl phosphorothionate (OOO), which prevented all signs of delayed toxicity, including weight loss. When administered alone, OOS was metabolized mainly (50–60%) via removal of the CH3S moiety, which was largely converted to expired CO2. Approximately 20% of the compound was O-demethylated, presumably by conjugation with glutathione, and then further metabolized to CO2. Major urinary products were identified as O,O-dimethyl phosphoric acid (50–60%) and O,S-dimethyl phosphorothioic acid (～20%). Coadministration of OOO caused a slight decrease (～5%) in the cleavage of the CH3S moiety, indicated by a reduction in 14CO2 from [14CH3S]OOS and a quantitatively similar increase in the formation of O,S-dimethyl phosphoric acid. Limited pharmacokinetic studies indicated that OOS was rapidly absorbed and distributed throughout the body. Coadministration of 1% OOO caused a slight increase in the blood half-life of parent OOS when administered at 60 mg/kg. It was concluded that a small proportion of the cleavage of the CH3S moiety from OOS is involved in the intoxication process, and that this intoxication reaction is specifically inhibited by OOO.  相似文献   

4.
It had been reported that a Japanese multiple-resistant strain of house fly, Hirokawa, had a high malathion-carboxylesterase activity as well as a normal level of esterase activity to α-naphthylacetate (NA). This is different from the situation in several other malathion-resistant strains, where high malathion-carboxylesterase activity goes together with a low level of activity to α-NA. This had been explained by the so-called “mutant ali-esterase theory,” which assumed that the opposite changes in activity to malathion and α-NA were the result of one and the same change in an ali-esterase. In the Hirokawa strain the esterase degrading malathion seems to be responsible for about 64% of the activity to α-NA. This was concluded since the two activities were equally sensitive to denaturation and to two organophosphorus inhibitors. Moreover activity of malathion was inhibited by α-NA, and that of α-NA by malathion. Most of the latter activity was inhibited competitively. Inhibition of activity to malathion was lower, however, than to be expected on the basis of competitive mutual inhibition. This case of resistance to malathion therefore seems to involve a different kind of “mutant ali-esterase” than in other strains. Increased hydrolysis of the insecticide seems to be achieved without loss of activity to α-NA, although Km is different. The strain further showed an unusually high β-NA hydrolysis and malaoxon-carboxylesterase activity (about 3- and 200-fold, respectively, that of another malathion-resistant strain G).  相似文献   

5.
The role of esterases in malathion resistance in Culex tarsalis has been investigated. When larvae of a resistant and a sensitive strain were placed in water containing [14C]malathion, malathion penetrated to give initially similar internal levels. With resistant mosquitoes, after 15 min the internal malathion concentration decreased to low levels while the monoacid degradation products accumulated in the larvae and were excreted into the surrounding water, whereas in susceptible larvae the internal malathion level stayed high and was lethal. It is suggested that the decrease in internal malathion and the resulting resistance were caused by an active malathion carboxylesterase in the resistant strain. A specific assay for malathion carboxylesterase with [14C]malathion showed 55 times more activity in resistant than in susceptible larvae, whereas when general esterase activity was assayed with α-naphthyl acetate only 1.7 times the activity was found. Analyses by starch gel electrophoresis showed a peak of malathion carboxylesterase, 60-fold higher from resistant than from susceptible larvae, in a gel zone which did not stain for general esterase activity. General esterases that did not hydrolyze malathion showed different electrophoretic patterns in the two populations, which are likely due to the nonisogenic character of the strains. These results show that use of a specific assay and the demonstration of degradation of malathion in vivo are essential for assessment of the contribution of esterase activity to the malathion-resistant phenotype in mosquito populations.  相似文献   

6.
The organophosphorus insecticides, parathion and azinphos (10?5-10?4M), significantly stimulate the Ca2+-pump activity of sarcoplasmic reticulum, while malathion has a limited effect. The rates of Ca2+ translocation and ATP hydrolysis are both stimulated and, apparently, the Ca2+ATP ratio is improved. Parathion and azinphos maximally increase this ratio by 26 and 14%, respectively. The organochlorine compounds, DDT and aldrin, also stimulate the Ca2+ pump, and lindane has a reduced effect. These effects are smaller than those observed for parathion and azinphos. The order of effectiveness is similar to the toxicity of the compounds to mammals and can be described as follows: parathion > azinphos > DDT ≈ aldrin > malathion ≈ lindane.  相似文献   

7.
The organophosphorus pesticides profenofos, sulprofos, O-ethyl O-(4-nitrophenyl) phenylphosphonothioate (EPN), and S,S,S,-tributyl phosphorotrithioate (DEF) administered intraperitoneally to mice at 0.5 to 5 mg/kg strongly inhibit the liver microsomal esterase(s) hydrolyzing trans-permethrin. Profenofos, EPN, and DEF at 25 mg/kg increase the intraperitoneal toxicity of fenvalerate > 25-fold and of malathion > 100-fold. Topically applied profenofos, sulprofos, and DEF significantly synergize the toxicity of cis-cypermethrin to cabbage looper larvae and house fly adults but these phosphorus compounds are much less effective in synergizing the toxicity of trans-permethrin. The magnitude of synergism appears to depend on the species, organophosphorus compound, and pyrethroid involved. Profenofos, sulprofos, and EPN do not significantly alter the persistence of trans-permethrin on bean foliage.  相似文献   

8.
The objective of the present study was to evaluate the concentration- and time-dependent effects of the organophosphorus insecticides malathion and azinphos-methyl on polyamine metabolism, and relate them to normal and altered embryonic development of the common toad Rhinella arenarum. Control embryos showed that the higher polyamines spermidine and spermine acquired importance with respect to the diamine putrescine as embryonic development progressed. The activity of ornithine decarboxylase significantly decreased in complete operculum embryos. Continuous exposure to malathion caused a decrease in polyamine levels during embryonic development. However, there was an increase in putrescine levels in complete operculum embryos exposed to a sublethal concentration of the insecticide. Embryos exposed to malathion displayed a decrease in fresh weight and size, along with an increase in the number of malformed individuals. R. arenarum embryos exposed to a lethal concentration of azinphos-methyl showed an increase in putrescine levels and a decrease in spermidine and spermine levels, accompanied by an increase in ornithine decarboxylase activity. In conclusion, as the embryonic development of the toad R. arenarum progresses, polyamine metabolism shifts to higher polyamine levels with a more preponderant contribution of spermidine and spermine with respect to putrescine and involves a dramatic change in ornithine decarboxylase activity, one of the key regulatory enzymes of the pathway. Organophosphorus insecticides are capable of altering polyamine metabolism, slowing embryo development in parallel with a reduction in spermidine and spermine levels. An increase in the oxidative degradation of polyamines might be involved in the toxic action of organophosphorus insecticides and might also be related to other effects such as teratogenesis.  相似文献   

9.
Chemical synthesis of malathion α- and β-monocarboxylic acid yields a mixture of the two structural isomers. These two isomers were separated by preparative anion-exchange chromatography on QAE-Sephadex. 13C-Nuclear magnetic resonance of the pure components shows that the main product is the β-isomer, with the α-isomer being present in much smaller quantities. This result was used for identification of hydrolytic malathion metabolites produced by rat tissues. On incubation of malathion with rat liver fractions in vitro it was found that α- and β-monoacid are formed in a ratio of 3:2, whereas this ratio is 9:2 for the metabolites excreted into the urine after intraperitoneal injection of malathion in rats.  相似文献   

10.
The aim of this study was to examine whether Satureja khuzestanica (Lamiaceae) essential oil (SKEO) might have protective effects on toxicity of malathion, a commonly used organophosphorus (OP), by measuring the activities of hepatic cells mitochondrial glycogen phosphorylase (GP) and phosphoenolpyruvate carboxykinase (PEPCK) activities and blood levels of glucose and acetylcholinesterase (AChE) in rats. Malathion (20 mg/kg/day) and SKEO (225 mg/kg/day) were administered alone or in combination by intragastric intubation for 28 days. Treatment by malathion increased blood glucose as measured at days 18 and 28 of treatment. Malathion inhibited erythrocyte AChE and increased hepatic cells GP and PEPCK activities. Coadministration SKEO resulted in restoration of malathion-induced changes in hepatic cells GP and PEPCK activities and levels of blood AChE and glucose. It is concluded that SKEO interferes with malathion-induced stimulation of hepatic cells glycogenolysis and gluconeogenesis through its antioxidant potential and increasing AChE activity.  相似文献   

11.
A microsomal malathion carboxylesterase present in Triatoma infestans eggs was active from the first day of embryonic development. This microsomal egg malathionase (MEM) showed a unique band in polyacrilamide gel electrophoresis (PAGE) when malathion was used as substrate. In vivo metabolism of [14C]malathion during all embryonic development showed a 10% degradation due to carboxylesterases. The in vitro evaluation of the same metabolic pathway catalyzed by the microsomal fraction of T. infestans eggs showed partial inhibition by paraoxon. α- and β-malathion monoacids were identified as the main metabolites of the in vivo and in vitro metabolic pathways. The carboxylesterase band that appeared in PAGE (MEM) from the first day of embryonic development could be the main cause of malathion tolerance in T. infestans eggs.  相似文献   

12.
Fourth instar larvae, the progeny from wild-caught Anopheles sacharovi females, were subjected to a number of biochemical tests and the results were compared to those from similar tests on laboratory insecticide resistant and susceptible strains of anopheline and culicine mosquitoes. DDT resistance in An. sacharovi is associated with the ability to rapidly metabolise DDT to DDE. The organophosphorus and carbamate resistance was not associated with quantitative changes in esterases, multifunction oxidases, or glutathione S-transferase. The acetylcholinesterase was less sensitive to malaoxon and propoxur than laboratory susceptible An. albimanus, and plots of inhibition suggest that the population was polymorphic for more than one form of acetylcholinesterase. Metabolism studies on malathion and pirimiphos methyl did not indicate resistance due to increased metabolism. There was no evidence of penetration barriers contributing to resistance to either DDT or malathion, and there was no indication of any resistance to pirimiphos methyl in our tests.  相似文献   

13.
The role of esterases as related to insecticide resistance was studied in an organophosphorus (OP)-resistant strain of the green rice leafhopper. As judged by p-nitrophenyl acetate hydrolysis, 21, 5, and 74% of the esterase activity was located in nuclei/mitochondria, microsomes, and the soluble fraction, respectively. All the fractions were active in hydrolyzing malathion, paraoxon, and fenvalerate. Hydrolysis of malathion and fenvalerate increased with time while that of paraoxon reached a plateau within 15 min. Since a considerable amount of p-nitrophenol was detected in the paraoxon reaction at 0°C and at zero time, the formation of p-nitrophenol may be due to phosphorylation of the esterases rather than phosphorotriesterase action. The results suggest a dual role for esterases in resistance mechanisms; a catalyst for hydrolysis of malathion and fenvalerate, and a binding protein for the oxygen analogs of other OP insecticides, both of which would protect the intrinsic target, acetylcholinesterase, from inhibition. Chromatofocusing of the soluble fraction resolved five esterase peaks, I–V. These esterases were active toward the three general substrates as well as for the three insecticides tested, except for Peak I in which the overall activity was too low. Thin-layer agar gel electrophoresis showed that the chromatofocusing peaks I–V corresponded to the electrophoretic bands E1–E5, some of which were previously shown to be associated with OP resistance. The dual role of these esterases may explain the cross-resistance between malathion and other OP insecticides as well as synergism between OP and carbamate insecticides.  相似文献   

14.
Enzyme preparations from Drosophila melanogaster flies degraded [14C]malathion to α- and β-malathion monoacids and, hence, were considered to contain malathion carboxylesterase (ME) activity. Although ME- activity was stable during preincubation in the absence of malathion, it decreased dramatically during the course of the reaction, and could not be completely recovered by Sephadex G-25 chromatography. Furthermore, the protein fraction after chromatography still contained 14C, suggesting that the enzyme had become inhibited by a bound, 14C-labeled derivative. Extracts from a resistant (malathion-selected), an intermediate control, and the susceptible Canton S strains of D. melanogaster differed in the lability of ME activity during the reaction. This difference was partly attributed to the production of small amounts of malaoxon (2–8%) by the extracts from the more resistant strains. No consistent strain differences were found when the rate of malathion degradation was measured during the first minute of reaction, either with or without a microsomal oxidase inhibitor (metyrapone) present. These results, together with the cross-resistance of the malathion-selected strain to other insecticides and the lack of a synergistic effect of two carboxylesterase inhibitors (triphenyl phosphate and S,S,S-tributylphosphorotrithioate) suggested that malathion carboxylesterase does not contribute significantly to the observed differences in malathion resistance between strains.  相似文献   

15.
Insecticides exert antilytic effects on pig erythrocytes by preventing osmotic disruption of membranes in critical hypotonic saline media. The order of effectiveness is the following: lindane > aldrin ≈ azinphos > parathion ≈ DDT > malathion; empirical protective indexes estimated for K+ leakage, at 0.09 M NaCl, were 5.6, 3.9, 2.9, 2.8, and 2.0, respectively. Erythrocytes swell and hemolyze in solutions containing glycerol below 0.6 M. At higher concentrations and temperatures below 20°C, the extent of cell lysis is very limited and virtually nil in 1 M glycerol. In hypertonic glycerol solutions, cells swell until the initial equilibrium volume is reached and, then, the swelling process ceases. Swelling in 1 M glycerol is related to its permeation through hydrophobic membrane domains. The activation energies of permeation are similar to the dehydration energies of glycerol molecules. As the temperature is increased above 20°C, erythrocytes undergo lysis. The organophosphorus insecticides, parathion and azinphos (10?4M), significantly increase the swelling rates and the extent of cell lysis. Malathion and chlorinated insecticides do not exert apparent effects. However, these compounds are effective in liposomes reconstituted with lipids extracted from erythrocyte membranes.  相似文献   

16.
Toxicity tests reveal that the zebrafish (Brachydanio rerio) is very sensitive to malathion, an organophosphorus insecticide, and 24 to 96-h LC50 values showed a gradual decrease as the exposure time was increased. Zebrafish exposed to long-term sublethal concentrations failed to spawn and invariably exhibited skeletal deformities. Possible causes of the reduced gonadosomatic index and skeletal deformities are discussed.  相似文献   

17.
The effect of the malathion impurities, isomalathion of O,S,S-trimethyl phosphorodithioate (OSS-Me), on the toxicokinetic behavior of [methoxy-14C]malathion in female rats was investigated. Malathion α- and β-monoacids and the diacid were the predominant metabolites in the blood of rats pretreated orally with corn oil followed 4 hr later with radiolabeled malathion. Pretreatment of rats with isomalathion or OSS-Me in corn oil followed by treatment with malathion resulted in a decrease of total radioactive metabolites in the blood. Moreover, a substantial reduction in the level of malathion β-monoacid and malathion diacid was observed in the blood of impurity pretreated animals. These results indicate that the impurities have a stronger effect in inhibiting carboxylesterases which preferentially hydrolyze the β-carboethoxy moiety of malathion. The major malathion metabolites excreted in the urine of pretreated and control rats generally matched those present in the blood. The potentiation of the acute toxicity of malathion by pretreatment with isomalathion or OSS-Me may be explained by the reduction in the rat's capacity to degrade malathion via carboxylesterase-catalyzed hydrolysis of the β-carboethoxy moiety.  相似文献   

18.
We have examined the chromosomal basis for reproductive and developmental defects that are associated with malathion resistance in a laboratory-selected population of Drosophila melanogaster. Strains homozygous for second or third chromosomes from this population were more resistant to malathion and had greater mixed-function oxidase activity, decreased fertility, and lower egg production when compared with first chromosome or susceptible strains. Some of the strains carrying resistant third chromosomes were developmentally delayed and required a significantly longer time to pupate. Delayed pupation was not associated with increased in vitro degradation of ecdysone by larvae having increased mixed-function oxidase activity, nor could it be reversed by feeding larvae ecdysone. Differences in mixed function oxidase activity among strains homozygous for second or third chromosomes were strongly correlated with malathion resistance but not with fitness. Although both second and third chromosome strains had high mixed-function oxidase activity, only fly extracts from the third chromosome strains oxidatively degraded [3H]juvenile hormone in vitro to a significant extent. A deficit of vitellogenic oocytes and increased egg laying by females in response to topically applied juvenile hormone-I supported the hypothesis that juvenile hormone titer was lower than normal in these strains. The results indicate that different polygenic systems control malathion resistance and associated fitness defects in this selected population of D. melanogaster. Although these systems are partly independent, they overlap due to pleiotropic effects of third chromosomal genes controlling mixed-function oxidase activity on female reproduction.  相似文献   

19.
Inhibitory effects of five organophosphorus pesticides (diazinon, malathion, chlorpyrifos, azinphos-methyl and phorate) and their oxo-analogs on human myeloperoxidase (MPO) activity were investigated. While inspecting separately peroxidase and chlorination activity, it was observed that investigated OPs affect peroxidase activity, but not chlorination activity. Among investigated pesticides, malathion and malaoxon have showed the highest power to inhibit MPO peroxidase activity with IC50 values of the order of 3 × 10−7 and 5 × 10−9 M, respectively. It was proposed that inhibition trend is rendered by molecular structure which invokes steric hindrance for OPs interaction with MPO active center responsible for peroxidase activity. In addition, it was concluded that physiological function of MPO is not affected by any of the investigated OPs.  相似文献   

20.
A study was conducted to determine the extent of resistance to malathion in field populations of insects collected from nine granaries located in different regions of Israel. The results showed that the maximum resistance factor calcuated from the LCso s of the different insect species tested was:Tribolium castaneum (Herbst), x 538.0;Oryzaephilus surinamensis (L.), x 8.0;Sitophilus oryzae (L.), x 1.2; andRhyzopertha dominica (F.), x 9.0. There were significant differences between the resistance level among strains collected from different locations in Israel. By using triphenyl phosphate (TPP), an inhibitor of carboxyesterase, it was shown that, in the case ofT. castaneum andR. dominica, the resistance is a malathion-specific type and that in the case ofO. surinamensis it is partially non-specific to malathion. The significance of these findings in selecting new insecticides to replace malathion as a grain protectant was considered.  相似文献   

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