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Behavioral and physiological effects of acute sublethal exposure to dimethoate on wood mice, Apodemus sylvaticus.

The effects on behavior and cholinesterase (ChE) of an OP pesticide, dimethoate, were examined in wood mice under laboratory conditions. Mice were administered 0, 5, 15, or 50 mg/kg intraperitoneal dimethoate and their behavior was recorded in an open field for one hour. In a second experiment, using only the 0 and the 50 mg/kg dose, mice were subjected to 10-min open field tests repeated at various time intervals during a 24-h period. Shortly after administration of dimethoate, there was a general, dose-dependent, behavioral depression that was characterized by increased inactivity and decreased grooming, rearing, and sniffing. The introduction of a novel object in the open field failed to elicit any reaction in mice treated with the two highest doses of dimethoate. The behavioral impairment completely disappeared 6 h after treatment. A stereotyped compulsive grooming was also observed in the first 30 min after administration of the two highest doses. Exposure to dimethoate caused a dose-dependent decrease in ChE activity in the brain and in serum. Behavioral impairment was associated with maximum levels of ChE inhibition of 65-75% (brain) and 75-85% (serum). Recovery of ChE activity lagged behind that of behavioral impairment and started 3-6 h after dimethoate administration. The possible implications for free-living wood mice which inhabit cereal fields and may be exposed to OPs are discussed.

Animals↗

Dimethoate effects on thyroid function in suckling rats.

The aim of our work is to study dimethoate effects on thyroid function given in drinking water (40 mg/kg body weight, equivalent to 0.2 g/L) to mothers from day zero until the 10th day after delivery. Pups and their mothers were sacrificed on day ten after parturition. Compared to a control group, dimethoate-treated pups showed a 48% decrease in body weight which could be attributed to a defect in thyroid hormones. Indeed, after treatment by dimethoate, plasma rates of free T4 and T3 decreased by 56% and 40% in the young and by 27% and 15% in dams respectively. We can attribute the reduction in plasma thyroxine and triiodothyronine rates to a decrease in thyroid iodine levels (-75%) in the young and (-24%) in their mothers. The decrease in production of thyroid hormones after dimethoate treatment affect thyroid stimulating hormone (TSH) levels. In fact, plasma TSH levels were multiplied in dimethoate-treated group by factors of 2.31 in dams and 1.96 in their offspring. These biochemical modifications confirmed the histological thyroid aspects of pups and dams. In fact, in dimethoate-treated rats, some thyroid follicles of pups presented vesicular cavities without colloid; others contained colloid. However in dams, thyroid follicles presented cubical epithelial cells which surrounded empty vesicular cavities.

Animals↗

A biochemical, histochemical, and ultrastructural evaluation of the effect of dimethoate intoxication on rat pancreas.

Organophosphorus compounds are widely used in industry, agriculture and for public health purposes. They are among the toxic compounds employed for insect control. The purpose of this work was to study biochemical, histochemical, and histological as well as ultrastructural changes that might occur in the pancreas of adult male Wistar rats as a result of chronic dimethoate intoxication. The treated group received dimethoate orally via gavage (21 mg/kg) daily for 2 months while, the control group was given saline orally (0.1 ml/100 g/day) for the same period. Plasma glucose level was significantly increased while, plasma insulin level was decreased in the intoxicated animals compared with the control group. A patchy reduction of histochemically-detected succinic dehydrogenase enzymatic activity was observed in the pancreas of the intoxicated rats. By contrast, acid phosphatase enzymatic activity was markedly increased in the pancreas of the intoxicated group. No changes were observed in alkaline phosphatase or alpha esterase activities of the intoxicated animals. Light microscopic examination revealed that dimethoate caused patchy degenerative changes of variable severity in many areas of the pancreas affecting both the pancreatic acini and islets of Langerhans. Ultrastructurally, some beta cells revealed dense nuclei with wide perinuclear cisternae. Diminution of the number of beta granules was evident. One month after discontinuation of the dimethoate, all the above mentioned changes induced by dimethoate intoxication persisted. These findings show that chronic exposure to dimethoate insecticide has clear toxic effect on the rat pancreas, which was not reversible within 1 month. Public health education is necessary to raise people awareness about the hazards accompanying the use of such compounds.

Acid Phosphatase↗

Effect of storage temperature on the degradation of dimethoate in fortified orange and peach juices.

The effect of storage temperature on dimethoate degradation in fortified orange and peach juices was studied. The insecticide was aseptically injected into packed orange and peach juices and stored at 40, 15, and 0 degrees C. Samples were taken at regular time intervals and were examined for dimethoate residues. The residues were determined with a simple gas chromatographic method; the recoveries of dimethoate from orange and peach juices were found to be from 88 to 114% for both products. The limits of determination were 0.004 and 0.003 mg/kg, respectively. From the experimental data, rate constants, half-lives, and activation energies for the decomposition of dimethoate in orange and peach juices were evaluated. During the storage of fruit juices in refrigerated rooms (0 degrees C) half-lives of dimethoate were found to be largely extended, being 1733 days for orange juice and 2310 days for peach juice. Corresponding times for storage at 15 degrees C were 533 days for both juices and for storage at 40 degrees C 24 days for orange juice and 24.6 days for peach juice. The activation energy for dimethoate in orange juice was 22.3 kcal/mol and for peach juice, 21. 2 kcal/mol.

Beverages↗

Effect of dimethoate administration schedules on compensatory ovarian hypertrophy, follicular dynamics, and estrous cycle in hemicastrated mice.

Dimethoate, a widely used organophosphate insecticide, was administered orally (28 mg/kg body weight) to hemicastrated (HC) virgin mice on day 1 and for 5, 10, and 15 days. Hemicastrated untreated control mice showed a significant increase in relative ovarian weight, with 42.74% hypertrophy and an increase in healthy and atretic follicles when compared with those of sham-operated control animals. The HC mice treated for 1 day or for 5 days showed no significant change in ovarian weight (36.64% and 25.19% hypertrophy, respectively) or in healthy and atretic follicles, when compared with HC-control mice. Treatment with dimethoate for 10 or 15 days, however, resulted in a significant decrease in ovarian weight (19.84% and 0.76% hypertrophy, respectively), a significant decrease in the number of healthy follicles, and a concomitant significant increase in the number of atretic follicles when compared with those in HC control animals. No significant change occurred in the number of estrous cycles or duration of each phase of the estrous cycle in HC mice treated with dimethoate for either 1 or 5 days. In HC mice treated with dimethoate for 10 or 15 days, however, a significant decrease in the number of estrous cycles, duration of proestrus, estrus, and metestrus, a concomitant significant increase in the diestrus phase, when compared with HC control animals. In mice receiving dimethoate for 15 days (but not for 1, 5, or 10 days) a significant decrease occurred in body weight and in the weights of the uterus, kidney, spleen, and liver when compared with the parallel weights in HC control animals. The overall findings suggest that following dimethoate treatment, a significant decrease in ovarian weight with a concomitant increase in compensatory ovarian hypertrophy and in the number of healthy follicles, with a concomitant increase in the number of atretic follicles and interrupted estrous cycles, may be due to the direct effect on the ovary or may be due to a hormonal imbalance in any stage of the hypothalamo-hypophysial ovarian axis.

Animals↗

Evaluation of dimethoate-induced implantation delay and nidation by progesterone in albino mice.

We investigated the effect of dimethoate, an organophosphorus insecticide, and progesterone on implantation. Virgin pregnant albino mice received dimethoate orally at a dose of 28 mg/kg body wt/d from days 1 to 7. Laparotomy on day 8 showed no implantation sites. Thereafter, graded doses of progesterone, 4, 9, and 12 mg/kg body wt/d, were administered up to day 15. A group of control mice received a similar quantity of distilled water. Autopsy on day 8 revealed that the control mice were pregnant, with a normal number of implantations and 8.08% pre-implantation loss, whereas treatment with dimethoate for 7 days or with dimethoate for 7 days followed by progesterone for 8 days totally abolished implantation, with a 100% pre-implantation loss. In all treated mice, a significant decrease occurred in body weight gain, as well as in the weight of the ovaries, uterus, and liver when compared with those of control mice. No significant changes were found in other organ weights (kidneys, adrenals, spleen, thymus, or thyroid). The observed effect of dimethoate could be due to an imbalance in the estrogen-progesterone ratio essential for implantation. Alternatively, dimethoate treatment could result in blastotoxicity or have an impact on the hypothalamic-pituitary axis.

Administration, Oral↗

Dimethoate inhibits steroidogenesis by disrupting transcription of the steroidogenic acute regulatory (StAR) gene.

Dimethoate is a widely used organophosphate insecticide that has been shown to disrupt reproductive function in animals. Although the pathogenesis of Dimethoate-induced reproductive toxicity remains to be determined, a reduction in serum testosterone levels is thought to play an important role in the development of Dimethoate-induced infertility. Since Leydig cells play a crucial role in male reproductive function by producing testosterone, the mouse MA-10 Leydig tumor cell line was used to determine if Dimethoate can directly block steroid hormone biosynthesis and to identify the site of steroidogenic inhibition. Dimethoate inhibited steroidogenesis in both a dose- and time-dependent manner without affecting total protein synthesis or protein kinase A activity. While it decreased the activity of the P450 side chain cleavage (P450 scc) enzyme, a reduction in the activity of this enzyme alone could not account for the level of Bu(2)cAMP-inhibited progesterone production. Instead, our results suggest that Dimethoate inhibited steroidogenesis primarily by blocking transcription of the steroidogenic acute regulatory (StAR) gene. This finding is significant since StAR protein mediates the rate-limiting and acutely-regulated step in steroidogenesis, the transfer of cholesterol from the outer to the inner mitochondrial membrane. This study indicates that StAR may be an important target for environmental pollutants which disrupt steroidogenesis and impair reproductive function.

3-Hydroxysteroid Dehydrogenases↗

Embryonic toxicity of a dimethoate containing insecticide formulation and Cu-sulphate in chicken after individual or combined administration.

The aim of this study was to determine the individual and combined toxic effects of a dimethoate containing insecticide formulation and Cu-sulphate on the development of chicken embryos. The test materials were injected directly into the air-chamber in a volume of 0.1 ml/egg, or eggs were treated by immersion technique on day 12. Applied concentration of Cu-sulphate was 0.01% and the concentration of insecticidE was 0.1%. After the injection treatment of a dimethoate containing insecticide on day 12 of incubation, the average body mass of embryos significantly decreased. The simultaneous injections of Cu-sulphate and a dimethoate containing insecticide a statistically significant reduction in embryonic body mass occurred. Embryonic mortality did not increase after the individual injection of test materials, while the combined injection of Cu-sulphate and a dimethoate containing insecticide killed 30% of embryos treated. After the individual and combined immersion treatment of Cu-sulphate and a dimethoate containing insecticide, the average body mass of embryos did not decrease significantly as compared to the control. After the combined immersion treatment the incidence of embryonic mortality and the number of embryos with developmental anomalies did not differ markedly from the control. In summary, it can be established that the combined injection treatment of Cu-sulphate and a dimethoate containing insecticide caused higher embryotoxicity with respect to the test of the combined immersion treatment of test materials.

Animals↗

[Muscarine receptor gene expression in brain and peripheral blood lymphocytes of rats pretreated with dimethoate for 28 days].

OBJECTIVE: To study the tolerance of rats induced by 28 day pretreatment with low dosage of dimthoate and the toxic effects challenged by higher dosage of dimethoate, and to investigate the change of M receptor and the mechanism of tolerance formation. METHODS: SD rats were given 25 mg/kg dimethoate daily(sc) while control group was given saline daily instead for 28 days. The activity of whole blood acetylcholinesterase (AChE) was examined. On the 29th day three groups of administrated rats were challenged by saline solution, 50 mg/kg and 100 mg/kg dimethoate, respectively. The density and mRNA level of brain M(1), M(2) receptor were determined. Lymphocytes of peripheral blood were isolated, and basal, inducible M(3) gene expression were measured by RT-PCR. RESULTS: During pretreatment, blood AChE activity decreased continually, it reached the lowest on the 13th day. And it decreased more after exposed to higher dosage of dimethoate. Brain AChE activity in the pretreated groups was lower than that in control group and decreased with the increase in challenging dosage. The density of M(1) receptor in negative control, pretreated, and 50, 100 mg/kg challenging groups were 979.15, 856.54, 539.46, 539.14 fmol/mg pro respectively. The change in relative levels of mRNA of M(1) receptor (2.59, 2.47, 2.20, 1.81) were consistent with the density of receptor but the level declined continually as the challenging dosage increased. The density of M(2) receptor were 507.38, 611.11, 548.42, 337.47 fmol/mg pro respectively, which were not obviously affected by pretreatment but decreased as the challenging dosage increased. The change in levels of M(2) receptor mRNA was not obvious. The basal gene expression of M(3) receptor mRNA was not different among all experimental groups while the inducible gene expression decreased with the increase in challenging dosage. CONCLUSION: Low level dosage of dimethoate could induce animals to tolerate dimethoate toxicity. Reduction of M(1) receptor density which may be induced by the decrease in its gene expression may be the mechanism of tolerance. The change of M(3) receptor mRNA inducible expression in lymphocyte accorded with M(1) receptor mRNA expression in the brain.

Animals↗

The effect of dimethoate and pyrantel on vitamin C concentration in the rat liver.

The aim of this study was to determine the content of vitamin C in the liver of rats exposed to dimethoate or pyrantel embonate as well as co-intoxication with both agents. Investigations were carried out in two stages. At each stage, the rats were divided into three experimental groups (I-III) and a control (C) group. In the first stage, rats from group I were administered pyrantel embonate at a two-week interval at a dose of 1/2 LD50, while the animals from group II received dimethoate for 28 days at a dose of 1/25 LD50, and those from group III - both mentioned compounds in an identical manner as in groups I and II. In the second stage, the rats from group I received pyrantel embonate at a dose of 1/5 LD50 for 3 consecutive days, while the animals from group II received dimethoate at a dose of 1/10 LD50 for 5 consecutive days, and those from III received both compounds, but pyrantel was administered on day 3, 4 and 5 of dimethoate administration. The concentration of vitamin C after pyrantel embonate and dimethoate administration was influenced not only by doses of the compounds used but also by the manner of their application (single or co-administration). Dimethoate delivered at a dose of 1/25 LD50 evoked an increase in vitamin C concentration that was observed to continue up to the 14th day after the exposure, whereas when applied at a dose of 1/10 LD50 it increased the vitamin C level only at the 3rd hour. A considerable decrease in the vitamin C level was reported after pyrantel treatment at a dose of 1/5 LD50. In rats from groups where the compounds were co-administered, increased level of vitamin C was observed at both stages of the experiment only in the first period after intoxication, i.e. up to the 6th hour.

Animals↗

[Effect of dimethoate on the expression of heat shock protein 70 in peripheral blood lymphocytes of human beings].

OBJECTIVE: To study the effect of dimethoate on the expression of heat shock protein 70 (HSP70) in peripheral blood lymphocytes of human beings and to explore the feasibility of HSP70 in biomonitoring among workers exposed to organophosphorous pesticides. METHODS: Peripheral blood lymphocytes were isolated from subjects, comprising 11 people of the control group and 35 workers of the exposure group exposed to dimethoate. Flow cytometry was used for detecting both the basic level and the level of the dimethoate-induced expression of HSP70. The activity of whole blood acetylcholinesterase (AChE) was examined at the same time. Then the potential influential factors to HSP70 expression and AChE activity were analyzed. RESULTS: The basic level of HSP70 expression in the exposure group and the control group was 41.24% +/- 10.45% and 23.97% +/- 4.29% respectively. The activity of AChE in these two groups were (125.23 +/- 7.97) and (145.36 +/- 8.78) U/ml respectively. Both differences were statistically significant (P < 0.01). Among the exposure group, the basic level of HSP70 expression of the two categories comprising operators and packers, were 47.34% +/- 11.87% and 38.05% +/- 8.20% respectively (P < 0.05), while there was no significant difference (P > 0.05) in AChE activity between these two categories. The factors that had significant influence on the HSP70 basic level of the exposure group were the health condition, the environmental concentration of dimethoate and the exposure time in order, according to their significance of influence. At least 88% variance of HSP70 could be explained by these factors. The only factor that could influence AChE activity significantly was the exposure time, and it could only explain about 12% variance of AChE activity. After the treatment of dimethoate in vitro, the level of the induced expression of HSP70 in the control group was significantly higher than that of the exposure group (P < 0.01). The increasing order was the control group, the group of packers and the group of operators according to the increasing extent and there were significant difference among them (P < 0.01). The factors that could significantly influence the change ratio of HSP70 expression were the environmental concentration and the exposure time. CONCLUSION: HSP70 is a potential index that can reflect the individual and environmental conditions of workers exposed to dimethoate comprehensively.

Acetylcholinesterase↗

Effect of dimethoate and chlorfenvinphos on plasma membrane integrity of Synechocystis sp. PCC 6803.

The organophosphorus (OP) insecticides dimethoate and chlorfenvinphos, at all selected concentrations (0-500 micromol liter-1), reduced the rate of accumulation of uranine and enhanced fluorescence quenching of 9-amino-6-chloro-2-methoxyacridine (ACMA). There was a significant nonlinear negative correlation between insecticide concentrations and uranine accumulation. The reduction in amount of uranine trapped inside the cells was greater in cultures treated with chlorfenvinphos, whereas quenching of ACMA fluorescence was found to be greater with dimethoate treatment. A marked difference between the effects of dimethoate and chlorfenvinphos on permeability changes in the plasma membrane of Synechocystis was also noted. The release of cellular organic carbon was observed at each concentration of chlorfenvinphos, whereas with dimethoate such an effect was noted at >/=200 micromol liter-1. The rate of uptake of substrates like 2-deoxyglucose and 2-aminoisobutyric acid (AIBA) was significantly (negatively) correlated with concentrations of both the insecticides. Chlorfenvinphos was more effective than dimethoate in reducing the active uptake of nonmetabolizable sugar and amino acid analogues.

Cell Membrane↗

Toxicological effects of an organophosphorus pesticide (dimethoate) on urinary collagen metabolites in normal and high protein diets fed female albino rats.

The effect of an organophosphorus pesticide (dimethoate) on the urinary excretion of hydroxyproline (total, nondialysable, dialysable and free fractions) and hydroxylysylglycosides, glucosylgalactosyl hydroxylysine and galactosehydroxylysine was investigated in two groups of female albino rats fed with normal and high protein diets. In comparison to controls, dimethoate treated animals were found to excrete significantly decreased amounts of urinary hydroxyproline fractions from 7th day onwards. The excretion of total hydroxylysylglycoside in urine parallels the excretion of hydroxyproline. The urinary output of both glu-gal-hyl and gal-hyl was also appreciably lower from dimethoate treated animals. The normal ratio of glu-gal-hyl and gal-hyl found in the urine of dimethoate treated animals was discussed in light of decreased turn over of collagen in both bone and skin. The effect of dimethoate in rats fed with high protein diet was comparatively less than those fed with normal diet.

Animals↗

Determination of dimethoate in blood and hemoperfusion cartridge following ingestion of formothion: a case study.

A 57-year-old male who had ingested not more than 22 g of formothion was semicomatose on admission to hospital, approximately 1.5 h after ingestion. Dimethoate, a hydrolyzed formothion, was found in blood samples collected from the patient and in the charcoal column in the direct hemoperfusion cartridge which was used 6 to 7.5 h after ingestion. It was extracted and purified by Extrelut column extraction. A gas chromatograph, equipped with a flame photometric detector and a gas chromatograph-mass spectrometer, were used to detect and confirm the presence of dimethoate. The blood dimethoate concentrations which were taken approximately 1.5 and 6 h after ingestion were 21.4 and 12.7 micrograms/g, respectively. A blood dimethoate concentration of 21.4 micrograms/g would appear to indicate a high level of formothion intoxication. The total amount of dimethoate found in the charcoal column used was 15 mg.

Adsorption↗

Dimethoate-induced effects on antioxidant status of liver and brain of rats following subchronic exposure.

Dimethoate, an organophosphate pesticide, is used in controlling the pests of a variety of crops. The study was carried out to understand the role of dimethoate in inducing oxidative stress leading to generation of free radicals and alterations in antioxidant enzymes and scavengers of oxygen free radicals. The effects of subchronic exposure of dimethoate in the production of oxidative stress were evaluated in male Wistar rats in the present study. Dimethoate was administered orally at doses 0.6, 6, and 30 mg/kg for 30 days in these rats. The results indicated an increase in levels of hepatic Cytochrome P450, lipid peroxidation, catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase in liver and brain at doses 6 and 30 mg/kg. There were no significant changes in the level of glucose-6-phosphate dehydrogenase activity except in liver at 30 mg/kg. A decrease in glutathione was observed at 30 and 6 mg/kg in both liver and brain. Glutathione-S-transferase increased at 30 and 6 mg/kg in liver and 30 mg/kg in brain. Erythrocyte acetylcholinesterase was inhibited at 30 and 6 mg/kg doses. Dose-dependent histopathological changes were seen in both liver and brain. This study concludes that oxidative stress due to dimethoate may be ascribed to induction of Cytochrome P450, inhibition of AChE and disturbance in activities of GSH and GST enzymes causing lipid peroxidation and histological and electron microscopic changes in liver and brain.

Administration, Oral↗

The effect of dimethoate and cypermethrin on soil-dwelling beetles under semi-field conditions.

The effect of cypermethrin and dimethoate exposure on soil-dwelling beetles, in spring barley at different growth stages, of doses of up to eight times maximum field application rate has been investigated. Doses up to eight times maximum field application rate of cypermethrin did not have any acute effects on larger beetles, such as P. melanarius and C. erratus. Small beetles (A. bilineata, A. dorsale, B. lanpros, B. obtusum) were not harmed by doses up to two times maximum field application rate. T. hypnorum was affected at maximum field rate. Dimethoate at maximum field application rate harmed all species, but in particular the smaller species. When dimethoate was applied in high foliage density fields in the summer, very severe acute effects on spring breeding beetles were found. In the autumn, when only a low crop cover existed, this very high effect was not observed. The severe effect in the summer may be explained by the mode of action of dimethoate on 'old beetles'. The observed high toxic effect of dimethoate on spring breeders in the summer is expected only to have limited effect on the population, because the spring breeders at this time of the year have finished their egg depositing in the soil.

Agriculture↗

Effect of dimethoate on the immune system of female mice.

The functional status of the immune system of female mice exposed to a single oral dose of dimethoate (16 mg/kg) was evaluated by assessing cell mediated and humoral immune responses, in addition to the effect of dimethoate on spleen and body weights after different time intervals. The data showed that dimethoate caused a time-depended decrease in spleen weights in the absence of a change in body weights. The immunologic effect of dimethoate to female mice produced a dose-dependent decrease in the number of the rosette forming cells (total and active erythrocyte rosette). The ability of splenocytes to proliferation in response to mitogens; phytohemagglutinin (PHA) for T cell and lipopolysaccharide (LPS) for B cell were significantly decreased at the different times. As compared to control, a significant decrease in serum total immunoglobulins (Ig) and IgM was found, while IgG was non-significant deceased. Results of this study also revealed that dimethoate caused a significant decrease in the number of plaque forming cell (PFC/10(6) splenocytes) in a time dependent manner.

Analysis of Variance↗

Behavior of dialifor, dimethoate, and methidathion in artificially fortified grape juice processed into wine.

Dialifor and methidathion were added to diluted "Zinfandel" grape concentrate at 25 ppm and dimethoate at 1.0 and 25 ppm prior to fermentation with Saccharomyces cerevisiae. The finished wine 56 days later contained 10% (2.5 ppm) of the dialifor, 46% (12 ppm) of the methidathion and 85% (21 and 0.98 ppm) of the dimethoate added to the grape must. Residues in wine stored at 24 degrees C dissipated by hydrolysis; half-lives in wine were 7 days for dialifor and methidathion and 30 days for dimethoate. Residues were unchanged in wine in frozen storage for one year. Analysis of seven commercial wines for dimethoate indicated less than 0.03 ppm dimethoate was present; identity could not be confirmed by thin-layer chromatography at this level.

Beverages↗