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PubMed1975

Central cholinergic activation by chlorfenvinphos, and organophosphate, in the rat.

Effects of 2-chloro-1-(2, 4-dichlorophenyl) vinyl diethyl phosphate, chlorfenvinphos, on spontaneous EEG, EMG and ChE activity in the brain and red blood cells were investigated in male Wistar rats. Chlorfenvinphos up to 1 mg/kg p.o. did not affect the ChE activity and the awake-sleep cycle. In doses over over 2 mg/kg, the ChE activity in the brain and red blood cells significantly decreased. The spontaneous EEG showed a prominent arousal pattern and appearance of slow wave sleep and parasleep was markedly depressed. Maximum inhibition of brain ChE activity was obtained 3 hr after the treatment and lasted for more than 72 hr. The duration of arousal pattern was proportional to the doses, however, the awake-sleep cycle returned to control on the 2nd day and a rebound increase in parasleep occurred on the 3rd day. Atropine depressed the EEG arousal pattern induced by chlorfenvinphos, without affecting ChE activity in the brain. The brain noradrenaline level was not altered with chlorfenvinphos. These results indicate that the appearance of EEG arousal pattern after chlorfenvinphos may be derived from central cholinergic activation.

Animals↗

PubMed1992

Influence of cow manure and composts on the effects of chlorfenvinphos on field crops.

Cauliflower crops were grown in several regions and seasons (spring and summer). Five days after planting, the plants were treated against the root fly by pouring onto soil around the plant stem an emulsion of chlorfenvinphos [2-chloro-1-(2,4-dichlorophenyl) ethenyl diethyl phosphate] in water. The fields were divided into plots. Onto each plot, one of the organic fertilizers, city refuse compost, mushroom cultivation compost, or cow manure was applied at the rate of 100 tons/ha, 1 or 3.5 months before the insecticide treatment. There were also control plots which were not treated with any of the organic fertilizers. During the first 50 days crop period which followed the insecticide treatment, the chlorfenvinphos soil concentrations were always greater in the organic fertilizer-treated plots, than in the untreated ones (controls). The intensity of the organic fertilizers effect as to the increase of chlorfenvinphos soil persistence was in the following increasing order: city refuse compost less than cow manure less than mushroom cultivation compost. The organic fertilizer effects were greater when they had been soil-incorporated 3.5 months--instead of 1 month--before the chlorfenvinphos soil treatment. The increase of the insecticide soil concentrations--due to the organic fertilizers treatments--should increase the plant protection efficiency during the period of the first 50 days, during which time the young plants are the most sensitive to insects.(ABSTRACT TRUNCATED AT 250 WORDS)

Biodegradation, Environmental↗

PubMed1991

[Pyruvic acid in the rat liver and myocardium after acute chlorfenvinphos poisoning].

The authors studied the effect of chlorfenvinphos on the pyruvic acid level in the liver and cardiac muscle of male Wistar rats. The animals were intoxicated with chlorfenvinphos in a single oral dose of 5 mg/kg (0.5 LD50). The pyruvate was assayed spectrophotometrically after 2, 4 and 24 hours following administration of the insecticide. The results obtained indicate that after intoxication with chlorfenvinphos there are no changes in the pyruvic acid level in the liver, but in the heart muscle, two hours after administration of insecticide, a significant decrease of this keto acid was observed. No alterations were found 4 and 24 hours after intoxication with chlorfenvinphos.

Acute Disease↗

PubMed1979

Hazards to wintering geese and other wildlife from the use of dieldrin, chlorfenvinphos and carbophenothion as wheat seed treatments.

Chemical treatments of cereal seeds are used in the United Kingdom to prevent damage by a number of pests including the wheat bulb fly, which is a serious pest of winter wheat. The persistent organochlorine dieldrin was introduced in the 1950s as a seed treatment but caused the death of large numbers of grain eating birds and gave rise to unacceptable environmental contamination. The withdrawal of dieldrin as a seed treatment was made possible by the introduction of two less persistent organophosphate insecticides, chlorfenvinphos and carbophenothion. Although the introduction of these chemicals has been beneficial in reducing environmental contamination, some side-effects on wildlife have still been discernible and carbophenothion has now been withdrawn from use in Scotland owing to the deaths of wintering geese from carbophenothion poisoning. Subsequent laboratory studies have demonstrated that Anser geese are particularly susceptible to carbophenothion poisoning, and the underlying biochemical mechanism has been investigated. The fundamental problem of species variation in toxicity among the organophosphorus and carbamate pesticides which this investigation illustrates presents difficulties for registration authorities when they are considered for clearance for agricultural use. The implications of the environmental problems encountered with dieldrin, chlorfenvinphos and carbophenothion for the pre-clearance testing of new chemicals are discussed and the critical surveillance of the early years of commercial use of a chemical is recommended to support pre-clearance studies aimed at assessing the potential hazard to the environment.

Animals↗

PubMed1992

[Examination of the effect of chlorfenvinphos on the activity of aminotransferase in plasma and liver in vitro].

In vitro experiments the effect of chlorfenvinphos on aminotransferases activities in rat plasma and liver homogenate cytoplasmic fraction was studied. As amino groups donors in the transamination reactions with plasma enzymes the next eight amino acids were used: alanine, aspartic acid, cysteine, phenylalanine, leucine, lysine, valine and asparagine, and with the liver cytoplasmatic enzymes--the same above mentioned without asparagine. In all these reactions as an amino groups acceptor alfa-ketoglutaric acid was used. To the incubation mixtures were added: 1 cm3 of the plasma or liver homogenate cytoplasmic fraction; 0.05 cm3 of chlorfenvinphos solution in ethyl acetate (0.17 mg/cm3) or 0.05 cm3 ethyl acetate. Aminotransferase activity was expressed as the amount of glutamate developing during 1 h incubation. Glutamic acid was determined spectrophotometrically after chromatographic separation on filter paper. Both in rat plasma and in liver cytoplasmic fraction all used amino acids as amino groups donors in the transamination reactions were shown. In the reactions with the blood plasma enzymes the most active donors were: alanine, aspartic acid and cysteine and with the participation of liver transaminases: alanine, aspartic acid and phenylalanine. As well in plasma, as in liver the greater activity of AlAT than of AspAT was observed. In the reaction with alanine and aspartate there was formed in the case of plasma 1.51 mumol Glu/cm3 and 1.00 mumol Glu/cm3 respectively and in the case of liver -69.07 mumol Glu/g and 53.26 mumol Glu/g respectively. Results of statistical analysis revealed that small plasma and liver aminotransferases inhibition was caused by the solvent, while the insecticide under test had no influence on the efficiency of transamination.

Animals↗

PubMed1991

[Studies on the combined effect of pesticide mixtures belonging to different chemical groups on calcium absorption in rat intestine. Part II. Chlorfenvinphos and cypermethrin].

In male Wistar rats study was made of the effect of multiple treatment (14 days) with single pesticides (chlorfenvinphos and cypermethrin) and with their mixture on intestinal calcium absorption. Pesticides were administered intragastrically through a stomach tube in a daily dose corresponding to 5% of LD50; in the case of the pesticide mixture, 5% of LD50 of each component were administered. Calcium uptake (active and passive) by duodenal sections were determined by the method of Papworth and Patrick, modified by the present authors. It was found that under the applied experimental conditions chlorfenvinphos influences the active transport of calcium, causing an increase in the values of the constants Jm (maximal transport rate) and Kt (affinity of calcium to carrier), whereas it inhibits the passive transport. Similar changes were displayed by rats exposed to cypermethrin. On the other hand, combined administration of both pesticides led to a lack of changes in the efficiency of active transport and to impairment of passive transport, as compared with control.

Animals↗

PubMed1990

Pretreatment of rats with an organophosphorus insecticide, chlorfenvinphos, protects against subsequent challenge with the same compound.

A single oral pretreatment of rats with chlorfenvinphos (CVP) reduced toxicity of the same compound subsequently administered. This protection occurred 8 hr and became maximal 24 hr after the oral pretreatment at a dose of 15 mg/kg (about half of its LD50). The 24-hr pretreatment with CVP increased the LD50 of CVP threefold, but did not change the type of toxic signs and time to death caused by CVP. The CVP pretreatment did not appreciably change the toxicities of the cholinergic agonists, carbachol and oxotremorine, but significantly increased the toxicity of another organophosphate, dichlorvos. Oral treatment of rats with CVP (15 mg/kg) inhibited brain acetylcholinesterase (AChE) activity. This inhibition became maximal at 4 hr (about 20% of control) and lasted more than 24 hr after the administration. Twenty-four hours after oral administration of CVP (15 mg/kg), the second dose (CVP 30 mg/kg, po) was less effective in inhibiting cholinesterase activities of the brain, erythrocyte, and plasma compared with naive rats treated with the same dose. The difference in brain AChE activity between control and CVP pretreatment groups was greater in magnitude than that measured in erythrocytes. CVP concentration in plasma after the oral administration of CVP (30 mg/kg) was decreased by the CVP pretreatment. Area under the concentration vs time curve (AUC) in the CVP-pretreated group was about one-fourth of AUC in the control group. This decrease in the AUC was comparable to the decrease in the toxicity of CVP. Thus, the protection against subsequent CVP challenge may be due to the reduction in the inhibition of brain AChE activity caused by the decrease in plasma CVP concentration.

Acetylcholinesterase↗

PubMed1991

Metabolic induction of the hepatic cytochrome P450 system by chlorfenvinphos in rats.

Previous studies have shown that a single oral pretreatment of rats with the organophosphorus insecticide 2-chloro-1-(2,4-dichlorophenyl)vinyl diethyl phosphate (chlorfenvinphos, CVP) afforded protection against the toxicity of a subsequent challenge with the same compound within 24 hr. This protection may be due to the reduction in brain cholinesterase inhibition caused by the decrease in plasma CVP concentration. The purpose of this study was to investigate the mechanism of the decrease in plasma CVP concentration in relation to metabolic induction. CVP was preferentially metabolized by a liver microsomal fraction with an NADPH-generating system, compared with serum or kidney subcellular fractions. A single oral 24-hr pretreatment with CVP (15 mg/kg) increased the oral LD50 of its next dosage to threefold. The same treatment also increased CVP metabolism (to 178%), cytochrome P450 content (to 130%), cytochrome P450 reductase activity (to 130%), cytochrome b5 content (to 121%), and cytochrome P450-linked activities such as aminopyrine demethylase (to 140%) and aniline hydroxylase (to 127%) in the hepatic microsomal fraction. A single oral 24-hr pretreatment of phenobarbital (50 mg/kg), which is known as an inducer of cytochrome P450, increased the oral LD50 of CVP and all the related metabolic parameters listed above in an order of magnitude similar to that of CVP, although the increments induced by the phenobarbital treatment were greater than those induced by the CVP treatment. These results indicate that the increase in hepatic CVP metabolism may be due to the induction of the hepatic cytochrome P450 system caused by the single oral short-term treatment with CVP. This induction may be one of the reasons for the decrease in plasma CVP concentration which may be responsible for the reduction in toxicity of its next dosage.

Animals↗

PubMed1992

Pharmacokinetic analysis of protection by an organophosphorus insecticide, chlorfenvinphos, against the toxicity of its succeeding dosage in rats.

We have previously reported that the acute oral toxicity of chlorfenvinphos (CVP) is reduced by the oral pretreatment of rats with the same compound. In this report, the mechanism of this protection was clarified mainly through the physiologically based pharmacokinetic analysis. The CVP pretreatment (15 mg/kg, po, 24 hr before) reduced the lethality of po CVP greatly, and that of iv CVP to a lesser extent. Brain acetylcholinesterase inhibition by po and iv CVP was also decreased by the pretreatment. The magnitude of reduction of the inhibition caused by the po CVP was greater than that of the iv CVP. The ratio of CVP concentration between the brain and plasma was the same, regardless of the route of administration or the pretreatment. The pretreatment greatly reduced the plasma concentration and the area under the plasma concentration versus time curve (AUC) of the po CVP, but did not change appreciably that of the iv CVP. The unbound fraction of CVP in the blood or the liver was not changed by the pretreatment. According to physiologically based pharmacokinetic analysis, the decrease in AUC of the po CVP may be mainly caused by an increase in intrinsic clearance of the liver and a decrease in the partition coefficient of CVP between the emergent blood and the liver. The increase in the intrinsic clearance may be related to the metabolic induction observed in vitro. The pretreatment decreased the absorption rate constant of the po CVP. This change in combination with the above two factors which reduce AUC might be the reason for the decrease in the plasma concentration after the po CVP, and the protection against the CVP toxicity of the succeeding dosage.

Administration, Oral↗

PubMed1990

[Evaluation of the status of nasal mucosa in workers engaged in the production of chlorfenvinphos (enolophos)].

In 41 men aged from 23 to 59 years (on an average--37.5 years) and employment duration from 1-10 years (on an average--4.9 years) working in the division of chlorfenvinphos synthesis and manufacturing "enolophos"--a preparation for agriculture, laryngological examinations were carried out including cytologic assessment of nasal mucosa and olfactometric tests. Rhinoscopy as well as cytological examinations confirmed the higher prevalence of nasal mucosa changes of inflammatory or allergic character as compared to the control group. The association between duration of employment and the changes perceived was found. Simultaneously olfactometric tests revealed in this group of workers frequent lowering of odours sensation and identification threshold.

Adult↗

PubMed1990