Impaired respiratory muscle function in chemical plant workers producing chlorfenvinphos.
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All employees of a chemical plant division producing chlorfenvinphos were studied, i.e. 35 males aged 25-57 years (mean 42.1); their employment period ranged from 1-15 years (mean 9.0). Chronic bronchitis was diagnosed in 13 workers (37.1%). Mean air chlorfenvinphos concentrations in the work environment estimated with gas-liquid chromatography were from 0.0008-0.0018 mg/m3 (maximum allowable concentration according to Polish standards is 0. 01 mg/m3). The activity of erythrocyte acetylcholinesterase was similar to that observed in people who were not exposed to chemicals, however, a slightly lowered activity of plasma cholinesterase in the studied population was evidently the result of mild liver impairment. Spirometric investigations performed in the studied workers revealed slight alterations manifested by increased intrathoracic gas volume (ITGV) (the value of the index was 138.6% of the mean value, 24 workers with an abnormally high index), as well as by decreased specific airway conductance (sGaw); its mean value in the studied group was 58.5% of the mean standard (11 people showed an abnormal index). Substantial functional changes were found in the respiratory muscles. Maximal inspiratory pressures (MIP = 97. 2 +/- 28.3 cm H2O) as well as maximal expiratory pressures (MEP = 113.9 +/- 44.2 cm H2O) in the studied group were significantly lower (p < 0.01) as compared to those observed in the control group (MIP = 120.7 +/- 31.7; MEP = 154.4 +/- 40.2 cm H2O) of 22 males having similar cigarette smoking habit, without occupational exposure to chemicals. It was also found that the people who had worked for more than 10 years under conditions of exposure to chlorfenvinphos showed significantly lower (p < 0.05) values of maximal inspiratory pressure (87.2 +/- 28.06 cm H2O, n = 17) compared to the workers whose period of employment was shorter than 10 years (106.6 +/- 26.8 cm H2O, n = 18). The two groups were comparable with regard to age and smoking habits. The values of maximal expiratory pressures were similar in both groups. No essential disturbances in neuro-muscular transmission were observed; only in 3 workers (8.5%) the electrostimulating myasthenic test showed some disturbances in neuro-muscular transmission. It seems that respiratory muscles impairment in humans exposed to chlorfenvinphos results from changes in the metabolism and structure of muscles, and partly from lung hyperinflation. (+info)
Hyposensitivity to amphetamine following exposure to chlorphenvinphos--protection by amphetamine preexposure.
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We investigated the effect of an acute exposure to chlorphenvinphos (CVP), an organophosphate anticholinesterase, on amphetamine-induced open-field locomotion in rats. CVP was administered in a single i.p. dose of 1.0 mg/kg (1/10 of the LD50). All animals were challenged with 1.0 mg/kg amphetamine (AMPH) three weeks after the CVP exposure, i.e. after a time sufficient for acetylcholinesterase recovery. Some rats were also given AMPH three weeks before the CVP exposure. In rats challenged with AMPH only once after the CVP exposure, AMPH-induced open-field locomotion was significantly reduced. Such an effect was not observed in rats given AMPH three weeks before the CVP exposure. The results suggest that a single CVP exposure may result in persistent dopaminergic hyposensitivity, and that an amphetamine pretreatment may protect the rat against this effect. (+info)
Behavioural responsiveness to amphetamine or scopolamine following repeated exposure to chlorphenvinphos in rats.
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A number of reports indicate that exposure to organophosphates (OPs), inhibitors of acetylcholinesterase (AChE), may result in long-lasting neurobehavioural alterations suggestive of an increased cholinergic tone. It is known that rats with cholinergic hyperreactivity are behaviourally hyposensitive to cholinergic antagonists and dopaminergic agonists. The purpose of the present study was to find out whether a similar trait would develop in rats exposed to chlorphenvinphos (CVP), an OP pesticide, in the past. The rats were given ten daily i.p. injections of CVP at doses of 0.5 mg/kg (group P-0.5) or 1.0 mg/kg (group P-1.0). The locomotion stimulating effect of i.p. injection of 1.0 mg/kg amphetamine (AMPH), or 0.7 mg/kg scopolamine (SCOP), was assessed on postexposure day 21 (group P-0.5) or 42 (group P-1.0), i.e. after a time sufficient for AChE recovery. The assessment revealed that in group P-1.0 the behavioural response to AMPH and SCOP was significantly depressed. In rats of the P-0.5 group, however, the behavioural response to each of the drugs was increased. The results suggest that, depending on the exposure level, contrasting alterations in some neurotransmitter systems may be induced by repeated exposure to CVP. (+info)
Electroretinographic changes induced by organophosphorus pesticides in rats.
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Electroretinographic changes induced by organophosphorus pesticides (OPs) were studied in rats. Male Wistar rats were intraperitoneally injected with fenthion, chlorpyrifos, fenitrothion, dichlorvos or chlorfenvinphos at doses of 0.01 mmol/kg and/or 0.05 mmol/kg. The electroretinogram (ERG) was recorded at 5 hours and 2 days after the administration, and brain and retinochoroid cholinesterase (ChE) activities was assayed at 3 days after the injections. The brain and retinochoroid ChE activities were reduced in rats treated with the OPs. Notably, the reduction of ChE activities by fenthion, chlorpyrifos and dichlorvos were similar. The administration of OPs induced a change in the ERG, characterized by alteration of the amplitudes of a- and b-waves. Nevertheless the ChE activities in the brain and retinochoroid were inhibited by all of the OPs, the OPs affected the amplitude of ERG differently. Fenthion and chlorpyrifos decreased the amplitudes; dichlorvos and chlorfenvinphos increased; and fenitrothion transiently decreased at 5 hours but increased 2 days after the injection. These results indicate that a factor or factors other than inhibition of ChE activities contributes to the alteration of ERG induced by OPs. (+info)
Albumin binding as a potential biomarker of exposure to moderately low levels of organophosphorus pesticides.
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Effects of stress pretreatment on the dynamics of blood cholinesterase activity after exposure to an organophosphorus pesticide in the rat.
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A single i.p. administration of 1.0 mg/kg of chlorphenvinphos (CVP), an organophosphorus pesticide, results in an acute stress response, evidenced by a marked (6-7 fold) rise in plasma corticosterone (CORT) concentration, and a diminished behavioural sensitivity to amphetamine (AMPH) three weeks postexposure. Surprisingly, in rats subjected to a single series of inescapable electric footshocks (60 10 msec triplets of 3.0 mA, 2 msec, square pulses during 20 min - IF ) two weeks prior to the CVP exposure, these effects are not observed. It has been assumed that the reduced effectiveness of CVP might be related to some persisting alterations in the functional state of the cholinergic system. The aim of the present work was to discover whether and in what way the IF pretreatment affects i) the cholinesterase activity in blood, and ii) the dynamics of the alterations in the cholinesterase (ChE) activity following the CVP exposure. The experiments were performed on 3 mo. old, male Wistar rats. In the first experiment, the blood samples were taken from the tail vein 15, 60 and 180 min after the IF. In the second experiment, the rats were pretreated with IF and 14 days later given 1.0 mg/kg of CVP i.p. Blood samples were taken 15 min, 60 min, 180 min, 24 h, 7 days, and 14 days after the CVP exposure. In the first experiment no differences in the ChE activity in plasma (pChE) and erythrocytes (rbcChE) were found between the shocked and control rats. In the second experiment, however, in rats pretreated with IF the rbcChE activity of was reduced by CVP less and pChE activity returned to normal faster than in rats not pretreated with IF. The results confirm that exposure to IF, a nonchemical stressor, induces some long-lasting adaptive changes which render the cholinergic system less susceptible to the harmful action of ChE inhibitors. It has been hypothesized that the changes consist in an increase of the antioxidant potential in blood and possibly other tissues. (+info)
Sites of methylation of DNA bases by the action of organophosphorus insecticides in vitro.
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Methylation in vitro of DNA by three methyl-14C-labelled organophosphorus insecticides has been studied. The ability of methylbromphenvinphos, methylparathion and malathion to methylate N-7 of guanine in DNA can be expressed as 100:40:15. Among the methylation products, no O6-methylguanine, a known mutagen, was found. Both in the reaction with dsDNA and with ssDNA 7-methyl-guanine was the main methylation product. However, all methyl derivatives of adenine (3-methyladenine, 1-methyladenine and 7-methyladenine) constituted about 40% and 50% of all methylation products in the case of dsDNA and ssDNA, respectively. The only methyl derivative of pyrimidine we have identified was 3-methylcytosine. In the case of dsDNA 3-methylcytosine appeared in small amounts but in the alkylated ssDNA 3-methylcytosine C constituted about 20% of all alkylation products. (+info)