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Neurotoxicology Dec 2013Patients exposed to organophosphate (OP) compounds demonstrate a central apnea. The Kölliker-fuse nuclei (KF) are cholinergic nuclei in the brainstem involved in...
Patients exposed to organophosphate (OP) compounds demonstrate a central apnea. The Kölliker-fuse nuclei (KF) are cholinergic nuclei in the brainstem involved in central respiratory control. We hypothesize that exposure of the KF is both necessary and sufficient for OP induced central apnea. We performed an animal study of acute OP exposure. Anesthetized and spontaneously breathing Wistar rats (n=24) were exposed to a lethal dose of dichlorvos using three experimental models. Experiment 1 (n=8) involved systemic OP poisoning using subcutaneous (SQ) 2,2-dichlorovinyl dimethyl phosphate (dichlorvos) at 100mg/kg or 3× LD50. Experiment 2 (n=8) involved isolated poisoning of the KF using stereotactic microinjections of dichlorvos (625μg in 50μl) into the KF. Experiment 3 (n=8) involved systemic OP poisoning with isolated protection of the KF using SQ dichlorvos (100mg/kg) and stereotactic microinjections of organophosphatase A (OpdA), an enzyme that degrades dichlorvos. Respiratory and cardiovascular parameters were recorded continuously. Animals were followed post exposure for 1h or until death. There was no difference in respiratory depression between animals with SQ dichlorvos and those with dichlorvos microinjected into the KF. Despite differences in amount of dichlorvos (100mg/kg vs. 1.8mg/kg) and method of exposure (SQ vs. CNS microinjection), 10min following dichlorvos both groups (SQ vs. microinjection respectively) demonstrated a similar percent decrease in respiratory rate (51.5 vs. 72.2), minute ventilation (49.2 vs. 68.8) and volume of expired gas (17.5 vs. 0.0). Animals with OpdA exposure to the KF during systemic OP exposure demonstrated less respiratory depression, compared to SQ dichlorvos alone (p<0.04). No animals with SQ dichlorvos survived past 25min post exposure, compared to 50% of animals with OpdA exposure to the KF. In conclusion, exposure of the KF is sufficient but not necessary for OP induced apnea. Protection of the KF during systemic OP exposure mitigates OP induced apnea.
Topics: Analysis of Variance; Animals; Apnea; Cholinesterase Inhibitors; Dichlorvos; Disease Models, Animal; Dose-Response Relationship, Drug; Hemodynamics; Male; Organophosphates; Rats; Rats, Wistar; Respiration; Respiratory Center; Time Factors
PubMed: 23928117
DOI: 10.1016/j.neuro.2013.06.009 -
Journal of Ayurveda and Integrative... 2017Parquetina nigrescens (Afzel.) Bullock of the family Asclepiadaceae is known for its antioxidant effects with wide range of uses in Southwestern Nigeria especially in...
BACKGROUND
Parquetina nigrescens (Afzel.) Bullock of the family Asclepiadaceae is known for its antioxidant effects with wide range of uses in Southwestern Nigeria especially in traditional medicine. This study was undertaken to explore if polyphenol-rich fraction (prf) from P. nigrescens will ameliorate dichlorvos-induced neurotoxicity and apoptosis. The exploration utilized evaluation of markers of oxidative stress, apoptosis and serum acetylcholinesterase (AchE) levels.
METHODS
Forty Wistar rats randomly placed in four groups were utilized for the study. Animals in Group A received corn oil, group B- dichlorvos (16 mg/kg), groups C and D- dichlorvos + 100 and 200 mg/kg prf of P. nigrescens respectively. Markers of oxidative stress, antioxidants and apoptosis were assessed in the serum and brain tissues using biochemical assay and immunohistochemistry.
RESULTS
Exposure to dichlorvos caused significant decreases in AchE, catalase, superoxide dismutase, glutathione peroxidase (GPx) and increases in hydrogen peroxide (HO) generation and malondialdehyde levels. Histopathology and immunohistochemistry of the cerebellum and cerebrum of rats exposed to dichlorvos revealed greater neurotoxic effects in the cerebellum as well as decreased expressions of AchE with a concomitant increase in Bax (proapototic) compared to prf of P. nigrescens treated rats.
CONCLUSION
This study showed that dichlorvos caused cellular and tissue neurotoxicity by inhibiting AchE activity, induced oxidative stress and apoptosis in rats with prominent effects on the cerebellum than cerebrum. The prf of P. nigrescens showed amelioration of neurotoxicity by its antioxidative and antiapoptotic properties in rats exposed to dichlorvos.
PubMed: 28256303
DOI: 10.1016/j.jaim.2016.09.002 -
Acta Medica Iranica Jan 2018Organophosphates (OPs) and carbamates are acetylcholine esterase inhibitors (AChEIs), which can cause seizure and lethality. Anticonvulsant properties of potassium...
Organophosphates (OPs) and carbamates are acetylcholine esterase inhibitors (AChEIs), which can cause seizure and lethality. Anticonvulsant properties of potassium channel openers including cromakalim have been determined in previous studies. In the present experiment, the possible effect of cromakalim on the convulsion and death induced by OPs and carbamates was studied in mice. Dichlorvos (an OP, 50 mg/kg) and physostigmine (a carbamate, 2 mg/kg) were used to induce seizure in animals. Cromakalim at doses of 0.1, 10, and 30 µg/kg was injected 30 min before dichlorvos and physostigmine, and 5 min before glibenclamide (a potassium channel blocker, 1 mg/kg) administration. All injections were performed intraperitoneally. After drugs administration, the onset of convulsion, death, the severity of seizure, and rate of mortality were investigated. Results revealed that both dichlorvos and physostigmine induced seizure activity and lethality in 100% of the animals. Cromakalim at doses of 0.1, 10, and 30 µg/kg significantly increased the latency of both seizure and death (P<0.05). Also, cromakalim decreased the mortality rate induced by dichlorvos and physostigmine (P<0.05). On the other hand, glibenclamide blocked all aspects of the anticonvulsant effect of cromakalim (P<0.05). This study revealed for the first time that cromakalim (a KATP channel opener) diminishes the seizure and death induced by dichlorvos and physostigmine in mice, and introduces a new aspect to manage the patients who suffer from OPs/carbamates-induced seizure.
Topics: Animals; Anticonvulsants; Carbamates; Cromakalim; Dichlorvos; Dose-Response Relationship, Drug; Glyburide; Male; Mice; Organophosphate Poisoning; Physostigmine; Potassium Channels; Seizures
PubMed: 29436790
DOI: No ID Found -
Journal of Food Protection Mar 2022This study investigated the concentration of the pesticide residues found in Fragaria and Myrica rubra sold in the city of Hangzhou, People's Republic of China. From an...
ABSTRACT
This study investigated the concentration of the pesticide residues found in Fragaria and Myrica rubra sold in the city of Hangzhou, People's Republic of China. From an analysis of 151 (77 Fragaria and 74 M. rubra) samples using gas chromatography-tandem mass spectrometry (GC-MS/MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), 41 pesticide residues were found to be present. Of the 41 residues, 14 were found using GC-MS/MS and 27 were found using LC-MS/MS. Of the 151 samples, 10 (13.0%) of the 77 Fragaria samples and 5 (6.8%) of the 74 M. rubra samples were found to contain a specific pesticide residue, and only 4 Fragaria samples and 2 M. rubra samples were found to be without pesticide residue. In addition, 18 of the 41 pesticides were not detected in either Fragaria or M. rubra samples. Of the 41 residues, 10 were detected in Fragaria samples and 20 were detected in M. rubra samples. In Fragaria, procymidone was the most commonly detected residue, with a detection rate of 88.3%, followed by prochloraz, with a detection rate of 53.2%. In M. rubra, prochloraz was the most commonly detected residue, with a detection rate of 71.6%, followed by carbendazim, with a detection rate of 68.9%. The pesticide residues in some samples exceeded the maximum residue limit set in China. The limit of dimethomorph was exceeded in three of the Fragaria samples, and that of dichlorvos was exceeded in two of the M. rubra samples.
Topics: Chromatography, Liquid; Food Contamination; Fragaria; Humans; Myrica; Pesticide Residues; Tandem Mass Spectrometry
PubMed: 34882199
DOI: 10.4315/JFP-21-372 -
Emergency Medicine Journal : EMJ Apr 2011To provide toxicokinetic and clinical evidence of the hydrolytic effect of paraoxonase-1 (PON1) on acute organophosphate poisoning in rats.
OBJECTIVES
To provide toxicokinetic and clinical evidence of the hydrolytic effect of paraoxonase-1 (PON1) on acute organophosphate poisoning in rats.
METHODS
40 male Wistar rats were randomised into four equal groups. Dichlorvos administration group (A group) underwent dichlorvos injection (dissolved in corn oil) using intraperitoneal (ip) dose of 10 mg/kg. PON1 pretreatment group (B group) was injected with PON1 in the tail vein (intravenous), dose 9600 U/kg, 30 min prior to dichlorvos administration. In the treatment group (C group), atropine 0.05 mg/kg and pyraloxime chloride (PAM-CI) 120 mg/kg were injected intravenously within 2 min after dichlorvos administration. Finally, in the co-treatment group (D group), PON1 was injected intravenously with a dose of 9000 U/kg 30 min prior to dichlorvos administration; atropine 0.05 mg/kg and PAM-CI 120 mg/kg were injected intravenously within 2 min after dichlorvos administration. Blood was collected after administration. Plasma dichlorvos concentration was detected by liquid chromatography-mass spectra (LC-MS) method and clinical signs were observed. Toxicokinetic parameters were calculated in a statistical moment model.
RESULTS
AUC (0→∞) in group B was statistically different from that in groups A and C (p<0.05), while it was not different from group D (p>0.05); there was no statistical difference between group A and group C (p>0.05). The statistical results of Cmax were the same as those of AUC (0→∞). There were no differences of MRT between four groups (p>0.05). Clinical signs can be improved by PON1 and atropine + PAM-CI, and co-treatment can relieve signs more effectively.
CONCLUSION
PON1 can decrease the amount of dichlorvos that entered the blood, lowered the peak concentration and relieved clinical signs.
Topics: Animals; Area Under Curve; Aryldialkylphosphatase; Cholinesterase Inhibitors; Chromatography, High Pressure Liquid; Dichlorvos; Male; Mass Spectrometry; Poisoning; Random Allocation; Rats; Rats, Wistar
PubMed: 20581384
DOI: 10.1136/emj.2009.088500 -
Environmental Research Dec 2020Extensive literature suggests an association between general pesticide use and Parkinson's disease (PD). However, with few exceptions, little is known about associations...
BACKGROUND
Extensive literature suggests an association between general pesticide use and Parkinson's disease (PD). However, with few exceptions, little is known about associations between specific pesticides and PD.
OBJECTIVE
We evaluated use of pesticides and incident PD in 38,274 pesticide applicators and 27,836 of their spouses in the Agricultural Health Study cohort followed over 20 years.
METHODS
We used self-reported information on ever-use of 50 specific pesticides as of enrollment for both applicators and spouses, and considered intensity-weighted lifetime days (IWLD) reported at enrollment and through the first 5-year follow-up among applicators. We estimated covariate-adjusted hazard ratios (HR) and 95% confidence intervals (CI) using Cox regression. We also examined heterogeneity in associations by history of head injury and chemical resistant glove use.
RESULTS
A total of 373 applicators and 118 spouses self-reported incident doctor-diagnosed PD. Ever-use of the insecticide terbufos (HR:1.31, 95%CI:1.02-1.68) and the herbicides trifluralin (HR:1.29, 95%CI: 0.99-1.70) and 2,4,5-T (HR:1.57, 95%CI:1.21-2.04) was associated with elevated PD risk. On the other hand, diazinon (HR:0.73, 95%CI: 0.58-0.94) and 2,4,5-TP (HR:0.39, 95%CI:0.25-0.62) were associated with reduced risk. We observed heterogeneity in ever-use associations by head injury and chemical-resistant glove use for some pesticides, with higher risk among those who reported a history of head injury, or who did not use gloves. PD risk was also elevated for applicators in the highest category of IWLD for dichlorvos, permethrin (animal use), and benomyl.
CONCLUSIONS
We found evidence of increased PD risk for some pesticides. Our results also suggest higher susceptibility for pesticide-associated PD among individuals with head injury as well as protection with use of chemical resistant gloves, although further research is needed to understand the impact of head injury. Research on current and newer pesticides, including mechanisms relevant to PD, is important given widespread pesticide use.
Topics: Agriculture; Cohort Studies; Farmers; Humans; Iowa; North Carolina; Occupational Exposure; Parkinson Disease; Pesticides; Spouses
PubMed: 32919961
DOI: 10.1016/j.envres.2020.110186 -
Scandinavian Journal of Work,... Feb 1994This text is the result of the authors' involvement in a working group on criteria for the identification and classification of neurotoxic chemicals. (The work of the... (Review)
Review
This text is the result of the authors' involvement in a working group on criteria for the identification and classification of neurotoxic chemicals. (The work of the group does not necessarily represent the official stand of the affiliated institutes.) A definition of neurotoxicity and criteria for evaluating studies dealing with neurotoxicology are presented. The evaluation is a stepwise process that ends with assigning the chemicals to groups depending on the available evidence for neurotoxicity (ie, neurotoxic, probably neurotoxic, possibly neurotoxic, probably not neurotoxic, or not classifiable). Finally, the description of the potency of neurotoxic chemicals is briefly discussed. The model has been tested by evaluating selected research papers on the following 10 chemicals: manganese, aluminum, tetrahydrofuran, cyclohexanone, dichlorvos, trichloroethylene, formaldehyde, tri-ortho-cresyl phosphate, n-hexane, and vinyl chloride. There was sufficient evidence for classifying five of the ten chemicals (aluminum, manganese, n-hexane, trichloroethylene, tri-ortho-cresyl phosphate) as definitely neurotoxic to humans, and three were considered to be possibly neurotoxic to humans (dichlorvos, tetrahydrofuran, vinyl chloride). Cyclohexanone and formaldehyde were not classifiable according to the model.
Topics: Animals; Dose-Response Relationship, Drug; Environmental Exposure; Humans; Nervous System Diseases; Neurologic Examination; Neurotoxins; Occupational Diseases; Occupational Exposure
PubMed: 8016593
DOI: 10.5271/sjweh.1435 -
Oncology Letters Apr 2013Cancer hazards from pesticide residues in food have been much discussed in the past decade. In this study, we showed that dichlorvos and dimethoate affect hemoglobin...
Cancer hazards from pesticide residues in food have been much discussed in the past decade. In this study, we showed that dichlorvos and dimethoate affect hemoglobin content and hematocrit value, but had no effect on red blood cell counts and total plasma protein in mice. A 40-mg/kg/day dose of dichlorvos upregulated the expression of , and genes in mouse gastric tissue. By contrast, expression of the , and genes induced by low doses (5, 10 and 20 mg/kg/day) of dichlorvos demonstrated no change in the control check group (CK; 200 l sterile saline perfused group; 0 mg/kg/day). Different doses of dimethoate all upregulated the expression of , and genes in mouse gastric tissue. The results further demonstrated that mouse gastric tissue, exposed in the long-term to low doses of dichlorvos and dimethoate, has the potential to become cancerous.
PubMed: 23599799
DOI: 10.3892/ol.2013.1155 -
Veterinary Research 2002The overall purpose ofthis paperwas to review the major and most recent literature relating the effects of anthelmintics on dung breeding invertebrates and dung... (Review)
Review
The overall purpose ofthis paperwas to review the major and most recent literature relating the effects of anthelmintics on dung breeding invertebrates and dung degradation. Faecal residues or metabolites of drugs belonging to the benzimidazole and levamisole/morantel groups are relatively harmless to dung fauna, on the contrary to other anthelmintics such as coumaphos, dichlorvos, phenothiazine, piperazine, synthetic pyrethroids, and most macrocyclic lactones which have been shown to be highly toxic for dung beetles (abamectin, ivermectin, eprinomectin, doramectin), among which moxidectin was the less toxic for dung beetles. To date, the detrimental impact upon non-target organisms has been considered acceptable in eradicating the parasites because of their economic importance to commercial livestock production. The consequences of routine treatments are discussed with consideration of the long-term consequences for cow pat fauna and sustainable pastureland ecology.
Topics: Animals; Anthelmintics; Drug Residues; Ecosystem; Feces; Invertebrates; Manure; Risk Factors
PubMed: 12387489
DOI: 10.1051/vetres:2002038 -
National Toxicology Program Technical... Sep 1989Toxicology and carcinogenesis studies of dichlorvos (99% pure), a contact and stomach poison for control of insects and parasites, were conducted by administering...
Toxicology and carcinogenesis studies of dichlorvos (99% pure), a contact and stomach poison for control of insects and parasites, were conducted by administering dichlorvos in corn oil by gavage to groups of F344/N rats and B6C3F1 mice of each sex for 13 weeks or 2 years. Previous feed studies were done by the National Cancer Institute using Osborne-Mendel rats and B6C3F1 mice. Thirteen-Week Studies: Thirteen-week studies with groups of 10 rats of each sex were conducted at doses of 0, 2, 4, 8, 16, 32, or 64 mg/kg dichlorvos in corn oil. All rats that received 32 or 64 mg/kg dichlorvos and 4/10 females that received 16 mg/kg died before the end of the studies. Final mean body weights of dosed and vehicle control rats were similar. Thirteen-week studies with groups of 10 mice of each sex were conducted at doses of 0, 5, 10, 20, 40, 80, or 160 mg/kg. All 10 male mice and 9/10 female mice that received 160 mg/kg and 5/10 male mice that received 80 mg/kg dichlorvos died before the end of the studies. Final mean body weights of dosed and vehicle control mice were similar. No compound-related gross or microscopic pathologic effects were observed in rats or mice. Two-year studies of dichlorvos were conducted by administering 0, 4, or 8 mg/kg dichlorvos, 5 days per week for 103 weeks, to groups of 50 F344/N rats of each sex. Groups of 50 male B6C3F1 mice were administered 0, 10, or 20 mg/kg dichlorvos on the same schedule, and groups of 50 B6C3F1 female mice were administered 0, 20, or 40 mg/kg dichlorvos. Body Weight and Survival in the Two-Year Studies: Mean body weights of dosed and vehicle control rats and mice were similar. No significant differences in survival were observed between any groups of rats or mice of either sex (rats--male: vehicle control, 31/50; low dose, 25/50; high dose, 24/50; female: 31/50; 26/50; 26/50; mice-- male: 35/50; 27/50; 29/50; female: 26/50; 29/50; 34/50). Neoplastic Effects in the Two-Year Studies: Adenomas of the exocrine pancreas occurred at greater incidences in dosed rats than in vehicle controls (male: vehicle control, 25/50; low dose, 30/49; high dose, 33/50; female: 2/50; 3/47; 6/50). Mononuclear cell leukemia in both dosed groups of male rats occurred more frequently than in vehicle controls (11/50; 20/50; 21/50). Mammary gland fibroadenomas and fibroadenomas or adenomas (combined) in dosed female rats occurred at increased incidences relative to the vehicle controls (9/50; 19/50; 17/50). Multiple fibroadenomas occurred in dosed female rats but not in vehicle controls (0/50; 6/50; 3/50); carcinomas occurred in two vehicle control and two low dose female rats. In mice, incidences of squamous cell papillomas of the forestomach were increased in the high dose groups compared with those in the vehicle controls (male: 1/50; 1/50; 5/50; female: 5/49; 6/49; 18/50). Two high dose female mice developed forestomach squamous cell carcinomas. Genetic Toxicology: Dichlorvos was mutagenic in Salmonella typhimurium strain TA100 with and without metabolic activation but was not mutagenic in strain TA98. Dichlorvos was mutagenic in the mouse lymphoma L5178Y/TK+/- assay without metabolic activation. Dichlorvos induced sister chromatid exchanges and chromosomal aberrations in Chinese hamster ovary cells in the absence and presence of metabolic activation. Conclusions: Under the conditions of these 2-year gavage studies, there was some evidence of carcinogenic activity of dichlorvos for male F344/N rats, as shown by increased incidences of adenomas of the exocrine pancreas and mononuclear cell leukemia. There was equivocal evidence of carcinogenic activity of dichlorvos for female F344/N rats, as shown by increased incidences of adenomas of the exocrine pancreas and mammary gland fibroadenomas. There was some evidence of carcinogenic activity of dichlorvos for male B6C3F1 mice, as shown by increased incidences of forestomach squamous cell papillomas. There was clear evidence of carcinogenic activity of dichlorvos for female B6C3F1 mice, as shown by increased incidences of forestomach squamous cell papils cell papillomas. Synonyms: 2,2-dichloroethenyl dimethyl phosphate; 2,2-dichlorovinyl dimethyl phosphate; O,O-dimethyl-O-(2,2-dichlorovinyl)phosphate; DDVP Trade Names: BAY-19149; DDVF; ENT-20738; OMS-14; SD 1750; Canogard®.; Crossman's Fly-Cake®.; Dedevap®.; De-Pester Insect Strip®.; Estrosol®.; Herkol®.; Kill-fly Resin Strip®.; Lethalaire®.; Mafu®.; Misect®.; Nogos®.; Nuvan®.; No-Pest Strip®.; Oko®.; Phoracide®.; Phosvit®.; Vapona®.; Vaponicide®.; Vaporette Bar®. Anthelmintics: Atgard®.; Dichlorman®.; Equigard®.; Task®.
PubMed: 12724783
DOI: No ID Found