Joint toxicity assessment reveals synergistic effect of chlorpyrifos and dichlorvos to common carp (Cyprinus carpio).

Common carp (Cyprinus carpio) is an important aquaculture species. However, their production and health is sometimes threatened by pesticides. In common carp, extensive studies have been done for exposures of single pesticides, but effects of mixtures such as those of the commonly used chlorpyrifos and dichlorvos, are still unknown for this species. In the first phase of this work, an acute lethal exposure experiment was conducted to estimate 24 h to 96 h lethal concentrations (LC10-90) of chlorpyrifos, dichlorvos and their mixture. Compared to dichlorvos, chlorpyrifos was found to be highly toxic to the tested species. Joint toxicity assessment of these pesticides in binary mixtures was dominated by synergism. In the second experimental phase, common carp were exposed to sub-lethal concentrations (LD-10% and HD-50% 96 h-LC50) of individual pesticides and their mixture. General fish behaviors, buccal movements and feeding attempts by fish were recorded after 1 h, 24 h, 48 h, 72 h and 96 h whereas aerobic metabolism of fish was recorded for 0-24 h, 24-48 h 48-72 h and 72-96 h of exposure. All pesticide treatments elevated buccal movements and oxygen uptake in a dose dependent manner. Feeding depression was also observed by pesticide exposure. The augmented deleterious effect of these pesticides in a mixture suggests that joint toxicity assessment is critical to develop more realistic water quality standards and monitoring guidelines.

Study of the principles in the first phase of experimental pharmacology: the basic step with assumption hypothesis.

BACKGROUND: Experimental pharmacology deals with effects of various test substances studied on different animal species which is aimed at finding out safe therapeutic agent suitable for public health as well as mechanism and site of action of a test substance. It is the basic step in the discovery of new drugs or studying the pharmacological actions of already developed one using both preclinical and clinical study designs in a stepwise phase of investigations. However, the investigations in the first phase of experimental pharmacology are usually concluded with assumption hypothesis without any adequate validation of the scientific evidence. Single dose acute toxicology had been conducted on Balb c mice with three different level of doses prepared from each of three different test chemicals (Dichlorvos, Chlorpyrifos and Cypermethrin) with known median lethal dose (LD50) to define the fundamental principles, cause of toxicity and investigation timeframe in the first phase of experimental pharmacology. METHODS: The methods used for data collection were: procurement of test chemicals, investigation of single dose acute toxicity on Balb c mice and quantitative immunoglobulins test. Data was thematically compiled for validation of the findings from each of the sources. RESULTS: The result showed that the dose had never limited the toxic property of tested chemicals but the magnitude of adverse effect and length of time at which adverse effect was manifested on treated Balb c mice. The toxicity of tested chemicals was however limited by the toxic reaction rate of a dose in the biological process of exposed Balb c mice. The toxic effect of tested chemicals became magnified within a short period of time when large amount administered orally. It also remained after a long period of time when small amount administered in the same route. CONCLUSION: Adequate investigation time for acute toxicity study was therefore essential for comprehensive analysis of pharmacological property of tested chemicals at different level of doses.

Organophosphate pesticide trichlorfon induced neurotoxic effects in freshwater silver catfish Rhamdia quelen via disruption of blood-brain barrier: Implications on oxidative status, cell viability and brain neurotransmitters.

The aim of this study was to evaluate whether rupture on blood-brain barrier (BBB) can be a pathway for trichlorfon-induced neurotoxic effects, and to investigate its implications on oxidative status, cell viability and brain neurotransmitters in silver catfish (Rhamdia quelen). The BBB permeability was increased in fish exposed for 24 h to 22 mg/L of trichlorfon compared to the control group, as well as in those exposed to 11 and 22 mg/L of trichlorfon for 48 h. Compared to the control group, brain reactive oxygen species and lipid peroxide levels were higher when exposed to 22 mg/L of trichlorfon and 11 and 22 mg/L of trichlorfon after 24 h and 48 h, respectively, while the antioxidant capacity against peroxyl radical levels was lower. Exposure to 22 mg/L of trichlorfon for 24 h reduced brain cell viability compared to the control group, together with 11 and 22 mg/L of trichlorfon for 48 h. Also, brain AChE, Na+ and K+-ATPase activities were reduced in those fish exposed to trichlorfon compared to the control group. Thus, the rupture of BBB can be considered an important pathway involved in trichlorfon-induced neurotoxic effects, which contributes to brain oxidative damage and important changes on brain neurotransmitters.

Cromakalim, a Potassium Channel Opener, Ameliorates the Organophosphate and Carbamate-Induced Seizure in Mice.

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.

Polyphenol-Rich Fraction of Parquetina nigrescens Mitigates Dichlorvos-Induced Cardiorenal Dysfunction Through Reduction in Cardiac Nitrotyrosine and Renal p38 Expressions in Wistar Rats.

Parquetina nigrescens is commonly used to treat diseases in humans and animals in developing countries, including Nigeria. This study evaluates the effects of its polyphenol-rich fraction (prf) on dichlorvos-induced cardio- and renal toxicity. There were several factors assessed during this study, including cardiac and renal markers, serum myeloperoxidase and xanthine oxidase, and electrocardiograph (ECG) changes. The changes in electrocardiograph (ECG) were recorded. Immunohistochemistry of cardiac and renal p38 and nitrotyrosine was determined. Dichlorvos exposure caused a significant decrease in L-glutathione (reduced glutathione) and other antioxidant enzymes with increases in malondialdehyde, myeloperoxidase, advanced oxidation protein products, and protein carbonyl levels. It also brought about alterations in microanatomy of the heart and kidneys accompanied by increases in serum creatinine and urea levels. Exposure to dichlorvos induced prolonged QRS interval and shortened QT durations in rats. Immunohistochemistry revealed lower expressions of cardiac nitrotyrosine and renal p38 (mitogen-activated protein kinase; MAPK) in rats treated with prf of P. nigrescens. Combining all, prf of P. nigrescens demonstrated antioxidant as well as protective properties in the heart and kidneys of rats exposed to dichlorvos. It ameliorated dichlorvos-induced cardio- and nephrotoxicity giving credence to its use in ethnomedicine.

High intensity of Tunga penetrans infection causing severe disease among pigs in Busoga, South Eastern Uganda.

BACKGROUND: Towards the improvement of stakeholders' awareness of animal tungiasis, we report 10 unusual severe clinical cases of pig tungiasis which were associated with very high infection intensities of T. penetrans in an endemic area. RESULTS: Morbidity of ten pigs with high sand flea intensities detected during high transmission seasons in an endemic area in Busoga sub region, Uganda is described in detail. The cases of pigs presented with a very high number of embedded sand fleas (median = 276, range = 141-838). Acute manifestations due to severe tungiasis included ulcerations (n = 10), abscess formation (n = 6) and lameness (n = 9). Chronic morphopathological presentations were overgrowth of claws (n = 5), lateral deviation of dew claws (n = 6), detachment (n = 5) or loss of dew claws (n = 1). Treatment of severe cases with a topical insecticidal aerosol containing chlorfenvinphos, dichlorvos and gentian violet resolved acute morbidity and facilitated healing by re-epithelialisation. CONCLUSIONS: The presentations of tungiasis highlighted in this report show that high intensities of embedded T. penetrans can cause a severe clinical disease in pigs. Effective tungiasis preventive measures and early diagnosis for treatment could be crucial to minimize its effects on animal health.

Captures of Wild Ceratitis capitata, Bactrocera dorsalis, and Bactrocera cucurbitae (Diptera: Tephritidae) in Traps with Improved Multilure TMR Dispensers Weathered in California.

During 2012­2013, solid Mallet TMR (trimedlure [TML], methyl eugenol [ME], raspberry ketone [RK]) wafers impregnated with DDVP (2, 2-dichlorovinyl dimethyl phosphate) insecticide were weathered during summer (8 wk) and winter (12 wk) in five California citrus-growing counties (Kern, Ventura, Orange, Tulare, and Riverside). In addition, TMR wafers without DDVP and with a Hercon Vaportape II insecticidal strip were compared with TMR dispensers with DDVP at Exeter and Riverside. Weathered treatments were shipped every week (overnight delivery) to Hawaii and frozen for a later bioassay in a 1,335-ha coffee plantation near Numila, Kauai Island, HI, where Mediterranean fruit fly, Ceratitis capitata (Wiedemann), oriental fruit fly, Bactrocera dorsalis Hendel, and melon fly, Bactrocera cucurbitae Coquillett, were all present. We compared trap captures of the three species, C. capitata, B. dorsalis, and B. cucurbitae, for the five different weathering locations. Captures of C. capitata, B. dorsalis, and B. cucurbitae with Mallet TMR dispensers (with DDVP) were not significantly different for the five locations. Captures with the Mallet TMR dispenser without DDVP and Vaportape were similar to those for Mallet TMR with DDVP, although there were some slight location differences. In conclusion, based on these results, the Mallet TMR dispenser could potentially be used in California habitats where large numbers of detection traps are currently deployed. Use of Vaportape with dispensers would not require them to be registered with US Environmental Protection Agency (EPA). Dispensers for use as Male Annihilation Technique (MAT) devices will be tested further in Hawaii.

Detoxification of Organophosphate Poisoning Using Nanoparticle Bioscavengers.

Organophosphate poisoning is highly lethal as organophosphates, which are commonly found in insecticides and nerve agents, cause irreversible phosphorylation and inactivation of acetylcholinesterase (AChE), leading to neuromuscular disorders via accumulation of acetylcholine in the body. Direct interception of organophosphates in the systemic circulation thus provides a desirable strategy in treatment of the condition. Inspired by the presence of AChE on red blood cell (RBC) membranes, we explored a biomimetic nanoparticle consisting of a polymeric core surrounded by RBC membranes to serve as an anti-organophosphate agent. Through in vitro studies, we demonstrated that the biomimetic nanoparticles retain the enzymatic activity of membrane-bound AChE and are able to bind to a model organophosphate, dichlorvos, precluding its inhibitory effect on other enzymatic substrates. In a mouse model of organophosphate poisoning, the nanoparticles were shown to improve the AChE activity in the blood and markedly improved the survival of dichlorvos-challenged mice.

Sub-chronic exposure to arsenic and dichlorvos on erythrocyte antioxidant defense systems and lipid peroxidation in rats.

The effect of combined exposure to arsenic (25 ppm in drinking water) and dichlorvos (2.5 mg kg1, orally) for 56 days on biochemical variables, indicative of lipid peroxidation, antioxidant enzyme system and AChE activity in erythrocytes of rats, were examined. While arsenic caused a significant increase in AChE, DDVP produced marked depletion. Combined exposure to arsenic and DDVP produced no additional decrease in AChE activity, which was comparable to DDVP. Arsenic and DDVP also increased the levels of reactive oxygen species (ROS) and thiobarbituric acid reactive substances (TBARS), suggesting free radical generation. Interestingly, glutathione linked enzymes (GSH, GPx, GST and GR) significantly increased on arsenic and DDVP exposure. SOD activity also increased significantly in the individually exposed groups, while catalase activity remained unchanged. Blood arsenic level increased significantly on coexposure to arsenic alone and with DDVP exposed group. However, arsenic content in co-exposed group depleted marginally as compared to arsenic alone group, indicating possible arsenic redistribution. It might be concluded from the study that the combined exposure to arsenic and DDVP may lead to synergistic effects on certain biochemical indicators of oxidative stress like ROS, GSH and SOD, suggesting a more pronounced induction of lipid peroxidation in erythrocytes.

A comparison of three different methodologies for evaluating Rhipicephalus (Boophilus) microplus susceptibility to topical spray compounds.

This study aimed to compare three different methodologies (Adult Immersion Tests, field trials with naturally infected animals, and a Stall Test using artificially infested cattle) to evaluate the efficacy of two topical formulations that we administered as whole body sprays (15% Cypermethrin+30% Chlorpyriphos+15% Fenthion-Colosso(®) FC 30, Ouro Fino Agronegócios; and 60% Dichlorvos+20% Chlorpyriphos-Ectofós(®), Vallée Saúde Animal Ltd.), against a susceptible strain of Rhipicephalus (Boophilus) microplus. To achieve this objective, two natural infestation trials were conducted, as well as two artificial infestation trials (Stall Tests) and two Adult Immersion Tests (AIT). The AIT results showed that both spray formulations achieved 100% efficacy against R. (B.) microplus fully engorged females. However, when observing results obtained by field trials (natural infestations) and Stall Tests, none of these topically applied compounds reached 100% efficacy or affected the reproductive capacity of the fully engorged female ticks. Additional studies must be conducted to compare these in vivo methodologies with different in vitro techniques, such as the Larval Packet Test. However, based on results obtained here, we can conclude that depending on the spray formulations used, the AIT can overestimate acaricidal efficacy and values of reproductive efficiency of such compounds against R (B.) microplus. Specifically, when dealing with spray formulations in the Stall Tests, the period of residual action can increase because these animals are sheltered from contact with environmental factors that might interfere with the efficacy of the products tested. It may be necessary to take in vivo trial results into consideration (such as field trials with naturally infested animals or Stall Tests) to standardize a specific in vitro assay, such as the Adult Immersion Test.

A metabonomic analysis of the effect of quercetin on toxicity induced by chronic exposure to low-level dichlorvos in rat plasma.

A previous study of ours has reported that chronic exposure to low-level dichlorvos (DDVP, 7.2 mg per kg bw) damages the liver, interferes with fatty acid metabolism, and disturbs the antioxidant defense system in rats. This study aims to investigate whether or not quercetin can protect against DDVP-induced toxicity through metabonomics and to elucidate the mechanism underlying this protective effect. Rats were randomly assigned into the control group, DDVP-treated group, quercetin-treated group, and quercetin plus DDVP-treated group. DDVP and quercetin were administered to the rats daily via drinking water and gavage, respectively, continuously for 90 d. The metabonomic profiles of rat plasma were analyzed using ultra-performance liquid chromatography-mass spectrometry. Finally, 11 metabolites were identified, including those of quercetin, isorhamnetin, and quercetin-3-glucuronide. The 11 metabolites showed significant changes in some treatment groups compared with the control group. Arachidonic acid, phytosphingosine, and C16 sphinganine significantly decreased while p-cresol, lysoPE (16:0/0:0), lysoPC (15:0/0:0), lysoPC (16:0/0:0), lysoPC (0:0/18:0), and tryptophan significantly increased in the DDVP-treated group compared with the control group. The tendency of the aforementioned metabolites to change was significantly ameliorated in the high-dose quercetin (50 mg per kg bw per day) plus DDVP-treated group compared with the DDVP-treated group. However, the levels of these metabolites in the high-dose quercetin plus DDVP-treated group were still significantly different from those in the control group. The results indicate that high-dose quercetin (50 mg per kg bw per day) elicits a partial protective effect on DDVP-induced toxicity. The histopathology of the liver tissues was consistent with the above results. Quercetin demonstrated regulatory effects on the metabolism of lipids and amino acids, the antioxidant defense system, etc. Therefore, increasing the daily intake of quercetin can ameliorate the toxicity induced by chronic exposure to low-level DDVP residue in food and/or water.

Effect of DDVP on urinary excretion levels of pyrethroid metabolite 3-phenoxybenzoic acid in rats.

Pyrethroid insecticide (PYR) is used worldwide in agriculture and for indoor extermination of harmful insects. Urinary PYR metabolites (e.g. 3-phenoxybenzoic acid, 3PBA) have been used as the most sensitive biomarker for environmental PYR exposure since the late 1990s. In this study, we examined the effect of organophosphorus insecticide (OP) dichlorvos (DDVP) on excretion levels of urinary cis-permethrin-derived 3PBA in rats. Concentration of urinary 3PBA and cis-permethrin in plasma was monitored using gas chromatography-mass spectrometry and high-performance liquid chromatography after cis-permethrin injection (20 mg/kg) via the tail vein of rats pretreated intraperitoneally with DDVP (low dose, 0.3 mg/kg; high dose, 1.5 mg/kg). The amount of urinary 3PBA excretion over 48 h after cis-permethrin administration in control was 21.5±5.1 µg (mean±S.D.). In the low- and high-dose DDVP groups, the amounts of urinary 3PBA excretion were decreased to 81.1% (17.4±2.7 µg) and 70.3% (15.1±2.6 µg) of control, respectively. The plasma concentrations of cis-permethrin-derived 3-phenoxybenzyl alcohol (3PBAlc), which is a metabolite derived following hydrolysis of cis-permethrin, in high-dose DDVP group (0.18±0.01 µg) were significantly lower than in control (0.23±0.03 µg) 1h after cis-permethrin injection. Both in the control and high-dose DDVP group, no differences were observed in the excretion levels of urinary 3PBA after injection of 3PBAlc (25mg/kg, i.v.). These results suggested that the effect of DDVP on the amount of urinary 3PBA excretion was caused by the DDVP-induced modification of the cis-permethrin metabolic pathway. In conclusion, the possible decrease in urinary excretion level of 3PBA due to co-exposure to OPs should be considered in the biological monitoring of PYR exposure.

Dichlorvos-induced central apnea: effects of selective brainstem exposure in the rat.

The area of the brain responsible for organophosphate (OP)-induced central apnea is unknown. Automatic breathing is governed by circuits in the medulla and pons. Respiratory-related neurons in the brainstem are concentrated in a few areas, including ventral regions of the medulla, which contains a number of sites critical for respiratory rhythmogenesis, including the pre-Bötzinger complex (preBötC). The preBötC contains cholinergic receptors, making it a candidate site of action for the apnea-inducing effect of OP. We analyzed respiratory output during a series of experiments using both intact and reduced Wistar rat preparations exposed to dichlorvos (2,2-dichlorovinyl dimethyl phosphate). Exposure of the brainstem using a working heart-brainstem preparation resulted in a central apnea similar to that seen in intact animal models. In contrast, microdialysis of locally toxic doses of dichlorvos to the ventral region of the medulla resulted in delayed and mild respiratory depression in most animals and apnea in only 29% of the animals. We conclude that exposure of the entire brainstem to OP is sufficient to induce central apnea. Our microdialysis experiments suggest that the neural substrate for OP-induced central apnea involves a specific brainstem site other than the ventral region of the medulla, or apnea might result from a distributed effect involving cholinergic toxicities of multiple brainstem sites.

Study of paraoxonase-1 function on tissue damage of dichlorvos.

To examine the protective efficacy of paraoxonase-1 (PON1) against tissue damage caused by dichlorvos, purified rabbit PON1 was injected intravenously into rats 30min before they were given dichlorvos, while dichlorvos administration group and corn coil administration group were conducted to compare. Blood was collected at different time points after dichlorvos administration to examine the acetyl cholinesterase (AChE) inhibition level and clinical signs were observed after poisoning. 72h later, animals were anesthetized and the hippocampus, liver, lung and kidney were removed for observation of ultrastructure. AChE activities in PON1 pretreament group were statistically significant from dichlorvos administration group (P<0.01). The clinical signs were alleviated by PON1 significantly (P<0.05). The most common change of organophosphorus poisoning damage to liver was small lipid-like structures could be seen throughout the liver structure. In kidney, dense bodies were seen. The most significant changes in lung were lost of lamellar structure of lamellar bodies in type II alveolar epithelial cell. As for changes of hippocampus, demyaliation takes place after acute organophosphorus, but neural edema was not improved significantly in our study. In conclusion, PON1 can decrease the AChE inhibition, and alleviated clinical signs and tissue damage caused by dichlorvos.

Effects of combined exposure to dichlorvos and monocrotophos on blood and brain biochemical variables in rats.

Dichlorvos (DDVP) and monocrotophos (MC) are systemic insecticides and known to produce cholinergic and non-cholinergic effects. Individual toxic effects of these chemicals are known but their combined effects have not been studied. We studied the effect of concomitant exposure to DDVP and MC on selected biochemical variables suggestive of liver damage, changes in whole brain biogenic amines levels, acetylcholinesterase (AchE) and monoamine oxidase (MAO) activities in rats. Female rats were exposed to DDVP (2.5 mg/kg subcutaneously) and MC (1.8 mg/kg oral) either individually or in combination for 4 weeks. We observed significant decrease in more pronounced depletion in norepinephrine (NE) and dopamine (DA) levels during co-exposure to DDVP and MC. Brain AChE activity increased and activity of MAO showed significant depletion on co-exposure to DDVP and MC. Brain glutathione (GSH) and oxidized glutathione (GSSG) ratio decreased significantly during exposure to DDVP or MC while co-exposure to these toxicants led to a more pronounced depletion of GSH: GSSG ratio. Serum aspartate amino transferase (AST) and alkaline phosphatase (ALP) activities increased significantly on exposure to MC suggesting liver injury, while DDVP alone had no effect on these variables. There were no effects of DDVP and MC exposure on haematological biochemical variables except for depletion in serum glucose level after MC exposure which was more pronounced DDVP + MC during co-exposure. It can be concluded that only moderate synergistic effects occur between MC and DDVP during co-exposure. A more detailed study with variable doses, prolonged exposure and alterations in different brain regions is recommended.

Impaired mitochondrial functions in organophosphate induced delayed neuropathy in rats.

Acute exposure to organophosphates induces a delayed neurodegenerative condition known as organophosphate-induced delayed neuropathy (OPIDN). The mechanism of OPIDN has not been fully understood as it does not involve cholinergic crisis. The present study has been designed to evaluate the role of mitochondrial dysfunctions in the development of OPIDN. OPIDN was induced in rats by administering acute dose of monocrotophos (MCP, 20 mg/kg body weight, orally) or dichlorvos (DDVP, 200 mg/kg body weight, subcutaneously), 15-20 min after treatment with antidotes [atropine (20 mg/kg body weight) and 2-PAM (100 mg/kg body weight) intraperitoneally]. MDA levels were observed to be higher and thiol content was lower in mitochondria from brain regions of OP exposed animals. This was accompanied by decreased activities of the mitochondrial enzymes; NADH dehydrogenase, succinate dehydrogenase, and cytochrome oxidase. In addition, mitochondrial functions assessed by MTT reduction also confirmed mitochondrial dysfunctions following development of OPIDN. The spatial long-term memory evaluated using elevated plus-maze test was observed to be deficit in OPIDN. The results suggest impaired mitochondrial functions as a mechanism involved in the development of organophosphate induced delayed neuropathy.

Effect of short-term exposure to dichlorvos on synaptic plasticity of rat hippocampal slices: involvement of acylpeptide hydrolase and alpha(7) nicotinic receptors.

Dichlorvos is the active molecule of the pro-drug metrifonate used to revert the cognitive deficits associated with Alzheimer's disease. A few years ago it was reported that dichlorvos inhibits the enzyme acylpeptide hydrolase at lower doses than those necessary to inhibit acetylcholinesterase to the same extent. Therefore, the aim of our investigation was to test the hypothesis that dichlorvos can enhance synaptic efficacy through a mechanism that involves acylpeptide hydrolase instead of acetylcholinesterase inhibition. We used long-term potentiation induced in rat hippocampal slices as a model of synaptic plasticity. Our results indicate that short-term exposures (20 min) to 50 microM dichlorvos enhance long-term potentiation in about 200% compared to the control condition. This effect is correlated with approximately 60% inhibition of acylpeptide hydrolase activity, whereas acetylcholinesterase activity remains unaffected. Paired-pulse facilitation and inhibition experiments indicate that dichlorvos does not have any presynaptic effect in the CA3-->CA1 pathway nor affect gabaergic interneurons. Interestingly, the application of 100 nM methyllicaconitine, an alpha(7) nicotinic receptor antagonist, blocked the enhancing effect of dichlorvos on long-term potentiation. These results indicate that under the exposure conditions described above, dichlorvos enhances long-term potentiation through a postsynaptic mechanism that involves (a) the inhibition of the enzyme acylpeptide hydrolase and (b) the modulation of alpha(7) nicotinic receptors.

Hematotoxic and hepatotoxic effects of dichlorvos at sublethal dosages in rats.

The present study was designed to understand the effects of sublethal concentrations of dichlorvos (DIC) on hematological constituent [red blood corpuscles, white blood corpuscles (WBC), mean cell volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet counts, hemoglobin and hematocrite levels] and serum damage marker enzymes (aspartate aminotransferase, alanin aminotransferase, alkaline phosphatase, and lactate dehydrogenase) in rats at subacute period under laboratory conditions. DIC at dosages of 5 and 10 ppm was administered orally to six male rats ad libitum during the tests for 4 weeks consecutively. According to the results, DIC treatments increased significantly the levels of serum marker enzyme activities, whereas they did not change hematologic constituent except for WBC number treated with both dosages of DIC. The observations presented led us to conclude that the administrations of subacute DIC induced the levels of damage marker enzymes and leukocytosis.