Use of bone marrow for detection of toxic chemicals for the elucidation of poisoning in forensic veterinary medicine / Uso de medula óssea para detecção de produtos químicos tóxicos para a elucidação de intoxicação em patologia veterinária forense

In forensic toxicology, the detection of toxic chemicals from human bone marrow is often used in cases with an extended post mortem interval; however, in veterinary medicine, this practice is not used. Therefore, this study was performed to investigate the suitability of bone marrow for toxicological analysis in dogs and cats. Six animals with suspected poisoning were selected; the carcasses were sent for necropsy, and the organs were collected and preserved in buffered formalin and processed routinely for histological examination. In addition, bone marrow samples from the femur, humerus, and tibia were collected for toxicological analysis by liquid chromatography coupled to mass spectrometry detection (LC-MS). This analysis confirmed the presence of aldicarb, aldicarb sulfone, asulam, carbendazim, chlorpyrifos, dichlorvos, thifensulfuron methyl and trifloxysulfuron-sodium and associated with clinical symptoms and anatomo-histopathological alterations it was recognized the poisonings. It is expected that this study will promote the toxicological investigation of bone marrow and open avenues for the use of this tissue as an option for the detection of toxic chemicals in cases of forensic pathology.(AU)

Na toxicologia forense, a detecção de substâncias químicas tóxicas provenientes da medula óssea humana é frequentemente usada em casos com intervalo post mortem prolongado; no entanto, na medicina veterinária, essa prática não é utilizada. Portanto, este estudo foi realizado para investigar a utilização da medula óssea nas análises toxicológicas em cães e gatos. Seis animais com suspeita de intoxicação foram selecionados; as carcaças foram enviadas para necropsia e os órgãos foram coletados e preservados em formalina tamponada e processados rotineiramente para exame histológico. Amostras de medula óssea de fêmur, úmero e tíbia foram coletadas para análise toxicológica por cromatografia líquida acoplada à espectrometria de massa-massa (LC-MS). A análise por LC-MS confirmou a presença dos agrotóxicos aldicarbe, aldicarbe sulfona, asulam, carbendazim, clorpirifós, diclorvós, tifensulfuron metil e trifloxisulfuron-sódico, e em associação com sinais clínicos e achados anatomo-histopatológicos comprovou-se as intoxicações. Espera-se que este estudo promova a utilização da medula óssea como uma opção na investigação toxicológica para a detecção de produtos químicos tóxicos em casos de patologia forense.(AU)

Assessment of nephrotoxicity and histopathological lesions of albino rats exposure to DD-force and baygon insecticides / Evaluación de la nefrotoxicidad y lesiones histopatológicas tras la exposición de ratas Albino a los insecticidas DD-Force y Baygon

Although studies suggest adverse effects of pesticides, human exposure to insecticides in homes is increasing and reports on their health effects are limited. The study investigated nephrotoxic effects of organo phosphate and carbamate insecticides, DD-Force and Baygon, in albino rats. Forty-five albino rats divided into groups were exposed to DD-Force (dichlorvos) or Baygon (propoxur) indoor insecticidein wooden boxes in separate exposure duration of 1, 2, 3 and 4 hours/day for 14 consecutive days. Serum and kidney tissue obtained after sacrifice were used to determine markers of renal damage and histopathological analysis, respectively. Exposure of rats to the insecticides showed duration-dependent significant increases (p<0.05) in serum levels of urea, uric acid and creatinine compared to control. However, rats exposed to DD-Force insecticide induced significantly higher levels of urea, uric acid and creatinine compared to Baygon (p<0.05). Histopathological lesions were observed in rats exposed to the insecticides, particularly in the exposure duration of 3 or 4 hours/day. These findings suggest that acute exposure to DD-Force and Baygonis nephrotoxic and may induce renal damage in rats.

Aunque los estudios sugieren efectos adversos de los pesticidas, la exposición humana a los insecticidas en los hogares está aumentando y los informes sobre sus efectos sobre la salud son limitados. Este estudio investigó los efectos nefrotóxicos de los insecticidas órgano fosfato y carbamato, DD-Force y Baygon, en ratas albinas. Cuarenta y cinco ratas albinas divididas en grupos fueron expuestas a DD-Force (diclorvos) o Baygon (propoxur) insecticidas de interior en cajas de madera en una duración de exposición separada de 1, 2, 3 y 4 horas / día durante 14 días consecutivos. Muestras séricas y de tejido renal obtenidas después del sacrificio se utilizaron para determinar los marcadores de daño renal y el análisis histopatológico, respectivamente. La exposición de las ratas a los insecticidas mostró aumentos significativos dependientes de la duración (p<0.05) en los niveles séricos de urea, ácido úrico y creatinina en comparación con el control. Sin embargo, las ratas expuestas al insecticida DD-Force indujeron niveles significativamente más altos de urea, ácido úrico y creatinina en comparación con Baygon (p<0.05). Se observaron lesiones histopatológicas en ratas expuestas a los insecticidas, particularmente en la duración de exposición de 3 o 4 horas/día. Estos hallazgos sugieren que la exposición aguda a DD-Force y Baygonis nephrotóxico y puede inducir daño renal en ratas.

Acute Kidney Injury after Intravenous Injection of an Organophosphate Compound

Poisoning may result from self-injection. Previous reports have described acute cholinergic crisis, intermediate syndrome, and delayed toxicity resulting from parenteral organophosphate administration. These complications have been managed with antidotal and conservative treatment. Acute kidney injury was not listed among the complications. We report a case of acute kidney injury after intravenous injection with an unknown liquid. After chemical composition analysis, organophosphate dichlorvos has been identified as the injected liquid substance. A 50-year-old man injected this into his left arm. He visited the emergency department with a mental change accompanied by seizure. During admission, there were no typical cholinergic symptoms or intermediate syndrome; however, there was a development of acute oliguric kidney injury. The patient was treated successfully with a combination of hemodialysis, hemoperfusion, and conservative management. The manifested seizure, altered mental state, and acute kidney injury could have been caused by several types of poisoning. Based on patient history, which was obtained during the early treatment period, there was no information of what the injected material may have been, and there were no signs of a typical organophosphate toxidrome. However, the patient was successfully treated with rapid initiation of renal replacement treatment, without the use of antidotes. Poisoning by unknown causative substances poses a diagnostic challenge to emergency physicians. In many cases, treatment may be delayed while the physician tries to identify the toxin. However, the basic toxicology principle of focusing on the patient treatment rather than the poisonous substance should not be forgotten.

acetylcholinesterase [AChE] inhibition analysis of medaka [Oryzias latipes] in the exposure of three insecticides

The continuous effects on Acetylcholinesterase [AChE] activity of medaka [Oryzias latipes] caused by dichlorvos, methomyl and deltamethrin in vivo were investigated, and the trends of AChE activity inhibition due to the influence of these insecticides were discussed. The LC[50]-24 h of dichlorvos, methomyl and deltamethrin on medaka were 2.3 mg/L, 0.2 mg/L, and 2.9×10[-3] mg/L respectively. The result suggested that at the beginning of the exposure, the AChE activity might increase, and the AChE activity in dead individuals was obviously lower than the live individuals. Though the de novo synthesis of AChE in medaka might help the AChE activity recover, the trends during the exposure in different treatments were downward, and it showed both exposure time and concentration dependent. Meanwhile, higher temperature might cause the AChE inhibition earlier due to the higher metabolic rate. Therefore, as a specific biomarker for organophosphate, carbamate pesticides and pyrethroids, the degree of the AChE inhibition with in vivo conditions is a good tool in continuous monitoring of insecticides, which may induce the nerve conduction disorders

Analysis of reports of cases of pesticide poisoning in Jiangsu Province, China, from 2006 to 2013 / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the characteristics of pesticide poisoning in Jiangsu Province, China, and to provide a scientific basis for developing effective intervention measures and prevention strategies.</p><p><b>METHODS</b>The data from report cards of pesticide poisoning in Jiangsu Province from 2006 to 2013 were arranged using EXCEL tables, and assessed. Statistical analysis was applied to the epidemiological data using SPSS.</p><p><b>RESULTS</b>From 2006 to 2013, a total of 32672 cases of pesticide poisoning were reported in Jiangsu Province. Most of the cases were caused by non-occupational poisoning (life poisoning) (72.78%). A majority of patients with pesticide poisoning were 35-54 years old (40.85%) or older than 65 years (15.69%). There were more female patients (58.22%) than male patients (41.78%). Among patients with occupational poisoning, male patients (50.90%) were more than female patients. Among patients with non-occupational poisoning, female patients were more than male patients (38.37%). Pesticide poisoning mainly occurred from July to September. The case-fatality rate of occupational poisoning (0.47%) was lower than that of non-occupational poisoning (7.10%). All 13 cities in Jiangsu Province reported cases of pesticide poisoning. There were more cases in the northern regions than in the southern regions. Pesticide poisoning was mainly caused by organophosphorus insecticides including methamidophos, dichlorvos, dimethoate, omethoate, and parathion, which accounted for 65.58%of all cases. Paraquat had the highest case-fatality rate (10.06%) among all pesticides, followed by tetramine (10.00%), dimethoate or omethoate (7.85%), methamidophos (7.79%), and dimehypo (7.68%).</p><p><b>CONCLUSION</b>Pesticide poisoning cannot be ignored. The management and control should be improved in production and usage of highly toxic pesticides including organophosphorus insecticides, rodenticides, and herbicides. More attention should be paid to the protection of vulnerable groups including women, children, and the elderly.</p>

Renal corpuscles were protected from dichlorvos: induced morphological alterations in rats by antioxidant vitamins / Protección de corpúsculos renales ante alteraciones morfológicas inducidas por el diclorvos en ratas mediante el uso de vitaminas antioxidantes

Dichlorvos (DDVP), an organophosphorus pesticide is a volatile compound which enters the human body through oral, dermal and inhalational routes and is excreted via the kidney. This study assessed the effects of DDVP on the histology of the kidney. Twenty five male rats (75.05 ± 5.55 g) were divided into 5 groups of 5 rats per group as follows: Unexposed group, exposure to DDVP alone for 5 weeks, and 3 other groups exposed to DDVP for 5 weeks in addition to supplement with Vitamin E, vitamin C, and red palm oil (RPO). Rats were exposed to DDVP in poorly ventilated cardboard cages for 4 hours daily. On completion of exposure, rats were euthanized and tissue processed by routine paraffin wax method and stained with H&E. Morphological alterations monitored by histological and morphometric studies using the graticule and software packages. Data were analyzed with ANOVA and p<0.05 considered as significant. DDVP caused significant reduction (10%) in the maximum glomerular diameter and 18% reduction in the maximum width of the renal corpuscle when compared with unexposed rats. However, VTE, VTC, and RPO significantly elevated the maximum glomerular diameter by 21%, 22%, 23% the respectively. Similarly, VTE, VTC, and RPO significantly elevated the maximum width of the renal corpuscle by 17%, 19%, 20% respectfully. Glomerular tuft cellularity was neither affected by DDVP treatment nor by vitamin augmentation. Inhaled DDVP caused histological alterations in the microscopic anatomy of renal corpuscles of rat which was mitigated by vitamin supplementation. Data suggest involvement of prolonged DDVP use in the aetiology of renal failure.

El diclorvos (DDVP), un pesticidas organofosforado, es un compuesto volátil que entra en el cuerpo humano a través de la vía oral, dérmica y por rutas inhalación, excretándose por vía renal. Este estudio evaluó los efectos histológicos del DDVP sobre el riñón. Veinticinco ratas machos (75,05±5,55 g) se dividieron en 5 grupos de 5 ratas cada uno: grupo no expuesto, expuesto a DDVP durante 5 semanas, y otros 3 grupos expuestos a DDVP durante 5 semanas, suplementados con vitamina E (VTE), vitamina C (VTC) y aceite de palma roja (APR). Las ratas fueron expuestas a DDVP en jaulas de cartón con poca ventilación por 4 horas diarias. Al término de la exposición, las ratas se sacrificaron y el tejido fue procesado para inclusión en parafina y tinción con H&E. Las alteraciones morfológicas se evaluaron mediante estudios histológicos y morfométricos utilizando retículas y software. Los datos se analizaron con la prueba ANOVA considerado un p<0,05 como significativo. El DDVP causó una reducción significativa (10%) en el diámetro máximo glomerular y ancho máximo del copúsculo renal (18%), en comparación con las ratas no expuestas. Sin embargo, el diámetro máximo glomerular fue significativamente elevado con VTE, VTC y APR en 21%, 22% y 23%, respectivamente, así como para el ancho máximo del corpúsculo renal por 17%, 19% y 20%, respectivamente. La celularidad de la red glomerular no fue afectada por el DDVP ni aumentó con el tratamiento de vitamina. El DDVP inhalado provocó alteraciones histológicas en la anatomía microscópica de los corpúsculos renales de rata, las que fueron mitigadas por la suplementación de vitamina. Los datos sugieren relación entre la exposición prolongada a DDVP y la etiología de la insuficiencia renal.

Left Facial Swelling Caused by Organophosphate (Dichlorvos) Poisoning: A Case Report and Review of the Literature

In organophosphate intoxication, the neurotransmitter acetylcholine accumulates in synapses, causing excessive stimulation of nicotinic and muscarinic receptors, producing various signs and symptoms. Organophosphates are highly toxic compounds that are readily absorbed through the skin, mucous membranes, and gastrointestinal and respiratory tracts. Organophosphate intoxication leads to many well defined complications, including cholinergic crisis, intermediate syndrome, and acute pancreatitis. However, parotitis caused by organophosphate intoxication is very rare. We experienced such a case of a 55 year old woman who visited the emergency center because of organophosphate intoxication. The next day, she complained of left facial redness, swelling, and pain. We checked serum lipase, amylase, and amylase-isoenzymes, and found elevation of salivary type amylase only. The mechanism of parotitis due to organophosphate intoxication is assumed to be similar to that of pancreatitis caused by organophosphate. In patients with elevated amylase caused by organophosphate intoxication, the possibility of parotitis must be considered.

Protective role of vitamins C and E in diclorvos-induced oxidative stress in human erythrocytes in vitro

Organophosphate (OP) pesticides such as dichlorvos (DDVP) intoxication has been shown to produce oxidative stress due to the generation of free radicals, which alter the antioxidant defense system in erythrocytes. In this study, the effects of DDVP (1, 10, 100 µM) or DDVP + vitamin C (VC; 10 µM) or vitamin E (VE; 30 µM), on the levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities in human erythrocytes were examined in vitro. There were no statistical differences between all groups for 1 µM concentration of DDVP. Treatment with DDVP alone produced an increase in the level of MDA and decreased activities of antioxidant enzymes (P < 0.05). Groups treated with vitamins and DDVP showed protective effects of vitamins against DDVP-induced changes in antioxidant enzyme activity and lipid peroxidation (LPO) (10 µM). At 100 µM concentration of DDVP vitamins had no effect on DDVP-induced toxicity. The results show that administration of DDVP resulted in the induction of erythrocyte LPO and alterations in antioxidant enzyme activities, suggesting that reactive oxygen species (ROS) may be involved in the toxic effects of DDVP. Also the data show that the plasma level of VC and VE may ameliorate OP-induced oxidative stress by decreasing LPO in erythrocytes at certain doses of OP pesicides.

Method for determining concentration of dichlorvos in serum by gas chromatography / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To develop a method for determining the concentration of dichlorvos in serum by gas chromatography and to provide a basis for clinical diagnosis and monitoring of dichlorvos poisoning.</p><p><b>METHODS</b>The serum (0.5 ml)collected from patients with dichlorvos poisoning was mixed with ethyl acetate (2.0 ml) and underwent shaking/extraction; the obtained liquid was subjected to standing (5 min) and centrifuging (4000 rpm); the obtained supernatant was collected and blow-dried with nitrogen and was then dissolved in ethanol (50 µl); 1.0 µl of the obtained liquid was collected and loaded into a glass-packed column; gas chromatography was performed using a nitrogen-phosphorus detector.</p><p><b>RESULTS</b>A linear relationship was found when the concentration of dichlorvos in serum was 5.0 ∼ 50.0 µg/ml, with a regression equation of y = 804.13x-691.8 (r = 0.9992). The minimum detectable concentration was 2.0 µg/ml, the recovery rate was 86.8% ∼ 94.5%, the relative standard deviation (RSD) was 4.6% ∼ 5.5%, with an intra-day RSD of 4.52% ∼ 5.21% and an inter-day RSD of 3.56% ∼ 5.52%.</p><p><b>CONCLUSION</b>This determination method is easy to operate, efficient, and accurate, and can be used for quickly diagnosing dichlorvos poisoning and quantitatively evaluating treatment outcome.</p>

Protective effects of penehyclidine hydrochloride on acute lung injury caused by severe dichlorvos poisoning in swine / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Organophosphate poisoning is an important health problem in developing countries which causes death mainly by inducing acute lung injury. In this study, we examined the effects of penehyclidine hydrochloride (PHC), a selective M-receptor inhibitor, on dichlorvos-induced acute lung injury in swine.</p><p><b>METHODS</b>Twenty-two female swines were randomly divided into control (n = 5), dichlorvos (n = 6), atropine (n = 6), and PHC (n = 5) groups. Hemodynamic data, extravascular lung water index (EVLWI), and pulmonary vascular permeability index (PVPI) were monitored; blood gas analysis and acetylcholinesterase (AchE) levels were measured. PaO2/FiO2, cardiac index (CI), and pulmonary vascular resistance indices (PVRI) were calculated. At termination of the study, pulmonary tissue was collected for ATPase activity determination and wet to dry weight ratio (W/D) testing 6 hours post-poisoning. TUNEL assay, and Bax, Bcl-2, and caspase-3 expression were applied to pulmonary tissue, and histopathology was observed.</p><p><b>RESULTS</b>After poisoning, PHC markedly decreased PVRI, increased CI more effectively than atropine. Anticholinergic treatment reduced W/D, apoptosis index (AI), and mitigated injury to the structure of lung; however, PHC reduced AI and caspase-3 expression and improved Bcl-2/Bax more effectively than atropine. Atropine and PHC improved ATPase activities; a significant difference between groups was observed in Ca(2+)-ATPase activity, but not Na(+)-K(+)-ATPase activity.</p><p><b>CONCLUSIONS</b>The PHC group showed mild impairment in pathology, less apoptotic cells, and little impact on cardiac function compared with the atropine group in dichlorvos-induced acute lung injury.</p>

Avaliação do grau de efeito toxicológico do diclorvós, após exposição inalatória em ambiente sem ventilação / Evaluation of the toxicological effect grade of dichlorvos after its exposure in environment without ventilation

Os inseticidas de uso domissanitário são utilizados para proteger o ambiente urbano. Porém, esses produtos propiciam risco à saúde. Neste experimento preliminar foi avaliado o grau de efeito tóxico em ratos, após a exposição inalatória ao diclorvós, um inseticida de uso domissanitário, em ambiente sem ventilação. O inseticida foi pulverizado no interior de uma câmara de vidro e os ratos foram expostos durante 6 e 24 h. A atividade da colinesterase plasmática foi analisada antes e após a exposição. O efeito da exposição inalatória refletiu-se sobre a depressão enzímica em até 37 por cento. A permanência em ambiente sem ventilação ou arejamento por maior tempo acarretou maior grau de intoxicação.

Evaluation of respiratory dysfunction in a pig model of severe acute dichlorvos poisoning / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Respiratory failure is the main cause of death in acute organophosphorus pesticide poisoning. In this study, a pulse-induced contour cardiac output monitor was used to evaluate the respiratory status in a pig model of acute dichlorvos poisoning.</p><p><b>METHODS</b>Twenty female pigs were randomly allocated to dichlorvos (n = 7), atropine (n = 7), and control (n = 6) groups. In the dichlorvos group, pigs were administered 80% emulsifiable dichlorvos (100 mg/kg) via a gastric tube. In the atropine group, pigs were similarly administered dichlorvos, and 0.5 hours later, atropine was injected to attain and maintain atropinization. The control group was administered saline solution. Arterial blood gas was measured at 0, 0.5, 1, 2, 4, and 6 hours post-injection. The extravascular lung water index and pulmonary vascular permeability index were recorded by the pulse-induced contour cardiac output monitor. At termination of the study, the animals were euthanized, the lung wet-to-dry weight ratio was determined, and histopathology was observed.</p><p><b>RESULTS</b>In the dichlorvos group, the extravascular lung water index and pulmonary vascular permeability index were substantially increased from 0.5 hours and were particularly high within 1 hour. In the atropine group, these indices increased initially, but decreased from the 1-hour mark. The control group exhibited no obvious changes. In both the dichlorvos and atropine groups, the extravascular lung water index was negatively correlated with partial pressure of oxygen/fraction of inspiration oxygen (PO2/FiO2) and positively correlated with the pulmonary vascular permeability index. Compared with the control group, the lung wet-to-dry weight ratio markedly increased and the histopathological findings obviously changed in the dichlorvos group, but only mildly increased and changed, respectively, in the atropine group.</p><p><b>CONCLUSION</b>The extravascular lung water index is an appropriate and valuable parameter for assessment of respiratory function in acute dichlorvos poisoning.</p>

A Case of Amyotrophic Lateral Sclerosis in a Worker Treating Pesticide Wastes / 대한산업의학회지

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease involving the motor neuron of the cerebrum, brain stem, and spinal cord. It has been suggested that various occupational or environmental agents could be a cause of ALS. We report upon a case of a person contracting ALS who experienced a long-time exposure to pesticides, implying that pesticides are probable causal agents of ALS. CASE REPORTS: The patient has been experiencing shoulder pain and limitation of movement that started abruptly about three years ago. Over time, these symptoms have become aggravated despite ongoing therapies including medication. After two years, he was diagnosed with ALS through electromyography, nerve conduction velocity and many laboratory tests at a university hospital in Seoul. His social and medical history was non-specific. The patient had worked for about 15 years at a waste disposal site and mainly destroyed glass bottles containing pesticides. During this period, his respiratory tract and skin were exposed to various raw pesticides without appropriate personal protective equipment. He did this job one or two times a week and worked for two or more hours without a break. Through an investigation into the patient's working environment, significant levels of dichlorvos, one of the organophosphates, were detected. CONCLUSIONS: The study results revealed that the patient was exposed to considerable doses of pesticides as opposed to men spraying pesticides. Although controversial, pesticide exposures have been associated with ALS. However, we suggest that in this case the possibility that these pesticide exposures acted as a causal agent for the diagnosed ALS based on plausible biological mechanisms and epidemiologic data.

Synergistic effect of dichlorvos, dimethoate and malathion mixture on reproduction toxicity in male mice / 中华预防医学杂志

<p><b>OBJECTIVE</b>To evaluate the reproduction toxicity of the mixture composed of dichlorvos, dimethoate and malathion synergistic effect on male mice, and further explore its possible mechanisms.</p><p><b>METHODS</b>The 105 male mice were divided into 7 groups, including control (0 mg/kg), mix low (10.8 mg/kg), mix medium (21.5 mg/kg), mix high dose (43.0 mg/kg), dichlorvos (5.1 mg/kg), dimethoate (12.6 mg/kg) and malathion (25.3 mg/kg) group. The oral gavage for successive 35 days, and the mice were sacrificed on the 36(th) day. The body weight, and the quantity, activity and morphology of sperms were examined. The levels of sexual hormone were measured, including testosterone (T), follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E(2)). Pathological changes of testicle and epididymis were observed by morphology, pathology and electron microscope.</p><p><b>RESULTS</b>After 14 days exposure, the body weights of the mice were lower in the mix-high dose group ((22.40 ± 3.07) g) than those in control group ((26.73 ± 2.82) g) (P < 0.05). After 28 days exposure, the body weights of the mice were also lower in the mix-medium dose group ((30.00 ± 4.93) g) than those in control group ((33.13 ± 3.29) g) (P < 0.05). The sperm counts and sperm motility decreased significantly as the toxic concentration arised. Comparing to control group ((373.33 ± 14.65)×10(6)/g weight of epididymis and (75.17 ± 7.68)%), the spermatozoa count and sperm motility had decreased in mix-medium and mix-high dose groups ((321.17 ± 18.19)×10(6)/g weight of epididymis, (225.00 ± 19.67)×10(6)/g weight of epididymis, and (64.67 ± 9.91)%, (57.83 ± 9.66)%), and the sperm abnormality rates were higher in mix-medium and mix-high groups ((43.33 ± 8.66)‰ and (55.00 ± 13.80)‰) comparing to those in control group ((32.67 ± 8.17)‰). Compared to those in control group (FSH (1.41 ± 0.20), E(2)(17.32 ± 2.72), LH (8.75 ± 1.32) and T (3.45 ± 0.80) nmol/L), the serum level of FSH (3.14 ± 0.62) and (3.85 ± 0.37) nmol/L, E(2) (36.81 ± 6.68) and (43.76 ± 9.82) nmol/L in mix-medium and mix-high dose group increased (P < 0.01), while the level of LH (5.21 ± 1.23) and (4.27 ± 1.09) nmol/L and T (1.37 ± 0.38) and (0.73 ± 0.18) nmol/L decreased (P < 0.01). The morphological and ultramicrostructure results of testicle and epididymis indicated that the mature sperm numbers were decreased, and the cacoplastic sperm head and the tail of spermatozoon were observed in mix-high dose groups.</p><p><b>CONCLUSION</b>The dichlorvos, dimethoate and malathion mixture had synergistic reproductive toxicity to the testicle and epididymis structure and function, and thus leading to the process of generation cell cytopoiesis abnormalities, simultaneously the hypothalamus-pituitary-gonad axis were also affected and thus resulted in parasecretion.</p>

In utero exposure to dichlorvos induces apoptosis of Leydig cells in rats / 中华男科学杂志

<p><b>OBJECTIVE</b>To observe the influence of the organophosphate insecticide dichlorvos on the apoptosis of Leydig cells in the male offspring of the SD rats exposed to dichlorvos, and to investigate the role of the changes of Leydig cells in genitourinary malformation.</p><p><b>METHODS</b>Twenty-one pregnant SD rats were divided into a corn oil control group and 6 dichlorvos groups, the former given by gavage 1.0 ml corn oil daily, and the latter dichlorvos at the dose of 1, 4, 8, 16, 20 and 24 mg/kg daily from the 12th to 17th day of conception. After birth, 5 male neonates were randomly selected from each of the control and dichlorvos groups, and their testes were harvested to be analyzed by HE staining, immunohistochemistry with anti-caspase-3 antibodies and DAPI fluorescent staining. At 90 days after birth, another 5 of the male offspring were taken from each group and their testes were collected for the same analyses.</p><p><b>RESULTS</b>Statistically significant differences were found in the number of both the caspase-3 positive and DAPI labeled Leydig cells in the testes of the rat offspring between the corn oil and the 4, 8, 16, 20 and 24 mg/kg dichlorvos groups (P < 0.05), but not between the control and the 1 mg/kg dichlorvos groups (P > 0.05). The apoptosis of Leydig cells was increased in the male offspring of the dichlorvos-exposed SD rats in a dose-dependent manner.</p><p><b>CONCLUSION</b>Exposure of pregnant rats to dichlorvos can increase the apoptosis of Leydig cells in the male offspring, which, in turn, may reduce the number of Leydig cells, interfere with the testis function during the embryonic period, and damage the development of the genitourinary system.</p>

Differences of acetylcholinesterase level in variety classes and strains of Culex pipiens pallens / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the diversity of acetylcholinesterase (AChE) activity in variety classes and strains of Culex pipiens pallens and provide a basis for the insecticide-resistance detection of mosquito by biochemical method.</p><p><b>METHODS</b>AChE insensitivity of single mosquito was determined, using acetythiocholine iodide (ATch) as the substrate, 5,5'-dithio-bis (2-nitrobenzoic acid) (DTNB) as the developer, and propoxur as the inhibitor.</p><p><b>RESULT</b>There were significant differences in AChE activity among the four types of IV instar larvae and 3-day-old adult female of sensitive strain mosquito (P<0.01). The AChE activity of the 3-day-old adult female was higher than that of IV instar larvae of the four types of sensitive strain mosquito (P<0.01). The AChE activity of anti-DDVP (Rd) and anti-propoxur (Rp) strains of Culex pipiens pallens was significantly higher than that of sensitive (S) strain (P<0.01), while the AChE activity of anti-cypermethrin (Rc) strain of Culex pipiens pallens was similar to that of S strain (P>0.05). The individual frequency of insensitive AChE of Rd and Rp strains of Culex pipiens pallens was significantly higher than that of sensitive (S) strain (P<0.01), while the individual frequency of insensitive AChE of Rc strain of Culex pipiens pallens was similar to that of S strain(P>0.05).</p><p><b>CONCLUSION</b>The AChE activity determination can be used to examine the insecticide-resistance of mosquito.</p>

The Variations in Clinical Features According to Intoxicants in High Toxicity Organophosphorus Intoxication

PURPOSE: Organophosphorus (OP) pesticides are differentiated into 3 groups according to their toxicity. The differences in chemical composition of each OP pesticide determines its toxicokinetic characteristics. There are few human studies that address the clinical results of poisoning according to the OP pesticide. In this study, we aimed to examine the differences in clinical features among self-poisoning from 4 highly toxic OP pesticides. METHODS: The 4 kinds of OP poisonings included 17 cases of Dichlorvos, 17 cases of EPN, 17 cases of methidathion, and 13 cases of phosphamidon. We set primary outcomes as GCS, atropine dose required, duration of patient need for atropine, proportion who required ventilation, duration on ventilation, and the interval from ingestion to ventilation. Secondary outcomes were the proportion of OP-induced delayed neuropathy, duration of ICU stay, and proportion who required additional infusion of pralidoxime chloride (PAM). RESULTS: The EPN group required the largest amount of atropine, the longest duration of atropine use, the longest duration for support of mechanical ventilation, and the longest ICU stay. Furthermore the proportion who required additional PAM and neuropathy were in the EPN group. However, the EPN group had the longest interval from ingestion to ventilatory support. Meanwhile, the Dichlorvos group exhibited comparatively mild clinical features. CONCLUSION: Throughout this study, we found different clinical features to each OP pesticide poisoning. It can be explained by differences in chemical composition, which determined the speed of aging, the reactivation rate of OPenzyme, the metabolism, the fat solubility, and other characteristics of the pesticides.

Acute toxicity of organophosphate insecticide, dichlorvos in relation to selected water hardness for the freshwater zooplankters.

Toxicity of organophosphate insecticide, i.e. dichlorvos has been investigated in relation to selected water hardness for the freshwater zooplankters such as Moina, Daphnia, cyclops and nauplii. Results revealed that dichlorvos was highly toxic to the tested zooplankters, as the LC50 values are noticed in ppb. Trend of sensitivity for different zooplankters to dichlorvos was recorded as Moina < Daphnia < nauplii < cyclops. The LC50 were found to change significantly with the change in water hardness. The zooplankters were more susceptible to dichlorvos at water hardness of 275 mgl(-1) as compared to water hardness of 540 mgl(-1) as revealed from low LC50 values. The range of safe dischargeable concentrations (1.063-1.137ppb) were too low as compared to harmless or safe concentrations (43.895-89.194 ppb) for the zooplankters at both the hardness.

Clinical Characteristics of Acute Dichlorvos Poisoning in Korea

Purpose: Dichlorvos has been in widespread use as an organophosphate (OP) insecticide compound. The purpose of this study was to access the epidemiology and clinical features of dichlorvos in Korea. Methods: This was a 38 multi-center prospective study of dichlorvos poisoning using surveys, a structural reporting system and review of hospital records from August 2005 to July 2006. A total of 54 patients with acute dichlorvos poisoning on a national basis were enrolled. We analyzed the epidemiologic characteristics and clinical manifestations of dichlorvos poisoning. In addition, the clinical features of dichlorvos poisoning were compared with others OP compounds. Results: During the study period, compounds involving pure OP poisoning were dichlorvos (22.7%), methidathion (8.4%), and phosphamidon (6.7%). In acute dichlorvos poisoning, all ingestion routes were oral. Intentional poisoning involved 74.1% of cases. The common initial complaints involved gastrointestinal (64.8%), systemic (61.1%), central or peripheral nervous system (53.7%), and respiratory symptoms (50.0%). The median arrival time to hospital after dichlorvos poisoning was 2.6 hours and mean hospitalization duration was 7.1 days. 2-PAM was administered in 35 patients in mean doses of 6.3 g/day intravenously. Atropine was administered in 30 patients with a mean dose of 62.8 mg/day (maximal 240 mg/day). Overall mortality rate for dichlorvos poisonings were 14.8% (8/54). Immediate causes for death included sudden cardiac arrest or ventricular dysrhythmias (50%), multi-organ failure (25%), acute renal failure (12.5%), and unknown causes (12.5%). Conclusion: When compared to previous reports, dichlorvos poisoning displayed relatively moderate severity. The presence of a lower GCS score, altered mental status, serious dysrhythmias, systemic shock, acute renal failure, and respiratory complications upon presentation were associated with a more serious and fatal poisoning.

TLC-spectrophometric separation and trace determination of monocrotophos and dichlorvos in enviromental and biological samples.

Organophosphorus insecticides, monocrotophos and dichlrovos are increasingly being used in agriculture to control insects on a wide range of crops. Their ready access has resulted in misuse in many instances of homicidal and suicidal poisoning cases. This paper describes about a chromogenic spray reagent for the detection/determination of monocrophos and dichlrovos in environmental and biological samples by TLC and spectrophotometric method. Monocrotophos and dichlorvos on alkaline hydrolysis yield N-methyl acetoacetamide and dichlroacetaldehyde respectively, which in turn react with diazotized p-amino acetophenone to give red-violet and red coloured compounds. Other organophosphorus insecticides do not give this reaction. Moreover, organochlorine and synthetic pyrethroid insecticides and constituents of viscera (amino acids, peptides, proteins etc), which are generally coextracted with the insecticides, do not interfere. However, phenolic compounds and hydrolysed product of carbamate insecticides may interfere and differentiate from monocrotophos and dichlrovos by Rf values. The lower limit of detection is 0.2 mg for monocrotophos and 0.1 mg for dichlorovos. The absorption maxima of the reddish-violet and red colour formed by monocrotophos and dichlrovos, are measured at 560 nm and 540 nm respectively. Beer's Law is obeyed over the concentration range of 1.2 to 6.8 mg and 6.2 to 35 mg in the final solution volume of 25 mL. The molar absorptivity and Sandell's sensitivity of monocrotophos and dichlrovos were found to be 7.1 x 10(5) (+100) 1 mole(-1) cm(-1) and 0.008 mg cm(-2), 1.2 x 10(5) 1 mole(-1) cm(-1) and 0.003 mg cm(-2) respectively. The standard deviation and relative standard deviation were found be +/- 0.005 and 2.05% +/- 0.007 and 2.02% respectively. The developed method has been successfully applied to the detection and determination of monocrotophos and dichlrovos in environmental and biological samples.