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1.
The effect of several subtoxic doses of parathion on water intake was studied in conscious rats with centrally induced thirst. A potent and long-lasting antidipsogenic effect was obtained when single doses ranging from 100 to 600 μg of parathion/100 g body wt were ip given to rats in which thirst was induced either by 24 hr water deprivation or sc injection of hypertonic NaCl solution. A significant thirst inhibition was also obtained when paraoxon or dichlorvos (DDVP) was given. The antidipsogenic effect was prevented by the previous administration of diacetylmonoxime (DAM), an acetylcholinesterase reactivator, but not prevented by pralidoxime (2-PAM), another reactivator that is unable to cross the blood-brain barrier (BBB). Thirst inhibition induced by parathion administration was also prevented when muscarinic cholinergic blockers were previously given, such as atropine sulfate. Acetylcholinesterase activity (AChE) was not inhibited on either blood or hypothalamic tissue with the different doses of parathion given. Locomotor activity and emotionality also remained unaltered. The results obtained indicate that the antidipsogenic effect of the organophosphorus pesticide is centrally produced by stimulation of muscarinic cholinergic pathways.  相似文献   

2.
Effects of ambient temperature on the acute oral toxicity of parathion were investigated in Japanese quail (Coturnix japonica) maintained at thermoneutral temperature (26°C) or exposed to elevated (37°C) or reduced (4°C) temperatures commonly encountered by free-ranging wild birds. Based upon estimates of the median lethal dosage, there was up to a twofold enhancement of parathion toxicity in birds chronically exposed to heat or cold. Twenty-four hours after administration of a low dosage (4 mg/kg body wt, po), there was markedly greater cholinesterase inhibition in surviving heat-exposed quail compared with those reared at 26°C (e.g., brain acetylcholinesterase depression of 42% versus 12%). There were no differences in hepatic activities of parathion oxidase, paraoxonase, or paraoxon deethylase which could account for greater toxicity to chronically heat-exposed birds. In contrast, 4 mg parathion/kg wt elicited less plasma cholinesterase inhibition in cold-exposed quail compared to thermoneutral controls (e.g., <10% versus 48% depression after 24 hr). Increased liver weight and a doubling of paraoxonase activity may have been associated with greater tolerance to sublethal doses of parathion in chronically cold-exposed quail. These findings, together with limited field observations, indicate that the hazard associated with anticholinesterase exposure of wild birds is substantially influenced by environmental temperature.  相似文献   

3.
为明确氯吡脲对大鼠的毒性作用,采用150、300和600 mg/kg剂量分别向SD大鼠灌胃 (ig) 给予氯吡脲,每日1次,连续给药4周。每日观察大鼠的中毒状况和死亡情况,每周记录体质量和摄食量;于停药后第1天和第15天分别处死SD大鼠,检测血常规、血清生化和凝血功能;取主要脏器进行称量,计算其脏器系数并进行常规病理组织学检查。结果发现:连续给药4周,氯吡脲对大鼠体质量、摄食量、血常规和凝血均无明显影响。停药后第1天,与溶剂对照组比较,氯吡脲300 mg/kg及以上剂量处理组雄性大鼠的尿素氮和肌酐含量明显升高 (P < 0.05),600 mg/kg剂量组血糖显著升高 (P < 0.05),其中,600 mg/kg处理组雄性大鼠的尿素氮、肌酐和血糖分别是对照的1.9、1.6和1.3倍。氯吡脲300 mg/kg及以上剂量组雌、雄性大鼠的肾脏系数均明显升高 (P < 0.05),其中300 mg/kg剂量组雌、雄性大鼠的肾脏系数分别是对照的1.2和1.1倍,600 mg/kg剂量组雌、雄性大鼠的肾脏系数分别是对照的1.4和1.1倍;300 和600 mg/kg剂量组雌性大鼠的肝脏系数明显升高 (P < 0.01),分别是对照的1.3和1.9倍。病理切片检查可见肾脏病理组织学改变,主要表现为轻度肾管萎缩,明显的白细胞管型、透明管型、间质炎性细胞浸润及肾小管扩张。停药后第15天,上述毒性反应症状有所恢复。研究表明,SD大鼠经连续灌胃给予氯吡脲4周,在600 mg/kg剂量下表现为明显肾脏毒性反应,在300 mg/kg剂量下表现为较轻微的肾脏毒性反应,推测氯吡脲的主要毒性靶器官可能是肾脏;其未见明显毒性反应剂量为150 mg/kg。  相似文献   

4.
为阐明杀虫剂哌虫啶在SD大鼠体内的代谢动力学过程,以期为进一步的毒理学研究提供依据,采用所建立的高效液相色谱-串联质谱(HPLC-MS/MS)分析方法,测定了单次灌胃给药后大鼠血浆、组织(心、肝、脾、肺、肾、脑、骨骼肌、脂肪)、粪便和尿液样品中哌虫啶的含量,对该药在大鼠体内的吸收、分布和排泄进行了研究。结果表明:哌虫啶750 mg/kg单次经口灌胃给药,雌性大鼠血药浓度-时间曲线下面积(AUC)高于雄性大鼠,且达到峰值时间(T_(max))明显长于雄性大鼠,具有统计学差异,提示在此剂量下,哌虫啶在代谢及毒性效应上可能存在性别差异;在100~750 mg/kg受试剂量范围内,哌虫啶的平均半衰期为4~8 h,表观分布容积为10~30 L/kg,给药剂量与血药浓度-时间曲线下总面积(AUC_(0-inf))呈线性相关性(雄:r=0.996 4,雌:r=0.991 3)。组织分布试验表明,哌虫啶经口给药后,能迅速、广泛地分布到各组织中,并可有效地透过血脑屏障,其中肝、肾中哌虫啶的含量最高,提示其可能主要经肝、肾代谢。排泄试验显示,经尿液及粪便排出的原形哌虫啶含量极低,提示哌虫啶在大鼠体内可能发生广泛的代谢后再排出体外。  相似文献   

5.
化学发光酶联免疫分析法同时检测3种有机磷农药残留   总被引：2，自引：0，他引：2  
利用能同时识别对硫磷、甲基对硫磷和杀螟硫磷的宽谱特异性单克隆抗体,建立了同时测定这3种有机磷农药残留的化学发光酶联免疫分析方法（chemiluminescence enzyme immunoassay,CLEIA）,比较了间接竞争（ic-CLEIA）和直接竞争（dc-CLEIA）2种反应模式,优化了相关理化参数,确立了最适反应条件。结果表明:间接竞争CLEIA法检测对硫磷、甲基对硫磷和杀螟硫磷的抑制中浓度（IC50）分别为5.57、2.30和2.62 μg/kg,检测线性范围分别为0.39~100、0.39~25和0.39~25 μg/kg;直接竞争CLEIA法检测对硫磷、甲基对硫磷和杀螟硫磷的抑制中浓度（IC50）分别为5.43、1.34和1.24 μg/kg,检测线性范围分别为0.39~100、0.10~25和0.10~25 μg/kg。所建立的CLEIA方法基本能满足对硫磷、甲基对硫磷和杀螟硫磷在谷物和果蔬中最大残留限量的检测要求,为研制有机磷农药多残留检测试剂盒提供了技术依据。  相似文献   

6.
The main objective of this study is to investigate the 24 h kinetic effect of acute administration of malathion, an organophosphorus insecticide, on glucose homeostasis in adult rats. A single dose of malathion (400 mg/kg, 1/5 of LD50) was administered orally to rats, blood glucose was measured, liver and pancreas were removed to determine the level of hepatic glycogen, the activity of pancreatic acetylcholinesterase and butyrylcholinesterase, as well as the level of TBARs. Blood glucose increased in rats treated with a single dose of malathion. This effect was observed in the first hours of treatment, reached a 2.2 fold peak after 2 h, and then decreased after 4 h, followed by a decrease in the level of hepatic glycogen. The storage of glycogen starts from 6 to 12 h of administration. A decrease in cholinesterase activities was noted. The level of TBARs increased considerably in liver and pancreas. Results of this study can be explain by a stimulation of glycogenolysis and gluconeogenesis by liver, with a temporarily loss of endocrine functions of pancreas leading to hyperglycemia.  相似文献   

7.
Thirty-week-old female bobwhite quail (Colinus virgininus), maintained at 26 ± 1°C, were provided diets containing 0,25, or 100 ppm parathion ad libitum. After 10 days, birds were exposed to mild cold (6 ± 1°C) for 4, 8, 12, 24, or 48 hr. Brain acetylcholinesterase activity was inhibited in a dose-dependent manner in birds receiving 25 and 100 ppm parathion. Body weight, egg production, and plasma luteinizing hormone and progesterone concentrations were reduced in birds receiving 100 ppm parathion compared with other groups. Cold exposure did not alter plasma corticosterone levels in the 0- and 25-ppm parathion groups, but a two- to fivefold elevation of plasma corticosterone was observed in birds fed 100 ppm parathion. These findings indicate that (i) short-term ingestion of parathion can impair reproduction possibly by altering gonadotropin or steroid secretion, and (ii) tolerance to cold may be reduced following ingestion of this organophosphate.  相似文献   

8.
During subacute toxicological testing of PYR-VU-TO2, a novel cypermethrin-like pyrethroid with a high (150:1) cis: trans ratio, its distribution in skeletal muscle and internal organ tissues of two groups of experimental sheep was investigated after oral administration of two different doses (1/10 and 1/20 of the LD10). Residual levels of PYR-VU-TO2 were also observed in sheep blood after administration of a single dose of the compound. Homogenized internal organ tissues and blood samples were extracted in light petroleum distillate+acetone for 15 min. After filtration, the extract was cleaned up on a ‘Florisil’R and sodium sulfate layer. The pyrethroid elution was processed with acetone+light petroleum distillate (2+98 by volume). Recoveries ranged from 80.7 to 93.5%. Unchanged PYR-VU-TO2 residues were determined on a 1.5-m stainless steel packed column under isothermal conditions with an electron-capture detector. The results were evaluated by the calibration curve method. The coefficients of variation were generally lower than 5% and determination limit for PYR-VU-TO2 was 20 μg kg?1. Mean unchanged PYR-VU-TO2 residues lay within a wide range. After six weeks of treatment the following order of tissue residue levels could be stated: heart>lung>muscle>spleen>kidney>liver>brain, and spleen>muscle>lung>heart>liver>kidney>brain for experimental groups I and II, respectively. Only small differences between the residues in the tissues of males and females were found in the first group (daily PYR-VU-TO2 dose of 50 mg kg?1 live weight). The experimental females of the second group (daily PYR-VU-TO2 dose of 200 mg kg?1 body weight) revealed higher levels (other than spleen) than did the males. Maximum PYR-VU-TO2 residues in sheep blood were found 24 h after administration of a single dose. Confirmation of the results was carried out by determination of 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid methyl ester by capillary GC.  相似文献   

9.
The distribution and elimination of dicamba (3,6-dichloro-2-methoxy benzoic acid) and another isomer present in dicamba formulation (3,5-dichloro-2-methoxy benzoic acid) were studied in rats following single intravenous injections. Concentrations of dicamba and the isomer were measured at various times in whole blood by EC-GLC after extraction and derivatization with diazomethane. The isomer had different toxicokinetic parameters compared to dicamba. The elimination of dicamba from the blood was rapid with a biological half-life of 0.64 hr (following 100 mg/kg iv dose) while the elimination of the isomer from the blood was much slower with a biological half-life of 16.5 hr (following 20 mg/kg iv dose). However, upon combined dosing of the two compounds the elimination rate constant of dicamba significantly decreased. The isomer had a greater degree of binding to blood serum proteins than dicamba.  相似文献   

10.
This investigation concerns transport of DDT, dieldrin and parathion in the blood of the rat and roach. Using gel filtration, ion-exchange chromatography, and disc gel electrophoresis, a method for the isolation of some of the plasma proteins that bind DDT and dieldrin has been demonstrated. By a variety of staining procedures, these macromolecules were shown to be of a lipoprotein nature. A tentative molecular weight of 520,000 was obtained for one of the binding proteins in roach hemolymph.  相似文献   

11.
After male Wistar rats were fed a diet containing 25 ppm γ-hexachlorocyclohexane (γ-HCH) for 6 months, a single dose of [γ-3H]HCH was administered to each rat by gavage at a dose of 1 mCi/kg body wt. Renal specific activity of the γ-HCH-treated rats, especially that of the renal cortex, was significantly higher than that of a group of rats (controls) not previously treated with γ-HCH. Thin-layer chromatographic analysis of the petroleum ether fraction of renal homogenates indicated that the parent [γ3H]HCH amounted to more than 60% of the total radioactivity. Results of microautoradiography indicated that the silver grains shown in the epithelial cells of the renal proximal convoluted tubule were more dense. [γ-3H]HCH was probably mainly in the free form. The results obtained were consistent with the location and severity of the granular hyaline degeneration observed microscopically. One month following termination of γ-HCH treatment, the radioactivity and silver grains in the kidney sections were significantly decreased, while the pathological changes were gradually reversed.  相似文献   

12.
Mirex, an organochlorine compound, was administered as a single oral dose (100 mg/kg body wt) to both intact and adrenalectomized juvenile male Sprague-Dawley rats. Both mirex-treated intact and adrenalectomized animals (dosed 24 hr postsurgery) exhibited significant increases in liver weight to body weight ratios compared to controls. However, the liver weight to body weight ratios in mirex-treated intact animals were significantly greater than those observed in mirextreated adrenalectomized animals. Significant increases were observed in liver weight to body weight ratios in adrenalectomized animals treated with mirex 4 days after surgery. However, the 96-hr mortality in mirex-treated adrenalectomized animals increased from 20% (mirex dose given 1 day postadrenalectomy) to 56% (mirex dose given 4 days postadrenalectomy). Mirex treatment of intact and adrenalectomized animals had no significant effect upon either serum or hepatic activities of glutamic oxalacetic transminase, glutamic pyruvic transaminase, sorbitol dehydrogenase, or protein concentrations. Bromsulfophthalein clearance also was not affected by mirex treatment in adrenalectomized animals. Serum glucose concentrations were significantly decreased in both intact and adrenalectomized animals by mirex treatment. Daily corticosterone supplements to adrenalectomized animals restored liver hypertrophy and serum glucose concentrations to levels observed in mirex-treated intact animals. These results suggest that mirex-induced liver enlargement may be mediated by corticosterone.  相似文献   

13.
α-Hexachlorocyclohexane was administered as a single oral dose (100 mg/kg body wt) to both intact and adrenalectomized male Sprague-Dawley rats. In the intact rats there was a peak in [3H]thymidine incorporation into DNA at 30 hr and an increase in relative liver weight (liver weight/body wt × 100) which peaked at 60 hr post α-HCH dose. However, in α-HCH-dosed adrenalectomized rats [3H]thymidine incorporation into DNA remained elevated throughout the study period and relative liver weight was not significantly increased. In corticosterone-supplemented α-HCH-dosed Adx rats, [3H]thymidine incorporation into DNA was significantly reduced and RLW was increased comparable to that seen in intact animals. These results suggest that α-HCH-induced liver growth is mediated by corticosterone.  相似文献   

14.
The levels of peripheral acetylcholinesterase and carboxylesterases and their organophosphate sensitivities were studied in two populations of mosquitofish (Gambusia affinis). One population, highly resistant to organochlorine insecticides, demonstrated a low tolerance to parathion and methyl parathion. The organochlorine resistant fish possessed higher levels of both peripheral acetylcholinesterase and carboxylesterases. The sensitivities of these esterases to organophosphate inhibition were the same in both populations. The esterases were more sensitive to paraoxon than to methyl paraoxon. Carboxylesterases were far more sensitive to organophosphate inhibition than was acetylcholinesterase. Carboxylesterases, by their higher affinity for the organophosphates, may serve to protect acetylcholinesterase from inhibition.  相似文献   

15.
Exposure of Israeli agricultural spray pilots and ground crews to parathion was studied. Measurements were made with personal samplers contianing wet midget impingers; samples were analyzed by gas chromatography. Cockpit air exposure levels during 11-21-minute sampling periods for 12 flights ranged from nearly 0 to 430 microgram/m3. During sampling periods of 30 minutes to 4 hours the threshold limit value (TLV) of 100 microgram/m3 was exceeded in 2 of 19 instances. In seven measurements of ground crew exposures, TLV was not exceeded. Air washing with parathion resulted in airborne contamination of the ground level area at more than three times the TLV. Skin exposure data suggested that this route of exposure was significant for ground crew workers but not for pilots. Calculations based on the present data and standard absorption formula suggested that total daily intake for ground crew, but not for pilots, exceeded the Accepted Daily Intake (ADI) of 5 microgram/kg body weight. Sources of exposure and contamination for ground crew and pilots were identified. Recommended environmental control measures for parathion exposure should include cockpit air filtration, modification in flight patterns, paving landing areas, installation of hosing and drainage, NaOH neutralization point, and separate loading and unloading sites. Personal control measures were suggested as a supplement.  相似文献   

16.
Tissue distribution and excretion of the rodenticide, [14C] diphacinone (2-diphenylacetyl-1,3-indandione), following intragastric administration were investigated in male and female mice. The first body burden study tested 13 tissues plus excreta and utilized tissue digestion prior to counting. Plasma and whole blood were additionally tested in the second study; tissues and excreta were prepared for counting in a commercial sample oxidizer. Of the administered dose 76 and 68% were excreted in feces of male and female mice, respectively, by 48 hr during the first study. Accountability of the administered dose never exceeded 74%. The two studies revealed that liver had the highest specific activity followed by fallopian tubes, plasma, whole blood, and lungs. Adipose tissue contained the lowest concentration. In the second study, the specific activity increased in male liver up to 7.5 hr. Radioactivity in female livers peaked around hr 3. These were the only significant differences between sexes.  相似文献   

17.
The penetration of insecticides into houseflies, with and without the factor that delays penetration, was studied by measuring the amounts of the insecticides on the surface of the flies at intervals after treatment. The factor slowed the entry of all the insecticides tested, but its effect depended on the dose, and had little or no effect when the dose applied was big (20 μmUg/fiy). Penetration in all strains, susceptible and resistant, increased but not proportionally to the size of the dose. The rate insecticide was lost from the surface slowed with time and increasing age of the insects. It was faster in males than females, and was always faster in flies without the penetration factor. The differences in penetration between the flies with and without the factor was less with n-dodecane as solvent than with acetone. With all strains, rate of loss from the surface was slowest with dieldrin. Diazinon, parathion and chlorthion-ethyl were lost at about the same rate; diazoxon penetrated fastest.  相似文献   

18.
采用单次灌胃染毒法,通过高效液相色谱仪测定,研究了苯肽胺酸(N-phenylphthalamicacid,PPA)在大鼠体内的吸收、组织分布及排泄情况,以及其血药浓度经时变化过程和毒物动力学参数。结果表明:苯肽胺酸经消化道吸收速率较快,其半吸收期t1/2ka仅为(0.15±0.11) h,血药浓度的达峰时间(tmax)为(0.68±0.37) h,血药峰浓度(Cmax)值为(141.48±27.87) mg/L;苯肽胺酸在大鼠体内分布快且分布范围广,半分布期(t1/2α)为(0.22±0.18) h,表观分布容积(Vz/F)为(17.54±7.71) L/kg;苯肽胺酸从大鼠体内消除较快,其清除率(CLz/F)为(1.32±0.51) (L/h)/kg,在体内平均驻留时间(MRT(0-∞))为(25.69±2.93) h,消除半减期(t1/2z)为(7.77±1.44) h,约35 h后95%以上的苯肽胺酸可从大鼠体内消除。研究发现:苯肽胺酸的浓度-时间曲线呈现双峰现象,提示其在大鼠体内可能存在肠-肝循环。从大鼠灌胃染毒后至24 h内,被测各组织、脏器中均可检出苯肽胺酸,其浓度由高到低依次为:肾脏> 肺> 肝脏> 心脏> 脾脏> 肌肉> 睾丸> 脂肪> 大脑,肾脏中药物含量达192.7 μg/g,同时仅肾脏组织的靶向分布系数(te)值大于1(4.77),提示苯肽胺酸在大鼠体内分布时对肾脏具有相对较高的选择性。排泄物研究结果显示,苯肽胺酸随粪便排出的总量仅占给药量的1.45%,而尿液中未检出苯肽胺酸。  相似文献   

19.
Various methanesulfonates, notably of 3-isoxazolols, exhibit interesting insecticidal activity, especially against Musca domestica and Locusta migratoria. Although the symptoms of poisoning are very similar to those caused by parathion, no correlation between in-vitro inhibition of acetylcholinesterase and insecticidal activity was observed. This is also true for several methanesulfonates of hydroxy-heterocycles and phenols included in this study for comparison.  相似文献   

20.
The gene producing insensitive acetylcholinesterase in a tetrachlorvinphos-resistant strain of house fly was introduced into the genome of a susceptible strain. The resistance to a number of organophosphorus insecticides, which was high in the original strain (234- and more than 800-fold for paraoxon and tetrachlorvinphos, respectively), was much lower in the resulting strain, ranging from 53-fold for paraoxon to 3.9-fold for tetrachlorvinphos. Synergists further decreased these factors. The reduction in sensitivity of the acetylcholinesterase in vitro was about 20-fold for both inhibitors. The Michaelis parameters for hydrolysis of acetylcholine and acetylthiocholine of the mutant and normal acetylcholinesterase showed only minor differences. An increased rate of metabolism of the insecticides was found in the original strain. In vitro, glutathione-dependent detoxication was from 9- to 120-fold that of a susceptible strain, depending on the insecticide and the conditions used. The enzyme de-alkylated parathion and methylparaoxon, but there was no de-arylation of parathion, although it is important in other strains. In vitro, paraoxon and methylparaoxon were also hydrolysed, and this is not so in the susceptible strain. The high resistance present in the original strain seems to be due to joint action of at least three mechanisms.  相似文献   

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