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1.
The oral toxicity of 5-benzyl-3-furylmethyl-(1R, cis)-chrysanthemate (cismethrin) to female rats decreased as their environmental temperature was raised. Acute oral LD50 values increased from 157 mg/kg at 4°C to 197 mg/kg at 20°C and to > 1000 mg/kg at 30°C. Cismethrin was much more toxic given intravenously when the LD50 was 4.5 mg/kg. This value did not change at different environmental temperatures. Irrespective of the environmental temperature, or route of adminstration, following the respective LD50's cismethrin caused tremors in rats when brain levels of 0.5–1.0 μg/g were reached and, at death, brain concentrations were 3.9–5.1 μg/g. These results suggested that the accumulation of cismethrin by the brain could be used as a model for the nervous system as a whole. The isomeric 5-benzyl-3-furylmethyl-(1R, trans)-chrysanthemate (bioresmethrin) was about 50 times less toxic to rats than cismethrin. After an intravenous LD50, tremors started when brain concentrations were 4–5 μg/g. At death, brain levels were 25–35 μg/g. Plasma esterases were about equally active in hydrolysing cismethrin and bioresmethrin, whereas liver microsomal esterases hydrolyzed bioresmethrin over 10 times more rapidly than cismethrin. It is suggested that the lower toxicity of bioresmethrin is not only due to its faster metabolism but to an intrinsically lower toxicity at the critical site of action in the nervous system.  相似文献   

2.
Capillary gas-liquid chromatographic analysis of seven commercial samples of bioresmethrin [5-benzyl-3-furylmethyl (1R)-trans-chrysanthemate] demonstrated that each contained toxicologically significant amounts (1-5%) of the (1R)-cis-isomer (cismethrin) as an impurity. Intravenous injection of the labelled compounds to rats indicated that the concentrated solutions of these compounds may precipitate in the blood and subsequently become trapped in the lung. Slow release of the toxic isomer impurity probably accounts for the delay in appearance of symptoms after intravenous administration of impure bioresmethrin. Similarly, higher doses of cismethrin can be tolerated when concentrated solutions are administered intravenously.  相似文献   

3.
The distribution of 14C-acid-, 14C-alcohol-, and 14C-cyano-labeled deltamethrin and selected metabolites were followed in the liver, blood, cerebrum, cerebellum, and spinal cord after iv administration of a toxic, but nonlethal dose (1.75 mg/kg) to rats. Approximately 50% of the dose was cleared from the blood within 0.7–0.8 min, after which the rate of clearance decreased. 3-Phenoxybenzoic acid (PBacid) was isolated from the blood in vivo, and was also the major metabolite when 14C-alcohol-labeled deltamethrin was incubated with blood in vitro. Deltamethrin levels in the liver peaked at 7–10 nmol/g at 5 min and then decreased to 1 nmol/g by 30 min. In contrast, peak central nervous system levels of deltamethrin were achieved within 1 min (0.5 nmol/g), decreasing to 0.2 nmol/g at 15 min, and remaining stable until 60 min. peak levels of deltamethrin did not correspond to the severity of toxicity, although the levels of non-pentane-soluble radiolabel did appear to correlate with motor signs of toxicity. Experiments with brain homogenates, using in vivo concentrations of deltamethrin, failed to reproduce the pentane-unextractable radioactivity in vitro nor was any metabolism demonstrated.  相似文献   

4.
Abstract

Laboratory studies were carried out to determine the course of poisoning and toxicity of some synthetic pyrethroid insecticides (bioresmethrin, cismethrin, cypermethrin, deltamethrin, fenpropathrin, fenvalerate and permethrin) against the desert locust. From doses in excess of the LD99 all the insecticides were quick acting; from doses of about the LD99 or less the insects are rapidly knocked down or show symptoms of poisoning, but may recover. The symptoms which follow treatment by the various insecticides are described. Although these insecticides are all highly toxic to locusts there are many other insecticides which are similarly toxic, can be sprayed at high concentrations and are much cheaper.  相似文献   

5.
Solutions of tetramethrin, RU 11679, or cismethrin caused uncoupled convulsions in 30–40 min in exposed thoracic ganglia from SNAIDM house flies at concentrations down to 10?10M: whereas these same compounds at 10?6M concentrations failed to produce poisoning symptoms when perfused onto the exposed ganglia of the kdr strain of house fly. The pyrethroid analogs examined had a negative temperature coefficient of action on the exposed thoracic ganglia from SNAIDM flies. DDT and GH-74 possessed positive temperature coefficients of action on the exposed thoracic ganglion of susceptible house flies. It is concluded that the central nervous system of the kdr strain of house fly is resistant to pyrethroid action; furthermore, the resistance appears to be widespread throughout the house fly nervous system, involving sensory, motor, and central neural elements.  相似文献   

6.
The tissue distribution and excretion of [14CH3S]methamidophos was followed in female Sprague-Dawley rats after intravenous injection at a toxic, but nonlethal, dose (8 mg/kg). Radiolabel was rapidly distributed to all tissues at approximately equal concentrations. Peak tissue levels were achieved within 1–10 min except in the central and peripheral nervous system where peak levels (40 nmol/g) were found between 20 and 60 min, corresponding to peak signs of toxicity. Within 24 hr of dosing, 47% of the radioactivity was recovered in the urine and 34% as 14CO2 with <5% in the feces over 7 days. Cholinesterase (ChE) inhibition was measured in erythrocytes, plasma, and various regions of the central nervous system (CNS) at selected times after administration of methamidophos at 8 mg/kg. The degree of acetylcholinesterase (AChE) inhibition in the three CNS regions was similar, reaching a minimum of 15–20% of control values at 30–60 min, when toxicity was most severe. The degree of erythrocyte AChE inhibition was less than that of the CNS although the time course was similar. Plasma ChE inhibition was more rapid than that of the CNS or erythrocytes and reactivation was slower. When similar concentrations of methamidophos to those found in vivo were incubated with CNS homogenates, plasma, or erythrocytes in vitro (5 × 10?5M) a similar degree of inhibition occurred over the same time course. It is, therefore, concluded that the cholinergic toxicity produced by methamidophos is a result of the in vivo stability of this compound combined with its entry into the nervous system in sufficiently high concentrations to inhibit AChE.  相似文献   

7.
The metabolism of the chiral isomers of 35S-labeled fonofos was examined in the house fly and white mouse. Metabolism of the chiral isomers of fonofos oxon also was investigated in the mouse. Little difference in either the rate of penetration or pattern of metabolism was observed between house flies treated with the (R)P and (S)P enantiomers of fonofos. At the higher dosage of 8 mg/kg the less toxic (S)P enantiomer was degraded in mice and eliminated in significantly larger amounts than (R)P-fonofos. However, at the sublethal dosage of 4 mg/kg little difference in degradation and total elimination was observed between the two isomers although the excretion rate appeared to be faster initially with the less toxic enantiomer. Overall, metabolism and excretion of the chiral isomers of both fonofos and fonofos oxon took place more rapidly and to a greater extent with the less toxic enantiomer.  相似文献   

8.
The dissipation rate of endosulfan isomers (α and β) in seawater and sediment was studied. The disappearance rate of both isomers from seawater and pure water was compared, and the same measurements were made in both sterile and unsterile marine sediment. Flasks of water and sediment, fortified with a dispersion of a commercial endosulfan 350 g litre−1 EC, Protodan 35®, were incubated under laboratory light at room temperature for 82 days. A micro on‐line extraction method and GC‐ECD was used to determine the pesticide and its metabolites. The dissipation of endosulfan (in two phases of first‐order kinetics) occurred more rapidly in seawater than in pure water. At the end of the experiment, the concentration of α‐endosulfan in sterile sediment was four times greater than in unsterile sediment, while the dissipation rate of β‐endosulfan in unsterile sediment was approximately double that observed in sterile sediment. The dissipation of both forms in sediment occurred in a single stage. Endosulfan β‐isomer was more persistent than α‐isomer in both sterile and unsterile sediment. Dissipation of endosulfan sum of α‐ and β‐isomers in sediment at the end of the experiment ranged from 80% (sterile) to 95% (unsterile). Endosulfan sulfate was detected in water and sediment as the main metabolite. © 2000 Society of Chemical Industry  相似文献   

9.
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   

10.
Comparisons of the susceptibility of several strains of adult Aedes aegypti were made. Mosquitoes from Bangkok and Jakarta were found to be highly resistant to DDT and resistant to pyrethroids relative to a laboratory strain. A strain from Singapore, where less DDT has been used, was susceptible to DDT and pyrethroids. Two strains from the Caribbean had LC50 values to DDT 3 times that of the reference strain while the LC50 values against bioresmethrin synergised with piperonyl butoxide were 1 1/2 times raised. Another two strains from central Africa were 2 times tolerant of DDT and 1 1/2 times tolerant of bioresmethrin plus piperonyl butoxide. Agents which block DDT-dehydrochlorinase, esterases and oxidases each caused small increases in the mortality of the Bangkok strain due to DDT and bioresmethrin as well as augmenting toxicity to the susceptible reference strain. It is tentatively suggested that resistance in the Bangkok strain is due to a combination of the actions of these and perhaps other resistance mechanisms.  相似文献   

11.
The metabolism and transport of [14C]-naphthol were investigated in sacs of rat small intestine to better understand metabolism of the pesticide carbaryl (which contains naphthol) in the intestine. The capacity to synthesize polar 14C-labeled metabolites was approximately saturated at 50 μM naphthol. The metabolic capacity of the cranial small intestine was about two times the capacity of the caudal. Anaerobic incubation severely suppressed naphthol metabolism. Sodiumfree medium suppressed metabolism only slightly but altered transport of water and of the polar 14C-labeled metabolites to serosal and mucosal fluids; the effect on metabolite transport cannot be explained by the effects of sodium on water movements, however. Calcium-free medium did not affect metabolism or metabolite transport; 2,4-dinitrophenol, and possibly phlorizin, but not ouabain, suppressed naphthol metabolism in specific regions of the intestine. Each of the three inhibitors altered metabolite transport. It is concluded that the capacity to conjugate naphthol in the small intestine is greater in the cranial than caudal regions; the quantity of naphthol taken up from the medium is proportional to the rate of formation of the polar metabolite, naphthyl glucuronide; addition of 2,4-dinitrophenol, phlorizin, or ouabain, or deletion of sodium, perturbed the transport of the polar metabolite, but the perturbance could not be explained by the effect on rate or direction of fluid transfer and indicated an effect on cellular permeability or on transport mechanisms; the effect of the three inhibitors and possibly of elevated naphthol concentrations (to 520 μM) in the medium on metabolite transport may be by a sodium interaction; the latter suggests that naphthol may be toxic to the intestine at concentrations approaching 100 to 1000 μM.  相似文献   

12.
The resolved isomer of metolachlor, S-metolachlor, was registered in 1997. New formulations based primarily on the S-metolachlor isomer are more active on a gram for gram metolachlor basis than formulations based on a racemic mixture of metolachlor containing a 50:50 ratio of the R and S isomers. The labelled use rates of S-metolachlor-based products were reduced by 35% to give equivalent weed control to metolachlor. However, several companies have recently registered new metolachlor formulations with the same recommended use rates for weed control as S-metolachlor. This research was done to compare the soil behaviour and the biological activity of metolachlor and S-metolachlor in different soils under greenhouse and field conditions. Although K(d) ranged from 1.6 to 6.9 across the five soils, there were no differences in the binding of metolachlor and S-metolachlor to soil or in the rate of soil solution dissipation in a given soil. However, both greenhouse and field studies showed that S-metolachlor was 1.4-3-fold more active than metolachlor against Echinochloa crus-galli (L.) Beauv. in five different soils and that S-metolachlor was more active than metolachlor in three Colorado field locations. When the rates of metolachlor and S-metolachlor were adjusted for S isomer concentrations in the formulations, there were no differences between the formulations in field, greenhouse or bioassay studies. Thus herbicidal activity is due to the S isomers, with the R isomers being largely inactive.  相似文献   

13.
The effect of a single low dose of parathion on renal water and electrolyte excretion was studied in anesthetized mongrel dogs. Sodium excretion significantly increased 20 min after iv administration of 1.5 μg parathion/kg body wt, while urine output slightly increased and potassium excretion significantly decreased. No change was observed in glomerular filtration rate, renal plasma flow, filtration fraction, and plasma sodium concentration. Respiratory frequency, heart rate, and arterial blood pressure remained unchanged throughout the experiments. With the doses used, no inhibition of acetylcholinesterase in red blood cells or renal tissues was found. The administration of a single dose of 1 μg atropine sulfate/kg body wt iv had no effect in all the parameters measured but was able to completely block the natriuretic effect of parathion when given ten minutes prior to parathion. Since the dose used showed no inhibitory effect on acetylcholinesterase, it is unlikely that the natriuretic effect of parathion could be due to changes in enzyme activity but rather to conformational changes in tubular membranes altering sodium reabsorption.  相似文献   

14.
The cis and trans isomers of the synthetic pyrethroid resmethrin, labelled with radiocarbon in either the alcohol or acid moiety, were individually administered orally to White Leghorn laying hens at a dosage of 10 mg kg?1. With each isomer and label position, greater than 90% of the radiocarbon was eliminated in the excreta within 24 h after the treatment. Radiocarbon residues in the egg white and yolk fractions were low, with peak levels observed 1 and 4-5 days after treatment in white and yolk, respectively. In birds sacrificed 12 h after treatment, radiocarbon residues in tissues were low; the highest levels were found in the liver and kidney.  相似文献   

15.
A study of the toxico‐kinetics, recovery percentage from different substrates, cytotoxicity and role of cytochrome P450 and b5 of liver microsome in the metabolism of deltamethrin were carried out in female black Bengal goat. The ALD50 value of deltamethrin in goat by intravenous route lies between 0.2 and 0.6 mg kg?1. Intravenous disposition kinetics using a dose of 0.2 mg kg?1 showed that the maximum blood concentration of deltamethrin was recorded at 0.5 min, followed by rapid decline, and a minimum concentration was detected at 6 min after administration. The following values were obtained : Vdarea 0.148 (± 0.02) litre kg?1; t1/2 (α) 0.22 (± 0.02) min; t1/2 (β) 2.17 (± 0.37) min; Kel 1.05 (± 0.24) min?1; AUC 4.30(± 0.45) µg min ml?1; ClB 0.05 (± 0.006) litre kg?1 min?1; T～B 1.93 (± 0.58); fc 0.40(± 0.05). After 10 min, liver retained the maximum residue, and heart, adrenal gland, kidney, spleen, fat and brain also held the insecticide; liver, fat, heart and spleen retained residue after 30 min, and bone, liver and fat retained residue after 60 min of intravenous administration. Oral absorption of deltamethrin was poor and inconsistent, and approximately 65% of administered dose was recovered from faeces and gastrointestinal contents. The excretion of deltamethrin through urine was meagre, and only 0.01 and 0.013% of the administered dose was recovered after 3 and 5 days of oral administration respectively. All the tissues retained the residue after 3 days; while fat, rumen, reticulum, omasum, abomasum, large and small intestine and bone retained the residue after 5 days of oral administration; and the percentage recoveries were 1.73 and 0.027 respectively. Deltamethrin reduced the level of cytochrome P450 content of liver microsomal pellet of goat after 5 days of oral administration. Histopathological examination of liver, kidney, heart, spleen brain and lung sections of treated goats did not reveal any pathological changes. © 2001 Society of Chemical Industry  相似文献   

16.
Analogs of aldrin and dieldrin have been synthesized, the molecules of which lack a methylene bridge but have two methyl groups attached to olefinic or oxirane ring carbon atoms. Their metabolism was studied using NADPH-supplemented 12,000g × 30-min supernate of livers from Wistar and CD strains of rats. The dimethylated olefin was not metabolized to its epoxide but was converted by supernate of liver from rats of both sexes to a labile hydroxylated metabolite. Exogenous NADPH increased the rate at which the olefin was metabolized, but concentrations of NADPH which increased the yield of the labile metabolite when added to female rat liver preparations decreased the yield when added to those from the male. This metabolite had a mass spectrum which was consistent with it being a hydroxymethyl derivative. The dimethylated epoxide was metabolized more slowly than the olefin, and a notable sex difference in the route of metabolism was evident. With supernate from livers of female rats the only metabolite detected by gas-liquid chromatography had a mass spectrum consistent with it being a ring-hydroxylated epoxide. Male rat liver supernate formed small quantities of the same compound, but the major metabolite had a mass spectrum indicative of a hydroxymethyl epoxide. No hydrolysis of the oxirane ring of the epoxide has been detected. The relevance of these results to the planned synthesis of cyclodienes of optimal biodegradability is mentioned.  相似文献   

17.
An esterase or esterases in acetone powder preparations of mouse liver microsomes hydrolyze the cyclopropanecarboxylate ester linkage of pyrethroid insecticide chemicals derived from primary alcohols. The rate of cleavage of (+)-trans-chrysanthemates with various alcohol moieties decreases in the following order: 5-propargyl-2-furylmethyl; 5-benzyl-3-furylmethyl (bioresmethrin); 3-phenoxybenzyl; tetrahydrophthalimidomethyl esters. The hydrolysis rate of benzylfurylmethyl esters with various acid moieties decreases in the order: (+)- or (?)-trans-chrysanthemate; (+)-trans-ethanochrysanthemate; tetramethylcyclopropanecarboxylate; (+)- or (?)-cis-chrysanthemate or (+)-cis-ethanochrysanthemate. The trans-isomers of chrysanthemates and ethanochrysanthemates are hydrolyzed from 2.6- to more than 50-fold more rapidly than the corresponding cis-isomers. This enzyme system does not hydrolyze secondary alcohol esters, i.e., allethronyl (+)-trans- and (+)-cis-chrysanthemates.On intraperitoneal administration to mice, the (+)-trans-chrysanthemate and -ethanochrysanthemate of benzylfurylmethanol are of very low toxicity relative to the corresponding (+)-cis-isomers and the tetramethylcyclopropanecarboxylate. S,S,S-tributyl phosphorotrithioate (DEF) pretreatment increases the toxicity of these five compounds by 2.6- to more than 188-fold, with the exception of bioresmethrin whose toxicity is not altered. When the toxicity is increased, it is probably the result of esterase inhibition since DEF strongly inhibits the esterase activity of fresh liver microsomes while the mixed-function oxidase system remains active. The oxidase system metabolizes the chrysanthemates more rapidly than the ethanochrysanthemates of benzylfuryl-methanol. Depending upon the pyrethroid involved, the esterase or the mixed-function oxidase system, or both may be responsible for limiting the toxicity of these pyrethroids to mice.  相似文献   

18.
Experiments were conducted with the freshwater fish Macrognathus aculeatum to study the toxicity and metabolism of endosulfan and the effect of the pesticide on the oxygen consumption and total nitrogen excretion. The 96-hr LC50 value was 3.5 ± 0.2 ppb. In brain, gills, gut, liver, and kidney, endosulfan was metabolized to endosulfan sulfate, but this appears to be only an intermediary step as the nontoxic endosulfan ether was found only in the liver and kidney, the principal organs of elimination of toxicants in fish. The pesticide, both at sublethal and lethal concentrations, decreased oxygen consumption and total nitrogen excretion.  相似文献   

19.
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20.
These data were obtained by use of a total and continuous portal vein fistula which virtually eliminated vascular redistribution of compounds absorbed from the gastrointestinal tract to nondigestive tissues (i.e., liver). The method allows direct measurement of the compounds absorbed, which is especially important in metabolism studies of ingested toxic compounds. These studies demonstrated that in vivo metabolism did occur within the intestine during the process of absorption of the pesticide carbaryl (naphthyl N-methylcarbamate) and naphthol, the hydrolysis product of the pesticide. Portal absorption of naphthol from a liquid diet (46 ± 4% of dose/120 min) was slower than from Ringer medium (75 ± 1%/120 min); portal absorption accounted for 82 ± 8 and 83 ± 4%, respectively, of the 14C absorbed from the intestine. The proportion of hydrophilic 14C-metabolites (water soluble) in portal blood varied from 6 to 89% and was a function of the substrate, dose vehicle (liquid diet vs Ringer), and time of portal fluid collection. Metabolism in the small intestine before absorption was confirmed for both substrates. The principal lipophilic constituent in portal fluid was the unmetabolized substrate for both carbaryl and naphthol; the principal ampholyte metabolite was naphthyl glucuronide. Although these in vivo data are qualitatively similar to evidence from previous in vitro studies, this in vivo evidence demonstrated that the extent of metabolism (and possibly detoxication) was considerably less than would be predicted from in vitro studies and indicates that the hazard of ingestion of carbaryl and other lipophilic toxic agents may be greater than realized.  相似文献   

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