Toxicity Of Propoxur Research Articles

A suspected intermediate syndrome and intussusception following propoxur toxicity in a dog

AbstractAn 8‐month‐old, mixed breed dog was referred because of vomiting, generalised muscle tremors and miosis. A few hours before the presentation, the owners saw the dog eating something during the daily walk. The dog was initially treated with fluids, atropine, dexmedetomidine, maropitant and midazolam. Complete blood exams showed a marked reduction of cholinesterase activity. Blood toxicology tests revealed the presence of propoxur. Twenty‐four hours after the presentation, the dog developed a small intestinal intussusception. After an initial improvement, the dog developed weakness and respiratory difficulties. The neurological examination showed obtundation, severe generalised muscle weakness of neck and limbs, reduced flexor reflexes in the four limbs and a short and shallow respiratory pattern, suggesting suspected intermediate syndrome. The dog's neurologic conditions progressively improved, and he was discharged 5 days after presentation with only mild impairment of the neck strength.

Time-Course Changes in Urine Metabolic Profiles of Rats Following 90-Day Exposure to Propoxur

As a major kind of carbamate insecticide, propoxur plays an important role in agriculture, veterinary medicine, and public health. The acute toxicity of propoxur is mainly neurotoxicity due to the inhibition of cholinesterase. However, little is known regarding the toxicity of propoxur upon long-term exposure at low dose. In this study, Wistar rats were orally administrated with low dose (4.25 mg/kg body weight/day) for consecutive 90 days. And the urine samples in rats treated with propoxur for 30, 60, and 90 days were collected and analyzed by employing 1H NMR-based metabolomics approach. We found that propoxur caused significant changes in the urine metabolites, including taurine, creatinine, citrate, succinate, dimethylamine, and trimethylamine-N-oxide. And the alteration of the metabolites was getting more difference compared with that of the control as the exposure time extending. The present study not only indicated that the changed metabolites could be used as biomarkers of propoxur-induced toxicity but also suggested that the time-course alteration of the urine metabolomic profiles could reflect the progressive development of the toxicity following propoxur exposure.

Status and preliminary mechanism of resistance to insecticides in a field strain of housefly (Musca domestica, L)

Resistance profiles of houseflies (Gol-RR) collected from a field in Golmud city, Qinghai province, China, were determined for seven insecticides using topical bioassays. Resistance ratios of >1219.51, 153.17, >35.43, 6.12, 3.24, 1.73, and 0.86-fold were obtained for propoxur, cypermethrin, imidacloprid, indoxacarb, chlorpyrifos, fipronil, and chlorfenapyr, respectively, relative to a laboratory susceptible strain (SS). Synergism experiments showed that piperonyl butoxide (PBO), triphenylphosphate (TPP), and diethyl maleate (DEM) increased propoxur toxicity by >105.71, >7.88, and >5.15-fold in the Gol-RR strain, compared with 5.25, 2.00, and 1.39-fold in the SS strain, indicating the involvement of P450 monooxygenases, esterases, and glutathione-S-transferase in conferring resistance. Although cypermethrin resistance was significantly suppressed with PBO, TPP, and DEM in the Gol-RR strain, the synergistic potential of these agents to cypermethrin was similar in the SS strain, demonstrating that metabolism-mediated detoxification was not important for conferring resistance to cypermethrin in the Gol-RR strain. However, the three agents did not act synergistically with imidacloprid, indicating that other mechanisms may be responsible for the development of resistance to this insecticide. Acetylcholinesterase (AChE) activity was 13.70-fold higher in the Gol-RR than in the SS strain, suggesting the properties of the AChE enzyme were altered in the Gol-RR strain. Thus, rotation of chlorfenapyr insecticide with other agents acting through a different mode with minimal/no resistance could be an effective resistance management strategy for housefly.

Evaluation of cytotoxicity, genotoxicity and embryotoxicity of insecticide propoxur using flounder gill (FG) cells and zebrafish embryos

Cytotoxicity, genotoxicity and embryotoxicity of carbamate insecticide propoxur were evaluated using flounder gill (FG) cells and zebrafish embryos. The cytotoxicity of propoxur in FG cells was analyzed by MTT, neutral red uptake (NRU), lactate dehydrogenase (LDH) release and Hoechst 33342 and propidium iodide double staining, and acute cytotoxic effects were observed in a concentration-dependent manner. The 24h-IC50 values of 89.96±1.04, 103.4±1.14 and 86.59±1.13μg/ml propoxur were obtained by MTT, NRU and LDH assays, respectively. The lethal effects were induced in FG cells mainly through necrosis but not apoptosis as evidenced by double fluorescence staining. Comet assay showed weak genotoxic effects and statistically significant DNA damages were recorded in the cells exposed to highest tested concentration of 75μg/ml propoxur (p<0.05). Propoxur exerted obvious acute toxic effects on the survival, spontaneous movement, hatching and heart rate, and development (yolk and pericardial sac edema) of zebrafish embryos in both time- and concentration-dependent manner only at ⩾100μg/ml. The corresponding 24h-, 48h- and 96h-LC50 values of propoxur in zebrafish embryos were 166.4±1.06, 146.3±1.07 and 134.8±1.06μg/ml, respectively. The above data obtained suggest a low acute toxicity of propoxur to the in vitro cultured FG cells and zebrafish embryos.

Applying Biofluid Metabonomic Techniques to Analyze The Combined Subchronic Toxicity of Propoxur And Permethrin in Rats

NMR combined with pattern recognition was recently introduced as a new technique for rapid xenobiotic toxicity evaluation. In this article, metabolic changes in the biofluid of rats after 90-day oral treatment with propoxur, permethrin and a combination of these two pesticides were investigated. Propoxur dosing induced increased urinary taurine, creatinine and glucose, whereas urinary lactate and acetate were increased in the highest permethrin dose group. Urinary acetate, alanine, lactate and trimethylamine levels were increased in the mixture group, accompanied by decreased urinary tricarboxylic acid cycle intermediates. In addition, the highest dose of the mixture displayed raised 3-D-hydroxybutyrate, acetate and lactate levels in the serum sample. Chronic exposure to a combination of propoxur and permethrin may induce hepatotoxicity and nephrotoxicity. An increase in acetate, alanine and formate in the urine could be a potentially sensitive biomarker of the chronic, combined effects of permethrin and propoxur.

Sublethal propoxur toxicity to juvenile common carp (Cyprinus carpio L., 1758): biochemical, hematological, histopathological, and genotoxicity effects

The sublethal toxicological and genotoxic potential of propoxur, a widely used carbamate insecticide against household pests, in veterinary medicine, and in public health, was evaluated on carp as a model species (Cyprinus carpio L., 1758) using the erythrocyte micronucleus test. Based on the 96-h lethal concentration, 50% (LC50) data from the U.S. Environmental Protection Agency ECOTOX Database (10 mg/L), a sublethal exposure concentration of 5 mg/L was used under static bioassay laboratory conditions. Histopathological evaluation showed no significant changes in spleen, intestine, muscle, or skin tissues. However, the following conditions were recorded: hyperemia, branchitis in primary lamella, and telangiectasis, hyperplasia, fusion, epithelial lifting, and epithelial desquamation in secondary lamella of gill tissues; hemorrhage, destruction, prenephritis, and inflammation and desquamation in the tubules; edema in the kidney; passive hyperemia, albumin, and hydropic degeneration in the liver; and hyperemia, chromatolysis, and glial proliferation in brain tissues. No statistically significant increases in micronuclei frequencies were found. Hematological parameters showed decreased hematocrit values and mean corpuscular volume values, as well as increased erythrocyte and leukocyte counts compared with the control group (p < 0.01). Plasma glucose, cholesterol, triglycerides, phosphorus, sodium, total plasma protein, chloride, and aspartate aminotransferase levels were increased (p < 0.01). Only plasma calcium and potassium levels decreased in the experimental group. Propoxur has an ecotoxicological potential on fish, a nontarget organism.

Evaluation of protective effect of bee pollen against propoxur toxicity in rat

In this study, 28 Wistar female rats (200–250 g) were used and divided into four equal groups. Group 1 was allocated as the control group. Groups 2–4 were administered 100 mg/kg/bw/day bee pollen, 20 mg/kg/bw/day propoxur, and 100 mg/kg/bw/day bee pollen plus 20 mg/kg/bw/day propoxur by gavage for 14 days, respectively. At the end of the 14th day, blood and tissues (the liver, kidney, brain, and heart) were collected from all animals. Oxidative stress markers (MDA, CAT, SOD, GSH-Px) and some other biochemical parameters (total protein, albumin, glucose, cholesterol, triglyceride, BUN, creatinine, uric acid, magnesium, sodium, potassium, chloride, total bilirubin, GGT, LDH, AST, ALT, and ALP) were analyzed. According to the data obtained, propoxur was determined to lead to negative changes in most of the biochemical parameters investigated and the administration of bee pollen was determined to alleviate these effects.

Effects of Propoxur on the Reproductive System of Male Rats

The reproductive toxicity of propoxur (2-isopropoxy-phenyl-N-methylcarbamate), a carbamate pesticide, was investigated in adult male Wistar rats exposed to 0, 1.73, 2.6, and 5.2 mg/kg body weight/day for 90 successive days. Results obtained from this study showed a significant (p < 0.05) concentration-dependent increase in food consumption, relative weights of testis, epididymis and kidneys with maximum effects observed at the highest dose of propoxur (5.2 mg/kg) compared to the control. On the contrary, there was a significant (p < 0.05) decrease in the body weight gain, sperm density, serum and intratesticular total cholesterol concentrations, and intratesticular total proteins in rats treated with propoxur at the dose of 5.2 mg/kg body weight. Propoxur had no significant effect on gestation, fertility and parturition indices, average birth weight, litter size and pups sex ratio of untreated female rats mated with treated males rats. These results suggested that propoxur increased food consumption, relative weight of reproductive and detoxication organs, decreased body weight gain and sperm density per gram of cauda epididymis without affecting the reproductive performances.

Effects of the synergists piperonyl butoxide and S,S,S-tributyl phosphorotrithioate on propoxur pharmacokinetics in Blattella germanica (Blattodea: Blattellidae).

Effects of the synergists piperonyl butoxide (PBO) and S,S,S-tributyl phosphorotrithioate (DEF) on propoxur pharmacokinetics were examined in the German cockroach, Blattella germanica (L.). Treatment of adult male German cockroaches with the cytochrome P450 monooxygenase inhibitor, PBO, or the esterase inhibitor, DEF, increased propoxur toxicity by 2- and 6.8-fold, respectively, implicating hydrolysis as a major detoxification route of propoxur in the German cockroach. However, significant hydrolytic metabolism could not be demonstrated conclusively in vitro resulting in a conflict between in situ bioassay data and in vitro metabolic studies. In vitro propoxur metabolism with NADPH-fortified microsomes produced at least nine metabolites. Formation of metabolites was NADPH-dependent; no quantifiable metabolism was detected with cytosolic fractions. However, microsomal fractions lacking an NADPH source did produce a low, but detectable, quantity of metabolites (1.6 pmol). PBO inhibited NADPH-dependent propoxur metabolism in a dose-dependent fashion, implicating cytochrome P450 monooxygenases as the enzyme system responsible for the metabolism. Interestingly, DEF also inhibited the NADPH-dependent metabolism of propoxur, albeit to a lower extent. Treatment with PBO or DEF also caused a significant reduction in the cuticular penetration rate of propoxur. The data demonstrate that unanticipated effects are possible with synergists and that caution must be exercised when interpreting synergist results.

Toxic interaction of tetraisopropylpyrophosphoramide and propoxur: Some insights into the mechanisms

Propoxur with a non-toxic dose (5 mg/kg) administered intraperitoneally (ip) in tetraisopropylpyrophosphoramide (iso-OMPA, 1 mg/kg) pretreated rats subcutaneously, sc) produced severe intoxication of anticholinesterase nature. The observed severity was comparable to that caused by an acute sublethal dose of propoxur (15 mg/kg) suggesting at least threefold potentiation of toxicity. Either drug given alone produced neither signs of toxicity nor alterations in acetylcholinesterase (AChE) activity, while carboxylesterase (CarbE) activity was markedly reduced indicating tremendous nonspecific binding. The administration of iso-OMPA followed by propoxur elicited inhibition of AChE to a critical level and produced severe intoxication. These results suggested that iso-OMPA induced potentiation of propoxur toxicity stemmed through irreversible inhibition of CarbE.

Fatal poisonings with propoxur

The insecticide propoxur (2-isopropoxyphenyl-N-methylcarbamate) acts by blocking cholinesterase. This inhibition is fast and, unlike that brought about by organophosphorus compounds, reversible. The toxicity of propoxur to man is stated to be low compared with that of parathion. Only a small number of fatal intoxications have been published; at the Würzburg University Institute of Legal Medicine eight cases have been observed since 1978. In seven cases death occurred after deliberate oral ingestion of solutions of propoxur with suicidal intent, while in the other, intoxication was accidental, following inhalation of an aerosol containing propoxur. Organs and body fluids were investigated toxicologically and histologically. The results are presented and discussed. Special attention is paid to the combination of propoxur and alcohol.

Sorghum (Sorghum bicolor) Seed Safeners as Insecticide Synergists

Certain oximes, including cyometrinil [(Z)-α-(cyanomethoxy)iminobenzeneacetonitrile], CGA-92194 [N-(1,3-dioxolan-2-yl-methoxy)-iminobenzeneacetonitrile], 2-pyridinealdoxime-O-benzyl ether (PA-B), and 2-pyridinealdoxime-O-phenethyl ether (PA-PE), which are known to protect sorghum from chloroacetanilide herbicides, increased the toxicity of the insecticide propoxur (o-isopropoxyphenyl-methyl carbamate) to a resistant strain of housefly (Musca domesticaL.). Flurazole [5-thiazolecarboxylic acid, benzyl ester, 2-chloro-4-(trifluoromethyl)], a nonoxime protectant for grain sorghum, had less effect on the toxicity of propoxur than did the oximes. Metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl)acetamide], which can be used as a herbicide in sorghum [Sorghum bicolor(L.) Moench.] only if the seed have been treated with a protectant, also increased the toxicity of propoxur to houseflies. Commercially available insecticide synergists increase insecticide activity by inhibiting NADPH-dependent microsomal mixed-function oxidase activity. Sorghum coleoptiles possessed the enzyme system necessary to oxidize aldrin (1,2,3,4,10,10-hexachloro-1,4,4a,5,8,8a-hexahydro-1,4-endo-exo-5,8-dimethanonaphthalene) to dieldrin (1,2,3,4,10,10-hexachloro-6, 7-epoxy-1,4,4a,5,6,7,8,8a-octahydro-1,4-endo-exo-5,8-dimethanonaphthalene), which is a standard test for oxidative metabolism in insects. Under the conditions of these tests, the aldrin epoxidase activity in sorghum coleoptiles was not affected by pretreatment with cyometrinil or flurazole.

Multiple Logit Analyses of the Effects of Temperature and Humidity on the Toxicity of Propoxur to German Cockroaches (Orthoptera: Blattellidae) and Western Spruce Budworm Larvae (Lepidoptera: Tortricidae)

The effect of temperature and humidity on the toxicity of propoxur to adult female German cockroaches, Blattella germanica (L.), was examined. With high humidity, propoxur was found to be least toxic near 25°C. At either temperature extreme (10 or 3.5°C), increased mortality indicated a quadratic relationship between temperature and mortality. Mortality also increased at low humidities. In contrast, the effect of temperature on the toxicity of propoxur to western spruce budworm, Choristoneura occidentalis Freeman, was a simple linear relationship which increased with increasing temperature. Exposure time was also related to changes in the toxicity of propoxur to the spruce budworm in both a linear and quadratic fashion. Multiple logit models were used to evaluate these multifactor toxicity experiments.

Unidirectional cross-tolerance between the carbamate insecticide propoxur and the organophosphate disulfoton in mice

Previous studies have shown that subchronic treatment of mice with the organophosphate insecticide, disulfoton, or the carbamate insecticide, propoxur, leads to the development of tolerance to their toxicity. Tolerance to disulfoton was due to a decrease in the number of muscarinic cholinergic receptors, while tolerance to propoxur appeared to be due to an induction of hepatic microsomal enzymes. In the present study we investigated if cross-tolerance between disulfoton and propoxur would occur. Cross-tolerance was evaluated by measuring acute toxicities, cholinesterase and carboxylesterase inhibition and hypothermic and antinociceptive effects. Mice tolerant to propoxur were cross-tolerant to the hypothermic and anticholinesterase effects of disulfoton. Similarly, when mice were pretreated with the microsomal enzyme inducer, phenobarbital, the toxicity of disulfoton was decreased. Mice made tolerant to disulfoton were cross-tolerant to the organophosphate chlorpyrifos, but were more sensitive than controls to the toxicity of propoxur. The acute toxicity of the organophosphate malathion was also increased in disulfoton-tolerant mice. Propoxur is metabolized by mixed function oxidases and possibly by a carboxylesterase. While hepatic microsomal enzymes appeared to be unchanged in disulfoton-tolerant mice, brain and liver carboxylesterase activities were significantly inhibited. Pretreatment of mice with the specific carboxylesterase inhibitor triorthotolylphosphate is known to greatly potentiate the toxicity of malathion and also potentiated, to a lesser extent, the toxicity of propoxur. The results indicate that chronic exposure to an anticholinesterase insecticide may lead to tolerance to the toxicity of the inducing compound by more than one mechanism and that the toxicity of other insecticides may be either increased or decreased.

Unidirectional Cross-Tolerance Between the Carbamate Insecticide Propoxur and the Organophosphate Disulfoton in Mice

Previous studies have shown that subchronic treatment of mice with the organophosphate insecticide, disulfoton, or the carbamate insecticide, propoxur, leads to the development of tolerance to their toxicity. Tolerance to disulfoton was due to a decrease in the number of muscarinic cholinergic receptors, while tolerance to propoxur appeared to be due to an induction of hepatic microsomal enzymes. In the present study we investigated if cross-tolerance between disulfoton and propoxur would occur. Cross-tolerance was evaluated by measuring acute toxicities, cholinesterase and carboxylesterase inhibition and hypothermic and antinociceptive effects. Mice tolerant to propoxur were cross-tolerant to the hypothermic and anticholinesterase effects of disulfoton. Similarly, when mice were pretreated with the microsomal enzyme inducer, phenobarbital, the toxicity of disulfoton was decreased. Mice made tolerant to disulfoton were cross-tolerant to the organophosphate chlorpyrifos, but were more sensitive than controls to the toxicity of propoxur. The acute toxicity of the organophosphate malathion was also increased in disulfoton-tolerant mice. Propoxur is metabolized by mixed function oxidases and possibly by a carboxylesterase. While hepatic microsomal enzymes appeared to be unchanged in disulfoton-tolerant mice, brain and liver carboxylesterase activities were significantly inhibited. Pretreatment of mice with the specific carboxylesterase inhibitor triorthotolylphosphate is known to greatly potentiate the toxicity of malathion and also potentiated, to a lesser extent, the toxicity of propoxur.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of propoxur on rats fed diets differing in protein content

In 6-week-old Wistar rats fed for 30 and 93 days either 4.5 or 26% casein diets containing 0, 500, 1500, 4500, and 9000 ppm of propoxur several biological changes were found which were more pronounced when propoxur was added to low-protein diet for 93 days, particularly in concentrations of 4500 and 9000 ppm. The changes were as follows. (1) In the liver—decreased activity of aromatic amino acids aminotransferases (AAA) and β-glucuronidase (β-GR) as well as diminished protein content in supernatant; unchanged activity of aspartate aminotransferase (AspAT), glucosephosphate isomerase (PHI) and fructosediphosphate aldolase (ALD). (2) In the serum—decreased activity of acetylcholinesterase (AChE) as well as β-GR and increased PHI activity; unaltered activity of ALD and sorbitol dehydrogenase, (SDH). (3) In the brain—decreased activity of AChE, PHI, ALD, AAA, reduced protein content in supernatant; unchanged activity of AspAT and biogenic amines level. (4) Decreased rate of rat body weight gain on contaminated normoprotein diet and weight loss on contaminated low-protein diet. (5) Changes in the relative weight of certain internal organs; no detectable anatomical changes in the examined organs. The acute oral toxicity of propoxur was definitely enhanced by the previous feeding of low-protein diet: 1.7 times in males and 1.3 times in females after 30 days, and after 93 days 4.3 and 2.7 times, respectively.

Microsomal oxidases in a cockroach, Gromphadorhina portentosa.

Enzymes effecting aldrin epoxidation and dihydroisodrin hydroxylation were studied in various tissues of Gromphadrohina portentosa Schaum, and optimal in vitro assay conditions were established. Enzyme activity was associated with the midgut, gastric caeca, fat body, and malpighian tubules and only slightly with the hindgut and crop. The enzymes in the midgut and caeca required NADPH and oxygen for optimum activity and were inhibited completely by carbon monoxide. Electron micrographs of various subcellular fractions from the midgut and caeca showed that enzyme activity was associated with a fraction comprising membranous vesicles derived from both the rough and smooth endoplasmic reticulum. Large variations in enzyme activity were observed through several in stars, and activity was lowest during the internymphal molts. These changes in enzyme activity correlate favorably with the toxicity of propoxur to cockroaches of different ages.