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PubMed1999

Comparative studies on tissue distributions of organophosphorus, carbamate and organochlorine pesticides in decedents intoxicated with these chemicals.

This paper describes the tissue distributions of dichlorvos, an organophosphate, chlorpyrifos-methyl, an organophosphorothioate, methomyl, a carbamate, and endrin, an organochlorine, in three individuals (Cases 1-3) who died after ingesting insecticidal preparations containing these chemicals. In Case 1 involving dichlorvos and chlorpyrifos-methyl, no dichlorvos was detected in most of the blood and tissue samples. Tiny amounts of dichlorvos (0.067 mg/L and 0.027 mg/L) were detected in the vitreous humor and cerebrospinal fluid, respectively. The chlorpyrifos-methyl concentrations in the blood samples were very site-dependent with a range of 0.615-2.24 mg/L. The tissue concentrations of chlorpyrifos-methyl were within the range 0.379-8.60 mg/kg. The total amounts of dichlorvos and chlorpyrifos-methyl in the stomach were 879 and 612 mg, respectively. The serum cholinesterase activity was 3 IU/L/37 degrees C. In Case 2 involving methomyl, the methomyl concentrations in the blood samples were very site-dependent with a range of 0.56-4.75 mg/L. The tissue concentrations of methomyl were 2.61 mg/kg or less, no methomyl being detected in the spleen, liver and kidney. The methomyl concentrations in the cerebrospinal fluid and vitreous humor were 5.37 and 4.75 mg/L, respectively. The stomach contained 85 mg methomyl. The serum cholinesterase activity was 73 IU/L/37 degrees C. In Case 3 involving endrin, the victim underwent medical treatment for 7 h after ingesting an endrin preparation. The differences in the endrin concentrations among the blood samples were small, with a range of 0.353-0.615 mg/L. The tissue concentrations of endrin were within the range 0.467-13.3 mg/kg. The endrin in the stomach (66 mg) was adsorbed almost completely on the activated charcoal that was administered for medical treatment.

Aged↗
PubMed1994

Genotoxic effects of the carbamate insecticide, methyomyl. II. In vivo studies with pure compound and the technical formulation, "Lannate 25".

The carbamate insecticide, methomyl, and the methomyl-containing technical formulation, "Lannate 25", were tested for the induction of DNA damage in vivo. Swiss CD1 mice were treated intraperitoneally with test substances and the following tests were performed: alkaline elution of liver and kidney DNA, 8-hydroxyguanosine detection in liver DNA, and 32P-postlabelling analysis of DNA adducts in liver DNA. The clastogenic activity of the two pesticide preparations was also evaluated as micronucleus frequency in bone marrow. No DNA adducts were detected in liver DNA of mice treated with pure methomyl, while a dose-related increase in DNA adducts was found in Lannate 25-treated animals. All other tests were positive with both methomyl and Lannate 25. A summary of genotoxic activity of methomyl is also presented. The hypothesis that the observed genotoxic effects of methomyl are induced indirectly, through formation of active oxygen species, is discussed.

Animals↗
PubMed1993

Mitochondrial dysfunction in yeast expressing the cytoplasmic male sterility T-urf13 gene from maize: analysis at the population and individual cell level.

The urf13TW gene, which is derived from the mitochondrial T-urf13 gene responsible for Texas cytoplasmic male sterility in maize, was expressed in Saccharomyces cerevisiae by targeting its translation product into mitochondria. Analysis by oxygraphy at the population level revealed that in the presence of methomyl the oxygen uptake of intact yeast cells carrying the targeted protein is strongly stimulated only with ethanol as respiratory substrate and not with glycerol, lactate, pyruvate, or acetate. When malate is the substrate oxidized by isolated mitochondria, interaction between the targeted protein and methomyl results in significant inhibition of oxygen uptake. This inhibition is eliminated and oxygen uptake is stimulated by subsequent addition of NAD+. Using 3,3'-dihexyloxacarbocyanine iodide [DiOC6(3)] as probe, interactive laser scanning and flow cytometry, which permit analysis at the individual cell level, demonstrated that specific staining of the mitochondrial compartment is obtained and that DiOC6(3) fluorescence serves as a measure of the membrane potential. Finally, it was shown that, as in T cytoplasm maize mitochondria, HmT toxin and methomyl dissipate the membrane potential of yeast mitochondria that carry the foreign protein. Furthermore, the results suggest that the HmT toxin and methomyl response is related to the plasmid copy number per cell and that the deleterious effect induced by HmT toxin is stronger than that of methomyl.

Carbonyl Cyanide m-Chlorophenyl Hydrazone↗
PubMed2002

Mechanisms of resistance to organophosphates in Tetranychus urticae (Acari: Tetranychidae) from Greece.

We investigated the mechanisms conferring resistance to methyl-parathion (44-fold) and to methomyl (8-fold) in Tetranychus urticae from Greece by studying the effect of synergists on the resistance and the kinetic characteristics of various enzymes in a resistant strain (RLAB) and a susceptible reference strain (SAMB). It is shown that S,S,S-tributyl phosphorotrithioate, a synergist that inhibits esterases and glutathione S-transferases, and piperonyl butoxide, a synergist that inhibits cytochrome P450 mediated monooxygenases, did not affect the level of methyl-parathion or methomyl resistance in RLAB and that resistance ratios to both insecticides did not change significantly in the presence of either synergist. Isoelectric focusing of esterase allozymes on single mites revealed no differences in staining intensity and glutathione S-transferase activity was not significantly different in the two strains. The activity of two cytochrome P450 monooxygenase groups was compared. No significant difference of 7-ethoxyresorufin-O-diethylase activity was observed between strains that were two-fold higher in RLAB than in SAMB. The kinetic characteristics of acetylcholinesterase, the target enzyme of organophosphates and carbamates, revealed that acetylcholinesterase in RLAB was less sensitive to inhibition by paraoxon and methomyl in comparison with SAMB. I(50), the inhibitor concentration inducing 50% decrease of acetylcholinesterase activity was greater (119- and 50-fold with paraoxon and methomyl, respectively) and the bimolecular constant k(i) was lower (39- and 47-fold with paraoxon and methomyl, respectively) in RLAB compared to SAMB.

Acetylcholinesterase↗
PubMed1998

The efficacy of entomopathogenic nematodes for controlling housefly infestations of intensive pig units.

The efficacy of the entomopathogenic nematodes Steinernema feltiae and Heterorhabditis megidis after formulation into a housefly bait was compared with a commercial bait formulation of methomyl for the control of houseflies in a U.K. pig farm. The housefly infestation was confined to the farrowing unit, which consisted of ten farrowing houses, where two adjacent houses were sequentially re-stocked with pregnant sows at weekly intervals. Shortly after re-stocking, one house was baited with one of the nematode species and the other with methomyl. Significantly fewer flies (P < 0.05) were counted in the houses baited with either S. feltiae or H. megidis than those baited with methomyl. The efficacy of S. feltiae sprayed on to the manure was also compared with methomyl bait. Counts of houseflies carried out in the farrowing cycle before this treatment were not significantly different (P > 0.05); however, significantly fewer flies (P < 0.05) occurred after S. feltiae was sprayed. The efficacy of encapsulated S. feltiae was also compared with methomyl bait and no significant difference was observed (P > 0.05).

Agriculture↗
PubMed1993

Baculovirus expression of the maize mitochondrial protein URF13 confers insecticidal activity in cell cultures and larvae.

The URF13 protein, which is encoded by the mitochondrial gene T-urf13, is responsible for cytoplasmic male sterility and pathotoxin sensitivity in the Texas male-sterile cytoplasm (cms-T) of maize. Mitochondrial sensitivity to two host-specific fungal toxins (T toxins) is mediated by the interaction of URF13 and T toxins to form pores in the inner mitochondrial membrane. A carbamate insecticide, methomyl, mimics the effects of T toxins on isolated cms-T mitochondria. URF13 was expressed in Spodoptera frugiperda (fall army-worm) cells (Sf9) in culture and in Trichoplusia ni (cabbage looper) larvae with a baculovirus vector. In insect cells, URF13 forms oligomeric structures in the membrane and confers T toxin or methomyl sensitivity. Adding T toxin or methomyl to Sf9 cells producing URF13 causes permeabilization of plasma membranes. In addition, URF13 is toxic to insect cells grown in culture without T toxins or methomyl; even a T-toxin-insensitive mutant form of URF13 is lethal to cell cultures. Baculoviruses expressing URF13 are lethal to T. ni larvae, at times postinjection comparable to those obtained by injecting a baculovirus expressing an insect neurotoxin. This result suggests that URF13 could be useful as a biological control agent for insect pests. Our data indicate that URF13 has two independent mechanisms for toxicity, one that is mediated by T toxin and methomyl and one that is independent of these toxins. Similarly, male sterility and toxin sensitivity in cms-T maize may be due to independent mechanisms.

Animals↗
PubMed2006

Variation of Musca domestica L. acetylcholinesterase in Danish housefly populations.

Anti-cholinesterase resistance is in many cases caused by modified acetylcholinesterase (MACE). A comparison was made of toxicological data and AChE activity gathered from 21 field populations and nine laboratory strains of houseflies, Musca domestica L., to elucidate the best way of generating data to provide advice for management strategies and gathering information for resistance risk assessment on the organophosphates azamethiphos and dimethoate and the carbamate methomyl, which have been the primary insecticides used against adult houseflies in Denmark. Cluster analysis was performed and > 2000 houseflies were assigned to one of three phenotypes based on total acetylcholinesterase activity as well as inhibition by azamethiphos, methomyl or omethoate. A cluster, i.e. a phenotype, with high total AChE activity and high sensitivity to azamethiphos and less sensitivity to inhibition by methomyl and omethoate was shown to be linked to methomyl resistance. It was not possible to define any clusters that could be linked to azamethiphos or dimethoate resistance. The five mutations V180L, G262A, G262V, F327Y and G365A causing anticholinesterase resistance in houseflies were all identified in the Danish housefly strains. The data are very heterogeneous, and a correlation of molecular genetic background and resistance of phenotypes is not obvious with the available data.

Acetylcholinesterase↗