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Inhibition of monocyte esterase activity by organophosphate insecticides.

Organophosphate insecticides, such as Vapona, Naled, and Rabon, are highly potent inhibitors of an enzyme found in human monocytes. The enzyme, a specific monocyte esterase, could be inhibited by Vapona in blood samples via airborne contamination at levels easily achieved from commercial slow-release insecticide strips. Fifty percent inhibition (I50)--as measured on the Hemalog D (Technicon Corp.)--occurred at solution concentrations of 0.22, 1.5, and 2.6 X 10(-6) g/liter for Vapona, Rabon, and Naled, respectively. Parathion (a thiophosphate) and Baygon (a carbamate) were less potent, with I50 values of 3.7 X 10(-5) and 1.5 X 10(-4) g/liter, respectively. Dursban (another thiophosphate) and Carbaryl (a carbamate) showed only marginal inhibition. Eserine, malathion, nicotine and pyrethrum had no inhibitory effect up to 0.5 g/liter. The occurrence of this effect in vivo has not yet been shown, nor is it clear what the implications of such an effect would be. The inhibition of this enzyme by airborne contaminants, however, may interfere with the proper functioning of the Hemalog D.

Esterases↗

Insecticidal activity of some new synthetic compounds against different mosquito species.

Insecticidal activity of an organosilane (HOE 84498, OMS 3055), Organophosphorous (MAT 9460, OMS 3052) and a synthetic pyrethroid compound (Trebon, OMS 3002) was evaluated against adult and larval stages of eight species of mosquitoes. Insecticidal activity of these compounds was limited to larval stages only. Highest activity of HOE 84498 was found against both Cx. tritaeniorhynchus and Anopheles culicifacies (LC50-0.0065 mg/I), MAT 9460 against Armigeres subalbatus (LC50-0.00043 mg/I) and Trebon against Cx. quinuefasciatus (LC50-0.00579 mg/I). Adulticidal effect was observed at higher dosages of 25-100 ug/cm2 of MAT 9460 and HOE 84498 against all the species with LT50 ranging from 22.15-33.76 min. No appreciable residual effect was evident for the three compounds on the surfaces treated at the rate of 1-100 mg/m2 against any mosquito species.

Animals↗

[Insecticidal properties of sumitrin].

The study of insecticidal properties of sumitrin demonstrated that in contact action it was a highly effective insecticide; in topical application LD50 for domestic flies, bedbugs and cockroaches was 0.47, 1.25 and 3.26 mug/g, respectively. Sumitrin possessed high action selectivity for insects and low toxicity for warm-blooded animals (LD50 for albino mice greater than 7500 mg/kg). In the form of aerosols sumitrin and its mixtures with DDVF were less active than compositions on the neopinamine base.

Aerosols↗

Ion channels as targets for insecticides.

Most insecticides are neurotoxicants causing various forms of hyperexcitation and paralysis in animals. A variety of neuroreceptors and ion channels have been identified as the major target sites of these neurotoxic insecticides. This paper gives the highlights of some of the recent development in this area. Pyrethroids keep the sodium channel open for unusually long times causing a prolonged flow of sodium current. The prolonged sodium current elevates and prolongs the depolarizing after-potential which reaches the threshold membrane potential to initiate repetitive after-discharges. We have developed the method with which the percentage of sodium channel population that needs to be modified to cause repetitive after-discharges can be measured accurately. In rat cerebellar Purkinje neurons, only 0.6% of sodium channels needs to be modified for hyperexcitation resulting in a large toxicity amplification. This concept is applicable to other neuroactive drugs that act through the threshold phenomenon. The mechanisms of selective toxicity of pyrethroids in mammals and insects have been quantitatively determined to be due mainly to the different sensitivity of the sodium channels to pyrethroids and the negative temperature dependence of pyrethroid action on the sodium channels. The degradation of pyrethroids play only a minor role. The negative temperature dependence of pyrethroid action is due to the increased sodium current flow at low temperature. The major site of action of dieldrin and hexachlorocyclohexane is the GABA(A) receptor chloride channel complex. Dieldrin exerts a dual action, initial stimulation and subsequent suppression, and the latter is responsible for hyperexcitation of animals. Dieldrin stimulation requires the gamma2s subunit in the GABA receptor, whereas dieldrin suppression occurs in the presence or absence of the gamma2s subunit.

Animals↗

Organochlorine insecticide residues in bovine milk and manufactured milk products in Illinois, 1971-76.

Monitoring activities were initiated in 1971 to survey the occurence and levels of organochlorine insecticide residues in bovine milk and manufactured milk products in Illinois. Dieldrin residues were the most prevalent, and were found in 96 percent of the samples. Dieldrin also accounted for the highest average residue concentration (0.09 ppm). Only 0.3% of the samples contained illegal insecticide residues. Levels of DDT and lindane were generally declining, but those for dieldrin and heptachlor epoxide tended to remain constant.

Acetonitriles↗

Susceptibility of the malaria vectors to insecticides in Bangladesh.

Insecticide susceptibility tests with diagnostic dosages of 4% DDT and 5% malathion concentrations conducted at field sites on the two important principal malaria vectors namely, Anopheles dirus and An. philippinensis have been reported. They are found to be susceptible to DDT and malathion. The implication of the use of insecticides in controlling malaria is also discussed.

Animals↗

Action of the pyrethroid insecticide cypermethrin on rat brain IIa sodium channels expressed in xenopus oocytes.

Pyrethroid insecticides bind to a unique site on voltage-dependent sodium channels and prolong sodium currents, leading to repetitive bursts of action potentials or use-dependent nerve block. To further characterize the site and mode of action of pyrethroids on sodium channels, we injected synthetic mRNA encoding the rat brain IIa sodium channel alpha subunit, either alone or in combination with synthetic mRNA encoding the rat sodium channel beta1 subunit, into oocytes of the frog Xenopus laevis and assessed the actions of the pyrethroid insecticide [1R,cis,alphaS]-cypermethrin on expressed sodium currents by two-electrode voltage clamp. In oocytes expressing only the rat brain IIa alpha subunit, cypermethrin produced a slowly-decaying sodium tail current following a depolarizing pulse. In parallel experiments using oocytes expressing the rat brain IIa alpha subunit in combination with the rat beta1 subunit, cypermethrin produced qualitatively similar tail currents following a depolarizing pulse and also induced a sustained component of the sodium current measured during a step depolarization of the oocyte membrane. The voltage dependence of activation and steady-state inactivation of the cypermethrin-dependent sustained current were identical to those of the peak transient sodium current measured in the absence of cypermethrin. Concentration-response curves obtained using normalized tail current amplitude as an index of the extent of sodium channel modification by cypermethrin revealed that coexpression of the rat brain IIa alpha subunit with the rat beta1 subunit increased the apparent affinity of the sodium channel binding site for cypermethrin by more than 20-fold. These results confirm that the pyrethroid binding site is intrinsic to the sodium channel alpha subunit and demonstrate that coexpression of the rat brain IIa alpha subunit with the rat beta1 subunit alters the apparent affinity of this site for pyrethroids.

Action Potentials↗

THE DEVELOPMENT AND TREND OF INSECTICIDE-RESISTANCE IN ANOPHELES ACONITUS DOENITZ AND ANOPHELES SUNDAICUS RODENWALDT.

The spread of insecticide-resistance in the two main vectors of malaria in Java, Anopheles aconitus Dönitz and A. sundaicus Rodenwaldt, has been of concern to workers in the Indonesian malaria eradication programme since DDT-resistance was first detected, in A. sundaicus, in 1954. The history of development of resistance in these two vectors has been summarized in this paper by assembling the available records in chronological order, thus facilitating reference.The picture which emerges is that of somewhat erratic occurrence of DDT-resistance in A. sundaicus and more stable, expanding areas of DDT-resistant A. aconitus. Dieldrin-resistance is more widespread than DDT-resistance in both species and preceded the onset of DDT-resistance in A. aconitus but not in A. sundaicus. These features should not be regarded as species characteristics, however, since selection pressures on the two species have been far from uniform.Malathion appears to be a promising alternative to DDT and dieldrin for the control of the two vectors in the circumstances described.

Animals↗

ADDITIONAL STUDIES WITH NEW INSECTICIDES AS RESIDUAL SPRAYS IN BUILDINGS NATURALLY INFESTED WITH ANOPHELES QUADRIMACULTATUS.

Because some species of Anopheles mosquitos have been developing resistance to DDT and dieldrin, field studies have been conducted to evaluate the effectiveness of recently developed insecticides as residual sprays in buildings naturally infested with adults of Anopheles quadrimaculatus. As a deposit at 2 g/m(2), o-isopropoxyphenyl methylcarbamate remained highly effective for more than one year. This compound and 6-chloro-3,4-xylyl methylcarbamate were still producing excellent control 11-12 weeks after application at 1 g/m(2). Other highly effective materials were m-isopropylphenyl methylcarbamate and 4-(methylthio)-3,5-xylyl methylcarbamate at 2 g/m(2). At the present time, o-isopropoxyphenyl methylcarbamate appears to offer the best prospects for use in residual spray programmes because it has long residual action, affects mosquitos rapidly, has only a slight odour and appears to be safe to use if spraymen take reasonable precautions.

Animals↗

Induction of chromosomal aberrations and sister chromatid exchange in vivo and in vitro by the insecticide cypermethrin.

The induction of chromosomal aberrations and sister chromatid exchange in vivo in mouse spleen and bone marrow as well as in vitro in cultured mouse spleen cells by the insecticide 'Cypermethrin' (cis-trans 1:1) was investigated. The percentage of chromosomal aberrations in the spleen and in the bone marrow as almost the same and reached its maximum 6 h following i.p. injection. The aberrations induced were chromatid and chromosome gaps, fragments and tetraploidy. The insecticide caused a significant and dose-dependent increase in the frequency of sister chromatid exchanges (SCEs) in mouse bone-marrow cells: it reached 11.12 +/- 0.05 per cell after treatment with Cypermethrin at 300 mg kg-1 body wt. compared with 3.7 +/- 0.14 per cell and 4.4 +/- 0.26 per cell in the solvent and control, respectively. The percentage of viable cells in mouse spleen cell cultures reached 87.4% and 99.9% relative to the control after treatment of the cell cultures with 10(-3) and 10(-7) Cypermethrin, respectively. All the tested concentrations of Cypermethrin (0.25-400 micrograms ml-1) induced a high percentage of metaphases with chromosomal aberrations after 4 h of treatment. The mean frequency of SCEs per cell reached 15.1 +/- 0.05 after treatment with Cypermethrin at 4.00 micrograms ml-1 compared with 8.6 +/- 0.23 and 5.9 +/- 0.39 in the solvent and control, respectively. The results indicate that Cypermethrin is genotoxic in mouse spleen and bone marrow as well as in cultured mouse spleen cells.

Animals↗

Detoxification of organophosphorus compounds by recombinant carboxylesterase from an insecticide-resistant mosquito and oxime-induced amplification of enzyme activity.

Currently, bioremediation is a promising approach to the degradation of environmental pollutants. Here we describe the application of the recombinant insecticide-resistant mosquito carboxylesterase B1 to detoxify organophosphorous compounds. However, this approach has a major limitation: 1:1 stoichiometry of the enzyme detoxification of those organophosphorous compounds containing no carboxyl ester bonds, such as paraoxon, chlorpyrifos etc. To improve the effectiveness of the enzymatic detoxification of organophosphorous compounds, we used a combination of carboxylesterase B1 with the uncharged oxime diacetylmonoxime. It was demonstrated that the repeated addition of 20 times the molar concentration of paraoxon to carboxylesterase B1 every 2 h in the presence of 4 mM diacetylmonoxime did not result in significant inhibition of the enzyme. The stoichiometry of enzyme detoxification was higher than 45:1 and 20:1 for paraoxon and chlorpyrifos, respectively. The kinetic experiments on reactivation of organophosphorus compound-inhibited carboxylesterase B1 showed that the half-life for paraoxon- and chlorpyrifos-inhibited carboxylesterase reactivation is 0.75 and 0.88 h, respectively. Using the recombinant insecticide-resistant mosquito carboxylesterase with oxime is an effective approach for detoxification of organophosphorous compounds.

Animals↗

Comparative effects of a genetically engineered insect virus and a growth-regulating insecticide on microbial communities in aquatic microcosms.

The effects of a genetically engineered insect baculovirus on indigenous aquatic microbial communities were determined in closed, recirculating aquatic microcosms, and compared with the effects of a natural strain of the virus and of a growth-regulating insecticide, Dimilin. The recombinant virus was a nuclear polyhedrosis virus (NPV) of the spruce budworm (Choristoneura fumiferana (Cf)) with a lacZ marker gene inserted into the egt region of the CfNPV. The natural virus was Ireland strain CfNPV. Microbial measurement endpoints included decomposition activity (mass loss of organic material), respiration on two different substrates (O2 consumption), heterotrophic bacterial abundance (plate counts), and microbial community metabolic profiles (carbon source utilization patterns in Biolog GN microplates). Viral DNA of both the natural strain and the recombinant viruses, detected by polymerase chain reaction techniques, settled out of the microcosm water and accumulated on bottom substrates within 3 days of the microcosm inoculations. The viral DNA persisted in bottom substrates for the duration of the 21-day experimental period, although there was some evidence that the recombinant virus was less stable than the natural strain in particulate organic matter. No significant changes in microbial decomposition or respiration activity, bacterial abundance, or average metabolic responses were detected by a time trend analysis in microcosms inoculated with either the lacZ recombinant virus or the natural Ireland strain CfNPV. Significant effects on microbial decomposition and respiration activity were detected in microcosms treated with the growth-regulating insecticide at, and above, the expected environmental concentrations. Despite significant effects on microbial community functional attributes in Dimilin-treated microcosms, there were no detectable changes in community structure in terms of metabolic profiles or bacterial abundance.

DNA, Viral↗

Comparative toxicology of the pyrethroid insecticides.

The toxic effects elicited by synthetic pyrethroids in animals are varied in degree and nature. Their relative safety to birds and mammals contrasts sharply with their acute effects on fish and arthropods. Explantation of their differences in toxicity depends on examination of all factors of their comparative toxicology. Routes of exposure are important, as are metabolism and elimination rates, especially for mammals and birds with their considerable capabilities for biotransformation. Significant differences in sensitivity at the sites of toxic action may also play a role in differential responses to these insecticides. Finally, physical properties that influence the environmental disposition and subsequently affect bioavailability of the compounds in water, soil, air, produce, and nontarget species are also instrumental in determining the impact of current and future synthetic pyrethroid insecticides.

Amphibians↗

Fate and effects of the insecticide Dursban 4E in indoor Elodea-dominated and macrophyte-free freshwater model ecosystems: II. Secondary effects on community structure.

Secondary effects of a single dose of the insecticide Dursban 4E (active ingredient chlorpyrifos) were studied in indoor experimental freshwater ecosystems intended to mimic drainage ditches. Two experiments were performed, one in which all model ecosystems were dominated by the macrophyte Elodea muttallii, and one using systems devoid of macrophytes. In the Elodea-dominated and macrophyte-free model ecosystems, populations of primary producers, herbivores, carnivores and detritivores were indirectly affected via the loss of populations of Arthropoda as a direct result of insecticide application. However, the taxa in which secondary effects were observed differed considerably between these two types of model ecosystem. In macrophyte-dominated systems secondary effects were observed on populations of periphytic algae, the macrophyte Elodea nuttallii, the gastropod Bithynia tentaculata, Turbellaria, and sediment dwelling Oligochaeta. In open water systems it were populations of phytoplankton, the rotators Polyarthra and Asplanchna, bivalves (Sphaeriidae), Hirudinea, sediment dwelling Oligochaeta, and that of the isopod Proasellus coxalis in which secondary effects were observed. In aquatic ecosystems the presence or absence of a well-developed macrophyte vegetation may be a very important characteristic that determines the nature and route of secondary effects induced by pesticides. The differences in secondary effects observed between Elodea-dominated and macrophyte-free model ecosystems indicate that the system's structure and trophic dynamics should be taken into account when predicting ecological effects.

Chlorpyrifos↗

Aquatic hazard assessment of the organophosphate insecticide fonofos.

This study determined the acute and chronic toxicity of the organophosphate insecticide fonofos to standard freshwater aquatic organisms under laboratory conditions. Fonofos was acutely toxic to bluegill (Lepomis macrochirus), Daphnia (D. magna), and midge (Chironomous riparius) at 5.3, 2.7, and 39 micrograms/L, respectively. Three fonofos formulations (technical, 94.8% A.I.; 20G, field granular 20% A.I.; and 4E, field liquid 4#/gal A.I.) exhibited similar acute toxicities to bluegill. Exposure to fonofos delayed reproduction and decreased the intrinsic rate of increase of Daphnia during 21-d chronic exposure at the lowest tested concentration (0.08 micrograms/L). The no observable effect concentration (NOEC) for Daphnia survival was 0.42 micrograms/L; 0% survival occurred at the lowest observable effect concentration (LOEC) of 1.45 micrograms/L. The NOEC for midge emergence was 3.42 micrograms/L; only 34% emergence occurred at the LOEC of 8.24 micrograms/L. Chronic 30-d exposure of juvenile bluegills decreased growth and survival at 5.65 micrograms/L (LOEC), but no effects occurred at 2.33 micrograms/L (NOEC). The relative hazard of fonofos to aquatic life is similar to other carbamate and organophosphate corn insecticides.

Animals↗

Transformation of synthetic pyrethroid insecticides by a thermophilic Bacillus sp.

Employing a mineral salts medium containing Tween 80 as the primary carbon source, a strain of Bacillus stearothermophilus was isolated which was able to hydrolyse selected second and third-generation pyrethroids to non-insecticidal products. Of a range of pyrethroid insecticides the trans-isomer of permethrin was the most readily transformed by this microbial isolate, whilst flumethrin was the least. 3-Phenoxybenzoic acid and the respective halovinyl or haloacid moieties were detected as the major hydrolytic products of the pyrethroids. It is believed that 3-phenoxybenzoic acid was formed from 3-phenoxybenzyl alcohol which was not however detected as an intermediate in these systems. 3-Phenoxybenzoic acid was further transformed to 4-hydroxy-3-phenoxybenzoic acid. A potential metabolic pathway has been described.

Benzoates↗

Characterization of a carbofuran-degrading bacterium and investigation of the role of plasmids in catabolism of the insecticide carbofuran.

A bacterium capable of using the carbamate insecticide carbofuran as a sole source of carbon and energy, was isolated from soil. The ability to catabolise carbofuran phenol, produced by cleavage of the carbamate ester linkage of the insecticide, was lost at very high frequency when the bacterium was grown in the absence of carbofuran. Plasmid analyses together with curing and mating experiments indicated that the presence of a large plasmid (pIH3, greater than 199 kb) was required for the degradation of carbofuran phenol.

Biodegradation, Environmental↗

Primary irritant contact dermatitis from synthetic pyrethroid insecticide exposure.

Synthetic pyrethroids are widely used insecticides with numerous applications, varying from food protection to general pest control. Humans are capable of tolerating greater acute and chronic exposures to the pyrethroids than to many other insecticides. An abnormal cutaneous sensation (paresthesia) is known to occur after dermal contact with the pyrethroids. Recent field studies have indicated that a primary irritant contact dermatitis may also develop. This investigation evaluated dermal irritancy from cutaneous synthetic pyrethroid application to albino rabbits. Through repeated daily applications of either fenvalerate or permethrin, a slight erythema was noted visually which correlated with increased cutaneous blood flow measured by laser Doppler velocimetry. Histopathological changes were also documented, but no significant differences were detected in edema or thermal variation.

Animals↗