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A malaria control trial using insecticide-treated bed nets and targeted chemoprophylaxis in a rural area of The Gambia, west Africa. 8. Cost-effectiveness of bed net impregnation alone or combined with chemoprophylaxis in preventing mortality and morbidity from malaria in Gambian children.

In The Gambia, insecticide impregnation of bed nets, used alone or combined with Maloprim, reduced morbidity and mortality from malaria amongst children between one and 4 years of age. Taking expenditure of both time and money by public authorities and village volunteers into account, the costs and cost-effectiveness of each intervention were estimated. Bed net impregnation alone and the combined strategy cost US $5.65 and US $7.49 per child-year protected respectively (1990 figures). Insecticide (and drugs) accounted for more than 80% of the costs of each intervention strategy. They were both highly cost-effective. Estimated costs per death and per clinical episode of malaria averted were US $188 and US $28 for bed net impregnation and $257 and $19 for impregnation combined with chemoprophylaxis. Estimated costs per healthy year of life saved, discounted at 3%, were US $7.90 and US $10.84.

Antimalarials↗

The protective effect of bed nets impregnated with pyrethroid insecticide and vaccination against Japanese encephalitis.

A population-based case-control study to evaluate the protective effect of bed nets impregnated with pyrethroid insecticide and of vaccination against Japanese encephalitis was carried out in Gusi county, Henan province, China from June to September 1991; 50 cases and 100 matched controls were studied. Bed nets impregnated with pyrethroid insecticide greatly decreased the risk of infection among children under 10 years old, and vaccine efficacy was 78% (95% CI 16%-94%). We suggest that impregnated bed nets could be used as a quick response during outbreaks of Japanese encephalitis.

Bedding and Linens↗

Neurotoxic and teratogenic effects of an organophosphorus insecticide (phenyl phosphonothioic acid-O-ethyl-O-[4-nitrophenyl] ester) on mallard development.

Phenyl phosphonothioic acid-O-ethyl-O-[4-nitrophenyl] ester (EPN) is one of the 10 most frequently used organophosphorus insecticides and causes delayed neurotoxicity in adult chickens and mallards. Small amounts of organophosphorus insecticides placed on birds' eggs are embryotoxic and teratogenic. For this reason, the effects of topical egg application on EPN were examined on mallard (Anas platyrhynchos) embryo development. Mallard eggs were treated topically at 72 hr of incubation with 25 microliter of a nontoxic oil vehicle or with EPN in the vehicle at concentrations of approximately 12, 36, or 108 micrograms/g egg, equivalent to one, three, and nine times the agricultural level of application used to spray crops. Treatment with EPN resulted in 22 to 44% mortality over this dose range by 18 days of development compared with 4 and 5% for untreated and vehicle-treated controls. EPN impaired embryonic growth and was highly teratogenic: 37-42% of the surviving embryos at 18 days were abnormal with cervical and axial scoliosis as well as severe edema. Brain weights were significantly lower in EPN-treated groups at different stages of development including hatchlings. Brain neurotoxic esterase (NTE) activity was inhibited by as much as 91% at 11 days, 81% at 18 days, and 79% in hatchlings. Examination of brain NTE activity during the course of normal development revealed an increase of nearly sixfold from Day 11 through hatching. The most rapid increase occurred between Day 20 and hatching. Brain acetylcholinesterase (AChE) activity was inhibited by as much as 41% at 11 days, 47% at 18 days, and 20% in hatchlings. Plasma cholinesterase and alkaline phosphatase activities were inhibited and plasma aspartate aminotransferase activity was increased at one or more stages of development. Hatchlings from EPN-treated eggs were weaker and slower to right themselves. Histopathological examination did not reveal demyelination and axonopathy of the spinal cord that was characteristic of delayed neurotoxicity in adult birds.

Animals↗

Arthropod toxins as leads for novel insecticides: an assessment of polyamine amides as glutamate antagonists.

In the search for new toxins, preferably with new sites of action, the polyamine amides represent a new class of compounds with potential as insecticides and as pharmaceutical agents due to their antagonism of ligand-gated cation channels. In particular, they are potent antagonists of the L-glutamate receptors of insect skeletal muscle. In this paper, we report on synthetic studies to produce hybrid analogues based upon the argiotoxin spider toxins and philanthotoxin-433 which is obtained from a solitary, parasitic wasp. We speculate upon possible modes and sites of action for these antagonists and we discuss their potential as insecticides and in the possible treatment of ischaemic damage. The synthesis and characterization of 4-hydroxyphenylpropanoylspermine is reported and the locust muscle biological assay is described. Using this pharmacological screen, structure-activity relationships have been determined in our laboratories. These are reviewed in the light of the current literature. Voltage clamp studies of the synthetic analogue philanthotoxin-343 and the effects of this polyamine amide on glutamate receptors expressed in Xenopus oocytes are outlined. In conclusion, a description of our current ideas and understanding of the many sites and modes of action of the polyamine amides, based both upon our own studies and also upon those recently reported, is presented.

Animals↗

Evaluation of humic-pesticide interactions on the acute toxicity of selected organophosphate and carbamate insecticides.

The ability of water resource managers to accurately predict the toxicity of agricultural chemicals in aquatic ecosystems is essential for the development of reliable water quality standards. At present, accurate predictions are difficult due to the paucity of data concerning the interaction of these chemicals with organic constituents of the freshwater chemical matrix. Dissolved humic materials are ubiquitous components of freshwater ecosystems and can affect the availability and toxicity of chemicals in the environment. In the present investigation, the influence of humic acid (HA) on the acute toxicity of selected organophosphate and carbamate insecticides was examined using a bacterial bioluminescence inhibition assay. EC50 values for the pesticides were determined in the presence of 0, 0.5, 5.0, 50, and 100 mg/liter HA. A combination of antagonistic and synergistic effects was observed with the selected organophosphate and carbamate insecticides examined. HA significantly reduced the toxicity of azinophos-methyl, chlorpyrifos, and carbofuran, while enhanced toxicity was observed with methyl parathion and carbaryl. These results indicate that humic-pesticide interactions can alter the toxicity of agricultural chemicals. Moreover, the influence of humic materials on the toxicity of these chemicals is dependent on temporal relationships and HA concentration.

Carbamates↗

Effects of benzofuran and seven benzofuran derivatives including four carbamate insecticides in the in vitro porcine brain tubulin assembly assay and description of a new approach for the evaluation of the test data.

The influence of benzofuran and 7 benzofuran derivatives, including the carbamate insecticides benfuracarb, carbofuran, carbosulfan, and furathiocarb, on the in vitro assembly kinetics of porcine brain tubulin was investigated. A new approach to the evaluation of the raw data was made based on polynomial regression and the calculation of a polynomial function of the 11th degree fitting the raw data. By this procedure it is possible to calculate the parameters defining the shape of the absorbance curves and more parameters than those used so far can be included in the analysis of substance effects. In detail, the following curve parameters of the dependence of optical absorption on time were included in the evaluation of the substances of interest: the difference between maximum and minimum absorbance as a measure for the polymerization degree, the coordinates of the turning point of the curve, the slope of the tangent at the turning point which represents the maximum reaction velocity, the mean slope between the points with 10% absorbance increase and 90% absorbance increase and the duration of the lag phase. Out of the eight compounds tested, only the carbamate insecticides had distinct effects on the in vitro polymerization of tubulin, whereas benzofuran and the three 2,3-dihydro-2,2-dimethylbenzofuran derivatives without a carbamate function were inactive. Benfuracarb, carbofuran, carbosulfan, and furathiocarb led to a dose-dependent reduction of the polymerization degree of tubulin as well as to reduction of the maximum and mean reaction velocities. The strongest effects were obtained with furathiocarb and benfuracarb.

Animals↗

The mutagenic effect of the new insecticide and acaricide pyridathion.

The potential mutagenic effect of the new organophosphate insecticide and acaricide, pyridathion, was tested on Escherichia coli, strains WP2, WP2 uvrA, and on Salmonella typhimurium, strains TA100 and TA98, both with and without metabolic activation. The compound was tested at 1, 10 and 100 micrograms/ml. The analysis of chromosomal aberrations in mouse bone marrow was performed after a single peroral application of pyridathion at doses of 0.6, 1.11, 6.0, 12.0 and 24.0 mg . kg-1 b.w., i.p. application at 6.0 mg . kg-1 b.w., and repeated application (5 times) p.o. at 1.0, 2.5 and 5.0 mg . kg-1 b.w. Analysis of rat bone marrow was performed after a 3-month peroral application of pyridathion at 0.07, 0.175 and 0.35 mg . kg-1 b.w. An analysis of chromosomal aberrations in human peripheral lymphocytes in vitro was performed 24 h after the application of pyridathion into the culture in concentrations of 9.2 X 10(-3), 9.2 X 10(-4) and 9.2 X 10(-5) moles. The insecticide did not exert any mutagenic effect on the bacteria. There was no significant increase in the frequency of chromosomal abnormalities in bone marrow of mice of rats, or in human peripheral lymphocytes in vitro, compared with controls.

Animals↗

An evaluation of the genotoxic properties of insecticides following plant and animal activation.

Commercial and technical grades of 10 insecticides were evaluated for genotoxicity with Salmonella typhimurium and Saccharomyces cerevisiae directly and following plant and animal activation. Field-grade formulations of each insecticide were also tested for mutations at the waxy (wx) locus in Zea mays in situ. Carbofuran, chloropyrifos, curacron, metham and phorate were negative in all assays. Ethoprop and terbufos were each positive in 1 assay, and chlordane, fonofos and heptachlor were each positive in 2 assays. Fonofos and terbufos were positive directly and following animal activation while chlordane and heptachlor were positive following both plant and animal activation. Chlordane, ethoprop, and heptachlor were positive in Z. mays.

Animals↗

Clinical problems in organophosphate insecticide poisoning: the use of a computerized information system.

A computerized medical information system has been constructed, which contains clinical data from 236 case records of organophosphate and carbamate insecticides poisoning in Israel. A computer program was used to retrieve, analyze, and cross- tabulate data contained in 162 variables per patient. Clinical criteria were used to distinguish mild (66%) from moderate (19%) and severe (15%) cases. The majority of exposures were occupational (58%), whereas the rest were accidental (31%) or suicidal (11%). Parathion was the toxic compound most frequently involved (153 cases). Grouping signs and symptoms according to the cholinergic synapse systems showed peripheral muscarinic signs to be the most prevalent (92.5% of cases), whereas involvement of all three synapse systems was rare (17%). Listing individual symptoms emphasized the high prevalence of nonspecific symptoms such as vomiting (142 cases) and abdominal pain (115 cases). The mean atropine dose given to adult patients during the first 24 hr after poisoning ranged from 6.0 +/- 0.7 mg in mild cases to 49.8 +/- 4.5 mg in severe cases. Evaluation of clinical decision making was demonstrated through analysis of the guidelines used by physicians to gauge atropine administration. Five of the eighteen fatalities were delayed deaths, one of which was due to a polymorphous ventricular arrhythmia. The same arrhythmia occurred also in four nonfatal cases. Other delayed effects included nonspecific EEG changes and neuropsychiatric symptoms. Matching individual cases with comparable cases in the data bank was demonstrated, using a previously published case report. Computerized consultation may help inexperienced physicians to improve the quality of medical care given to cases of organophosphate insecticide poisoning in small hospitals located in rural areas.

Adolescent↗

Inhibition of human serum complement activity by diisopropylfluorophosphate and selected anticholinesterase insecticides.

Activation of the human complement (C') system, a major line of defense against infections, requires the participation of serine esterases. Since the widely used anticholinesterase insecticides inhibit serine esterases, the present study evaluated potencies of carbaryl, carbofuran, dichlorvos, and paraoxon to inhibit C' activities of a panel of normal human sera. C'-mediated lysis of sheep red cells was measured with a modified assay (1) incorporating suboptimal concentrations of sensitizing antibody and (2) exhibiting increased sensitivity to serine esterase inhibitors. Test chemicals were added to diluted sera 2 hr prior to incorporation into C' reaction mixtures. Potencies to inhibit C' and serum cholinesterase (CHE) were compared to potencies of diisopropylfluorophosphate (DFP), a potent serine esterase inhibitor and a standard probe for C' esterases. At 0.5 to 3.0 mM, carbaryl, carbofuran, dichlorvos, and DFP produced a dose-dependent inhibition of lysis, whereas paraoxon was not inhibitory. On a molar basis, carbaryl was three times more potent than DFP, and inhibited lysis 15-25 and 26-45% at 1.0 and 3.0 mM, respectively. Carbofuran, dichlorvos, and DFP were equipotent. Mean IC50's for inhibition of CHE (a marker for occupational exposure to organophosphates and carbamates) by DFP, paraoxon, dichlorvos, carbofuran, and carbaryl were 1.0 X 10(-8), 4.1 X 10(-8), 1.0 X 10(-7), 3.3 X 10(-6), and 1.8 X 10(-5) M, respectively. Potencies of the insecticides to inhibit CHE did not predict absolute or relative potencies to inhibit serum C' activity.

Adult↗

Potential consequences of a fire in an insecticide storage facility.

Assumptions are identified and made in an attempt to model the acute human health risk associated with a hypothetical fire in an insecticide storage facility. The insecticides used in the model are endrin and dimethoate. The model indicates that persons residing a few hundred meters from the facility could suffer a variety of adverse effects, including possible death from contact with smoke from a prolonged, low-temperature fire. Knowledge of the special hazards of cool toxic smoke as well as current atmospheric conditions could be of use to fire fighters. That is, fire fighters might wisely choose to promote a fast, hot fire which would propel toxicants high into the atmosphere rather than risk local fumigation.

Animals↗

Clinical evaluation of insecticide-impregnated tags attached to chains and used as backrubbers for control of Haematobia irritans.

Fenvalerate and permethrin insecticide tags were tested for horn fly (Haemotobia irritans) control. Three fenvalerate-impregnated ear tags attached to a chain and used as a backrubber controlled horn flies on steers for 8 weeks, and six tags provided 18 weeks control. Ten tags impregnated with permethrin failed to control horn flies. The choice of insecticide in tags attached to chains and used as backrubbers for horn fly control may be important, as fenvalerate and permethrin (both pyrethroids) varied in effectiveness.

Animals↗

Intrinsic lethality of chloride-channel-directed insecticides and convulsants in mammals.

The intrinsic lethality of a series of chloride-channel-directed convulsants and insecticides was determined by intracerebral injection into mice. The toxicities of the cyclodiene insecticides and picrotoxinin were potentiated by intracerebral injection, when compared to their reported intraperitoneal LD50s. In contrast, the toxicities of lindane, abamectin, and the bicyclic convulsants TBPS and a TBOB analog were approximately the same by either route of administration. These results suggest that the brain is the primary target site for the cyclodienes and picrotoxinin, while the peripheral nervous system may be relatively more important in the toxic action of lindane, abamectin, and bicyclic convulsants such as TBPS. With the exception of picrotoxinin these compounds showed, overall, a good correlation between acute intracerebral toxicity and potency for inhibiting GABA-dependent chloride uptake. The evidence that multiple chloride-channel subtypes serve as targets for these compounds and the potential impact this had on the results of these studies are discussed.

Animals↗

Mutagenicity, insecticidal and trypanocidal activity of some Paraguayan Asteraceae.

The insecticidal, moulting inhibition and trypanocidal effects of crude extracts of 7 Paraguayan Asteraceae were evaluated on Triatoma infestans and bloodstream forms of Trypanosoma cruzi, respectively. Both mutagenicity and toxicity were evaluated by sister chromatid exchange (SCE) in human peripheral lymphocyte culture and by the lethality test of Artemia salina. The ethanolic extracts from Chromolaena christieana (stem and bark), Achyrocline satureoides (leaves and flowers) and Mikania cordifolia (root and stem), at a concentration of 250 micrograms/ml, showed the highest percentage of lysis on bloodstream forms of Trypanosoma cruzi. The extracts of Chromolaena christieana and Achyrocline satureoides also presented high mutagenic and toxic capacity when they were evaluated by the SCEs assay and Artemia salina test, respectively. Insecticidal activity was only observed in the hexane extract of flowers of Achyrocline satureoides (45% of mortality), when 0.05 microgram of crude concentration was applied on Triatoma infestans. The ethanolic extracts of stem from Mikania cordifolia and Vernonia brasiliana inhibited the moulting of Triatoma infestans when it was compared with their controls. Since no ethnobotanical information on these plants has been found related to similar use in Paraguay, our findings suggest, for the first time, the potential anti-trypanocidal and moulting inhibition of these Asteraceae.

Animals↗

Binding of insecticides to serum proteins in mosquitofish (Gambusia affinis).

Incubation of various organochlorine insecticides with mosquitofish serum leads to their association with, primarily, the vitellogenin/lipoprotein and albumin fractions. A significant variation in the quantity of each insecticide bound in the particular fractions was observed. Binding appeared to increase with compounds of increasing polarity, suggestive of protein binding. Preincubation of serum with endrin or aldrin significantly reduced the quantity of [3H]DDT subsequently bound while the reverse was not observed. Although the reason for the apparent quantitative decrease in binding is unknown, the reduction in binding of a particular xenobiotic, due to the presence of a second, has serious toxicological implications.

Animals↗

Characterization and cloning of insecticidal peptides from the primitive weaving spider Diguetia canities.

Three potent insecticidal peptide toxins were purified from the venom of the primitive weaving spider, Diguetia canities. The toxins share significant homology (> 40%) in their amino acid sequences and are of related size (masses of 6371-7080 Da). In lepidopteran larvae, the toxins cause a progressive spastic paralysis, with 50% paralytic doses (PD50S) ranging from 0.38 to 3.18 nmol/g, suggesting them to be among the most potent insecticidal compounds yet described from arthropod venoms. The most potent of these toxins, DTX9.2, was cloned using a reverse transcription-polymerase chain reaction (RT-PCR). The cDNA encodes a 94 amino acid precursor which is processed to the active 56 amino acid peptide by removal of a signal and propeptide sequence. The gene encoding DTX9.2 was isolated and characterized. The transcriptional unit spans 5.5 kilobases and is segregated into five exons. DNA sequences upstream from the first exon contain a TATA box and two palindromic sequences (one with homology to a CAAT consensus) which together may constitute a functional promoter. The highly segmented gene structure observed for this small peptide suggests that a mechanism such as exon shuffling may have played a role in the evolution of this toxin family.

Amino Acid Sequence↗

Insecticidal and cytotoxic effects of natural and hemisynthetic destruxins.

The insecticidal and cytotoxic effects of 13 natural and hemisynthetic destruxins have been studied. DE shows insecticidal effects similar to those of DA, while DE and DA are more active than all the other natural compounds and analogues tested. Brominated destruxin is a relatively active analogue displaying particular modalities of cytotoxic effects which reflect a certain originality of its mode of action. The linear molecule resulting from the opening of the DA cycle is not toxic. The most hydrophilic destruxins showing e.g. charged radicals (COO-) appear the least toxic probably because they do not penetrate easily the cellular membranes.

Administration, Oral↗

Hapten synthesis for enzyme-linked immunoassay of the insecticide triazophos.

Two haptens of the insecticide triazophos (O,O-diethyl O-[1-phenyl-1H-1,2,4-triazol-3-yl] phosphorothioate) were synthesized by introducing appropriate spacers in the O-ethyl site of the analyte molecular structure. First, thiophosphoryl chloride (PSCl(3)) reacts with methanol at low temperature to give O-ethyl dichlorothiophosphate. After reacting with 1-phenyl-3H-1,2,4-triazol, the O-ethyl dichlorothiophosphate was transformed into the intermediate O-ethyl O-(1-phenyl-1H-1,2,4-triazol-3-yl) chlorothiophosphate. Then the intermediate reacts with 4-aminobutyric acid and 6-aminobutyric acid to produce hapten I and hapten II, respectively. The molecule structures of the two haptens were identified by (1)H nuclear magnetic resonance spectrum and mass spectrum. An enzyme-linked immunosorbent assay (ELISA) based on monoclonal antibody was also developed to evaluate the two haptens. Results showed that the monoclonal antibodies with high titers were obtained after immunizing with protein conjugates of these haptens and that the immunoassay has high affinity and specificity to triazophos. These results suggested that the haptens were synthesized successfully and could be used for immunoassay for the rapid screening and sensitive determination of this insecticide.

Animals↗