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[Perspectives in the treatments of poisonings by organophosphorus insecticides and warfare nerve agents].

INTRODUCTION AND DEVELOPMENT: Organophosphorus compounds are worldwide employed as insecticides and are yearly responsible of several millions of poisonings. The chemical structure of most of the warfare nerve agents also corresponds with an organophosphorus compound. Organophosphorus insecticides and warfare nerve agents exert their main toxicological effects through inhibition of acetylcholinesterase. Current treatments of patients poisoned with organophosphorus compounds include atropine (in order to protect muscarinic receptors), oximes (in order to accelerate the reactivation of the inhibited acetylcholinesterase) and benzodiazepines (in order to avoid convulsions). The administration of phosphotriesterases (enzymes involved in the detoxication of organophosphorus compounds through hydrolysis) is a very effective treatment against poisonings by organophosphorus insecticides and warfare nerve agents. There are experimental preventive treatments based on the simultaneous administration of carbamates and certain antimuscarinic drugs, different from atropine, which notably improve the efficacy of the classical treatments applied after poisonings by warfare nerve agents. CONCLUSIONS: The treatments based in the administration of phosphotriesterases might be the response to the call of the World Health Organization for searching new treatments with capability to reduce the high mortality recorded in the cases of poisonings by organophosphorus compounds. These treatments can be applied in a preventive way without the intrinsic neurotoxicity associated to the preventive treatments based on carbamates and antimuscarinic drugs. Therefore, these treatments are specially interesting for people susceptible to suffer severe exposures, i.e. sprayers in the farms.

Antidotes↗

Toxicity of a dichlorvos containing insecticide formulation and an atrazine containing herbicide formulation in chicken embryos after individual administration.

A 50% dichlorvos containing insecticide formulation (Unifosz 50 EC) and a 50% atrazine containing herbicide formulation (Hungazin PK 50 WP) were studied in chicken embryos after administration as single compounds. Applied concentrations of dichlorvos were 0.1% (corresponding to the plant protection practice), 0.05%, 0.02%, 0.01%. Applied concentrations of atrazine were 0.66% (corresponding to the plant protection practice), 0.33%, 0.132%, 0.066%. The test materials were injected directly into the air-chamber of eggs on day 0 of the hatching period and evaulation was carried out on day 19 of incubation. The chicken embryos were examined for the following: rate of embryo mortality, body mass, type of developmental anomalies. After the single administrations of dichlorvos containing insecticide formulation and atrazine containing herbicide formulation on day 0 of incubation, the average body weight of chicken embryos significantly did not decrease as compared to the control. After the individual administrations of pesticides the incidence of developmental anomalies was sporadic. The embryonic mortality markedly increased at the highest concentrations of pesticides. The rate of embrio mortality were 61% (dichlorvos insecticide containing formulation) and 52% (atrazine containing herbicide formulation). In summary, the 50% dichlorvos containing insecide formulation (Unifosz 50 EC) and the 50% atrazine containing herbicide formulation (Hungazin PK 50 WP) were toxic to the developing chicken embryos at the highest concentration in our study. The toxic effect was expressed in the high rate of embrio mortality.

Animals↗

[Status of resistance to insecticides in field strains of the Blatella germanica species (Dictyoptera: Blattellidae) from Pinar del Río municipality].

A study of the levels of resistance to 10 insecticides: 4 organophosphate compounds (malathion, clorpirifos, methylpyrimifos and diazinon), 2 carbamates (propoxur and bendiocarb) and 4 pyrethroids (cypermethrin, deltamethrin, lamdacyhalothrin and cyfluthrin) was conducted in 5 strains of Blatella germanica (Linnaeus, 1767) collected in the field of Pinar del Rio. High levels of resistance to bediocarb, cypermethrin and deltamethrin insecticides; low level of resistance to diazinon; from moderate to high resistance to methyl-pyrimifos, as well as susceptibility to one insecticide in each study group: clorpirifos (organophosphate), propoxur (carbamate) and cyfluthrin (pyrethroid); were detected. Only a strain presented low resistance to malathion (Inicio Carlos Manuel) and to lambda-cyhalothrin (Consejo Celso Maragoto). Cypermethrin-deltamethrin cross resistance was evidenced. It did not affect the susceptibility to lambda-cyalothrin and cyfluthrin.

Animals↗

[Acute organophosphate insecticide poisonings in the province of Almería. A study of 187 cases].

BACKGROUND: The aim of the present study was to analyze the epidemiological and clinical characteristics of poisoning by organophosphorus insecticides in the province of Almería. METHODS: One hundred eighty-seven patients diagnosed with organophosphorus insecticide poisoning were included from 1981-1986. In all the cases a previously established clinic and therapeutic protocol was applied. RESULTS: Eighty-six percent of the patients were males with a mean age of 31 years. The poisoning was accidental in 62% of the cases and attempted suicide in 38%. The via of absorption was cutaneous-respiratory in 57% and digestive in 43% of the patients. All the patients presented florid initial cholinergic symptomatology. The presence of bronchorrhea, tremor-fasciculations, respiratory depression and diminution in the level of conscience was associated with severe intoxication. The quantification of acetylcolinesterase was useful as a diagnostic parameter. Global mortality was 4%. Ten percent of the patients developed delayed signs of neurotoxicity. CONCLUSIONS: The high hospital demand for poisoning by organophosphorus insecticide is of note. Hospital mortality is low. The severity of intoxication is related with attempts of autolysis, digestive absorption, appearance of respiratory manifestations and of the central nervous system and the development of complications.

Acute Disease↗

Multiresidue screen for organophosphorus insecticides using gel permeation chromatography--silica gel cleanup.

A multiresidue screen for quantitative determination of 43 organophosphorus insecticides in 5 g of plant and animal tissues is described. The organophosphorus insecticides are extracted with methanol-dichloromethane (10 + 90, v/v) and cleaned up using automated gel permeation chromatography with hexane-ethyl acetate (60 + 40) eluant and in-line silica gel minicolumns. Concentrated extracts are analyzed by gas chromatography with flame photometric detection. The method recovers 43 organophosphorus insecticides in the range of 72 to 115%. Analysis of fortified bovine liver (n = 5) shows an average 95.9 +/- 4.8% recovery at the 0.05 micrograms/g level and 93 +/- 3.8% at the 0.5 micrograms/g level. Analysis of fortified bovine rumen content (n = 5) shows an average 98 +/- 4.2% recovery at the 0.1 micrograms/g level and 98.7 +/- 2.8% at the 1 micrograms/g level. Method detection limits ranged from 0.01 to 0.05 micrograms/g for the compounds studied using a nominal 5 gram sample.

Animals↗

[Residues of organochlorine insecticides in human and bovine milk in Colombia].

Studies carried out in various countries have determined the presence of organochlorine insecticides in human and cow's milk. To quantify this contamination in Colombia, the concentrations of these insecticides were measured in 170 samples of milk from lactating mothers in Bogotá (105 samples) and three agricultural areas where fumigation is done frequently (65 samples). Also, for purposes of comparison, the study included 75 samples of fresh cow's milk, 10 samples of pasteurized milk, and 10 samples of whole powdered milk. In all the samples of human or cow's milk, high concentrations of total DDT were found. In some samples there were also appreciable amounts of benzene hexachloride (BHC) and other insecticides not included in the study. The samples of cow's milk contained lower concentrations of sufficient total DDT. In a comparison of the means, the samples of human milk showed contamination several times greater than the cow's milk. The pasteurized and powdered milk had lower levels of contamination. The average amount of total DDT in the samples of human milk (0.075 ppm, or micrograms/ml) far exceeded the DDT contamination limit established for milk by FAO/WHO (0.050 ppm). However, there was a wide range in the levels found (the lowest being 0.002, and the highest, 0.680), which means that in some of the samples the concentrations of total DDT were more than 10 times greater than the maximum set by FAO/WHO while in many other cases they were close to the recommended limit.

Animals↗

[The appearance of insecticide resistance in Blattella germanica in the German Democratic Republic].

A review is given on the situation of resistance in the German cockroach (Blattella germanica) to insecticides during the last 15 years in the GDR, and conclusions are drawn for the future. From 23 samples trapped in various localities and subsequently reared in the laboratory, susceptibilities were measured against lindane, pyrethrin + PBO, trichlorfon, dichlorvos, and propoxur, the most used insecticides against cockroaches in our country. Detection of resistance was done with discriminating doses and the degree of resistance was measured with the doses-mortality method in deposit tests. In no case we found any resistance to propoxur but, for the first time, strains with a low resistance to dichlorvos. There was a distinct increase in the resistance to lindane, trichlorfon and pyrethrins + PBO during the lost years. A strain selected with pyrethrins in the laboratory showed marked group resistance to all tested pyrethroids (permethrin, cyfluthrin, cypermethrin, tetramethrin, deltamethrin, bioresmethrin, bioallethrin), but no cross resistance to the other insecticides.

Animals↗

Inhibition and recovery of selected target enzyme activities in tissues of penaeid prawn, Metapenaeus monoceros (Fabricius), exposed to different insecticides.

The target enzymes, acetylcholinesterase (for phosphamidon and carbaryl) and Mg2+ ATPase (for DDT and fenvalerate) have been assayed during exposure and reclamation of these insecticides in M. monoceros. Toxicity of these insecticides are in the order: fenvalerate greater than DDT greater than carbaryl greater than phosphamidon. Reclamation studies show that fenvalerate is rapidly degradable while DDT is slowly degradable. It is suggested that pyrethroid, organophosphate and carbamate insecticides may be preferred over organochlorine compounds in farm operations.

Acetylcholinesterase↗

[Risk factors related with occupational and environmental exposure to organochlorine insecticides in the state of Bahia, Brazil, 1985].

In the cacao-growing region in the southern part of the state of Bahia, the organochlorine insecticides, mainly gamma-benzene hexachloride (BHC) and dichlorodiphenyltrichloroethane (DDT), have been used for about 40 years on cacao crops and in public health programs for control of the insect vectors of different diseases, especially malaria. This paper presents the results of tests performed on 127 persons, all males, between the ages of 15 and 52 years, divided into eight groups as follows: three groups consisted of persons occupationally exposed to 1.5% BHC, that is, technical hexachlorocyclohexane (HCH); two groups consisted of individuals who had had occasional contact with the products or worked in areas near those in which they were used; two groups were appliers of DDT, and the last group--the control group--consisted of 50 individuals who had had no history of occupational exposure to insecticides. All the participants underwent testing to determine the parameters of biochemistry, hematology, and organochlorine insecticide residues in the blood. It was found that improper handling of the products and failure to use individual protective equipment, together with longer time of exposure, significantly increased the rates of GOT and GPT in the appliers of DDT and technical HCH, and in the latter the rates of alkaline phosphatase, albumin, and cholesterol were also found to be higher. In view of the high morbidity among pesticide appliers in agriculture and public health campaigns, it is important to institute programs to teach these workers to avoid contamination of their persons and of the environment by developing good hygiene habits, using individual protective equipment, and correctly handling the products. Rural workers and public health authorities must become aware of the importance of protective equipment, periodic health examinations, and reduced environmental pollution in order to lessen occupational risks of field workers and promote improved conditions of life for the rural population at large.

Adolescent↗

[Acute poisoning by insecticides with anticholinesterase activity. Evaluation of the efficacy of a cholinesterase reactivator, pralidoxime].

Pralidoxime is the most frequently used antidote in anticholinesterase insecticide poisoning, owing to its cholinesterase reactivating action. The efficiency of Pralidoxime has been retrospectively evaluated by comparing two groups of 31 patients, the first one treated by Pralidoxime in the most commonly used doses (1200mg/24H), the second one untreated. Age, sex and nature of poison were taken in consideration to make a matched distribution in both groups. The clinical and biological initial features were nearly the same in both groups; the other therapeutic measures were the same. There was no statistical difference between the both groups for evolutive criteria such as that mortality, duration of artificial ventilation, intubation, atropine administration, decrease in plasma cholinesterase. The results pleading against the use of Pralidoxime, at least at this dose, in anticholinesterase insecticide poisoning, warrant confirmation by prospective randomized studies. The efficiency of Pralidoxime warrants confirmation firstly in the course of poisonings by some clearly identified insecticides, to which pralidoxime is supposed to be the most effective, cater used in high doses, as recommended by some authors.

Cholinesterase Inhibitors↗

Age structure and abundance levels in the entomological evaluation of an insecticide used in the control of Anopheles albimanus in southern Mexico.

Applications of bendiocarb produced a high insecticidal residual effect lasting up to 3 months on the most common indoor house surfaces. No significant decreases in mosquito man-biting rate levels were observed between treated and untreated villages. It was shown that almost equal proportions of intra- and peridomicillary mosquitoes came into contact with the insecticide, indicating that mosquitoes commonly enter houses, rest on treated surfaces and return to bite both indoors and outdoors. Although the insecticide was found to have a significant effect on the percentage parity (interpreted as abundance of older individuals) of intra- and peridomicillary Anopheles albimanus mosquitoes, parity recovered and continued a normal cyclic pattern that appeared to be dependent on relative abundance. The proximity of a treated village to an untreated village (1.2 km) can affect the age structure of mosquito populations through shared common resting and breeding sites.

Age Factors↗

Indoor spraying with the pyrethroid insecticide lambda-cyhalothrin: effects on spraymen and inhabitants of sprayed houses.

In March 1990 a study was carried out in the village of Kicheba, United Republic of Tanzania, in which the pyrethroid insecticide lambda-cyhalothrin was sprayed on all the internal surfaces of houses and other shelters at a coverage of about 25 mg of active ingredient per m2. Every day for 6 days, 12 spraymen and 3 squad-leaders were interviewed about symptoms of overexposure to the insecticide. Each sprayman used up to 62 g of lambda-cyhalothrin over 2.7-5.1 hours every day. All the spraymen complained at least once of symptoms that were related to exposure to lambda-cyhalothrin, the commonest being itching and burning of the face, and nose or throat irritation frequently accompanied by sneezing or coughing. Facial symptoms occurred on non-protected areas only. The symptoms were experienced at various times after the beginning of exposure and disappeared before the following morning. The number of subjects affected and the duration of their facial symptoms were proportional to the amount of compound sprayed. A sample of individuals was interviewed 1 day and 5-6 days after their houses had been sprayed. One woman, who entered her house 30 minutes after the end of spraying, complained of periorbicular itching, but this lasted only a few minutes. No other significant, insecticide-related adverse effect was reported by the inhabitants of the sprayed houses.

Aerosols↗

Effect of subacute insecticide exposure on body weight, drug responses & electrical convulsions in mice.

Effect of subacute insecticide exposure was studied in male albino mice treated with phosphamidon, propoxur or aldrin at 1/40 LD50 dose intraperitoneally daily for 8 wk. The parameters studies included body weight, pentobarbitone (50 mg/kg) sleeping time, chlorpromazine (6 mg/kg) induced motor incoordination and convulsions induced by leptazol (100 mg/kg) and electrical stimulation (18 mA for 0.2 msec). While body weight and electrically induced convulsions were not affected, the effect of various drugs was significantly decreased. The observed changes may be due to the induction of hepatic drug metabolising enzymes by the insecticides. The study suggests that certain dose adjustment of drugs may be necessary in those exposed to insecticides over long periods.

Animals↗

[Proposal for a testing protocol of insecticides against the copepod crustacean Mesocyclops aspericornis Daday 1906].

A method to determine the susceptibility of Mesocyclops aspericornis to insecticides is proposed. Tests were carried out by placing adults females in 100 ml of insecticide solution at 3 temperatures (20 degrees C, 25 degrees C, 30 degrees C). Mortality was scored 24 h after treatment. The results show a low variability of the insecticide effectiveness at these temperatures.

Animals↗

[The effects of six kinds of insecticides on gamasid mites].

The present paper reports on the results of six kinds including 14 chemical or biological insecticides on the gamasid mites. (1) Using organophosphorus compounds such as quinothion, supracide, bromochlophus, sumithion at a dose of 0.2g per m2, at a dose of 1 g per m2 abate, and malathion at a dose of 49 per m2, they were all sufficient to produce 100% mortality on the mites Eulaelaps stabularis; trichlorphon at a dose of 4g per m2 produced 96.4% kill of the mites. (2) Organochloride insecticide BHC containing 93% gamma HCH was not effective on the same mites. (3) at a dose of 0.1 g per m2 of pyrethroid; decis, all the Eulaelaps stabularis were knocked down immediately, but 87% of the mites recovered in 24 hours. (4) The acaricides and cycloprate, the molt-inhibiting hormone Su-urea No. 1 and No. 2, and Bacillus thuringiensis var, Isralensis had not effect on the mites Eulaelaps stabularis and/or Haemolae laps glasgowi, It is suggested that organophosphorus compounds should the insecticide of choice against the gamasid mites.

Animals↗

Maintenance of effective control of Simulium damnosum in the face of insecticide resistance.

The control of onchocerciasis through reduction of its vector Simulium damnosum depends on highly effective insecticide treatments directed against the larvae. As these treatments must be applied weekly over wide areas for many years, ideal conditions for the development of resistance have been created. Resistance to organophosphate compounds has occurred. To maintain effective vector control, an intense operational research effort has been necessary. Close and constant monitoring of susceptibility, combined with cytotaxonomic identification of the tested larvae, has revealed the pattern of spread of the resistance by migration and apparently by hybridization between populations. These studies have helped indicate when it might be possible to contain or eliminate a resistant population. Screening of all available appropriate compounds has led to the selection of replacement compounds in the microbial (Bacillus thuringiensis H14), pyrethroid (permethrin), and carbamate (carbosulfan) groups. Laboratory studies have revealed esterase and multi-function oxidase mechanisms for the existing organophosphate resistance. Cross-resistance tests have shown no cross-resistance to carbamate insecticides with these mechanisms, but negative correlations with most pyrethroids. These considerations, along with estimated risk of future resistance, effects on non-target organisms, and costs have led to a complex alternation pattern of insecticides, with Bacillus thuringiensis H14 being used in the dry season and a series of classical chemical compounds in the wet season. Through these measures, vector control remains a viable method of onchocerciasis control for the WHO Onchocerciasis Control Programme in West Africa.

Africa, Western↗

Pyrethroid insecticides: stereospecific allosteric interaction with the batrachotoxinin-A benzoate binding site of mammalian voltage-sensitive sodium channels.

Pyrethroid insecticides are synthetic neurotoxins patterned after the naturally occurring pyrethrins. Their mechanism of action is thought to involve effects primarily at the voltage-sensitive sodium channel of both insect and mammalian neurons, although recent studies have raised the possibility that these compounds may also act at the gamma-aminobutyric acid receptor-chloride ionophore complex. Here we show that active pyrethroids of the alpha-cyano-3-phenoxybenzyl class allosterically enhance the binding of [3H]batrachotoxinin-A 20-alpha-benzoate to voltage-sensitive sodium channels of rat brain in a dose-dependent and stereospecific manner. Comparison of the rank order of potency for enhancement of [3H]batrachotoxinin-A 20-alpha-benzoate binding and insecticidal activity in a series of toxic stereoisomers of cypermethrin, representative of the class, reveals a correlation between the two measures. These results support a sodium channel site model for pyrethroid action and suggest a useful and practical method to help evaluate the relationship between effects at the sodium channel and insecticidal potency for members of this class of compounds.

Allosteric Regulation↗

Establishment of a standard test method for determining susceptibility of Mesocyclops to different insecticides.

A method to determine the susceptibility of Mesocylops sp. to insecticides was devised. Matured adults were used for the bioassays. Mesocyclops sp. (25 in number) were placed in 24.9 ml of sterilized paddy field water in 5 cm diameter petri dish and 0.1 ml of appropriate stock solution of the insecticide was added. Mortality was scored 24 h after treatment. Among the insecticides tested, Permethrin, Dichlorvos, Temephos, DDT, Carbendazim, Fenitrothion, Zolone and Aldrin were effective against Mesocyclops sp.

Animals↗