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PubMed1993

Intermediate syndrome in organophosphorus poisoning: a prospective study.

OBJECTIVES: To estimate the frequency of the intermediate syndrome in organophosphorus-poisoned patients, and examine its relationship to cholinesterase inhibition and electromyographic findings. Muscle biopsies were available in some patients. DESIGN: A 3-yr prospective study. SETTING: University teaching hospital intensive care unit. PATIENTS: Consecutive patients with acute organophosphorus poisoning (n = 19). MEASUREMENTS AND MAIN RESULTS: We determined the frequency of the intermediate syndrome in poisonings with various organophosphates, duration of (acetyl) cholinesterase inhibition and metabolite excretion, evolution of alterations on repetitive nerve stimulation, type and frequency of muscle lesions. A total of eight of 19 patients developed an intermediate syndrome. In some patients, short relapses of muscarinic symptoms superimposed on the intermediate syndrome. Agents such as methylparathion, fenthion, and dimethoate carry a high risk, but we also noted a prolonged intermediate syndrome in an ethyl-parathion-poisoned patient. Prolonged and severe cholinesterase inhibition occurred during the intermediate syndrome in all patients, and metabolite excretion was prolonged. As the intermediate syndrome evolved, repetitive nerve stimulation initially demonstrated decrement, then increment, and finally, normal responses. Necrotic fibers were noted in muscle biopsies, but these fibers were too sparse to explain severe muscle weakness and were similar in patients with and without the intermediate syndrome. No patients developed delayed neuropathy. CONCLUSIONS: The intermediate syndrome is not rare. Although it is more likely to occur with some organophosphates, it is not confined to a few distinct compounds. This syndrome coincides with prolonged cholinesterase inhibition, and is not due to muscle fiber necrosis. When viewed together, the clinical and electromyographic features are best explained by combined pre- and postsynaptic dysfunction of neuromuscular transmission. The intermediate syndrome is not related to an incipient delayed neuropathy.

Acute Disease↗
PubMed1999

Carbamate and organophosphate poisoning in young children.

OBJECTIVE: Retrospective evaluation of the clinical course of carbamate and organophosphate poisoning in young children. DESIGN: The records of 36 children intoxicated with carbamate and 16 children intoxicated with organophosphate (age range: 2 to 8 years, median: 2.8 years) were examined retrospectively. The carbamate agents were identified as methomyl or aldicarb, and the organophosphate as parathion, fenthion, malathion, and diazinon. The causes of poisoning were accidental ingestion in 46 children and inhalation in six children. CLINICAL SETTING: Pediatric Intensive Care Unit of a teaching hospital. INTERVENTIONS: Gastric lavage was performed, and activated charcoal was administered to all children who had ingested poisonous pesticides. Atropine sulphate was administered intravenously in repeated doses to all children with bradycardia, diarrhea, salivation, and miosis. Obidoxime chloride was administered to patients with organophosphate poisoning and to those in whom the ingested material was unidentified on admission. RESULTS: Predominant symptoms were related to central nervous system depression and severe hypotonia. Other clinical signs such as miosis, diarrhea, salivation, bradycardia, and fasciculation were less frequent, while tearing and diaphoresis were not observed. Pulmonary edema developed in six patients with organophosphte poisoning. Three children required mechanical ventilation for several hours. One child (organophosphate poisoning) died shortly after arrival at the emergency department. All other children recovered completely. CONCLUSION: Based on a relatively large group of young pediatric patients with carbamate and organophosphate poisoning, it is concluded that the clinical presentation differed from those described in adults. Absence of classic muscarinic effects does not exclude the possibility of cholinesterase inhibitor agents poisoning in young children with central nervous system depression.

Adult↗
PubMed1988

Effects of 'closed' houses on the Aedes aegypti eradication programme in Trinidad.

The effects of closed (i.e. locked) houses on the efficiency of control measures against Aedes aegypti (L.) were monitored weekly for 1 year (March 1981 to February 1982) using ovitraps in the towns of Felicity and Trincity, Trinidad. Regular anti-aegypti activities comprised source reduction, focal treatment with larvicidal 1% temephos sand granules and perifocal treatment with 40% wp fenthion. In Felicity, only 6% of houses were closed and after each treatment cycle ovitrap indices showed 100% control. In Trincity, 32% of houses were closed and after each treatment cycle reductions in ovitrap indices were less than 50%. Ae.aegypti eggs sampled in ovitraps totalled 493 (1-70 per positive paddle) in Felicity and 2310 (1-75 per positive paddle) in Trincity; twenty-three ovitraps were found to be positive in Felicity and 247 in Trincity. Ae.aegypti was successfully eliminated from Felicity during weeks 40-52 using focal/perifocal treatment monitored by ovitraps. Control failure in Trincity was attributed to the survival of untreated Ae.aegypti populations in closed houses. Recommendations to improve gaining access for inspection and treatment of closed houses include having control/surveillance workers commence activities at 06.00 hours on weekdays, to work at weekends or during school holidays, or as a last resort to invoke court orders against householders harbouring Ae.aegypti.

Aedes↗
PubMed1990

Distribution and insecticide resistance of the plague flea Xenopsylla cheopis in Maharashtra State, India.

Distributions are reported for commensal rat fleas, predominantly Xenopsylla cheopis (Rothschild), in the State of Maharashtra, India, including the city of Bombay, during 1965-80. The X.cheopis flea index was high in most parts of Maharashtra, but low in Bombay. Rattus rattus Linnaeus is the principal host of X.cheopis, but the host range includes Bandicota bengalensis Gray, Golunda ellioti Gray, Mus musculus Linnaeus, Rattus blandfordi Thomas, R. norvegicus Berkenhout, Suncus caerulaeus Lerr, S. murinus Linnaeus and Tatera indica Hardwicke. X.cheopis was found to have high degrees of resistance to DDT, malathion and fenthion, tolerance to gamma HCH (= gamma BCH) but susceptibility to dieldrin. This insecticide resistance situation may contribute to the high flea indices prevailing in the state, with consequent risks of plague outbreaks. Two other species of rat flea, X.astia Rothschild and X.brasiliensis (Baker) were found to be less common than previously recorded. Their apparent replacement by X.cheopis is tentatively attributed, at least partly, to the selective advantage of insecticide resistance in the latter species.

Animals↗
PubMed1991

The efficacy of insecticides against the screw-worm fly (Chrysomya bezziana).

A number of insecticides used for ectoparasite control in the livestock industry were screened for their efficacy against larvae of the screw-worm fly, Chrysomya bezziana, using in vivo and laboratory tests. Proprietary screw-worm fly treatments (after exposure to outdoor conditions for up to 10 days) were also tested against eggs and adults of C bezziana. Three of these were also evaluated on naturally acquired screw-worm infestations. Residual protection was generally of short duration. Among the organophosphorus compounds, the most effective formulations contained relatively high concentrations (3 to 4% al) of coumaphos, 2.5% fenchlorphos or low concentrations (0.05 to 0.5% al) of diazinon, chlorfenvinphos and fenthion methyl. Two chlorinated hydrocarbon insecticides containing 3% lindane and 5% dieldrin were very effective but are now prohibited for use in Australia. Preparations had serious deficiencies when used under field conditions, especially for treating large, deepseated myiases for which systemic insecticides are recommended. A comparison of methods demonstrated that a laboratory test could supersede live animal experimentation, at least for the initial screening of potential insecticides.

Animals↗
PubMed2002

Identification of an opd (organophosphate degradation) gene in an Agrobacterium isolate.

We isolated a bacterial strain, Agrobacterium radiobacter P230, which can hydrolyze a wide range of organophosphate (OP) insecticides. A gene encoding a protein involved in OP hydrolysis was cloned from A. radiobacter P230 and sequenced. This gene (called opdA) had sequence similarity to opd, a gene previously shown to encode an OP-hydrolyzing enzyme in Flavobacterium sp. strain ATCC 27551 and Brevundimonas diminuta MG. Insertional mutation of the opdA gene produced a strain lacking the ability to hydrolyze OPs, suggesting that this is the only gene encoding an OP-hydrolyzing enzyme in A. radiobacter P230. The OPH and OpdA proteins, encoded by opd and opdA, respectively, were overexpressed and purified as maltose-binding proteins, and the maltose-binding protein moiety was cleaved and removed. Neither protein was able to hydrolyze the aliphatic OP malathion. The kinetics of the two proteins for diethyl OPs were comparable. For dimethyl OPs, OpdA had a higher k(cat) than OPH. It was also capable of hydrolyzing the dimethyl OPs phosmet and fenthion, which were not hydrolyzed at detectable levels by OPH.

Amino Acid Sequence↗
PubMed1975

Inhibition of phenylamide hydrolysis by Bacillus sphaericus with methylcarbamate and organophosphorus insecticides.

The degradation of the phenylamide herbicides monolinuron, linuron, and solan by cultures of Bacillus sphaericus ATCC 12123 was inhibited by the methylcarbamate insecticides metmercapturon, aldicarb, propoxur, and carbaryl and by the organophosphorus insecticides fenthion and parathion. The extent of inhibition was largest with metmercapturon and smallest with parathion inhibition of hydrolysis of the two phenylurea herbicides was greater than of the acylanilide compound. Tests with crude enzyme preparations of aryl acylamidase derived from B. sphaericus showed that the inhibition of the hydrolysis of linuron with methylcarbamates is a competitive one. The insecticides tested did induce the enzyme, nor could they serve as its substrate.

Amidohydrolases↗
PubMed2006

Cluster analysis of the dermal permeability and stratum corneum/solvent partitioning of ten chemicals in twenty-four chemical mixtures in porcine skin.

Assumptions based on absorption from single solvent systems may be inappropriate for risk assessment when chemical mixtures are involved. We used K-means and hierarchical cluster analyses to identify clusters in stratum corneum partitioning and porcine skin permeability datasets that are distinct from each other based on mathematical indices of similarity and dissimilarity. Twenty-four solvent systems consisting of combinations of water, ethanol, propylene glycol, methyl nicotinate and sodium lauryl sulfate were used with 10 solutes, including phenol, p-nitrophenol, pentachlorophenol, methyl parathion, ethyl parathion, chlorpyrifos, fenthion, simazine, atrazine and propazine. Identifying the relationships between solvent systems that have similar effects on dermal absorption formed the bases for hypotheses generation. The determining influence of solvent polarity on the partitioning data structure supported the hypothesis that solvent polarity drives the partitioning of non-polar solutes. Solvent polarity could not be used to predict permeability because solvent effects on diffusivity masked the effects of partitioning on permeability. The consistent influence of the inclusion of propylene glycol in the solvent system supports the hypothesis that over-saturation due to solvent evaporation has a marked effect on permeability. These results demonstrated the potential of using cluster analysis of large datasets to identify consistent solvent and chemical mixture effects.

Animals↗
PubMed2005

Experiences of anticholinesterase pesticide poisonings in an Australian tertiary hospital.

There is limited information regarding the management and outcomes of patients presenting with anticholinesterase pesticide poisoning in Australia. Patients presenting to a tertiary referral hospital with anticholinesterase exposures were identified by discharge coding. The medical records of each patient were retrospectively reviewed. Based on clinical outcome, patients were classified as severe or non-severe poisonings. Forty-one presentations were noted between 1990 and 2003. Eight patients (20%) had severe poisoning of which tachycardia, fasciculations with weakness and metabolic acidosis were common manifestations. The diagnosis was delayed in four patients due to the absence of a clear history, which did not influence patient outcomes or put hospital staff at risk of nosocomial poisoning. The median length of hospital stay was prolonged in severe poisonings (20 days) compared to 12 hours in other patients. Two cases of intermediate syndrome were attributed to fenthion and diazinon, and one case of delayed polyneuropathy to trichlorfon. Cholinesterase activities were performed in only 49% of presentations. The overall mortality was 2.4% (1 death) and the mortality in patients with severe poisoning was 12.5%. The incidence of anticholinesterase poisoning in Australia is low. These outcomes were favourable and comparable with other published data. Measures to enhance the knowledge of medical staff supplemented by validated treatment protocols should be developed. For less significant exposures, an emphasis on adequate documentation of cholinergic signs and cholinesterase activities is necessary for rapid triage and may also have potential forensic implications if not performed.

Adolescent↗
PubMedDate not supplied

The relationship between maternal and fetal effects following maternal organophosphate exposure during gestation in the rat.

Organophosphates, a widely used class of insecticidal compounds, have been shown to cross the placental barrier, and thus potentially affect the developing fetus. This study compared the maternal and fetal effects, including cholinesterase inhibition, following gestational exposure to six organophosphates: tribufos, oxydemeton-methyl, azinphos-methyl, fenamiphos, isofenphos, and fenthion in the Sprague-Dawley rat. All test compounds were administered via oral gavage on gestation days 6-15. Maternal cholinesterase activities (plasma, PChe; erythrocyte, RChe; and brain, BChe) were measured on gestation days 16 and 20, and fetal brain cholinesterase activity was measured on gestation day 20. Effects on gestational parameters (clinical signs, food consumption, and body weight) in adult rats, when observed, were only observed at the highest dose tested for each compound. The inhibition of maternal cholinesterase activities associated with these clinical findings was, for all compounds, always greater than 20%. Moreover, cholinesterase activities were inhibited at dose levels below that which elicited clinical effects. Statistically significant inhibition of at least two of the three cholinesterase enzymes (PChe, RChe, or BChe) was observed on gestation day 16, 24 h following exposure, with all of the organophosphates tested. By gestation day 20, the inhibition of cholinesterase activity was reduced; however, the high dose for all test compounds (except BChe in fenamiphos-treated dams) continued to demonstrate statistically significant inhibition of RChe and BChe. Despite significantly affected cholinesterase activity in the dams, no remarkable effects on fetal BChe were observed with any test compound. No embryotoxicity or teratogenicity were observed with any of the test compounds. These results demonstrate that for the six organophosphates tested: (1) inhibition of maternal cholinesterase activity was the most sensitive indicator of organophosphate exposure; (2) the level of cholinesterase inhibition associated with clinical findings was always greater than 20%; and (3) no effect on fetal cholinesterase activity (BChe) was observed, even at dose levels that continued to demonstrate significant inhibition of maternal cholinesterase activity.

Administration, Oral↗
PubMed1990

Two cases of organophosphate poisoning with development of intermediate syndrome.

Two cases of intermediate syndrome caused by organophosphorus poisoning are reported. Trichlorfon, propoxur (a carbamate pesticide) and fenthion were ingested in both attempts at suicide. After successful conventional therapy during the cholinergic phase, but before the time when the onset of delayed neuropathy might be expected, an intermediate syndrome developed. It affected the proximal limb muscles, neck flexors and respiratory muscles 2 d after pesticide ingestion. The two patients needed respiratory support. Recovery from the intermediate syndrome was complete in both patients, although one subsequently developed delayed neuropathy.

Adult↗
PubMed1997

Determination of organophosphorous pesticides in biological samples of acute poisoning by HPLC with diode-array detector.

We have developed a simple and rapid method for measuring 11 organophosphorous pesticides (dichlorvos, methidathion, salithion, malathion, fenitrothion, fenthion, parathion, diazinon, ethylthiometon, O-ethyl O-(4-nitrophenyl)phenylphosphonothioate (EPN) and chlorpyrifos) and one metabolite (3-methyl-4-nitrophenol) of fenitrothion in serum and urine of acute poisoning patients by HPLC with a diode-array detector. An aliquot of the biological sample after deproteinization by acetonitrile was injected into C18 column using acetonitrile-water as a mobile phase. The detection limits in serum and urine ranged from 0.05 to 6.8 micrograms/ml at a wavelength of 230 nm. This method was successfully applied to two actual cases of acute poisoning.

Aged↗
PubMed2004

Laboratory evaluation of methanolic extract of Atlantia monophylla (Family: Rutaceae) against immature stages of mosquitoes and non-target organisms.

Methanolic extracts of the leaves of Atlantia monophylla (Rutaceae) were evaluated for mosquitocidal activity against immature stages of three mosquito species, Culex quinquefasciatus, Anopheles stephensi, and Aedes aegypti in the laboratory. Larvae of Cx. quinquefasciatus and pupae of An. stephensi were found more susceptible, with LC50 values of 0.14 mg/l and 0.05 mg/l, respectively. Insect growth regulating activity of this extract was more pronounced against Ae. aegypti, with EI50 value 0.002 mg/l. The extract was found safe to aquatic mosquito predators Gambusia affinis, Poecilia reticulata, and Diplonychus indicus, with the respective LC50 values of 23.4, 21.3, and 5.7 mg/l. The results indicate that the mosquitocidal effects of the extract of this plant were comparable to neem extract and certain synthetic chemical larvicides like fenthion, methoprene, etc.

Aedes↗
PubMed2004

Resistance and synergistic effects of insecticides in Bactrocera dorsalis (Diptera: Tephritidae) in Taiwan.

Oriental fruit flies, Bactrocera dorsalis (Hendel), were treated with 10 insecticides, including six organophosphates (naled, trichlorfon, fenitrothion, fenthion, formothion, and malathion), one carbamate (methomyl), and three pyrethroids (cyfluthrin, cypermethrin, and fenvalerate), by a topical application assay under laboratory conditions. Subparental lines of each generation treated with the same insecticide were selected for 30 generations and were designated as x-r lines (x, insecticide; r, resistant). The parent colony was maintained as the susceptible colony. The line treated with naled exhibited the lowest increase in resistance (4.7-fold), whereas the line treated with formothion exhibited the highest increase in resistance (up to 594-fold) compared with the susceptible colony. Synergism bioassays also were carried out. Based on this, S,S,S-tributyl phosphorotrithioate displayed a synergistic effect for naled, trichlorfon, and malathion resistance, whereas piperonyl butoxide displayed a synergistic effect for pyrethroid resistance. All 10 resistant lines also exhibited some cross-resistance to other insecticides, not only to the same chemical class of insecticides but also to other classes. However, none of the organophosphate-resistant or the methomyl-resistant lines exhibited cross-resistance to two of the pyrethroids (cypermethrin and fenvalerate). Overall, the laboratory resistance and cross-resistance data developed here should provide useful tools and information for designing an insecticide management strategy for controlling this fruit fly in the field.

Animals↗
PubMed2006

Development of resistance to spinosad in oriental fruit fly (Diptera: Tephritidae) in laboratory selection and cross-resistance.

In this study, we assessed the potential for the development of resistance to the insecticide spinosad in a laboratory colony of the oriental fruit fly, Bactrocera dorsalis (Hendel) (Diptera: Tephritidae). Resistance was selected by using topical applications of spinosad. After eight generations of selection, the LD50 of the selected line was 408 times greater compared with that of the untreated parental colony. This spinosad-resistant line did not exhibit cross-resistance to 10 other insecticides tested, including six organophosphates (naled, trichlorfon, fenitrothion. fenthion, formothion, and malathion) one carbamate (methomyl), and three pyrethroids (cyfluthrin, cypermethrin, and fenvalerate). However, using lines previously selected for resistance to these same insecticides, two of the 10 lines tested (naled- and malathion-resistant) did show some cross-resistance to spinosad. Also, oriental fruit flies from different field collections where naled and malathion have been used for control purposes displayed some resistance to spinosad. In addition, the effects of direct ingestion of spinosad through dietary supplementation also were tested. Overall, the laboratory resistance and cross-resistance data developed in this study provide new information that will be useful for managing the development of resistance when spinosad is used to control B. dorsalis in the field.

Animals↗
PubMed2001

Topical application as a method for comparing the effectiveness of insecticides against cat flea (Siphonaptera: Pulicidae).

A topical (micro-droplet) bioassay is described for the cat flea, Ctenocephalides felis (Bouche). Key parameters are the short carbon dioxide anesthetization and the use of 0.1 ml of acetone per flea. The method was used to compare the effectiveness of 13 insecticides. LD95 values in nanograms per flea were nitenpyram 0.68, fipronil 0.69, deltamethrin 0.70, imidacloprid 0.81, cypermethrin 5.4, fenthion 8.0, diazinon 12, permethrin 19, malathion 29, bendiocarb 170, DDT 710, propoxur 1,300, carbaryl >10,000. Experiments repeated 2-5 yr later, with five of the chemicals, in a different facility, showed only small shifts in potency (0.38- to twofold of the original LD50 values).

Animals↗
PubMed2005

Organophosphate-induced delayed polyneuropathy.

Organophosphate-induced delayed polyneuropathy (OPIDP) is a rare toxicity resulting from exposure to certain organophosphorus (OP) esters. It is characterised by distal degeneration of some axons of both the peripheral and central nervous systems occurring 1-4 weeks after single or short-term exposures. Cramping muscle pain in the lower limbs, distal numbness and paraesthesiae occur, followed by progressive weakness, depression of deep tendon reflexes in the lower limbs and, in severe cases, in the upper limbs. Signs include high-stepping gait associated with bilateral foot drop and, in severe cases, quadriplegia with foot and wrist drop as well as pyramidal signs. In time, there might be significant recovery of the peripheral nerve function but, depending on the degree of pyramidal involvement, spastic ataxia may be a permanent outcome of severe OPIDP. Human and experimental data indicate that recovery is usually complete in the young. At onset, the electrophysiological changes include reduced amplitude of the compound muscle potential, increased distal latencies and normal or slightly reduced nerve conduction velocities. The progression of the disease, usually over a few days, may lead to non-excitability of the nerve with electromyographical signs of denervation. Nerve biopsies have been performed in a few cases and showed axonal degeneration with secondary demyelination. Neuropathy target esterase (NTE) is thought to be the target of OPIDP initiation. The ratio of inhibitory powers for acetylcholinesterase and NTE represents the crucial guideline for the aetiological attribution of OP-induced peripheral neuropathy. In fact, pre-marketing toxicity testing in animals selects OP insecticides with cholinergic toxicity potential much higher than that to result in OPIDP. Therefore, OPIDP may develop only after very large exposures to insecticides, causing severe cholinergic toxicity. However, this was not the case with certain triaryl phosphates that were not used as insecticides but as hydraulic fluids, lubricants and plasticisers and do not result in cholinergic toxicity. Several thousand cases of OPIDP as a result of exposure to tri-ortho-cresyl phosphate have been reported, whereas the number of cases of OPIDP as a result of OP insecticide poisoning is much lower. In this article, we mainly discuss OP pesticide poisoning, particularly when caused by chlorpyrifos, dichlorvos, isofenphos, methamidophos, mipafox, trichlorfon, trichlornat, phosphamidon/mevinphos and by certain carbamates. We also discuss case reports where neuropathies were not convincingly attributed to fenthion, malathion, omethoate/dimethoate, parathion and merphos. Finally, several observational studies on long-term, low-level exposures to OPs that sometimes reported mild, inconsistent and unexplained changes of unclear significance in peripheral nerves are briefly discussed.

Animals↗
PubMed2006

Estimation of pesticide runoff from paddy fields to rural rivers.

The runoff characteristics of pesticides from paddy fields to rural rivers were investigated over a period of three years in Hokkaido Prefecture, Japan. High pesticide concentrations were usually observed in rivers during pesticide application periods. In one year, the growth of rice seedlings slowed down after transplantation owing to low temperatures and lack of sunshine, and many farmers delayed herbicide application. In that year, high-concentration runoff of herbicides in rivers was observed 1-3 weeks later than in average years. The pesticide runoff rates ranged from 0.3% for fenthion to 42% for benfuresate. The runoff rates of pesticides applied post-flood were large. Furthermore, the larger the water solubility of the pesticide, the larger the runoff rate. The highest concentrations of herbicides in paddy water were observed on the day of application or 1-2 days later, and the concentrations decreased exponentially afterwards. The half-lives of the herbicides ranged from 1.2 days for pretilachlor and esprocarb to 5 days for simetryn; the concentrations of the herbicides in paddy water had decreased to 1/10 of their initial concentrations by about 7 days after application. Therefore, the runoff amounts of pesticides from paddy fields could be decreased by improving irrigation-water management.

Acetanilides↗