Inhibitor Report for: Pirimiphos-methyl

A 63-year-old male was admitted to a district hospital after ingesting ethanol and pirimiphos-methyl (PM) with suicidal intentions. History included alcoholic cirrhosis with alcoholism, adiposity, diabetes with cerebral microangiopathy, chronic renal insufficiency, heparin-induced thrombocytopenia, and status post necrotizing fasciitis. Emergency medical service reported an alert patient without signs of cholinergic crisis; activated charcoal and atropine were administered. Upon hospital arrival, he received fluid resuscitation, activated charcoal, and atropine. He was transferred to a toxicology unit the next day. On admission, he had no cholinergic signs (dry mucous membranes, warm skin, and mydriatic pupils) requiring small atropine doses (0.5smg per hour). Four hours after admission, he developed bradycardia and respiratory distress, necessitating intubation. He received atropine by continuous infusion for 7sdays (248smg total) and obidoxime (bolus and continuous infusion). PM, pirimiphos-methyl-oxon (PMO), and phosphorylated tyrosine (Tyr) adducts derived from human serum albumin were analyzed in vivo. Cholinesterase status (acetylcholinesterase (AChE), butyrylcholinesterase (BChE), inhibitory activity of patient plasma and reactivatability, and phosphorylated BChE-derived nonapeptides) was measured in vivo. Obidoxime and atropine were monitored. PM and PMO were detectable, PM with maximum concentration -24sh post admission (p.a.) and PMO at -18sh p.a. Tyr adducts were detectable. AChE in vivo was suppressed on admission, increased continuously after starting obidoxime, and reached maximum activity after -30sh. AChE in vivo and reactivatability remained at the same level until the end of monitoring. BChE was already suppressed on admission; termination of the antidote treatment was possible after BChE had recovered to 1/5th of its normal value and extubation was possible after BChE had recovered to 2/5th. While a substantial part of BChE was already aged on admission, aging continued peaking at -24sh p.a. After initiating obidoxime treatment, plasma levels increased until obidoxime plasma levels reached a steady state. On admission, plasma atropine level was low; it increased with the start of the continuous infusion. Afterward, the level dropped to a steady state. The clinical course was characterized by bouts of pneumonia, necessitating re-intubation and prolonged ventilation, sepsis, delirium, and a peripheral neuropathy. After psychiatric evaluation, the patient was discharged to a neurological rehabilitation facility after 77 days of hospital care.

A 63-year-old male was admitted to a district hospital after ingesting ethanol and pirimiphos-methyl (PM) with suicidal intentions. History included alcoholic cirrhosis with alcoholism, adiposity, diabetes with cerebral microangiopathy, chronic renal insufficiency, heparin-induced thrombocytopenia, and status post necrotizing fasciitis. Emergency medical service reported an alert patient without signs of cholinergic crisis; activated charcoal and atropine were administered. Upon hospital arrival, he received fluid resuscitation, activated charcoal, and atropine. He was transferred to a toxicology unit the next day. On admission, he had no cholinergic signs (dry mucous membranes, warm skin, and mydriatic pupils) requiring small atropine doses (0.5smg per hour). Four hours after admission, he developed bradycardia and respiratory distress, necessitating intubation. He received atropine by continuous infusion for 7sdays (248smg total) and obidoxime (bolus and continuous infusion). PM, pirimiphos-methyl-oxon (PMO), and phosphorylated tyrosine (Tyr) adducts derived from human serum albumin were analyzed in vivo. Cholinesterase status (acetylcholinesterase (AChE), butyrylcholinesterase (BChE), inhibitory activity of patient plasma and reactivatability, and phosphorylated BChE-derived nonapeptides) was measured in vivo. Obidoxime and atropine were monitored. PM and PMO were detectable, PM with maximum concentration -24sh post admission (p.a.) and PMO at -18sh p.a. Tyr adducts were detectable. AChE in vivo was suppressed on admission, increased continuously after starting obidoxime, and reached maximum activity after -30sh. AChE in vivo and reactivatability remained at the same level until the end of monitoring. BChE was already suppressed on admission; termination of the antidote treatment was possible after BChE had recovered to 1/5th of its normal value and extubation was possible after BChE had recovered to 2/5th. While a substantial part of BChE was already aged on admission, aging continued peaking at -24sh p.a. After initiating obidoxime treatment, plasma levels increased until obidoxime plasma levels reached a steady state. On admission, plasma atropine level was low; it increased with the start of the continuous infusion. Afterward, the level dropped to a steady state. The clinical course was characterized by bouts of pneumonia, necessitating re-intubation and prolonged ventilation, sepsis, delirium, and a peripheral neuropathy. After psychiatric evaluation, the patient was discharged to a neurological rehabilitation facility after 77 days of hospital care.

Chronic occupational exposure to organophosphorus and carbamate-type pesticides significantly inhibits acetylcholinesterase activity and causes morbidity. This study on mice was designed to evaluate their amino profile and to identify signs of hepatic dysfunction following their chronic exposure to mixtures of organophosphorus pesticides. Laboratory mice were exposed to a formulated mixture of the six organophosphorus pesticides (Dimethoate, Chlorpyrifos, Profenofos, Pirimiphos methyl, Triazophos and Dimethoate) most commonly used in agriculture in this region of the Middle East. Doses (10% of LD50 of the mixture) were given once a week by gavage in corn oil for 7 weeks; the control group was given only corn oil. At the end of the exposure period, mice were culled and blood samples were collected to determine erythrocyte acetylcholinesterase activity, biochemical markers of liver function and concentrations of serum amino acids. Erythrocyte acetylcholinesterase activity and total serum proteins decreased significantly in the exposed group. Serum concentrations of alanine aminotransferase and aspartate aminotransferase, alanine, glutamic acid, glycine, isoleucine, leucine, methionine, ornithine, proline, serine, threonine and valine were significantly increased in the exposed mice, while serum levels of cystine were decreased significantly. There were also non-significant increases in serum alkaline phosphatase, gama-glutamyl transpeptidase and some of the other amino acids. Chronic exposure to mixtures of organophosphorus pesticides is associated with decreased acetylcholinesterase activity, hepatic dysfunction and disturbance of amino acids profile. Biochemical indices of hepatocellular injury and disturbed amino acid metabolism may be of value as markers of chronic exposure to such pesticides.

Oxidative damage was quantified in the liver of rats by measuring the levels of 8-OH-2-deoxyguanosine (8-OH-2DG) relative to 2-deoxyguanosine in DNA after treating rats for 10 days at a total dose of 1 mg/kg/day with a mixture of the 15 pesticides most commonly found in Italian foods (comprised of dithiocarbamate, benomyl, procymidone, methidathion, chlorpyrifos-ethyl, parathion-methyl, chlorpropham, parathion, vinclozolin, chlorfenvinphos, pirimiphos ethyl, thiabendazole, fenarimol, diphenylamine and chlorothalonil). We fractionated this pesticide mixture into subgroups in order to determine which molecules, if any, induced DNA oxidative damage. The administration of diphenylamine (0.09-1.4 mg/kg/day) and chlorothalonil (0.13-1 mg/kg/day) induced a dose-dependent increase in 8-OH-2DG levels in liver DNA. The other 13 pesticides of the mixture on the contrary, did not produce oxidative liver DNA damage. These results indicate that the toxicity of low doses of pesticide mixtures present in food might be further reduced by eliminating diphenylamine and chlorothalonil.

To elucidate whether pesticide toxicity in higher animals involves pesticide-induced dysfunction of the intracellular protein catabolic process, we have determined the effect in vivo of the organophosphate insecticide pirimiphos-methyl on the activities of representative protein catabolising cytoplasmic and lysosomal proteases (responsible for the various stages of the protein degradation cascade and essential for normal cell functioning) in heart, kidney, brain and liver target tissues in the rat. In liver tissue (the major site of pesticide metabolism), the activities of all of the cytoplasmic proteases investigated (alanyl-, arginyl-, leucyl aminopeptidases, dipeptidyl aminopeptidase IV, tripeptidyl aminopeptidase, proline endopeptidase) were significantly inhibited (by 20-40% of control activity) following administration of 10 mg pirimiphos-methyl/kg bodyweight, whereas of the lysosomal proteases investigated, only the activities of dipeptidyl aminopeptidase I and cathepsin D were significantly reduced (by 15-20% of control activity). In contrast, there was no insecticide-induced inhibition of protease activities in heart, kidney or brain tissues; some lysosomal enzymes (dipeptidyl aminopeptidase I, cathepsins L and D) showed significantly increased activities in these tissues (the reason for which remains to be determined). We conclude that the effect of pirimiphos-methyl on proteolytic enzyme activities differs in different target tissues, and that pirimiphos-methyl induced inhibition of proteases in liver tissue may represent a previously unrecognised toxicity hazard in higher animals.

A field population of Lutzomyia longipalpis from La Rinconada, Lara State, an endemic focus of visceral leishmaniasis in Venezuela, was tested for susceptibility to organochlorine (DDT 2%), carbamate (propoxur 0.01%), organophosphate (malathion 2%, fenitrothion 1%, and pirimiphos methyl 1%), and pyrethroid (deltamethrin 0.06%, lambdacyhalothrin 0.06%, and permethrin 0.2%) insecticides. Susceptibility to the insecticides tested was evaluated in the field population of L. longipalpis and compared with a laboratory reference strain. The (LT95) to propoxur and malathion insecticides for the field population was lower than the LT95 for the laboratory reference strain, demonstrating high susceptibility to these compounds. A low level of resistance at LT50 (< 3-fold) was found for fenitrothion, pirimiphos methyl, and permethrin insecticides, but no resistance was detected at LT95. No significant resistance at the LT50 and LT95 was detected for the pyrethroids deltamethrin and lambdacyhalothrin. The susceptibility levels of L. longipalpis to the insecticides tested are discussed in view of a future control program against endophilic vectors of leishmaniases based on the use of pesticides.

A rapid procedure has been developed that allows a single-step, selective extraction and cleanup of organophosphate (OP) pesticide residues from milk dispersed on solid-matrix diatomaceous material filled into disposable cartridges by means of light petroleum saturated with acetonitrile and ethanol. Recovery experiments were carried out on homogenized commercial milk (3.6% fat content) spiked with ethanolic solutions of 24 OP pesticides, viz., ethoprophos, diazinon, dimethoate, chlorpyrifos-methyl, parathion-methyl, chlorpyrifos-ethyl, malathion, isofenphos, quinalphos, ethion, pyrazophos, azinphosethyl, heptenophos, omethoate, fonofos, pirimiphos-methyl, fenitrothion, parathion, chlorfenvinphos, phenthoate, methidathion, triazophos, phosalone, azinphos-methyl, at levels ranging for the different OP pesticides from 0.02 mg/kg to 1.11 mg/kg. Average recoveries of four replicates were in the range 72-109% for the different OP pesticides, with relative standard deviations (R.S.D.) from ca. 1 to 19%, while dimethoate and omethoate were not recovered. Coextracted fatty material amounted to an average of about 4.0 mg/ml of milk. The extraction procedure requires about 30 min. The main advantages are that extraction and cleanup are carried out in a single step, emulsions do not occur, several samples can be run in parallel by a single operator, reusable glassware is not needed and simple operations are required.

Residue study was performed on several insecticides which could contaminate local Egyptian beans. The effect of storage periods and various processing steps on lowering the residues of malathion and pirimiphos methyl in treated seeds and their processed products were investigated. The data indicated that malathion and pirimiphos methyl persisted for more than 90 days on and in stored mature dry broad beans after postharvest treatment. However, stored broad beans could be safely used for human consumption after 90 days when the insecticide residues reached safe levels. Washing removed 69 and 75% of malathion and pirimiphos methyl residues of treated broad beans, respectively. Malathion residue was not detected in various processed products. More than 89 and 99% of malathion residues were absent in dehulled and heated dehulled broad beans. In addition, pirimiphos methyl residues were reduced to 92, 97, 87, 99, 99, and 95% from the initial levels in treated beans following dehulling, cooking of dehulled beans, germination, cooking of germinated beans and cooking of the beans by the common method and under pressure, respectively.

During Fiscal Years 1989-1994, the U.S. Food and Drug Administration (FDA) collected and analyzed 545 domestic surveillance samples of mixed feed rations (172 for cattle, 125 for poultry, 83 for swine, 61 for pets, 56 for fish, and 48 miscellaneous). All samples were analyzed by gas-liquid chromatography for organohalogen and organophosphorus pesticides. Of the 545 samples, 88 (16.1%) did not contain detectable pesticide residues. In the 457 samples with detectable pesticide levels, 804 residues (654 quantitable and 150 trace) were found. None of these 804 residues exceeded regulatory guidance. Malathion, chlorpyrifos-methyl, diazinon, chlorpyrifos, and pirimiphos-methyl were the most commonly detected pesticides. These 5 organophosphorus pesticides accounted for 93.4% of all pesticide residues detected (malathion, 52.9%; chlorpyrifos-methyl, 25.2%; diazinon, 7.7%; chlorpyrifos, 4.9%; and pirimiphos-methyl, 2.7%). Their median values in samples containing quantitable levels ranged from 0.014 to 0.098 ppm. The most commonly detected organohalogen compounds were methoxychlor, DDE, PCB, dieldrin, pentachloronitrobenzene, and lindane. These 6 compounds combined accounted for only 4.1% of all residues detected. FDA is continuing its pesticide surveillance of feeds to help ensure animal safety and prevent violative residues in food derived from animals.

The toxicity of dimethoate, azinphos-methyl, diazinon, pirimiphos methyl, organophosphorus insecticides, and benomyl (a benzimidazole fungicide) singly and in mixture was studied in a human neuroblastoma cell line, SH-SY5Y. The cells were incubated for 30 min and 4 h with pesticides at concentrations ranging from 0.4 to 100 micrograms/ml, or with the same compounds mixed as follows: (a) dimethoate-diazinon-azinphos; (b) benomyl-pirimiphos; (c) all together. Pesticides in the mixtures were at the same concentration used when tested singly. Diazinon, azinphos-methyl and pirimiphos, but not dimethoate and benomyl, inhibited acetylcholine esterase (AchE) activity, whereas all the compounds inhibited protein synthesis in the following order: benomyl > azinphos > diazinon >> pirimiphos = dimethoate. The mixtures showed a toxicity on AchE activity at a maximum equal to that of the most active compound in the mixture. On the contrary, the mixture were more toxic than the single compounds on protein synthesis, and in certain cases potentiation occurred. Therefore, we can conclude that it is not feasible to predict the toxicity of pesticide mixtures on the basis of the results of the toxicity of single components.

Although the recent distribution of yellowfever mosquito, Aedes aegypti (L.), in Pakistan has been restricted to the port city of Karachi, adult and immature mosquitoes breeding in imported tires in warehouses at Landi Kotal (North-West Frontier Province) were identified as Ae. aegypti. The patterns of tire trade and the current disjunct distribution of Ae. aegypti indicated that the introduction into Landi Kotal may have been either from Karachi or India. Thermal fog application of pirimiphos-methyl and residual spray of malathion during 1993 reduced abundance in October-November. Living larvae or adults were not found during January 1994, apparently because of cold weather. However, Ae. aegypti reappeared during May-June 1994, most probably from eggs that overwintered. Population increased during late August when another round of spray using the same insecticides and fenthion as an additional larvicide again reduced abundance. Although this mosquito apparently has not spread into neighboring areas, its survival at Landi Kotal through all seasons despite control measures indicates its potential of becoming established in other areas of Pakistan.

Populations of Culex pipiens were sampled from 8 locations in Cyprus between 1987 and 1993. All population samples generally revealed organophosphate resistance to malathion, temephos, chlorpyrifos, fenthion, dichlorvos, and pirimiphos methyl, in decreasing order of magnitude. Of 7 populations assessed with the carbamate propoxur, all proved to be resistant to different degrees. Of the 6 populations tested with permethrin, 2 were resistant to permethrin. Resistance was associated with the presence of 5 different overproduced esterases (esterases A1, A2, A5, B2, and B5) as well as an insensitive form of acetylcholinesterase. These results are discussed in relation to the ongoing mosquito abatement program in Cyprus and to similar programs in other parts of the world.

A Culex quinquefasciatus Say 1823 strain with resistant genes to organophosphates was tested in the laboratory to know the reproductive potential after exposure, as larvae, at the LC30 and LC70 (mg/l) of three organophosphorus insecticides: malathion, chlorpyrifos and methyl-pirimiphos. Data showed that fecundity was decreased significantly by malathion at LC30 = 0.0025 and LC70 = 0.0075, whereas fertility has a no significant decrement by chlorpyrifos and methyl-pirimiphos at the LC70 (0.000016, 0.00043). The sexual index was affected by chlorpyrifos and methyl-pirimiphos showing a greater number of adult females.

Three plant products with known insecticidal properties, a dry extract of flowers of Chrysanthemum cinerariaefolium (Trevir.) Vis. produced in Rwanda, an ethanol extract of seeds of neem, Azadirachta indica A. Juss, and crushed leaves of Tetradenia riparia Hochst Codd, a traditional Rwandan medicine, were mixed with beans, Phaseolus vulgaris L., for storage protection. These plant-protected beans were compared with "off the shelf' beans that were being sold to consumers by the Rwandan National Agricultural Products Marketing Organization (OPROVIA). A trained sensory panel determined that beans treated with neem and C. cinerariaefolium were as acceptable after 8 months storage as those being sold throughout Rwanda by the marketing organization. Beans marketed by this organization were all treated with the standard insecticide application in Rwanda, 0.01% weight/weight pirimiphos methyl in a powder formulation. Instrumental hardness (% hard-to-cook/mean gram force) after 20 months of storage was acceptable for beans stored with neem or with C. cinerariaefolium or with the conventional government application of pirimiphos methyl. Use of either neem or C. cinerariaefolium for storage protection should not affect consumer acceptance of dry beans.

Resistance to the organophosphates (OP) temephos, malathion, and pirimiphos methyl, and the carbamate propoxur was found to be low (< 5-fold) in 3 Aedes aegypti populations collected from Falcon and Aragua states of Venezuela. Resistance to chlorpyrifos (OP), permethrin, and lambda-cyhalothrin (pyrethroids) was moderate (7-fold) in both populations. Mechanisms of resistance were investigated with the synergists piperonyl butoxide (mixed function oxidase inhibitor) and S, S, S-tributyl phosphorothioate (DEF, an esterase inhibitor). Nonspecific esterase and oxidase enzymes played a significant role in OP and carbamate resistance, respectively. Resistance to pyrethroid insecticides was not affected by DEF or piperonyl butoxide. This suggested the presence of another mechanism such as altered target site sensitivity (kdr). Biochemical tests showed significantly greater amounts of esterase activity in field strains, whereas insensitive acetylcholinesterase was not involved in either OP or carbamate resistance. These results must be considered in future control programs for Ae. aegypti, because OPs and pyrethroids are currently used in vector control in most countries of Central and South America.

An outbreak of pediculosis at primary schools was recorded in the Czech Republic in 1992. Almost 20% of children in some schools were infested. This outbreak can be attributed to the resistance of head lice to permethrin, which has not been mentioned in literature yet. The resistance factors established in three towns range between 2 and 385 and between 5 and 557 for LC50 and LC90 values, respectively. This resistance has developed after exclusive use of pyrethroids lotion and shampoo in the Czech Republic since 1978, and it was accompanied by a cross-resistance to d-phenothrin and bioalethrin. But the susceptibility of head lice to malathion and pirimiphos-methyl in 1992 was very similar to that found in 1981. The lotion containing 0.3% of malathion (Diffusil H92 M) has been fully effective against the resistant lice. When introduced into the practice, it quickly reduced the infestation of children in primary schools. The other lotion and shampoo containing 0.3% and 0.7% of pirimiphos-methyl respectively were found to be effective as well.

Rat primary hepatocyte cultures have been used to study the effect of Benomyl alone or in combination with Pirimiphos-methyl. The results presented demonstrate that Benomyl alone is responsible for the microtubular disorganization in both a time- and dose-dependent manner, that the effect is reversible after the agent is removed, and that Benomyl is a potent glutathione-depleting agent. Pirimiphos-methyl, alone or combined with Benomyl had no effect on microtubule organization, but reinforced the decrease in glutathione.

Anopheles culicifacies (probably species A) is the main vector of malaria in Baluchistan, southeastern Iran. Adult mosquitoes were collected during 1990-92 by five methods of sampling: knock-down pyrethrum space-spray indoors, human and animal bait (18.00-05.00 hours), pit shelters and CDC light traps, yielding 62%, 3%, 6%, 4% and 25% of specimens, respectively. Whereas spray-catches comprised c. 70% gravid and semi-gravid females, light trap catches were mostly (c. 60%) unfed females, while females from pit shelters comprised all abdominal stages more equally (13-36%). An.culicifacies populations peaked in April-May and rose again during August-November. Densities of indoor-resting mosquitoes were consistently greater in an unsprayed village than in villages subjected to residual house-spraying with propoxur, malathion or pirimiphos-methyl. Monthly malaria incidence generally followed fluctuations of An.culicifacies density, usually with a peak in May-June.

Four organophosphorus pesticides (azinphos-methyl, diazinone, dimethoate, and pirimiphos-methyl), and one carbamate (benomyl) were tested for cytotoxicity, reverse mutation and gene conversion in Saccharomyces cerevisiae D7, with and without the S9 metabolic system. Furthermore, two mixtures of the above compounds, namely benomyl + pirimiphos-methyl (6/1 ratio) and dimethoate + diazinone + azinphos-methyl (10/4/6 ratio) were tested in the same experimental model. Azinphos-methyl, benomyl, and pirimiphos-methyl alone did not induce any genotoxic effect, whereas azinphos-methyl and diazinone were active in inducing reversion and gene conversion. The benomyl + pirimiphos-methyl mixture did not show any genotoxic activity. The dimethoate + diazinone + azimphos-methyl mixture was genotoxic, although an antagonistic effect between the components was observed. The addition of S9 post-mitochondrial liver fraction decreased the activity of both single and mixed genotoxic agents.

Lymphocytes obtained from 5 healthy donors were incubated with a mixture of 15 pesticides commonly found in foods of central Italy (dithiocarbamates (20.7%), benomyl (19.6%), thiabendazole (14.9%), diphenylamine (14.4%), chlorthalonil (13.1%), procymidone (8.0%), methidathion (2.3%), chlorpyrifos-ethyl (2%), fenarimol (1.9%), parathion-methyl (1%), chlorpropham, parathion, vinchlozolin, chlorfenvinphos and pirimiphos-ethyl (< 1%)). The percent of each pesticide in the mixture was proportional to its average concentration in foods. Incubated with the lymphocytes at a concentration of 1-20 micrograms/ml the pesticide mixture did not induce significant variations in the number of hypodiploid, hyperdiploid and polyploid cells or in the number of chromosome and chromatid aberrations. On the contrary, we observed a dose-dependent increase in the number of nonsynchronous centromeric separations which reached the level of 37.9% at 20 micrograms/ml of pesticide mixture in the incubation medium. This effect was not observed when benomyl was excluded from the mixture. These data show that the removal of benomyl could decrease the toxicity of pesticide residues present in human food.

A method for analysis of human cadaveric organs for actellik, an organophosphorus insecticide (pyrimiphos methyl), has been developed, consisting in the agent isolation using hexan, separation of extraction substances by extraction redistribution between hexan and dimethylformamide, and subsequent preparative chromatographic isolation in a sorbent layer (KSK silica gel or silicic acid) with chloroform used as solvent. This method permits isolation of 49-52% of actellic added to the liver. A method of purified extract analysis by thin-layer chromatography on silufol plates and KSK silica gel using a complex of chromogenic reagents and selective solvent system has been worked out. The method permits detection of 0.12 to 0.6 mg of actellic in 25 g of organic tissue depending on analysis conditions.

The level of 8-OH-2-deoxyguanosine in rat liver DNA was measured as an index of oxidative damage after treating rats for 10 days at a dose ranging from 0.75 to 10 mg/kg with a mixture of 15 pesticides (dithiocarbamate, benomyl, thiabendazole, diphenylamine, chlorthalonil, procimidone, methidathion, chlorpyrifos-ethyl, fenarimol, parathion-methyl, chlorpropham, parathion, vinclozolin, chlorfenvinphos, pirimiphos-ethyl) commonly found in foods of central Italy. At the doses of 0.75 and 1 mg/kg DNA levels of 8-OH-2-deoxyguanosine were significantly increased relative to controls, whereas at higher doses (2.5, 5, 10 mg/kg) the levels returned to control values. The administration of the pesticide mixture dose dependently reduced benzo(a)pyrene hydroxylase, N-demethylase activities, glutathione peroxidase, glutathione reductase, glutathione-S-transferase and thiol transferase activities in the liver. The results show that the pesticide mixture induced free radical DNA damage at low doses. However, at higher doses it produced a depression of cellular metabolism, inhibiting a further expression of oxidative damage.

Dimethoate, azinphos-methyl, diazinon and pirimiphos-methyl, widely used organophosphorous insecticides, and benomyl, a benzimidazole fungicide, induce different cytotoxic effects on the human leukemia cell line HL-60. Among the insecticides tested, only azinphos and diazinon induced a dose-related inhibition of protein synthesis in HL-60 cells at 24 h, at 60 and 40 micrograms/ml medium, respectively. Dimethoate and pirimiphos were not active up to 100 micrograms/ml. Benomyl strongly inhibited protein synthesis at 50 micrograms/ml and the polymerisation of actin to give cytoskeletal microfilaments (F-actin) at 30 micrograms/ml. Mixtures of benomyl-pirimiphos and dimethoate azinphos-diazinon were also investigated. Pirimiphos, when present in equal concentration, antagonized the inhibitory effect of benomyl on protein synthesis at 4 h, but not at 24 h. The effect of the other insecticide mixture on the same parameter was greater than that of the two active components, diazinon and azinphos given singly.

The response of Anopheles gambiae Giles s.s and Culex quinquefasciatus Say to insecticide-treated netting in a wind tunnel permeated with guinea pig odors was recorded on videotape. With no insecticide present, mosquitoes spent 99% of the time on the netting, either at rest or occasionally walking across it. On nylon netting, permethrin at 50, 400, and 1,000 mg m-2 irritated the mosquitoes, causing them to spend significantly more time away from the netting and relatively more time walking than at rest when they were on the netting. These effects increased with dose, but the total contact time was always enough to cause 100% mortality. At the two highest doses, knockdown occurred before the end of the 10-min observation period. A wash-resistant formulation of permethrin (ICI patent) reduced irritancy without affecting mortality or knockdown. A mixture of pirimiphos-methyl and permethrin also was less irritating than permethrin alone. Pirimiphos-methyl at 400 mg m-2 was the least irritating of all treatments tested. Lambda-cyhalothrin at 2.5, 6, and 25 mg m-2 was less irritating than permethrin, even though the doses of lambda-cyhalothrin used were far more toxic than the permethrin doses as measured by LT50. Cotton netting significantly reduced the toxicity and irritancy of the permethrin treatments. Cx. quinquefasciatus was less irritated by permethrin but more irritated by lambda-cyhalothrin, than was An. gambiae. Our study indicated that mosquitoes are so strongly attracted to a host protected by netting, they will tolerate relatively high doses of irritating insecticides long enough to pick up lethal doses.

The pesticides benomyl, a benzimidazole fungicide, and pirimiphos-methyl, an organophosphorus insecticide, were tested separately and in combination at a ratio of 6:1, a mixture frequently found in foodstuffs by residual analysis, to determine their possible genotoxic action. The effect was measured by the micronucleus test carried out on cultured rat hepatocytes stimulated to proliferate by epidermal growth factor (EGF). Adult rat hepatocytes were exposed in vitro for 48 h to the substances at increasing non-cytotoxic doses, chosen on the basis of cytotoxicity tests such as LDH and Neutral red assays. Benomyl induced a significant dose-related increase in micronucleus frequency; in contrast, pirimiphos-methyl was not genotoxic at any dose tested. When the hepatocytes were exposed to the two pesticides together at increasing doses, an enhancement in micronucleus frequency similar to that of benomyl alone was found, indicating that at this ratio and non-cytotoxic doses (up to 25 micrograms/ml benomyl + 4.2 micrograms/ml pirimiphos-methyl) no interaction occurs.

Technical hexachlorocyclohexane (100 mg/kg/d) and pirimiphosmethyl EC 50 (250 mg/kg/d) given individually and in combination to female rats for 7, 15 or 30 d by skin application caused poisoning, pathomorphological changes in vital organs, and significant enzymatic changes in liver and serum. The changes produced by the 2 compounds in combination did not suggest potentiation at the tested dose levels.

This study was carried out to investigate the effect of different washing solutions on the removal of Actellic residue from fresh and processed vegetables, namely; spinach and eggplant. Also, to identify the effect of Actellic residue on the health status of mice when fed these contaminated vegetables. The amount of insecticide residue detected using GLC indicated that, tap water, sodium hydroxide solution and potassium permanganate solution gave high percent removal. However, processing did not remove more than 45% except for grilling of eggplant which removed 88.17%. Meanwhile, changes in some hepatic biological parameters were well recognized in the groups of mice fed contaminated- unwashed either processed or unprocessed vegetables.

To determine the toxicological effects of complex mixtures of pesticides, we obtained data on 100 pesticide residues in common foods of central Italy. Fifteen pesticides were more regularly detected at higher levels (dithiocarbamates, benomyl/carbendazim, thiabendazole, diphenylamine, chlorthalonil, procymidone, fenarimol, chlorpropham, vinchlozolin, methidathion, chlorpyriphos-ethyl, parathion-methyl, parathion, chlorfenviphos, pirimiphos-ethyl). Using itemized data on daily food consumption in Italy, we calculated that the average exposure for an adult subject was 716 micrograms/day, ranging from 148 micrograms of dithiocarbamates to 1 microgram of pirimiphos-ethyl. We made a mixture of these 15 pesticides at concentrations proportional to the ratio determined in foods and tested it with the Salmonella-microsome assay, with and without metabolic activation with PCB-induced rat liver S9. No mutagenic activity was observed at concentrations up to 500 micrograms/plate. We also tested the same mixture at concentrations ranging from 0.1 to 20 micrograms/ml on human lymphocytes in vitro, and observed a slight but statistically significant increase in sister-chromatid exchanges at 1 microgram/ml. We also administered the mixture in corn oil by gavage to Wistar rats at doses of 1, 10, and 100 micrograms/kg. After 24 hr the ratio between bone marrow polychromatic and normochromatic lymphocytes (a sign of cellular toxicity) was decreased by the exposure, but we did not observe a significant increase in the frequency of micronuclei. We conclude that the pesticide mixture did not have appreciable genotoxic activity in the assays used.

Adult bedbugs, Cimex lectularius, were exposed for 24 h (25 degrees C) to filter paper treated with various dilutions of the technical grade of nine insecticides dissolved in acetone to determine the concentration-response relationships. The order of toxicity, from most to least based on the LC50's was: dichlorvos, pirimiphos methyl, lambda-cyhalothrin, bendiocarb, permethrin, malathion, carbaryl, tetrachlorvinphos, and fenvalerate. The residual toxicities of commercial formulations of six of the chemicals diluted with water and applied to wood, cardboard, cloth and galvanized metal, were determined by exposing adult bedbugs at 3, 7 and 12 weeks after treatment. The formulation of bendiocarb (FICAM 76% W) had little residual activity on all surfaces at 12 weeks after treatment. The formulation of carbaryl (SEVIN 21.5% L) was toxic to bedbugs on all surfaces at 12 weeks after treatment, but required high concentrations on wood, cardboard, and cloth. The formulation of pirimiphos methyl (ACTELLIC 57% EC) had no residual activity on any of the surfaces at 12 weeks after treatment. The formulation of tetrachlorovinphos (RABON 50% W) had residual activity for 12 weeks on all surfaces except metal. The formulation of permethrin (ATROBAN 11% EC) had residual activity on only metal and wood while the formulation of lambda-cyhalothrin (KARATE 13.1% EC) had residual activity 12 weeks on all surfaces.

The effect of three fungicides (Vitavax-Captan, Rizolex-T and Sumisclex) and one insecticide (Actellic), when incorporated into liquid medium or applied to corn grains and sunflower seeds, on the production of aflatoxin by A. flavus IMI 89717 was tested. In liquid medium, aflatoxin production was inhibited by 27%, 82%, 100% and 100% when Vitavax-Captan was added at 10, 25, 50 and 100 ppm, respectively. Sumisclex reduced to some extent the production of total aflatoxin, while Rizolex-T and Actellic did not affect quantitatively the mycotoxin production. Rizolex-T proved to be the most effective pesticides tested on aflatoxin production on both corn-grains and sunflower seeds, while Vitavax-Captan was the second most effective pesticide. Both Sumisclex and Actellic did not inhibit aflatoxin production on either corn grains or sunflower seeds at the levels tested.

1. Wheat-bound residues of 14C-pirimiphos-methyl were fed to albino rats at 1.17 and 7.5 ppm in the diet for 3.5 months. 2. In toxicological tests, 1.17 ppm of bound residues caused an increase of rat alkaline phosphatase activity and blood urea nitrogen, and reduction in lymphocyte and monocyte counts. A dietary level of 7.5 ppm showed a significant decrease in serum cholinesterase activity and in lymphocytes and monocytes, and an increase in alkaline phosphatase activity and of urea nitrogen. 3. Bioavailability data indicate that wheat-bound pirimiphos-methyl residues are absorbed by rat.

Observations made for a period of four years from 1985 to 1988 on post-spray impact of pirimiphos-methyl (25 per cent Wp) on malaria vectors in Tirap district of Arunachal Pradesh showed that a low density (0.0 to 0.02 PMH) of Anopheles dirus was maintained in the areas sprayed with the insecticide at the dosages of 1 and 2 g/m2 from 1981 to 1984. The post-spray data (1985 to 1988) showed a reduction of 62.5 to 62.8 per cent in SPR, 55.6 to 64.7 per cent in SRF and 72.3 to 75.5 per cent decline in API as compared to baseline data of 1980 in areas sprayed with pirimiphos methyl.

In Turkey, the mosquito Anopheles sacharovi has been under field selection pressure sequentially with DDT, dieldrin, malathion and pirimiphosmethyl over a period of 30 years for the purpose of malaria control. In 1984, the field population of An.sacharovi in the malarious Cukurova plain of Adana Province contained an altered acetylcholinesterase-based resistance gene giving broad spectrum resistance against organophosphorus and carbamate insecticides. The cross-resistance spectrum from this mechanism conferred resistance to malathion but not to the organophosphorus insecticide pirimiphos-methyl. Over the 6 years that pirimiphos-methyl has been applied for malaria vector control in this area, the frequency of the altered acetylcholinesterase resistance gene has declined, although in 1989 and 1990 it was still present at measurable frequencies in An.sacharovi from Cukurova. In addition to the acetylcholinesterase resistance mechanism there is evidence of an increased level of glutathione S-transferase in some of the An.sacharovi populations tested. This is known to be correlated with DDT resistance in other anophelines. In Turkish An.sacharovi, DDT resistance and elevated glutathione S-transferase occur in the same populations at similar frequencies. The continued prevalence of resistance to DDT and dieldrin, long after the 1971 cessation of DDT spraying for malaria control in Turkey, suggests that the DDT resistance gene has insufficient reduced fitness associated with it to have been lost from the field population during the past two decades. The implications of the slow decline in resistance gene frequencies in this field population are discussed in relation to mathematical models for managing resistance.

Village-scale trials of 50% emulsifiable concentrate (EC) and 40% wettable powder (WP) formulations of pirimiphos methyl (Actellic) were carried out against Anopheles sacharovi in Cukurova, Turkey. Susceptibility tests with wild caught, gonoactive and composite aged An. sacharovi over a range of chemical concentrations resulted in 100% mortality after exposure for 60 min to a 0.5% active ingredient concentration. Surface treatments of Actellic 50% EC at 0.9 g/m2 caused a significant decrease in parous rate and a 96.9% reduction in resting density. Persistence on concrete, wood, zinc and plywood was still high at the time of the second spray round, more than 7 wk postspray and ranged from 73% (zinc) to 98% (plywood). More than 50% mortality was still recorded 8 wk postspray using 1.6 g/m2 WP on wood, plywood, zinc and thatch substrates.

Stored wheat treated with radiolabelled pirimiphos-methyl (0-2-diethyl-amino-6-methyl-pyrimidin-4-yl 0,0-dimethyl phosphorothioate) formed bound (nonextractable) 14C residues. Supercritical fluid extraction, gas chromatography and mass spectrometric techniques were used to identify and quantitate the 14C bound residues in wheat grains. The amount of bound 14C residues present after 28 weeks of storage was about 9.9% of the applied radioactivity. Pirimiphos-methyl accounted for 80% of the bound residue. Grain-bound residues were fed to rats for 5 days. After a total period of 8 days a substantially large percentage of the administered bound 14C residues (72.9%) was eliminated in urine while feces contained only 17.9%. Bound pirimiphos-methyl in wheat grain was metabolized in rats by processes involving hydrolysis, N-dealkylation and 0-demethylation. The results indicate that wheat-bound residues of pirimiphos-methyl are highly bioavailable to the rat and may possess a toxicological potential as manifested by a significant reduction in body weight gain.

Wheat grains were treated with 14C-pirimiphos-methyl to generate bound residues for testing their bioavailability to rats. Bound residues accounted for 25% of the applied dose (50 ppm) at the end of one year. When the grain bound residues were fed to rats for 48 hours the animals eliminated 30 and 40% of the administered dose in urine and feces respectively, after 5 days. Radioactivity in some selected organs and blood accounted for 37% of the administered dose after 2 days, which gradually declined to 1% after 5 days. These data indicate that wheat-bound pirimiphos-methyl residues are moderately bioavailable to rats. In a 90-day feeding study, inhibition of plasma cholinesterase and brain acetylcholinesterase strongly suggest that the bound residues possess a toxicological potential.

Using a 14C-labelled pirimiphos-methyl preparation, the percentage of pirimiphos-methyl residues bound to maize grains after 32 weeks of storage was 13% of the applied dosage, or 38% of total terminal residues. Evidence is presented to show that bound residues of pirimiphos-methyl are bioavailable to the rat: 30%, 2% and approx. 6% of radioactivity were measured in urine expired air, and some organs respectively. A major portion of radioactivity (55%) was eliminated through faeces. Grain-bound pirimiphos-methyl residues (generated after storing whole maize grains with pirimiphos-methyl at concentrations of 10 ppm and 100 ppm) were administered to albino rats for 12 weeks. Body and organ weights, enzyme activities and blood chemistry were tested. There was a significant reduction in body weight gain in female rats. Also a significant reduction in blood cholinesterase activity was observed in both male and female rats fed on grain bound pirimiphos-methyl residues at two dose levels. The white blood cell count increased significantly in male rats fed on the high dose. No significant changes were observed in the other blood chemistry parameters tested. The results indicate that maize-bound pirimiphos-methyl residues can exert adverse biological effects in the rat.

Use of malathion for mosquito control in Cuba for 7 years up to 1986 has selected for elevated non-specific esterase and altered acetylcholinesterase (AChE) resistance mechanisms in populations of the pest mosquito Culex quinquefasciatus Say. These mechanisms are still present in relatively high frequencies in the Havana area, despite the replacement of malathion by pyrethroid insecticides for the last 3 years in the mosquito control programme. Samples of Culex quinquefasciatus populations from within a 100 km radius of Havana had high levels of resistance to malathion and lower levels of resistance to propoxur, but there was little or no cross-resistance to the organophosphorus insecticide pirimiphos-methyl. Selection with malathion for twenty-two consecutive generations in the laboratory increased the level of malathion resistance to 1208-fold and propoxur level to 1002-fold, but the maximum level of pirimiphos-methyl resistance was only 11-fold. Pirimiphos-methyl is still operationally effective, despite the resistance mechanisms segregating, so this insecticide if used for control is unlikely to select either of the known resistance factors directly in the field population. Since 1986, pyrethroids have been used extensively, and low levels of pyrethroid resistance were detected in two of five field population samples tested. Malathion selection did not increase the level of pyrethroid resistance, which indicates that one or more distinct pyrethroid resistance factors are now being selected in the field populations of Culex quinquefasciatus.

A control programme against subperiodic brugian filariasis was implemented in three villages, (Kg. Ampungan, Kg. Sebangkoi and Kg. Sebamban) in Sarawak, Malaysia. In Kampong Ampungan, the mass administration of diethylcarbamazine (DEC-citrate) combined with residual house spraying of pirimiphos-methyl reduced microfilarial rate to 8% of the pre-treatment level and microfilarial density (MfD50) to 44% of the pre-treatment level over a period of four years. In Kampong Sebangkoi and Kampong Sebamban, where only mass DEC therapy was applied, the microfilarial rate and MfD50 declined distinctly in the second blood survey but increased gradually in two subsequent follow-up blood surveys. In Kg, Ampungan, we observed a significant reduction of infective biting rate (88.3%), infection rate (62.5%) and transmission potential (88.1%) of Mansonia bonneae at the fourth spray round. The corresponding reduction rates in Kg. Sebangkoi and Kg. Sebamban were 35.3%, 26.7%, 42.2% and 24%, 30.8% and 15.4% respectively. The biting density of the vector was reduced by 79.8% indoors and 31.8% outdoors at the sprayed village, while only a slight decrease in densities (17.9% indoors and 12.4% outdoors) was observed at the unsprayed village. Bioassay tests revealed that pirimiphos-methyl had a substantial fumigant effect on the vector. The integrated control measure in controlling subperiodic brugian filariasis is discussed.

The effect of previous insecticide use patterns for horn fly control on the susceptibility spectrum of horn fly (Haematobia irritans [L.]) populations from Kentucky and Arkansas is described. Populations of horn flies from both states were tested with three pyrethroids (cyhalothrin, cypermethrin, and permethrin), three organophosphates (diazinon, pirimiphos methyl, and tetrachlorvinphos), and a chlorinated hydrocarbon (methoxychlor). Dose-mortality data indicated insecticide resistance in Arkansas and Kentucky. Two permethrin-resistant horn fly populations in Kentucky that did not have a history of exposure to methoxychlor were cross-resistant to this chlorinated hydrocarbon. Horn fly populations from both states with a history of at least three consecutive years of exposure to various pyrethroid ear tags were subsequently exposed to cattle tagged with cyhalothrin-impregnated ear tags for 15-16 wk. Such exposure resulted in a decrease in susceptibility to this pyrethroid (ranging from approximately 30 to greater than 100-fold) when compared with levels before treatment. Horn fly populations from Arkansas resistant to cyhalothrin (as a result of exposure to cyhalothrin ear tags) were cross-resistant to pirimiphos methyl. Seasonal exposure of an Arkansas and Kentucky horn fly population to cattle with ear tags impregnated with pirimiphos methyl resulted in a significant decrease in susceptibility to this organophosphate.

The relative toxicities of ten acaricides to northern fowl mite, Ornithonyssus sylviarum (Canestrini and Fanzago), and the chicken mite, Dermanyssus gallinae (De Geer), were determined simultaneously by holding the mites inside disposable glass Pasteur pipettes previously immersed in acetone solutions of various concentrations (w/v) of technical grade acaricides. The LC90s (parts per million) of the acaricides after 24 h exposure for the northern fowl mite and the chicken mite, respectively, were: bendiocarb (13.1, 0.18), tetrachlorvinphos (14.5, 4.07), carbaryl (15.0, 0.83), pirimiphos methyl (18.3, 2.03), permethrin (23.1, 8.46), lambda cyhalothrin (80.7, 11.4), dichlorvos (252.8, 3.75), malathion (238.4, 6.59), amitraz (6741, 9430) and fenvalerate (greater than 10,000, 60.2). After 48 h exposure there were only slight increases in mortalities of both species except for increased mortalities for the northern fowl mite with lambda cyhalothrin, amitraz and fenvalerate, and for the chicken mite with amitraz.

1. Nylon bednets impregnated with different insecticides were evaluated in 1988 against wild adult mosquito populations, mostly Mansonia africana (Theobald) and Anopheles gambiae Giles sensu lato, entering experimental verandah-trap huts in The Gambia. Each bednet had six 10 x 10 cm holes made in the walls to simulate torn conditions and permit female mosquitoes to enter and feed on sleepers. 2. Individual net treatments, determined by gas chromatography of net samples from before and after 12 weeks use of the bednets, were: permethrin 670 +/- 159 and 405 +/- 190 mg/m2 (40% loss), cypermethrin 37 +/- 8 and 16 +/- 9 mg/m2 (57% loss), deltamethrin 10 +/- 7 and 10 +/- 8 mg/m2 (no loss), lambda-cyhalothrin 2.6 +/- 0.9 and 1.6 +/- 0.5 mg/m2 (38% loss), pirimiphos-methyl 4017 +/- 117 and 1160 +/- 319 mg/m2 (71% loss). 3. Washing three times in the traditional manner with local cow-fat soap reduced the initial dosages by about 85% of cypermethrin and lambda-cyhalothrin, 99.8% of pirimiphos-methyl and left no detectable residues of deltamethrin or permethrin. 4. The unwashed permethrin-treated bednet reduced the number of mosquitoes entering a hut by 60% of An.gambiae s.l. and 68% of Mansonia spp. This deterrency was less pronounced with the other insecticides and was lost by washing the bednets. 5. Each insecticide, especially lambda-cyhalothrin and pirimiphosmethyl, caused significant mortality rates of mosquitoes that entered huts with impregnated bednets, and prevented the majority of An. gambiae s.l. and Mansonia females from bloodfeeding. Washing completely removed the efficacy of deltamethrin and permethrin treated bednets, whereas nets treated with cypermethrin, lambda-cyhalothrin or pirimiphos-methyl remained significantly insecticidal after washing. 6. Aerial toxicity from the pirimiphos-methyl treated bednet killed 80% of An.gambiae s.l. confined overnight in the hut at the end of the trial, whereas the pyrethroid-treated bednets gave negligible mortality rates of mosquitoes. 7. Sleepers using the bednets had no medical symptoms significantly associated with any of the treatments. On the contrary, from 216 interviews, 4/10 complaints were associated with the use of untreated nets (P approximately 0.05), perhaps because sleepers were kept awake by mosquitoes and became more aware of any ailments. 8. It is concluded that permethrin tends mainly to deter mosquitoes from house-entry, enhancing personal protection, whereas the other insecticides kill higher proportions of the endophilic mosquitoes, which would give better community protection against malaria transmission.

The main objective of this work is to develop a routine quality control method for pesticide residues in cocoa beans, using gas chromatography-mass spectrometry. The investigated pesticides, which are used to control pests in the growing of cacao, are: Acephate, Propoxur, HCH, Heptachlor, Fenitrothion, Pirimiphos-methyl, Aldrin, Dieldrin, pp'-DDE, op-DDE and DDT. Two extraction methods were tested. The first was based on strong attack by concentrated sulphuric acid and later extraction with n-hexane: the investigated residues were Acephate, HCH, Fenitrothion and DDT; recoveries were 68-95% and the detection limits 0.5-10 ppb. The second extraction method was based on the Universal Trace Residue Extractor (UNITREX), which consists of a distillation system for organophosphorus and organochlorine pesticides in fatty samples. The investigated residues were Heptachlor, Pirimiphos-methyl, Aldrin, Propoxur, Dieldrin, op-DDE and pp'-DDE; recoveries were 67-88% and the detection limits 1-10 ppb.

Broad spectrum organophosphate resistance in Culex quinquefasciatus Say from Saudi Arabia is inherited as a semi-dominant characteristic. The resistance has a metabolic basis and confers cross-resistance against the carbamate propoxur. Organophosphate-selected strains contain two elevated esterases with the same electrophoretic mobilities as those in resistant Cx quinquefasciatus from Sri Lanka and a range of African locations. Alteration in the sensitivity of acetylcholinesterase to insecticide inhibition does not play a major role in resistance. There was a significant increase in the amount of Cytochrome P450 in Cx quinquefasciatus lines selected with the pyrethroid permethrin or with the organophosphate pirimiphos-methyl, but no change in lines selected with five other organophosphates or propoxur, compared to the parental strain, which suggests that oxidases are involved in the P450 mediated resistance to both permethrin and pirimiphos-methyl.

This paper describes studies aimed at determining the acute anticholinergic and delayed neurotoxic potential of the organophosphate insecticide pirimiphos-methyl (O-2-diethylamino-6-methylpyrimidin-4-yl O,O-dimethyl phosphorothioate) in the hen. Delayed neuropathy was assessed by biochemical measurement of neuropathy target esterase (NTE) activities in the brain and spinal cord, clinical signs of neuropathy over two 21-day periods and histological assessment of nervous tissue. Acetylcholinesterase (AChE) activity was also determined in the brain and spinal cord. Hens were given a single oral dose of 100 mg kg-1 pirimiphos-methyl, which was followed by a repeated dose after 21 days. Tri-o-cresyl phosphate (TOCP), 500 mg kg-1, was used as a positive control. All pirimiphos-methyl-treated hens received prophylactic doses of N-methylpyridinium-2-aldoxime methanesulphonate (P2S) and atropine sulphate. Hens dosed with pirimiphos-methyl had very low AChE activities (less than 20% of control) in both the brain and spinal cord, 24 and 48 h after dosing. In the TOCP-treated hens, the activities were about 90% of control. NTE activities in the brain and spinal cord of pirimiphos-methyl-treated hens were identical to those in the controls, while they were profoundly inhibited (greater than 80%) in the TOCP-treated hens. All hens dosed with pirimiphos-methyl showed the expected signs of AChE inhibition and, following recovery, usually by Day 5, no clinical signs of delayed neuropathy were seen. The TOCP-treated hens developed clinical signs of neuropathy

Organosphosphorus and carbamate insecticides are quite often used in greenhouses. They represent a group of active principles of toxicological relevance. Initial residues on the surface of cucumber, tomato and ornamental plants, and half-life periods for residue degradation are outlined for carbendazim, dimethoate, fenazox, malathion, methamidophos and pirimiphos-methyl. Residues on plants, concentration in the air, dermal exposition, and inhibition of serum choline esterase activity are shown for methamidophos and aldicarb, respective reentry times being discussed. On harvest and cultivation in greenhouses, dermal exposition as a rule is more relevant than inhalation.

This study analyzes the level of total and bound pirimiphos-methyl residues in treated wheat grain and its toxic effects on rats. Wheat grain was treated with [14C]pirimiphos-methyl of 16.36 mCi/mmol specific activity to determine the bioavailability of bound residues in rats. At the same time, grain was treated with nonlabeled pirimiphos-methyl as required to determine any possible toxic effects of bound residues in a subacute feeding study in rats. Two dose levels were used: 10 and 100 ppm (the former being the recommended dose level in practical treatment). Estimation of the type of residues was performed at intervals of 0, 30, 90, 120, 150, and 180 days. During and after the animal feeding study, changes in body weight gain, organ weight, cholinesterase activity, serum enzyme activity, and hematology were investigated. There is an indication that bound residues of the pesticide pirimiphos-methyl provoke toxic effects to some extent.

Responses of Paramecium caudatum, a ciliated protozoan, to acute exposures of certain organic solvents and organophosphorus insecticides (OPI) were studied by determining their lethal concentration (10 min-LC100) and median lethal concentration (4 h-LC50). The solvents and OPI evoked a distinct sequence of responses. Among the five solvents tested, acetone proved most toxic [LC-2.9% and LC50-0.68% (v/v)], while dimethyl sulphoxide (DMSO) showed least toxicity [LC-11.0% and LC50-3.16% (v/v)]. The order of toxicity of solvents was: acetone greater than ethanol greater than methanol greater than N, N-dimethylformamide greater than dimethylsulphoxide. The LC values of six OPI dissolved in either acetone or DMSO indicated that they were more toxic when dissolved in acetone and least toxic in DMSO. Among the OPI, bromophos proved most toxic (LC-10 ppm) while malathion showed least toxicity (LC-200 ppm) in DMSO. The order of toxicity of OPI was: bromophos greater than pirimiphos-methyl greater than parathion methyl greater than dichlorvos greater than fenitrothion greater than malathion. The 4 h-LC50 values computed for bromophos and malathion (dissolved in DMSO) were 575 ppb and 19.9 ppm, respectively, indicating the high susceptibility of P. caudatum to bromophos. The results indicate that the Paramecium toxicity assay could be used as a complementary system to rapidly elucidate the cytotoxic potential of compounds.

In an acute study, albino rats of both sexes were orally administered graded doses of Pirimiphosmethyl, and the statistically computed median lethal dose (LD-50) were 1861 and 1667 mg/kg body weight for male and female rats respectively. No treatment related changes were discernible with regard to food intake, growth, gross or histopathology of the organs. In a time-course study, the correlation between symptoms and degree of esterase inhibition was examined in rats administered the minimum lethal dose (MLD: 1000 mg/kg b.w.) of the insecticide. Time-course inhibition pattern of both cholinesterase (ChE) and non-specific carboxylesterase (NSE) activities in brain and plasma revealed maximum inhibition at 24 h post-treatment which correlated well with the intensity of symptoms. In a subacute study, groups of male rats were fed dietary Pirimiphos-methyl at 0, 10, 250, 500 and 1000 ppm for 28 days. Food consumption and growth rate were not affected throughout the experimental period. At necropsy after 28 days, no gross pathological changes were seen in any of the organs except a slight increase in liver weight at 1000 ppm. Though no statistical differences were observed in the levels of hepatic transaminases, a significant increase in serum transaminase was evident. Significant increase in the activities of hepatic ALP, beta-GLR and serum ALP were evident at 500 and 1000 ppm. Further, significant inhibition of plasma PChE was evident at 250, 500 and 1000 ppm while the degree of inhibition of brain AChE was significant only at the higher dosages. No histopathological alterations were observed in any of the organs.

Growing male rats were fed dietary Pirimiphos-methyl at 0, 500, 1000 and 1500 ppm for 28 days and selected blood and urine constituents were measured at weekly intervals. Dietary intake of Pirimiphos-methyl induced an initial, transient hypoglycemia and a marked elevation in blood urea at all dosages. Though it did not produce any significant change in the urine output initially, marked oliguria was observed after 12 days of feeding. The alterations observed in urine constituents were: increased urea, proteinuria, transient increase in creatinine and significant increase in the excretion of glucuronic acid and ethereal sulfate at all intervals. However, since no pathological alterations were evident in the kidney, the anomalous urinary excretion of various body constituents might be due to the anticholinesterase action of the insecticide at the central nervous system.

A field trial of malaria vector control was conducted in Phulbani district, Orissa, during 1984 and 1985. Indoor-spraying of pirimiphos-methyl emulsion formulation was undertaken at an application rate of 2 g/m2 in two sections (population 14,692) of Nuagaon Primary Health Centre. Houses in two adjacent sections (population 21,450) were sprayed with DDT a water dispersible powder (wdp) formulation at 1 g/m2 for comparison purposes. Operational problems in this area come from the tendency of tribal people to re-plaster over wdp applications. Pre-spray malariological indices in the trial area were 38% slide positivity rate, 37% slide falciparum rate and 12.1% annual parasite incidence. Densities of Anopheles annularis Van der Wulp, An. culicifacies Giles, An. fluviatilis Theobald and other potential malaria vectors were reduced in the pirimiphos-methyl trial area 2-35-fold more than in the area sprayed with DDT. Malariological indices were reduced by 65-68% in the pirimiphos-methyl sprayed area compared with only 26-35% reduction in the DDT sprayed area. Spraymen and villagers experienced no adverse side-effects from residual house-spraying with pirimiphos-methyl emulsion and it is concluded that this organophosphate product has advantages for malaria vector control, especially in operationally difficult situations.

Esterases which can hydrolyse organophosphates without being inhibited by them are termed "A" esterases. Using paraoxon and pirimiphos-methyl oxon as substrates, high "A" esterase activity is found in the liver and plasma or serum of a range of mammalian species. In a study of serum "A" esterases of sheep and humans, over 80% of the activity separated into the high density lipoprotein (HDL) fraction following ultracentrifugation. When HDL fractions from sheep serum were run on Sepharose gel columns, most of the paraoxonase activity separated as a single peak of estimated molecular weight 360,000, which corresponds to that of HDL2 of humans. During the course of purification of "A" esterases by three different column procedures, contrasting esterase elution profiles were obtained with organophosphate and pyrethroid substrates. This was strong evidence for the existence of multiple forms of HDL "A" esterases. Levels of "A" esterase activity in plasma and liver of birds were much lower than those of mammals. This appears to be the main reason why birds are much more susceptible than mammals to organophosphates such as pirimiphos-methyl and diazinon which form active oxons that are good substrates for mammalian "A" esterases. No "A" esterase was detected in strains of rust red flour beetle (Tribolium castaneum) which were resistant to organophosphates. Similar observations have been made with strains of other insects resistant to organophosphates, raising the question to what extent esterases of this type are present in insects.

Dermal and respiratory exposure to pirimiphosmethyl, dimethoate and permethrin were determined for applicators and operators in greenhouse tomato spraying operations. Dermal exposure is several times higher than the degree of respiratory exposure. Dermal exposure in terms of different parts of the body shows significant differences. For applicators the exposure of hands, arms and legs is the greatest, and the operators are the most exposed on their hands and to a small extent on legs. This fact should be taken into account when providing the workers with suitable protective clothing. The carefully selected technology of spraying also has great significance in decreasing the degree of exposure. Because of the chronic toxicity of dimethoate, all possible methods should be taken to reduce exposure.

House dust mite sensitivity is very common in patients with bronchial asthma, yet dust mite avoidance frequently receives little attention in clinical management. It is likely that any reduction in allergen levels associated with routine cleaning is insufficient to allow clinical improvement. In the present study the acaricide pirimiphos methyl is shown to reduce the levels of Dermatophagoides pteronyssinus, antigen P1 in homes. Following a single application the level of antigen P1 in dust from carpets was reduced by up to 73% and by more than 50% in soft furnishings. Serial sampling showed a reduction for 6 weeks under conditions where carpets and chairs treated with solvent showed a progressive rise in allergen level. Furthermore the survival of mites in cultures or infested carpet segments was markedly inhibited, with antigen P1 accumulation reduced by greater than 90%. These results suggest major reductions in house dust mite allergen levels in the home can be achieved.

Studies were carried out on the combined effect of high relative humidity and temperature on stability and dynamics of skin actelic resorption. Actelic resorption with skin application was established to be uneven. The initial resorption of the substance by the skin, was followed by its increased concentration on skin surface, and a further decrease and maintenance with a general tendency to decrease of the concentration. Humidity accelerated resorption, whereas with the combination of high temperature and high relative humidity--an reverse tendency was observed.

Using paraoxon and pirimiphos-methyl as substrates, much of the "A'-esterase activity of sheep serum was found to be in the high-density lipoprotein (HDL) fraction. A method was developed for the partial purification of "A'-esterases by the preparation of a lipoprotein fraction, followed by preparative polyacrylamide gel electrophoresis. The properties of the partially purified preparations of "A'-esterase were studied. Although four different preparations all contained a major protein unit, which resembled the core protein of HDL, there was evidence of differences between preparations with regard to substrate specificity, suggesting the existence of multiple enzyme forms. Gel filtration of serum samples indicated that paraoxonase activity is expressed by proteins with mol. wts greater than 200,000, strongly suggesting that the "A'-esterase activity of the lipoprotein fraction is present in one or more forms of HDL2. The dependence of "A'-esterase activity upon Ca2+ and the problem of esterase classification are discussed.

The Onchocerciasis Control Programme (OCP) is realized in the major part of the treated area by weekly applications of temephos in biotopes of simulles larvae. This insecticide is very effective and its impact on the aquatic fauna is evaluated by means of periodic samplings of the fauna. Therefore, the most sensitive way of tracking down fish poisoning is by studying the brain acetylcholinesterase depression. Evaluated on Tilapia guineensis this lowering is moderate when operational doses are used by OCP. The discovery of resistence to temephos incited researchers of OCP to try remplacement insecticides. Among these, chlorphoxim, chlorpyrifos-methyl and pirimiphos-methyl proved to be the most effect of these three organophosphorus compounds to that of temephos on the acetylcholinesterasic activity of the brain of Tilapia but using a much higher dosage (0,05 mg/l during 24 hrs that is 144 times more than for temephos). The results demonstrate that the three remplacement insecticides have on inhibitive effect plainly more important than that of temephos and that the retour to normal activity requires a much longer time.

The emergence of strains of malaria vectors resistant to malathion in an area of Pakistan, and the continuing search for improved methods of control, necessitated the examination of alternative safe insecticides, with improved residual effects, for future use in the Malaria Control Programme in Pakistan. For these reasons, the effectiveness of pirimiphos-methyl, as Actellic 25 WP, was evaluated on a large scale in one sub-sector of Sheikhupura district of Punjab Province near Lahore. Entomological and parasitological evaluations demonstrated that 1 g of pirimiphos-methyl/m2 was as effective as 2 g/m2. Vector mosquito densities were reduced to zero, or almost so, in all areas sprayed with pirimiphos-methyl, and only began to approach vector levels in unsprayed areas after 9-10 months. No new cases of malaria were detected in those areas sprayed with pirimiphos-methyl. Blood cholinesterase determinations after the application of the pirimiphos-methyl spray confirmed the absence of any toxic effect on the spray operators, nor were there any toxic symptoms in the house occupants.

Granulated fertilizers [ammonium nitrate, synthetic fertilizer] were used as carriers to prepare an insecticide granulate suitable for the control of Aedes cantans and Aedes vexans mosquito larvae under field conditions. The insecticide granulate was obtained by mixing 1 volume unit of Actellic EC 50 with 50 volume units of fertilizer. The optimal dose required to ensure and effective control of Aedes mosquito larvae was 2--5 g of granulate per 1 m3 of water [i.e. 2--5 kg/ha per each 1- cm depth of water] in hatching areas with a relatively clean water or during periods of slow larval growth and development, and 10 g of granulate per 1 m3 of water for hatching places polluted with organic substances or for periods of accelerated larval growth during summer months. The described Actellic EC 50 application practice ensures a complete survival of numerous non-target water organisms, including Tubifex species, Rhynchelmis species, molluscs, flatworms [Turbellaria], Asellus aquaticus, water mites [Hydrachna sp.] water striders (Gerris lacustris] and Dixella species larvae].

Common house mosquito Culex pipiens molestus Forskal was used to test biologically the residual toxicity of 15 organophosphorus, 5 carbamate and 5 pyrethroid insecticide preparations sprayed on whitewashed or limewashed wall surfaces. The doses of 0.1 g and 1.0 g of active ingredient per 1 m2 of wall surface were used in this experiment. At the dose of 1 g/m2, organophosphates chlorpyriphos, diazinon, fenitrothion, malathion, pirimiphos-methyl and propetamphos, cambamates bendiocarb, dioxacarb, propoxur and promecarb, and pyrothroids bioresmethrin, decamethrin-permethrin and tetramethrin produced on whitewashed wall surfaces the residual toxicity persisting for at least four months. At the dose of 0.1 g/m2, a long-lasting residual toxicity persisting on whitewashed wall surfaces for at least two months was observed after bendiocarb, decamethrin, fenitrothion, permethrin, pirimiphos-methyl and propoxur application. The residual toxicity of organophosphates, carbamates except for bendiocarb and pyrethroids except for permethrin sprayed on limewashed wall surfaces was considerably shorter than on whitewashed surface.

Pirimiphos methyl is an organophosphorus insecticide which is rapidly metabolised by plants and animals to several modified triesters and free hydroxyprimidines. A method is described for the determination by reversed-phase high-performance liquid chromatography of pirimiphos methyl and its five major metabolites in plasma and urine. Separations were performed by isocratic and gradient elutions from short columns packed with SAS-Hypersil, a relatively new column packing.

A simple and rapid method for the determination of pirimiphos methyl (O-[2-(diethylamino)-6-methyl-4-pyrimidinyl] O,O-dimethyl phosphorothioate) in formulations by high performance liquid chromatography is described. The sample is dissolved in methanol, and biphenyl is added as an internal standard. Then the sample is chromatographed by reverse phase chromatography on a Zipax octadecylsilane column. A 4 mul injection containing 0.01% pirimiphos methyl produces a 50% full scale peak at the maximum absorbance at 254 nm.