Inhibitor Report for: Propoxur

To compare the toxicity of seven N-methyl carbamates, time course profiles for brain and red blood cell (RBC) cholinesterase (ChE) inhibition were established for each. Adult, male, Long Evans rats (n=4-5 dose group) were dosed orally with either carbaryl (30 mg/kg in corn oil); carbofuran (0.5 mg/kg in corn oil); formetanate HCl (10 mg/kg in water); methomyl (3 mg/kg in water); methiocarb (25 mg/kg in corn oil); oxamyl (1 mg/kg in water); or propoxur (20 mg/kg in corn oil). This level of dosing produced at least 40% brain ChE inhibition. Brain and blood were taken from 0.5 to 24 h after dosing for analysis of ChE activity using two different methods: (1) a radiometric method which limits the amount of reactivation of ChE activity, and (2) a spectrophotometric method (Ellman method using traditional, unmodified conditions) which may encourage reactivation. The time of peak ChE inhibition was similar for all seven N-methyl carbamate pesticides: 0.5-1.0 h after dosing. By 24 h, brain and RBC ChE activity in all animals returned to normal. The spectrophotometric method underestimated ChE inhibition. Moreover, there was a strong, direct correlation between brain and RBC ChE activity (radiometric assay) for all seven compounds combined (r(2)=0.73, slope 1.1), while the spectrophotometric analysis of the same samples showed a poor correlation (r(2)=0.09). For formetanate, propoxur, methomyl, and methiocarb, brain and RBC ChE inhibitions were not different over time, but for carbaryl, carbofuran and oxamyl, the RBC ChE was slightly more inhibited than brain ChE. These data indicate (1) the radiometric method is superior for analyses of ChE activity in tissues from carbamate-treated animals (2) that animals treated with these N-methyl carbamate pesticides are affected rapidly, and recover rapidly, and (3) generally, assessment of RBC ChE is an accurate predictor of brain ChE inhibition for these seven pesticides.

Susceptibility status of five populations of Ae. albopictus mosquitoes from Maharashtra state, to DDT, malathion, fenitrothion, bromophos, propoxur and deltamethrin was studied and compared with the laboratory population. Four populations survived when adults were exposed to 4 per cent DDT impregnated paper for 2 h; though three of these populations had lower DDT-LC50 values at larval stages in comparison with the laboratory population. Results of topical application of DDT on these four populations supported these findings by showing comparatively higher LD50 values at adult stages in comparison with the laboratory population. All the populations were highly susceptible to other pesticides tested i.e., malathion, fenitrothion, bromophos, propoxur and deltamethrin. These populations were distinguished from each other by esterase isoenzyme patterns.

A selected combination of carbamate pesticides (carbofuran, oxamyl and propoxur were examined for cholinesterase (ChE) inhibition. The enzyme source was rat plasma and erythrocytes. Enzyme activity was determined colorimetrically using the Ellman technique adapted for erythrocyte ChE activity. Enzyme inhibition was obtained for both plasma and erythrocyte ChE, but inhibition by the pesticides was greater in the plasma. All 3 pesticides interacted additively in vitro.

To compare the toxicity of seven N-methyl carbamates, time course profiles for brain and red blood cell (RBC) cholinesterase (ChE) inhibition were established for each. Adult, male, Long Evans rats (n=4-5 dose group) were dosed orally with either carbaryl (30 mg/kg in corn oil); carbofuran (0.5 mg/kg in corn oil); formetanate HCl (10 mg/kg in water); methomyl (3 mg/kg in water); methiocarb (25 mg/kg in corn oil); oxamyl (1 mg/kg in water); or propoxur (20 mg/kg in corn oil). This level of dosing produced at least 40% brain ChE inhibition. Brain and blood were taken from 0.5 to 24 h after dosing for analysis of ChE activity using two different methods: (1) a radiometric method which limits the amount of reactivation of ChE activity, and (2) a spectrophotometric method (Ellman method using traditional, unmodified conditions) which may encourage reactivation. The time of peak ChE inhibition was similar for all seven N-methyl carbamate pesticides: 0.5-1.0 h after dosing. By 24 h, brain and RBC ChE activity in all animals returned to normal. The spectrophotometric method underestimated ChE inhibition. Moreover, there was a strong, direct correlation between brain and RBC ChE activity (radiometric assay) for all seven compounds combined (r(2)=0.73, slope 1.1), while the spectrophotometric analysis of the same samples showed a poor correlation (r(2)=0.09). For formetanate, propoxur, methomyl, and methiocarb, brain and RBC ChE inhibitions were not different over time, but for carbaryl, carbofuran and oxamyl, the RBC ChE was slightly more inhibited than brain ChE. These data indicate (1) the radiometric method is superior for analyses of ChE activity in tissues from carbamate-treated animals (2) that animals treated with these N-methyl carbamate pesticides are affected rapidly, and recover rapidly, and (3) generally, assessment of RBC ChE is an accurate predictor of brain ChE inhibition for these seven pesticides.

To establish an insecticidal resistance surveillance program, Culex quinquefasciatus mosquitoes from So Paulo, Brazil, were colonized (PIN95 strain) and analyzed for levels of resistance. The PIN95 strain showed low levels of resistance to organophosphates [malathion (3.3-fold), fenitrothion (11.2-fold)] and a carbamate [propoxur (3.0-fold)]. We also observed an increase of 7.4 and 9.9 in alpha and beta esterase activities, respectively, when compared with the reference IAL strain. An alteration in the sensitivity of acetylcholinesterase to insecticide inhibition was also found in the PIN95 mosquitoes. The resistant allele (Ace.1R), however, was found at low frequencies (0.12) and does not play an important role in the described insecticide resistance. One year later, Cx. quinquefasciatus mosquitoes were collected (PIN96 strain) at the same site and compared to the PIN95 strain. The esterase activity patterns observed for the PIN96 strain were similar to those of the PIN95 mosquitoes. However the occurrence of the Ace.1R allele was statistically higher in the PIN96 strain. The results show that esterase-based insecticide resistance was established in the PIN95 Cx. quinquefasciatus population and that an acethylcholinesterase based resistant mechanism has been selected for. A continuous monitoring of this phenomenon is fundamental for rational mosquito control and insecticide application programs.

Resistance to the organophosphates temephos and chlorpyrifos, the carbamate propoxur, the pyrethroid permethrin, and the organochloride DDT was investigated in Tunisian populations of Culex pipiens pipiens (L.) collected between 1990 and 1996. Resistance to temephos was uniformly low, reaching 10-fold in the most resistant population. In contrast, resistance to chlorpyrifos was highly variable, reaching the highest level (> 10,000-fold) recorded worldwide. The chlorpyrifos-resistant populations also were highly resistant to propoxur. Some populations also showed high resistance to permethrin (up to 5,000-fold) and moderate resistance to DDT (approximately 20-fold). Bioassays conducted in the presence of synergists showed that increased detoxification had only a minor role in resistance, although several over-produced esterases known to be involved in organophosphate resistance were detected. To better understand the factors influencing the distribution of resistance in Tunisia, the polymorphism of genes involved in organophosphate resistance (i.e., over-produced esterases and insensitive acetylcholinesterase) was investigated in relation to the genetic structure of populations studied by analyzing the electrophoretic polymorphism of "neutral" genes. Over the area studied, and despite a high level of gene flow, resistance genes showed a patchy distribution. Results are discussed in relation to the selection pressure caused by insecticide treatments.

The distribution of organophosphate and carbamate resistance was investigated in 33 samples of Culex pipiens quinquefasciatus Say from 25 cities in Cte d'Ivoire and Burkina Faso. Organophosphate resistance levels were higher in Cte d'Ivoire than in Burkina Faso. Chlorpyrifos resistance ratios at LC95 ranged from 4 to 30 times in Cte d'Ivoire and from 3 to 6 times in Burkina Faso. For temephos, ratios ranged from 3 to 18 and from 1 to 2, respectively. Of 27 samples from Cte d'Ivoire, 25 also displayed cross resistance to carbamates as shown by a mortality plateau in bioassays with propoxur and carbosulfan (similar to chlorpyrifos). Cross resistance to organophosphates and carbamates was caused by an insensitive acetylcholinesterase allele (AceR). This gene was absent from Burkina Faso, except in Niangoloko near the Cte d'Ivoire border. Organophosphate resistance also was associated with the presence of A2-B2 overproduced esterases which had higher frequencies in Cte d'Ivoire (75-100%) than in Burkina Faso (40-50%). Two other esterases with the same electrophoretic mobility as C2 from Puerto Rico and B1 from California were identified for the 1st time in West Africa. "C2" was widespread, whereas "B1" was present in only a few mosquitoes from Cte d'Ivoire. These differences in resistance patterns should be taken into consideration in planning urban mosquito control strategies within 2 countries.

Using a combination of in vitro assays we have examined the capacities of contemporary-exposure chemicals to modulate human estrogen and human progesterone receptor (hER and hPR) activity in human breast and endometrial cancer cells. The carbamate insecticides aldicarb, Baygon (propoxur), bendiocarb, carbaryl, methomyl, and oxamyl were used in this study. The carbamates alone weakly activated estrogen- or progesterone-responsive reporter genes in breast and endometrial cancer cells. All of the carbamates decreased estradiol- or progesterone-induced reporter gene activity in the breast and endometrial cancer cells. In whole cell competition binding assays, the carbamates demonstrated a limited capacity to displace radiolabeled estrogen or progesterone from ER or PR. Based on the results presented here, the carbamate insecticides may represent a class of chemicals which function through a mechanism separate from ligand-binding and, therefore, may act as general endocrine modulators in mammalian cells.

It was analyzed the behavior of the resistance of 3 organophosphated insecticides (malathion, clorpirifos and methyl-pyrimifos), 3 pyrethroids (deltamethrin, lambda-cyhalothrin and cypermethrin), and 1 carbamate (propuxur) in populations of Culex quinquefasciatus from 2 municipalities of the province of Santiago de Cuba. The values of the resistance factor proved that there is resistance to malathion and clorpirifos. However, in spite of the existence of a high frequency of the mechanisms of elevated esterases and altered acetylcholinesterase no resistance to methylpymirifos, was observed which demonstrated that this insecticide is not affected by these mechanisms selected in our populations of Culex quinquefasciatus. There was resistence to deltamethrin, and lambda-cyhalothrin in Santiago de Cuba, whereas it was moderate to cypermethrin in Santiago and San Luis. Resistance to deltamethrin was also found in San Luis, but it was mild to lambda-cyhalothrin. The results obtained from the use of the synergists S,S,S tributyl phosphotritiade (DBF) and piperonyl butoxide (PB) indicated that the mechanisms of resistance of unspecific esterases and oxidases of multiple function are involved in the resistance to pyrethroids in both strains from Santiago de Cuba and San Luis. It was determined by the biochemical tests that there existed a high frequency of the mechanisms of esterases and altered acetylcholinesterase. The results of the polyacrylamide gel electrophoresis (PAGE) showed that esterase B1 appears more frequently associated with esterases A6 and B6. It was inferred that this association could be connected with the resistance to pyrethroids.

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.

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.

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.

In the present study the effect of ketamine on the contractions caused by propoxur and phoxim on the isolated guinea pig ileum was investigated. Ketamine was found able to inhibit in a concentration-dependent manner the contractile responses of the ileum to propoxur and phoxim, while it did not significantly modify the contractions induced by acetylcholine. Propoxur and phoxim augmented the contractile responses induced by acetylcholine in the presence of acetylcholinesterase. This augmentation was prevented by ketamine, in a concentration-dependent manner. These findings suggest that ketamine inhibits the contractile effect of propoxur and phoxim on the guinea pig ileum and this inhibition seems to be associated with the protection of acetylcholinesterase against the action of these two compounds.

Susceptibility status of five populations of Ae. albopictus mosquitoes from Maharashtra state, to DDT, malathion, fenitrothion, bromophos, propoxur and deltamethrin was studied and compared with the laboratory population. Four populations survived when adults were exposed to 4 per cent DDT impregnated paper for 2 h; though three of these populations had lower DDT-LC50 values at larval stages in comparison with the laboratory population. Results of topical application of DDT on these four populations supported these findings by showing comparatively higher LD50 values at adult stages in comparison with the laboratory population. All the populations were highly susceptible to other pesticides tested i.e., malathion, fenitrothion, bromophos, propoxur and deltamethrin. These populations were distinguished from each other by esterase isoenzyme patterns.

A selected combination of carbamate pesticides (carbofuran, oxamyl and propoxur were examined for cholinesterase (ChE) inhibition. The enzyme source was rat plasma and erythrocytes. Enzyme activity was determined colorimetrically using the Ellman technique adapted for erythrocyte ChE activity. Enzyme inhibition was obtained for both plasma and erythrocyte ChE, but inhibition by the pesticides was greater in the plasma. All 3 pesticides interacted additively in vitro.

A sensitive technique allowing to identify the three genotypes (AceSS, AceRR and AceRS) of the Ace gene existing in natural populations of Culex pipiens in southern France is described. The technique is based on the comparison of AChE (acetylcholinesterase) activity in 3 equal aliquots taken from the homogenate of a single mosquito (a) in absence of inhibitor (RA), (b) in presence of eserine that inhibits the AChE encoded by AceS and AceR alleles (RI) and (c) in presence of a concentration of propoxur inhibiting the AChE coded by the AceS allele but not by the AceR allele (RG). The mosquito tested is AceSS when RG = RI, AceRR when RG = RA and AceRS when RI less than RG less than RA.

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.

This method for determining carbamates is based on the inhibiting action of these substances on acetylcholinesterase activity. The use of radioactively labelled acetylcholine as a substrate, the ensuing extractive separation of the radioactive acetic acid (formed by hydrolysis) and its radiometric determination permit to detect very small amounts of carbamates. The limit of detection for aldicarb, baygon, benomyl, bux, carbaryl, CIPC, matacil, phenmedipham and promecarb lies in the picogram range; that for barban and methomyl, in the nanogram range. The lower, linear parts of the curves for the different carbamates fall within the range 0.001-10 ng. The sensitivity (expressed as delta% inhibition/delta lg ng carbamate) ranges from 1.0 to 9.7.