Inhibitor Report for: Bendiocarb

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.

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.

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

Effects of commonly used carbamate pesticides on rat neuronal nicotinic acetylcholine receptors expressed in Xenopus laevis oocytes have been investigated using the two-electrode voltage clamp technique. The potencies of these effects have been compared to the potencies of the carbamates to inhibit rat brain acetylcholinesterase. The potency order of six carbamates to inhibit alpha4beta4 nicotinic receptors is fenoxycarb > EPTC > carbaryl, bendiocarb > propoxur > aldicarb with IC50 values ranging from 3 microM for fenoxycarb to 165 microM for propoxur and >1 mM for aldicarb. Conversely, the potency order of these carbamates to inhibit rat brain acetylcholinesterase is bendiocarb > propoxur, aldicarb > carbaryl > EPTC, fenoxycarb with IC50 values ranging from 1 microM for bendiocarb to 17 microM for carbaryl and > mM for EPTC and fenoxycarb. The alpha4beta2, alpha3beta4, and alpha3beta2 nicotinic acetylcholine receptors are inhibited by fenoxycarb, EPTC, and carbaryl with potency orders similar to that for alpha4beta4 receptors. Comparing the potencies of inhibition of the distinct subtypes of nicotinic acetylcholine receptors shows that the alpha3beta2 receptor is less sensitive to inhibition by fenoxycarb and EPTC. The potency of inhibition depends on the carbamate as well as on a combination of alpha and beta subunit properties. It is concluded that carbamate pesticides affect different subtypes of neuronal nicotinic receptors independently of acetylcholinesterase inhibition. This implicates that neuronal nicotinic receptors are additional targets for some carbamate pesticides and that these receptors may contribute to carbamate pesticide toxicology, especially after long-term exposure.

A strain of the fall armyworm, Spodoptera frugiperda (J.E. Smith), collected from corn in Citra, Florida, showed high resistance to carbaryl (562-fold) and methyl parathion (354-fold). Biochemical studies revealed that various detoxification enzyme activities were higher in the field strain than in the susceptible strain. In larval midguts, activities of microsomal oxidases (epoxidases, hydroxylase, sulfoxidase, N-demethylase, and O-demethylase) and hydrolases (general esterase, carboxylesterase, beta-glucosidase) were 1.2- to 1.9-fold higher in the field strain than in the susceptible strain. In larval fat bodies, various activities of microsomal oxidases (epoxidases, hydroxylase, N-demethylase, O-demethylases, and S-demethylase), glutathione S-transferases (CDNB, DCNB, and p-nitrophenyl acetate conjugation), hydrolases (general esterase, carboxylesterase, beta-glucosidase, and carboxylamidase) and reductases (juglone reductase and cytochrome c reductase) were 1.3- to 7.7-fold higher in the field strain than in the susceptible strain. Cytochrome P450 level was 2.5-fold higher in the field strain than in the susceptible strain. In adult abdomens, their detoxification enzyme activities were generally lower than those in larval midguts or fat bodies; this is especially true when microsomal oxidases are considered. However, activities of microsomal oxidases (S-demethylase), hydrolases (general esterase and permethrin esterase) and reductases (juglone reductase and cytochrome c reductase) were 1.5- to 3.0-fold higher in the field strain than in the susceptible strain. Levels of cytochrome P450 and cytochrome b5 were 2.1 and 1.9-fold higher, respectively, in the field strain than in the susceptible strain. In addition, acetylcholinesterase from the field strain was 2- to 85-fold less sensitive than that from the susceptible strain to inhibition by carbamates (carbaryl, propoxur, carbofuran, bendiocarb, thiodicarb) and organophosphates (methyl paraoxon, paraoxon, dichlorvos), insensitivity being highest toward carbaryl. Kinetics studies showed that the apparent Km value for acetylcholinesterase from the field strain was 56% of that from the susceptible strain. The results indicated that the insecticide resistance observed in the field strain was due to multiple resistance mechanisms, including increased detoxification of these insecticides by microsomal oxidases, glutathione S-transferases, hydrolases and reductases, and target site insensitivity such as insensitive acetylcholinesterase. Resistance appeared to be correlated better with detoxification enzyme activities in larval fat bodies than in larval midguts, suggesting that the larval fat body is an ideal tissue source for comparing detoxification capability between insecticide-susceptible and -resistant insects.

Routes by which nontarget predatory insects can be exposed to turfgrass pesticides include topical, residual, and dietary exposure. We used each of these routes to evaluate potential lethal or sublethal effects of two novel turfgrass insecticides, imidacloprid and halofenozide, and a carbamate, bendiocarb, on survival, behavior, and fecundity of the ground beetle Harpalus pennsylvanicus DeGeer. Field-collected carabids were exposed to direct spray applications in turf plots, fed food contaminated by such applications, or exposed to irrigated or nonirrigated residues on turf cores. Halofenozide caused no apparent acute, adverse effects through topical, residual, or dietary exposure. Moreover, the viability of eggs laid by females fed halofenozide-treated food once, or continuously for 30 d, was not reduced. In contrast, topical or dietary exposure of carabids to bendiocarb inevitably was lethal. Exposure to imidacloprid by those routes caused high incidence of sublethal, neurotoxic effects including paralysis, impaired walking, and excessive grooming. Intoxicated beetles usually recovered within a few days in the laboratory, but in the field, they were shown to be highly vulnerable to predation by ants. One-time intoxication by imidacloprid did not reduce females' fecundity or viability of eggs. There was no apparent behavioral avoidance of insecticide residues, or of insecticide-treated food. Carabids exposed to dry residues on turfgrass cores suffered high mortality from bendiocarb, and some intoxication from imidacloprid, but these effects were greatly reduced by posttreatment irrigation. Implications for predicting hazards of insecticides to beneficial invertebrates in turfgrass are discussed.

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.

To optimize conditions for sample collection, preparation, storage, and analysis and to assure the validity of our previously published liquid chromatographic (LC) method for carbamate analysis in tissue, stabilities of 16 N-methylcarbamates in beef, duck, and chicken liver tissues were studied by using 2 sampling protocols. Tissue samples were fortified at room temperature to a concentration 5 to 10 times greater than either the Environmental Protection Agency tolerance level for each compound (if established) or the concentration used in the previously published method. Thereafter, samples were continuously frozen at -4 degrees C for varying time intervals. In the first study, samples were analyzed one day (initial) and 0.5, 1, 1.5, 2, 3, 4, 5, and 6 months after fortification. In the second study, samples were analyzed one day (initial) and 0.5, 1, 2, 3, and 6 months after fortification. For each residue and species, a minimum of 4 samples were analyzed by LC at each point in time, and the mean represented analyte concentration at the end of each time interval. Rates of residue depletion varied among analytes and among species. Depletion rates were greater in duck livers than in beef livers. Methomyl and oxamyl were depleted completely within 2 weeks. Between 2 and 6 months after sample fortification, residue depletions to levels below detection limits were observed for aldicarb, aldicarb sulfoxide, aldicarb sulfone, dioxacarb, promecarb, propoxur, and bendiocarb. The initial loss of certain carbamates during sample preparation in tissues exposed to room temperature for up to 8 h was greater than the subsequent rate of loss. Results indicate that cryogenic conditions are required for sample preparation and storage.

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 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.

An optical sensor for anticholinesterases (AntiChEs) was constructed by immobilizing fluorescein isothiocyanate (FITC)-tagged eel electric organ acetylcholinesterase (AChE) on quartz fibers and monitoring enzyme activity. The pH-dependent fluorescent signal generated by FITC-AChE, present in the evanescent zone on the fiber surface, was quenched by the protons produced during acetylcholine (ACh) hydrolysis. Analysis of the fluorescence response showed Michaelis-Menten kinetics with a Kapp value of 420 microM for ACh hydrolysis. The reversible inhibitor edrophonium (0.1 mM) inhibited AChE and consequently reduced fluorescence quenching. The biosensor response immediately recovered upon its removal. The carbamate neostigmine (0.1 mM) also inhibited the biosensor response but recovery was much slower. In the presence of ACh, the organophosphate (OP) diisopropylfluorophosphate (DFP) at 0.1 mM did not interfere with the ACh-dependent fluorescent signal quenching, but preexposure of the biosensor to DFP in absence of ACh inhibited totally and irreversibly the biosensor response. However, the DFP-treated AChE biosensor recovered fully after a 10-min perfusion with pralidoxime (2-PAM). Echothiophate, a quaternary ammonium OP, inhibited the ACh-induced fluorescence quenching in the presence of ACh and the phosphorylated biosensor was reactivated with 2-PAM. These effects reflected the mechanism of action of the inhibitors with AChE and the inhibition constants obtained were comparable to those from colorimetric methods. The biosensor detected concentrations of the carbamate insecticides bendiocarb and methomyl and the OPs echothiophate and paraoxon in the nanomolar to micromolar range. Malathion, parathion, and dicrotophos were not detected even at millimolar concentrations; however, longer exposure or prior modification of these compounds (i.e., to malaoxon, paraoxon) may increase the biosensor detection limits. This AChE biosensor is fast, sensitive, reusable, and relatively easy to operate. Since the instrument is portable and can be self-contained, it shows potential adaptability to field use.

A strain of Anopheles stephensi from Pakistan (MalR) was 8.7-fold resistant to malathion and 6.7-fold cross-resistant to phenthoate, but not to other carboxylesters; no cross-resistance to bendiocarb, fenitrothion, permethrin and carbaryl was detected. Resistance was not associated with elevated levels of general esterase activity, as determined by hydrolysis of naphth-l-yl acetate (alpha-NA), but was correlated with higher levels of malathion carboxylesterase (MCE) activity in vitro. The results suggest that a highly specific type of esterase mediated resistance, such as MCE, can best be detected by an enzyme specific assay rather than one for general esterase activity. A new, rapid and sensitive assay for mosquito MCE is given.

Four laboratories obtained 177 carbamate recovery values using a liquid chromatographic method. The average recovery of 11 carbamates (aldicarb, aldicarb sulfone, bufencarb, carbaryl, carbofuran, 3-hydroxy carbofuran, 3-keto carbofuran, methiocarb, methiocarb sulfoxide, methomyl, and oxamyl) from 14 crops was 99% with a coefficient of variation of 8% (0.03-1.8 ppm fortification levels). No statistical difference in recovery was found between oxime and phenyl carbamates, or between parent and metabolite carbamates. Average recovery of aldicarb sulfoxide was 59% due to loss in the liquid-liquid partitioning because of the polarity of this compound. A fifth laboratory contributed 34 carbamate recoveries (average 99%) on table-ready food products for 4 carbamates. Bendiocarb, dioxacarb, isoprocarb, and propoxur are also quantitatively recovered through the method. Previously reported carbamate and noncarbamate recovery data are also discussed. In the Food and Drug Administration's (FDA) analysis of 319 samples (mainly crops), 86 (27%) were found to contain residues of carbamate insecticides and/or toxic carbamate metabolites. Carbaryl and methomyl were the most common carbamate residues found on the food products excluding the aldicarb sulfone and sulfoxide residues found on potatoes. In one FDA Total Diet Program "market basket", 11 of 69 table-ready food commodities contained from 0.005 to 0.094 ppm carbamate residues. Carbaryl was the most prevalent residue. Several laboratories reported adverse effects on the determinative system when inadequately purified reagents were used.

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.