Inhibitor Report for: Azamethiphos

The organophosphate pesticide azamethiphos is the active ingredient in Salmosan, a product formerly registered in Canada for the treatment of cultured Atlantic salmon against infestations of the ectoparasite Lepeophtheirus salmonis. The 48-h LC50 of azamethiphos to female American lobsters was determined bimonthly for 2 years to determine whether the sensitivity of lobsters to azamethiphos varied with time of year, molt stage, or reproductive stage. The LC50's ranged from 0.61 to 3.24 microg/L. The lobsters were most sensitive to azamethiphos during the spawning and molting seasons which occur in the summer and early fall when seawater temperatures are highest. Testing of compounds on this species for regulatory purposes should take into account that there may be variations in sensitivity during the molt and reproductive cycles.

The safety of azamethiphos (AZA), an organophosphorous insecticide and the active ingredient of Salmosan, was evaluated in the European eel, seabass and rainbow trout. Fish were bathed in 0.1 ppm AZA for a period of 60, 120 or 240 min. After termination of each treatment fish were transferred to clean aquaria and randomly sampled over 21 days. Compared to controls, brain acetylcholinesterase (AChE) was inhibited up to 44, 56 and 62% in eels, seabass and trout, respectively, with the inhibition being significant for up to 4 days in eels and seabass and 7 days in trout. As result of the AChE depression, fish displayed motor hyperactivity and erratic jumping at the onset of treatment. Mortality was observed only in trout following exposure for 240 min. A variable correlation observed among species between the level of exposure, the reduced activity of brain AChE and the signs of toxicity suggest that brain AChE should be considered as an indicator of exposure rather than as an index of toxicity of AZA. The present data indicate that at the therapeutic dosage of 0.1 ppm AZA for 1h can be safely used in eels, seabass and trout. The extended treatment times up to 240 min were equally safe for eels and seabass but not for trout.

1. Acetylcholinesterase from the heads of a strain of houseflies selected for resistance to the carbamate insecticide methomyl, and from a methomyl-resistant field strain was found to be less sensitive to inhibition by methomyl than that from a susceptible strain. 2. The enzyme from resistant insects was also more tolerant to malaoxon, dichlorvos and bomyl but not to azamethiphos. 3. The decrease in sensitivity to inhibition appeared to be due to an increase in affinity for substrate.

Azamethiphos (AZA) is an insecticide and neurotoxic agent that causes the inhibition of acetylcholinesterase (AChE). AChE is a vital enzyme for neurotransmission because it metabolizes acetylcholine neurotransmitter at the synaptic cleft and terminates synaptic transmission. It is worth mentioning that organophosphates and carbamates inhibit AChE. These AChE inhibitors bind to the active site of the enzyme and inactivate it, leading to paralysis and death. Herein, for the first time, we develop a sensitive, low-cost, and rapid electrogenerated chemiluminescence (ECL) system for the detection of AZA. The designed ECL sensor was applied for the highly sensitive detection of AZA with a wide dynamic range (from 0.1 microM to 1000 microM) and low detection limit of 0.07 microM (S/N = 3). The practical utility of the sensor demonstrates high recoveries (96-102%) in real samples of lake water and wastewater.

The organophosphate pesticide azamethiphos is the active ingredient in Salmosan, a product formerly registered in Canada for the treatment of cultured Atlantic salmon against infestations of the ectoparasite Lepeophtheirus salmonis. The 48-h LC50 of azamethiphos to female American lobsters was determined bimonthly for 2 years to determine whether the sensitivity of lobsters to azamethiphos varied with time of year, molt stage, or reproductive stage. The LC50's ranged from 0.61 to 3.24 microg/L. The lobsters were most sensitive to azamethiphos during the spawning and molting seasons which occur in the summer and early fall when seawater temperatures are highest. Testing of compounds on this species for regulatory purposes should take into account that there may be variations in sensitivity during the molt and reproductive cycles.

In this study, different concentrations of some organophosphate insecticides (methyl parathion, azamethiphos, dichlorvos and diazinon) have been evaluated for genotoxicity in the wing somatic mutation and recombination test (SMART) of Drosophila melanogaster. Third-instar larvae trans-heterozygous for two genetic markers mwh and flr, were treated at different concentrations (1 ppm, 3 ppm, 5 ppm, 7 ppm, 10 ppm) of the test compounds. A positive correlation was observed between total mutations and the number of wings having mutations. In addition, the observed mutations were classified according to size and type of mutation per wing. Chemicals used were ranked in decreasing order according to their genotoxic effects as diazinon, dichlorvos, methyl parathion, azamethiphos.

Acetylcholinesterase (AChE) is the target of a major pesticide family, the organophosphates, which were extensively used as control agents of sea lice on farmed salmonids in the early 1990s. From the mid-1990s the organophosphates dichlorvos and azamethiphos were seriously compromised by the development of resistance. AChE insensitive to organophosphate chemotherapeutants has been identified as a major resistance mechanism in numerous arthropod species, and in this study, target-site resistance was confirmed in the crustacean Lepeophtheirus salmonis Kroyer isolated from several fish-farming areas in Norway and Canada. A bimolecular rate assay demonstrated the presence of two AChE enzymes with different sensitivities towards azamethiphos, one that was rapidly inactivated and one that was very slowly inactivated. To our knowledge this is the first report of target-site resistance towards organophosphates in a third class of arthropods, the Crustacea.

The safety of azamethiphos (AZA), an organophosphorous insecticide and the active ingredient of Salmosan, was evaluated in the European eel, seabass and rainbow trout. Fish were bathed in 0.1 ppm AZA for a period of 60, 120 or 240 min. After termination of each treatment fish were transferred to clean aquaria and randomly sampled over 21 days. Compared to controls, brain acetylcholinesterase (AChE) was inhibited up to 44, 56 and 62% in eels, seabass and trout, respectively, with the inhibition being significant for up to 4 days in eels and seabass and 7 days in trout. As result of the AChE depression, fish displayed motor hyperactivity and erratic jumping at the onset of treatment. Mortality was observed only in trout following exposure for 240 min. A variable correlation observed among species between the level of exposure, the reduced activity of brain AChE and the signs of toxicity suggest that brain AChE should be considered as an indicator of exposure rather than as an index of toxicity of AZA. The present data indicate that at the therapeutic dosage of 0.1 ppm AZA for 1h can be safely used in eels, seabass and trout. The extended treatment times up to 240 min were equally safe for eels and seabass but not for trout.

The toxicity of spinosad was determined in one susceptible and five insecticide-resistant laboratory strains of house fly, Musca domestica L. Spinosad was relatively slow-acting, but highly toxic to house flies. In a feeding bioassay, spinosad LC50 at 72 h was 0.51 microg of spinosad per gram of sugar, making it 6.3- and 3.5-fold more toxic to house flies compared with azamethiphos and methomyl, respectively. In topical application bioassay, the LD50 at 48 h of spinosad in susceptible house flies was 40 ng per 20 mg of house fly, making spinosad less toxic than the pyrethroid bioresmethrin synergized by piperonyl butoxide and the organophosphate dimethoate. The insecticide-resistant laboratory strains had resistance factors to spinosad at LC50 in feeding bioassay from 1.5 to 5.5 and at LD50 in topical application bioassay from 2.5 to 4.7, indicating that in house fly cross-resistance to the major insecticide classes will not initially be of major concern for the use of spinosad for house fly control. The toxicity of spinosad was also evaluated against 31 field populations of house flies collected from livestock farms across Denmark. The field populations were 2.2- to 7.5-fold resistant to spinosad at 72 h in feeding bioassay, but based on steep slopes in the bioassay and the limited variation of spinosad toxicity against the various field populations, we consider the field populations to be spinosad-susceptible. We propose a diagnostic dose of 12 microg of spinosad per gram of sugar in feeding bioassay with impregnated sugar for determination of resistant house flies, which is 10x the LC95 of the susceptible strain WHO and approximately = 2x the LD95 of the field populations. Spinosad showed no substantial cross-resistance to the pyrethroid bioresmethrin synergized by piperonyl butoxide, the anticholinesterases dimethoate, azamethiphos, methomyl, and spinosad in house fly field populations.

Samples of housefly (Musca domestica) field populations were collected from Danish livestock farms in 1997. The tolerance of the first-generation offspring was determined for a number of insecticides. Dose-response values were obtained by topical application for the pyrethroids bioresmethrin and pyrethrum, both synergised with piperonyl butoxide, and the organophosphate dimethoate. The organophosphates azamethiphos and propetamphos and the carbamate methomyl were tested in discriminating dose feeding bioassays. Resistance was low to moderate in most of the populations for most of the compounds tested, but this study also revealed the existence of high resistance to pyrethroid, organophosphate and carbamate insecticides in some populations. The resistance factors at LD50 for bioresmethrin/piperonyl butoxide ranged between 2 and 98, and for pyrethrum/piperonyl butoxide between 2 and 29. Our results indicate that pyrethroid resistance in Denmark is increasing, since four of the 21 farms showed more than 100-fold resistance at LD95, a level of resistance only observed once before. Resistance factors at LD50 for dimethoate ranged from 9 to 100, and showed two distinct trends: populations with either decreasing or increasing resistance. Resistance to azamethiphos was found to be widespread and high. Although two strains with high methomyl and propetamphos resistance were observed, methomyl and propetamphos resistance is moderate and appears not to be increasing.

The organophosphorus insecticide, azamethiphos, is widely used throughout the world to control the housefly, Musca domestica (L.). Since its commercial introduction to Denmark in 1983 for this purpose, we have monitored the toxicity of azamethiphos to housefly populations at livestock farms throughout the country and carried out regular field studies. The findings of our field studies, which have revealed a strong potential for resistance development, have been born out by regular surveys showing that resistance has increased in recent years. Through the analysis of a field derived laboratory strain, we have implicated oxidative and hydrolytic mechanisms together with altered acetylcholinesterase in this resistance. Our field and laboratory studies have also indicated that resistance is relatively unstable, and can revert in the absence of selection. The implications of our findings for the continued efficacy of azamethiphos are discussed.

The pesticide formulation Salmosan (47.5% w/w azamethiphos) is currently registered for use, in Canada, to treat salmonids for infestations of the copepod parasites, Lepeophtheirus salmonis and Caligus elongatus (sea lice). Determination was made of the acute lethality of this product to the three larval stages, the first postlarval stage, and the adult of the American lobster (Homarus americanus), a species of significant economic importance in Eastern Canada. The 48-h LC50 (as azamethiphos) is 3.57 microg/liter for Stage I, 1.03 microg/liter for Stage II, 2.29 microg/liter for Stage III, 2.12 microg/liter for Stage IV (the first postlarval stage), and 1.39 microg/liter for adults. These concentrations are not significantly different from each other, although the variability in response is greater in the larval stages than in the postlarvae or adults. These data when interpreted in conjunction with known physical oceanographic data and chemical dispersion studies indicate that single anti-louse treatments are unlikely to result in mortality among lobsters in the vicinity of salmon farms. However, the sublethal effects of this product and the effects of repeated exposures have yet to be determined.

The insecticidal baits Muscalik-AZA (dust formulation) and Snip (granulated formulation) contained the active ingredient azamethiphos--1% and special fly attractant Z-9-tricosen--0.2%. Toxicity of these baits was monitored in 4 wild resistant strains of M. domestica (Diptera: Muscidae) which were marked according to the locality of collection as J, KP, NC and NL and in 1 sensitive strain WHO/SRS. KT90 in resistant strains was in the range from 1.5 to 6.5 hrs at testing of Muscalik-AZA. The efficiency of Muscalik-AZA was manifested with 100% knock-down effect in all tested strains with exception of KP strain after 24 hrs. During the experiments with Snip the greater range of knock-down time for 90% of tested strain was observed. KT90 was in the range from 5 hrs to > 24 hrs. After 24 hrs a range between 83-97% of knock-down effect was found in all tested strains. In field conditions of the weaned piglets rearing, the efficiency of Muscalik-AZA in flies highly resistant to azamethiphos was in the range from 14 to 21.9% during 28 days. Efficiency of Muscalik-AZA in the the range between 80-91.7% was determined in the delivery room for sows in flies with low resistance to azamethiphos. The biological efficiency of Snip to flies with moderate resistance to azamethiphos was determined in the area of veterinary ambulance. The mean efficiency of Snip was 92.2% during the 28 days of test.

With the aim of proposing a nondestructive biomarker for monitoring the toxicological risk to birds of exposure to the organophosphorus insecticide azamethiphos and the carbamate insecticide methomyl, laboratory studies were performed on serum "B" esterases in Japanese quail (Coturnix coturnix japonica). The birds received two single dose treatments of each compound (azamethiphos and methomyl), i.e., 50 mg/kg and 250 mg/kg respectively. In the first treatment, serum butyrylcholinesterase (BChE) and carboxylesterase (CbE) were drastically inhibited in the azamethiphos-treated group, 24 h after the dose. No inhibition was detected for BChE and CbE activities in the methomyl-treated group, 24 h after the dose. In the second treatment, the birds died or were sacrificed 3 h after the dose. Serum BChE and brain acetylcholinesterase (AChE) were strongly inhibited after treatment with both insecticides. Serum CbE, hepatic microsomal CbE and 7-ethoxyresorufin dealkylation activities were also inhibited. A statistically significant correlation between serum BChE and brain AChE was found at lethal and sublethal doses of these xenobiotics. The experimental results indicate that the nondestructive biomarker BChE can give an early qualitative and semi-quantitative warning of the toxic effects of organophosphate and carbamate insecticides in birds.

Dermal and oral toxicities of azamethiphos were determined in two organophosphate-resistant and one susceptible strain of houseflies, Musca domestica L. The 594vb strain was 1,967-fold more resistant to azamethiphos when compared with the susceptible Chemical Specialties Manufacturers Association (CSMA) strain by dermal application. When the compound was administered orally to the 594vb strain, we observed only a 15-fold resistance. In contrast, the Yachiyo strain, which show 1,500-fold resistance to diazinon and which has known multiple mechanisms for organophosphate resistance, showed only 6-fold resistance to azamethiphos by topical application and 4-fold resistance by oral administration. Azamethiphos administered dermally and orally was equally toxic to the CSMA and Yachiyo strains. However, when azamethiphos was administered to the 594vb strain, the insecticide was 71 times more toxic orally than by the dermal route. This result indicated involvement of a cuticular penetration factor in the resistance mechanism. The effect on azamethiphos toxicity of piperonyl butoxide (PB), an inhibitor of the monooxygenases, and tributylphosphorotrithioate (DEF), an esterase inhibitor, was investigated in the three strains. Pretreatment of the flies with PB, DEF, or PB+DEF before topical application of azamethiphos resulted in a significant decrease in LD50s in all the strains. The degree of synergism, however, varied depending upon the strains and the synergists. Similar results were obtained when azamethiphos was administered orally following pretreatment of the flies with PB+DEF. We attribute the high level of azamethiphos resistance in the 594vb strain partly to increased degradation by oxidative and hydrolytic enzymes. The hydrolytic enzymes are more important, but other factors including reduced cuticular penetration and insensitive acetylcholinesterase may be involved.(ABSTRACT TRUNCATED AT 250 WORDS)

1. Acetylcholinesterase from the heads of a strain of houseflies selected for resistance to the carbamate insecticide methomyl, and from a methomyl-resistant field strain was found to be less sensitive to inhibition by methomyl than that from a susceptible strain. 2. The enzyme from resistant insects was also more tolerant to malaoxon, dichlorvos and bomyl but not to azamethiphos. 3. The decrease in sensitivity to inhibition appeared to be due to an increase in affinity for substrate.