Inhibitor Report for: Oxamyl

Oxamyl is a highly toxic carbamate molecule with toxicological risk from contamination, used as an insecticide, nematicide, and acaricide on many field crops, vegetables, fruits, and ornamentals. Suspected poisoned animals and baits were collected between January 2018 and August 2021 from Lombardy and Emilia-Romagna regions and analyzed at the chemical toxicology laboratory of the Experimental Zooprophylactic Institute of Lombardy and Emilia-Romagna, located in Brescia. The analyses were carried out by an ion trap GC-MS system in 2467 suspected samples and showed the presence of oxamyl in 67 of these. In this study, we analyzed 47 (out of 67) positive baits: the provinces in which more cases have been recorded are Mantua, Ferrara, and Cremona, which overall had 72% of positivity. The nature of the analyzed samples was mostly corn (55.3%), followed by bird carcasses (19.1%), apples (14.8%), meatballs (2.1%), bread (2.1%), and other (8.5%). The use of oxamyl to produce poisoned baits is constantly increasing, proving that it must be considered as a public health risk for the possible consequences on target and non-target organisms, including humans.

Microbial degradation is the main process controlling the environmental dissipation of the nematicide oxamyl. Despite that, little is known regarding the microorganisms involved in its biotransformation. We report the isolation of four oxamyl-degrading bacterial strains from an agricultural soil exhibiting enhanced biodegradation of oxamyl. Multilocus sequence analysis (MLSA) assigned the isolated bacteria to different subgroups of the genus Pseudomonas. The isolated bacteria hydrolyzed oxamyl to oxamyl oxime, which was not further transformed, and utilized methylamine as a C and N source. This was further supported by the detection of methylamine dehydrogenase in three of the four isolates. All oxamyl-degrading strains carried a gene highly homologous to a carbamate-hydrolase gene cehA previously identified in carbaryl- and carbofuran-degrading strains. Transcription analysis verified its direct involvement in the hydrolysis of oxamyl. Selected isolates exhibited relaxed degrading specificity and transformed all carbamates tested including the oximino carbamates aldicarb and methomyl (structurally related to oxamyl) and the aryl-methyl carbamates carbofuran and carbaryl which share with oxamyl only the carbamate moiety.

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.

Oxamyl is a highly toxic carbamate molecule with toxicological risk from contamination, used as an insecticide, nematicide, and acaricide on many field crops, vegetables, fruits, and ornamentals. Suspected poisoned animals and baits were collected between January 2018 and August 2021 from Lombardy and Emilia-Romagna regions and analyzed at the chemical toxicology laboratory of the Experimental Zooprophylactic Institute of Lombardy and Emilia-Romagna, located in Brescia. The analyses were carried out by an ion trap GC-MS system in 2467 suspected samples and showed the presence of oxamyl in 67 of these. In this study, we analyzed 47 (out of 67) positive baits: the provinces in which more cases have been recorded are Mantua, Ferrara, and Cremona, which overall had 72% of positivity. The nature of the analyzed samples was mostly corn (55.3%), followed by bird carcasses (19.1%), apples (14.8%), meatballs (2.1%), bread (2.1%), and other (8.5%). The use of oxamyl to produce poisoned baits is constantly increasing, proving that it must be considered as a public health risk for the possible consequences on target and non-target organisms, including humans.

Microbial degradation is the main process controlling the environmental dissipation of the nematicide oxamyl. Despite that, little is known regarding the microorganisms involved in its biotransformation. We report the isolation of four oxamyl-degrading bacterial strains from an agricultural soil exhibiting enhanced biodegradation of oxamyl. Multilocus sequence analysis (MLSA) assigned the isolated bacteria to different subgroups of the genus Pseudomonas. The isolated bacteria hydrolyzed oxamyl to oxamyl oxime, which was not further transformed, and utilized methylamine as a C and N source. This was further supported by the detection of methylamine dehydrogenase in three of the four isolates. All oxamyl-degrading strains carried a gene highly homologous to a carbamate-hydrolase gene cehA previously identified in carbaryl- and carbofuran-degrading strains. Transcription analysis verified its direct involvement in the hydrolysis of oxamyl. Selected isolates exhibited relaxed degrading specificity and transformed all carbamates tested including the oximino carbamates aldicarb and methomyl (structurally related to oxamyl) and the aryl-methyl carbamates carbofuran and carbaryl which share with oxamyl only the carbamate moiety.

BACKGROUND: The potential for enhanced degradation of the carbamoyloxime nematicides aldicarb and oxamyl and the organophosphate fosthiazate was investigated in 35 UK agricultural soils. Under laboratory conditions, soil samples received three successive applications of nematicide at 25 day intervals.
RESULTS: The second and third applications of aldicarb were degraded at a faster rate than the first application in six of the 15 aldicarb-treated soils, and a further three soils demonstrated rapid degradation of all three applications. High organic matter content and low pH had an inhibitory effect on the rate of aldicarb degradation. Rapid degradation was observed in nine out of the ten soils treated with oxamyl. In contrast, none of the fosthiazate-treated soils demonstrated enhanced degradation. CONCLUSION: The potential for enhanced degradation of aldicarb and oxamyl was demonstrated in nine out of 15 and nine out of ten soils respectively that had previously been treated with these active substances. Degradation of fosthiazate occurred at a much slower rate, with no evidence of enhanced degradation. Fosthiazate may provide a useful alternative in cases where the efficacy of aldicarb and oxamyl has been reduced as a result of enhanced degradation.

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.

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.

The suitability of Empore-activated carbon disks (EACD), Envi-Carb graphitized carbon black (GCB) and CPP-50 graphitized carbon for the trace enrichment of polar pesticides from water samples was studied by means of off-line and on-line solid-phase extraction (SPE). In the off-line procedure, 0.5-2 l samples spiked with a test mixture of oxamyl, methomyl and aldicarb sulfoxide were enriched on EnviCarb SPE cartridges or 47 mm diameter EACD and eluted with dichloromethane-methanol. After evaporation, a sample was injected onto a C18-bonded silica column and analysed by liquid chromatography with ultraviolet (LC-UV) detection. EACD performed better than EnviCarb cartridges in terms of breakthrough volumes (> 2 l for all test analytes), reproducibility (R.S.D. of recoveries, 4-8%, n = 3) and sampling speed (100 ml/min); detection limits in drinking water were 0.05-0.16 microgram/l. In the on-line experiments, 4.6 mm diameter pieces cut from original EACD and stacked onto each other in a 9 mm long precolumn, and EnviCarb and CPP-50 packed in 10 x 2.0 mm I.D. precolumn, were tested, and 50-200 ml spiked water samples were preconcentrated. Because of the peak broadening caused by the strong sorption of the analytes on carbon, the carbon-packed precolumns were eluted by a separate stream of 0.1 ml/min acetonitrile which was mixed with the gradient LC eluent in front of the C18 analytical column. The final on-line procedure was also applied for the less polar propoxur, carbaryl and methiocarb. EnviCarb could not be used due to its poor pressure resistance. CPP-50 provided less peak broadening than EACD: peak widths were 0.1-0.3 min and R.S.D. of peak heights 4-14% (n = 3). In terms of analyte trapping efficiency on-line SPE-LC-UV with a CPP-50 precolumn also showed better performance than when Bondesil C18/OH or polymeric PLRP-S was used, but chromatographic resolution was similar. With the CPP-50-based system, detection limits of the test compounds were 0.05-1 microgram/l in surface water.

The effects of single acute oral doses of 1, 2.1, and 3.5 mg/kg oxamyl (a carbamate insecticide) on selected biochemical parameters in male Sprague-Dawley rats were investigated. The animals exhibited significantly decreased weight gain when compared to control animals. The compound inhibited brain and blood acetylcholinesterase significantly in the first few hours of exposure. Liver glucose-6-phosphatase was inhibited substantially after 7 and 4 days at the levels of 2.1 and 3.5 mg/kg, respectively. Maximum inhibition of liver succinic acid dehydrogenase was noted after 1 day at the level of 1 mg/kg and after 6 hr at the level of 2.1 and 3.5 mg/kg. Significant changes in serum total lipids and glucose were observed when oxamyl was given at 2.1 and 3.5 mg/kg, but serum protein was not affected at any dose level. However, the absence of statistically significant effects between Days 7 and 14 in most of the investigated parameters is indicative of an overall moderate degree of toxicity of oxamyl following acute oral administration of the selected doses.

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.

The acute toxicity of oxamyl, an insecticide and nematicide, has been evaluated to establish proper handling guides. The material is highly toxic when given as a single oral dose; its LD50 is in fasted rats 2.5 to 3.1 mg/kg, 2.3 to 3.3 mg/kg in fasted mice, and 7 mg/kg in guinea pigs. A beagle dog given 30 mg/kg died, while 15 mg/kg was not lethal. In all species, clinical signs of cholinesterase inhibition (lacrimation, salivation, tremors) were observed. Cholinesterase activity was depressed in rats treated with a single oral dose. Atropine, when given immediately after oxamyl, was antidotal. When given by intraperitoneal injection, oxamyl was highly toxic to rats, mice, and guinea pigs. The material is a mild eye irritant with the reaction limited to the conjunctiva and iris, but systemic absorption via eye contact makes use of protective equipment essential. Oxamyl produces mild skin irritation and the dermal absorption toxicity in rats (LD50 is greater than 1,200 mg/kg) and rabbits (740 mg/kg) is relatively high suggesting limited absorption. No sensitization was produced when tested in guinea pigs. Oxamyl is highly toxic via inhalation with the 1-hr LC50 value in rats being 0.17 mg/liter (male) and 0.12 mg/liter (female). The corresponding 4-hr value is 0.064 mg/liter for male rats which indicates that concentration X time is a constant through the time periods tested. Repeated-dose studies, orally in rats and dermally in rabbits, showed oxamyl to be noncumulative, with the target system being the nervous system mediated through cholinesterase inhibition. No specific tissue or organ pathology was seen in either species tested.

The pH-disappearance rate profiles were determined at ca. 25 degrees C for 24 insecticides at 4 or 5 pH values over the range 4.5 to 8.0 in sterile phosphate buffers prepared in water-ethanol (99:1 v/v). Half-lives measured at pH 8 were generally smaller than at lower pH values. Changes in half lives between pH 8.0 and 4.5 were largest (greater than 1000x) for the aryl carbamates, carbofuran and carbaryl, the oxime carbamate, oxamyl, and the organophosphorus insecticide, trichlorfon. In contrast, half lives of phorate, terbufos, heptachlor, fensulfothion and aldicarb were affected only slightly by pH changes. Under the experimental conditions described half lives at pH8 varied from 1-2 days for trichlorfon and oxamyl to greater than 1 year for fensulfothion and cypermethrin. Insecticide persistence on alumina (acid, neutral and basic), mineral soils amended with aluminum sulfate or calcium hydroxide to different pH values and four natural soils of different pH was examined. No correlation was observed between the measured pH of these solids and the rate of disappearance of selected insecticides applied to them. These observations demonstrate the difficulty of extrapolating the pH dependent disappearance behaviour observed in homogeneous solution to partially solid heterogeneous systems such as soil.

A simple and fast gas-liquid chromatographic method has been developed to determine residues of oxamyl insecticide in peppers, tomatoes, and cucumbers. Following sample extraction with ethyl acetate and cleanup on an alumina column, the compound is determined using a thermionic nitrogen-phosphorus detector. The limit of detection is 0.02 ppm based on 40 g sample. Average recoveries for oxamyl at 0.025-1.0 ppm for all 3 products were 88-97%.

The gas-liquid chromatographic behavior of methomyl (methyl N-[(methyl-carbamoyl)oxy]thioacetimidate), oxamyl (methyl N',N'-dimethyl-N-[(methylcarbamoyl)oxyl]-1-thiooxamimidate), their respective oxime hydrolysis products and the trimethylsilyl (TMS) ethers of the oximes on 5% OV-1 was studied under isothermal conditions using a flame-photometric detector in the sulfur-selective mode. In contrast to the behavior of the parent carbamates and underivatized oximes, the oxime-TMS ethers readily produced symmetrical peaks of consistent size. Quantities of derivative equivalent to at least 0.25 ng of oxime were easily measurable. Derivative formation was reproducible for standards over the range 10.0 to 0.25 microgram/ml in benzene and at 10.0 and 0.50 microgram/ml in the presence of extractives from tomato, carrot and celery at concentrations equivalent to 10 g/ml of crop. Derivative yields from crop extract fotifications were 89% or better in most cases. Both the carbamates and oximes were simply and consistently recovered in high yield from crops fortified at 1.00 and 0.05 ppm using the procedures described. The inclusion of a second analytical step provided separate analysis for oximes and carbamates. The application of these observations to the analyses of residues in crops is discussed.

A reverse phase high pressure liquid chromatographic method is presented for the separation and determination of residues of the carbamates oxamyl and methomyl on vegetables. A liquid-liquid extraction and cleanup procedure is applied to the vegetable extract. Samples are eluted from a muBondapak C18 column and quantitated by ultraviolet absorbance at 240 nm. Recovery data for vegetable samples spiked at 2 ppm are presented.