Flubendiamide

682.4

682.39

608-064-7

GEV84ZI4K6

DTXSID4047672

White crystalline powder

101

4.2 at 25 deg C

1.659 at 20 deg C

217.5-220.7 °C @ Solvent: Diethyl ether, Hexane

578.6ºC at 760 mmHg

303.7ºC

1.539

In water, 29.9 ug/L at 20 deg C

Safe Storage of Pesticides. Always store pesticides in their original containers, complete with labels that list ingredients, directions for use, and first aid steps in case of accidental poisoning. Never store pesticides in cabinets with or near food, animal feed, or medical supplies. Do not store pesticides in places where flooding is possible or in places where they might spill or leak into wells, drains, ground water, or surface water. /Residential users/

<7.5X10-7 mm Hg at 25 deg C

Henry's Law constant = 2.25X10-4 atm-cu m/mole at 25 °C (est)

Does not dissociate

Hydroxyl radical reaction rate constant = 2.9X10-11 cu cm/molec-sec at 25 °C (est)

435 °C/ 815 °F. /Belt SC Insecticide/

UN 3077 9 / PGIII

1

P273

H400

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal and plant life; and conformance with environmental and public health regulations.|Wastes resulting from the use of this product may be disposed of on site or at an approved waste disposal facility. /Belt SC Insecticide/|CONTAINER DISPOSAL: Non-refillable container. Do not reuse or refill this container. Triple rinse container (or equivalent) promptly after emptying. Triple rinse as follows: Empty the remaining contents into application equipment or a mix tank and drain for 10 seconds after the flow begins to drip. Fill the container 1/4 full with water and recap. Shake for 10 seconds. Pour rinsate into application equipment or a mix tank or store rinsate for later use or disposal. Drain for 10 seconds after the flow begins to drip. Repeat this procedure two more times, then offer for recycling or reconditioning or puncture and dispose of in a sanitary landfill, or by other procedures approved by state and local authorities. /Belt SC Insecticide/|Safe Disposal of Pesticides. The best way to dispose of small amounts of excess pesticides is to use them - apply them - according to the directions on the label. If you cannot use them, ask your neighbors whether they have a similar pest control problem and can use them. If all of the remaining pesticide cannot be properly used, check with your local solid waste management authority, environmental agency, or health department to find out whether your community has a household hazardous waste collection program or a similar program for getting rid of unwanted, leftover pesticides. These authorities can also inform you of any local requirements for pesticide waste disposal. /Residential users/|Safe Disposal of Pesticides. An empty pesticide container can be as hazardous as a full one because of residues left inside. Never reuse such a container. When empty, a pesticide container should be rinsed carefully three times and the rinsewater thoroughly drained back onto the sprayer or the container previously used to mix the pesticide. Use the rinsewater as a pesticide, following label directions. Replace the cap or closure securely. Dispose of the container according to label instructions. Do not puncture or burn a pressurized container like an aerosol - it could explode. Do cut or puncture other empty pesticide containers made of metal or plastic to prevent someone from reusing them. Wrap the empty container and put it in the trash after you have rinsed it. /Residential users/

|Warning|H400 (100%): Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]|P273, P391, and P501|Aggregated GHS information provided by 196 companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|Danger|H302: Harmful if swallowed [Warning Acute toxicity, oral]|P201, P202, P260, P261, P264, P270, P271, P280, P281, P301+P312, P302+P352, P304+P312, P304+P340, P307+P311, P308+P313, P312, P314, P321, P322, P330, P363, P405, and P501

Applicators and other handlers must wear: Long-sleeved shirt and long pants; Chemical-resistant gloves (such as Natural Rubber). If you want more options, follow the instructions for Category A on the EPA chemical-resistance category selection chart.; Shoes plus socks. /Belt SC Insecticide/|... Restricted entry interval (REI) of 12 hours following application. PPE required for early entry to treated areas that is permitted under the Worker Protection Standard and that involves contact with anything that has been treated such as plants, soil or water, is: coveralls, chemical-resistant gloves such as barrier laminate, butyl rubber, nitrile rubber, or viton, and shoes plus socks. /Belt SC Insecticide/

Keep out of smoke. Fight fire from upwind position. Cool closed containers/ tanks exposed to fire with water spray. Do not allow run-off from fire fighting to enter drains or water courses. Firefighters should wear NIOSH approved self-contained breathing apparatus and full protective clothing. /Belt SC Insecticide/

Do not contaminate water when disposing of equipment washwater or rinsate. /Belt SC Insecticide/|If a spill occurs, clean it up promptly. Don't wash it away. Instead, sprinkle the spill with sawdust, vermiculite, or kitty litter. Sweep it into a plastic garbage bag, and dispose of it as directed on the pesticide product label./Residential users/|After Applying a Pesticide, Indoors or Outdoors. To remove pesticide residues, use a bucket to rinse tools or equipment three times, including any containers or utensils that you used when mixing the pesticide. Then pour the rinsewater into the pesticide sprayer and reuse the solution by applying it according to the pesticide product label directions. After applying any pesticide wash your hands and any other parts of your body that may have come in contact with the pesticide. To prevent tracking pesticides inside, remove or rinse your boots or shoes before entering your home. Wash any clothes that have been exposed to a lot of pesticide separately from your regular wash. /Residential users/

Use this product only in accordance with its labeling and with the Worker Protection Standard, 40 CFR part 170. /Belt SC Insecticide/|Do not enter or allow worker entry into treated areas during the restricted entry interval (REI) of 12 hours following application. /Belt SC Insecticide/|This pesticide is toxic to aquatic invertebrates. For terrestrial uses: Do not apply directly to water, or to areas where surface water is present or to intertidal areas below the mean high water mark. /Belt SC Insecticide/|Do not apply this product in a way that will contact workers or other persons, either directly or through drift. Only protected handlers may be in the same area during application. /Belt SC Insecticide/|For more Preventive Measures (Complete) data for Flubendiamide (18 total), please visit the HSDB record page.

Causes moderate eye irritation. /Belt SC Insecticide/

SOIL: Soil residues of flubendiamide were reported as <0.01 mg/kg 20 days after application of flubendiamide at 60 and 120 g/ha application rate on chili crops(1).

LC50 Rat inhalation > or = 0.0685 mg/L/4 hr|LD50 Rat dermal > or = 2,000 mg/kg|LD50 Rat oral > or = 2,000 mg/kg

/FIELD STUDIES/ In a mesocosm study, the ecological effects of the 480 SC formulation were determined for different trophic levels including phytoplankton, zooplankton, aquatic macroinvertebrates, and emergent insects (no fish). The SC formulation was applied once onto the water surface in May 2003 and included five treatment levels 0.4, 1.0, 2.3, 5.3 and 12 ug a.i./L. There were two replicates of the 0.4-5.3 ug a.i./L groups and no replication of the 12 ug a.i./L treatment group. There were three control tanks. The mesocosms were observed two weeks before and 16 weeks after treatment. A significant number of taxa developed in the mesocosms: 36 zooplankton species, 21 macrozoobenthic organisms, 49 emerging insect species, and 7 classes of phytoplankton. Of these, the Cladocera Daphnia longispina was the most sensitive species. Based on the observed effects on Daphnia longispina..., the NOAEC on the population and community level for the zooplankton was 1.0 ug/L. Persistent effects were not observed for any taxon in the study up to the highest treatment level (12 ug/L), but there was no replication at this level. As a result, the NOAEC for this study is 5.3 ug/L for the zooplankton. Regarding macroinvertebrates, the artificial substrate samplers did not indicate persistent effects for any taxon as well as for the macroinvertebrate community for all treatment levels. Additionally, no direct effects were observed on the phytoplankton.

Flubendiamide's production may result in its release to the environment through various waste streams; its use as an insecticide(1) will result in its direct release to the environment(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), a Koc value range of 1076 to 3318(2), indicates that flubendiamide is expected to have slight to low mobility in soil(SRC). Volatilization of flubendiamide from moist soil surfaces is expected to be an important fate process(SRC) given an estimated Henry's Law constant of 2.2X10-4 atm-cu m/mole(SRC), based upon its vapor pressure, <7.5X10-7 mm Hg(2), and water solubility, 29.9 ug/L(2). However, adsorption to soil is expected to attenuate volatilization. Flubendiamide is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(2). In three field soil biodegradation studies, flubendiamide had half-lives of 210 to 770 days(2). Soil photodegradation half-life of flubendiamide is reported as 11.6 days(2).|AQUATIC FATE: Based on a classification scheme(1), a Koc value range of 1076 to 3318(2), indicates that flubendiamide is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon an estimated Henry's Law constant of 2.2X10-4 atm-cu m/mole(SRC), derived from its vapor pressure, <7.5X10-7 mm Hg(2), and water solubility, 29.9 ug/L(2). However, volatilization from water surfaces is expected to be attenuated by adsorption to suspended solids and sediment in the water column. The estimated volatilization half-life from a model pond is 100 days if adsorption is considered(4). According to a classification scheme(5), an estimated BCF of 270(SRC), from its log Kow of 4.2(2) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is high(SRC). Flubendiamide is not expected to undergo hydrolysis in the environment; it is reported stable from pH 4 to 9(2). Flubendiamide has a reported aquatic anaerobic half-life of 365 days(2). Aqueous photodegradation of flubendiamide has a reported half-life of 5.5 days in distilled water at 25 °C(2).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), flubendiamide, which has a vapor pressure of <7.5X10-7 mm Hg at 25 °C(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase flubendiamide is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 4.4 hours(SRC), calculated from its rate constant of 2.9X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase flubendiamide may be removed from the air by wet or dry deposition(SRC). Flubendiamide contains chromophores that absorb at wavelengths >290 nm(4) and therefore may be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of flubendiamide with photochemically-produced hydroxyl radicals has been estimated as 2.9X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 4.4 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Flubendiamide is not expected to undergo hydrolysis in the environment, it is reported stable from pH 4 to 9(2). Flubendiamide contains chromophores that absorb at wavelengths >290 nm(3) and therefore may be susceptible to direct photolysis by sunlight(SRC). Aqueous photodegradation of flubendiamide has a reported half-life of 5.5 days in distilled water at 25 °C(2). Soil photodegradation half-life of flubendiamide is reported as 11.6 days(2).

An estimated BCF of 270 was calculated in fish for flubendiamide(SRC), using a log Kow of 4.2(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is high(SRC).

The Koc of flubendiamide has been reported to be 1076 to 3318(1). According to a classification scheme(2), this Koc value range suggests that flubendiamide is expected to have slight to low mobility in soil.

The Henry's Law constant for flubendiamide is estimated as 2.2X10-4 atm-cu m/mole(SRC) derived from its vapor pressure, <7.5X10-7 mm Hg(1), and water solubility, 29.9 ug/L(1). This Henry's Law constant indicates that flubendiamide is expected to volatilize from water surfaces(2). Based on this Henry's Law constant, the volatilization half-life from a model river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec)(2) is estimated as 18 hours hours(SRC). The volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec)(2) is estimated as 13 days(SRC). However, volatilization from water surfaces is expected to be attenuated by adsorption to suspended solids and sediment in the water column. The estimated volatilization half-life from a model pond is 100 days if adsorption is considered(3). Flubendiamide is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(1).

Residues of flubendiamide found in chili, also called red pepper, (Capsicum annuum L., C. frutescene L.) after application. Crop test site was located at the Entomological Research Farm, Punjab Agricultural University, Ludhiana, India(1).

Occupational exposure to flubendiamide may occur through inhalation and dermal contact with this compound at workplaces where flubendiamide is produced or used. Monitoring data indicate that the general population is not likely to be exposed to flubendiamide probably due to its rapid photodegradation. (SRC)

Flubendiamide (purified to 99.6% purity for non-labeled a.i. and for (14)C-labeled on the phthalic acid ring) was administered once by gavage (aqueous suspension of 2% sodium carboxymethylcellulose containing 0.4% Tween 80) to F-344 (F344/DuCrj) rats provided with biliary cannulae. Three males and 6 females received 2 mg/kg in the definitive study. (Additional rats were dosed twice at 16-hr intervals with 20 mg/kg a.i. to facilitate characterization of metabolites.) Investigators determined the excretion of label in bile, urine, feces over 48 hours, and determined the residues in gastrointestinal tract contents, in the rinsed gastrointestinal tract, the liver, and in residual carcass. Investigators also identified the major metabolites in bile, feces, and gastrointestinal tract contents at 48 hours. Absorption was slow: contents of the gastrointestinal tract at 48 hours contained 60% and 51% of administered label in males and females, respectively. Bile contained 11.1% and 3.3% of administered label in males and females, respectively. Feces in these cannulated rats contained 12.8% and 11.0% of administered label in males and females. Urine contained only 0.75% and 0.15% of administered label in males and females: thus urinary metabolites were not assessed in this study. Parent flubendiamide was the dominant component of (feces plus gastrointestinal content) in both sexes (94% of label recovered from these sources in males, and 99% in females). ...|Typically sets of 4 non-fasted rats/sex were gavage-dosed daily for 14 days with Flubendiamide (NNI-0001), (14)C-labeled on the phthalic acid ring, radiochemical purity after purification of 99.2%, in an aqueous suspension of 2% sodium carboxymethylcellulose containing 0.4% Tween 80. This study assessed ADME features including quantification of major metabolites. Rats were sacrificed either 9 hr, 24 hr, or 168 hr after the final (14th) dosing. Results from the present study should be compared to the primary single dose study (DPR Document No. 53013-0179, Record No. 226611). There was no substantial change in blood or plasma levels when comparing rats sampled 24 hr after 1, 6, or 13 daily doses. Distribution to tissues between 9 hr and 168 hr after repetitive dosing for 14 days found that label was moving through the g.i. tract more slowly in the present study than in the single-dose study during the first 24 hr. At 24 hours in the present study, much more of the label remained in the intestinal contents than was the case in the single-dose study. Also, tissue levels were not decreasing as rapidly in this study from 9 hr to 24 hr after dosing compared to the single dose study. By 7 days after dosing, tissue levels in the two studies were comparable. Overall absorption in the present study appeared to be markedly lower than was observed in the single dose study, based on percent of administered label found in the urine. This appears to reflect comparatively low absorption of a dose administered to non-fasted animals. ...|Typically sets of 4 fasted rats/sex were dosed once by gavage with Flubendiamide (NNI-0001), (14)C-labeled on either the phthalic acid ring or (to a limited extent) on the aniline ring, radiochemical content after purification > 99.5%, in an aqueous suspension of 1% sodium carboxymethylcellulose containing 0.2% Tween 80. This study assessed ADME features including identification of major metabolites following treatment with either 2 or 200 mg/kg flubendiamide. There was no significant excretion of label into expired air. Over 90% of administered dose was excreted in feces regardless of dose or sex. Although urine was a minor route (< 2% of administered dose), males consistently passed more label in urine than did females. High dose levels led to markedly reduced absorption. There was no obvious difference in excretion patterns and there were minimal differences in metabolite chromatograms between the two labeled forms, indicating that there was very little cleavage dividing major portions of the molecule. Tmax was 6 to 12 hours for blood and plasma. Tissue distribution of label was preferentially to the g.i. tract, liver and other highly perfused organs, and body fat. Low dose treatments found peak tissue levels in males several-fold higher than females. Tissue levels in males were lower by about 90% from 9 hrs to 24 hrs, and by another 90% from 24 hrs to 168 hrs. Females did not clear tissues as rapidly as males, however, so females had higher residual tissue concentrations at 168 hours than males. The primary substituent available for oxidation on flubendiamide is the methyl group on the aniline ring. The most common products were the benzyl alcohol (designated A-16) and the benzoic acid (designated A-18) of that methyl carbon. The less abundant intermediate benzaldehyde was designated as A-17. Substantial sex differences emerged in metabolic profiles. In the feces, the benzyl alcohol was the dominant metabolite in 2 mg/kg males (31-37% of administered dose), followed by parent flubendiamide (15-30% of administered dose), and the benzoic acid metabolite (15-16% of administered dose). In feces of 2 mg/kg females, 66% of administered dose was flubendiamide, 5-6% of administered dose was benzyl alcohol, and there was very little benzoic acid metabolite. There were no other major metabolites. Parent flubendiamide was the predominant labeled constituent in feces of both sexes at 200 mg/kg, indicating saturable absorption. Female rats were very slow to clear radioactivity: contrast liver label content in 2 mg/kg males dropping from 5.628% to 0.104% of administered dose at 9 hrs and 168 hrs after dosing vs. content in females of 1.623% and 1.305% of administered dose at the same sampling times. Female rats have limited hepatic metabolic capacity for flubendiamide, hence there was appreciable accumulation of parent flubendiamide in the livers of females at 24 hours (an order of magnitude more than all extractable metabolites combined). In males, very little parent flubendiamide was found in liver (less than half of the percent of dose represented by benzyl alcohol or benzaldehyde metabolites). Liver in males had smaller but measurable amounts of the sole identified product of cleavage between the two ring structures of flubendiamide (the aniline fragment).|F-344 (F344/DuCrj) rats and Crlj: CD1 (ICR) mice (4/species/sex/dosing period) were dosed with 200 mg/kg/day unlabeled flubendiamide, purity 96.7% by gavage in corn oil. Treatments were daily for 1, 7, or 14 days. Animals were sacrificed 24 hr after the final dose. Investigators determined concentrations of flubendiamide and of the iodophthalimide metabolite (A-14) in plasma, liver, and fat. Flubendiamide did not increase in the in these tissues over time in males. There was a marginal accumulation in females in all studied tissues, reaching steady state by day 7. A-14 appeared to be accumulating in fat in rats of both sexes, reaching steady state by day 7. Flubendiamide was always more concentrated in liver and fat than in plasma, and concentrations were much higher in females than in males. Day 7 concentrations of flubendiamide in liver and fat of male rats at day 7 were 1.3 and 8.9 mg/kg, respectively. Liver and fat concentrations in female rats were 26.7 and 68.0 mg/kg. A-14 concentrations in male and female rats for liver and fat at day 7 were identical at < 1.0 and 2.9 mg/kg, respectively. Flubendiamide concentrations on day 7 in liver and fat of male mice were 2.3 and 3.4 mg/kg, respectively. Corresponding levels in female mice were 2.4 and 1.9 mg/kg (i.e. much unlike the marked accumulation in female rats). A-14 levels were generally below quantification limits in both male and female mice. This study indicates that limited metabolic capacity of female rats toward flubendiamide and tendency to metabolize significant amounts of A-14 do not apply to either sex of mice.

Typically sets of 4 non-fasted rats/sex were gavage-dosed daily for 14 days with Flubendiamide (NNI-0001), (14)C-labeled on the phthalic acid ring, radiochemical purity after purification of 99.2%, in an aqueous suspension of 2% sodium carboxymethylcellulose containing 0.4% Tween 80. This study assessed ADME features including quantification of major metabolites. Rats were sacrificed either 9 hr, 24 hr, or 168 hr after the final (14th) dosing. ... Females showed less metabolized label and greater longterm tissue retention of label than males, consistent with other studies. Parent flubendiamide comprised 82% and 91% of fecal metabolites in males and females, respectively. Relative proportions of remaining fecal label consisted of the benzyl alcohol metabolite (A-16) (7.2% of excreted radioactivity in males, and 2.2% in females), the benzoic acid metabolite (A-18) (2.8% of excreted radioactivity in males and below detection in females), with other metabolites uncharacterized or in very small amounts. This study reported quantifiable amounts of the iodophthalimide metabolite (A-14) of flubendiamide in fat. This metabolite, involving cleavage of all components distal to the phthalamide nitrogen, had not been found in measurable amounts in excreta.|Typically sets of 4 fasted rats/sex were dosed once by gavage with Flubendiamide (NNI-0001), (14)C-labeled on either the phthalic acid ring or (to a limited extent) on the aniline ring, radiochemical content after purification > 99.5%, in an aqueous suspension of 1% sodium carboxymethylcellulose containing 0.2% Tween 80. This study assessed ADME features including identification of major metabolites following treatment with either 2 or 200 mg/kg flubendiamide. There was no significant excretion of label into expired air. Over 90% of administered dose was excreted in feces regardless of dose or sex. Although urine was a minor route (< 2% of administered dose), males consistently passed more label in urine than did females. High dose levels led to markedly reduced absorption. There was no obvious difference in excretion patterns and there were minimal differences in metabolite chromatograms between the two labeled forms, indicating that there was very little cleavage dividing major portions of the molecule. Tmax was 6 to 12 hours for blood and plasma. Tissue distribution of label was preferentially to the g.i. tract, liver and other highly perfused organs, and body fat. Low dose treatments found peak tissue levels in males several-fold higher than females. Tissue levels in males were lower by about 90% from 9 hrs to 24 hrs, and by another 90% from 24 hrs to 168 hrs. Females did not clear tissues as rapidly as males, however, so females had higher residual tissue concentrations at 168 hours than males. The primary substituent available for oxidation on flubendiamide is the methyl group on the aniline ring. The most common products were the benzyl alcohol (designated A-16) and the benzoic acid (designated A-18) of that methyl carbon. The less abundant intermediate benzaldehyde was designated as A-17. Substantial sex differences emerged in metabolic profiles. In the feces, the benzyl alcohol was the dominant metabolite in 2 mg/kg males (31-37% of administered dose), followed by parent flubendiamide (15-30% of administered dose), and the benzoic acid metabolite (15-16% of administered dose). In feces of 2 mg/kg females, 66% of administered dose was flubendiamide, 5-6% of administered dose was benzyl alcohol, and there was very little benzoic acid metabolite. There were no other major metabolites. Parent flubendiamide was the predominant labeled constituent in feces of both sexes at 200 mg/kg, indicating saturable absorption. Female rats were very slow to clear radioactivity: contrast liver label content in 2 mg/kg males dropping from 5.628% to 0.104% of administered dose at 9 hrs and 168 hrs after dosing vs. content in females of 1.623% and 1.305% of administered dose at the same sampling times. Female rats have limited hepatic metabolic capacity for flubendiamide, hence there was appreciable accumulation of parent flubendiamide in the livers of females at 24 hours (an order of magnitude more than all extractable metabolites combined). In males, very little parent flubendiamide was found in liver (less than half of the percent of dose represented by benzyl alcohol or benzaldehyde metabolites). Liver in males had smaller but measurable amounts of the sole identified product of cleavage between the two ring structures of flubendiamide (the aniline fragment).|Flubendiamide (purified to 99.6% purity for non-labeled a.i. and for (14)C-labeled on the phthalic acid ring) was administered once by gavage (aqueous suspension of 2% sodium carboxymethylcellulose containing 0.4% Tween 80) to F-344 (F344/DuCrj) rats provided with biliary cannulae. Three males and 6 females received 2 mg/kg in the definitive study. (Additional rats were dosed twice at 16-hr intervals with 20 mg/kg a.i. to facilitate characterization of metabolites.) ... The only quantifiable metabolite observed in feces or gastrointestinal content was the benzyl alcohol metabolite, possibly resulting from intestinal microbial action of non-absorbed material. Much of the biliary profile in males consisted of oxidation products of the methyl group on the aniline ring ... . There was also some oxidation of the methyl groups between the phthalamide nitrogen and the sulfonyl group (including compounds designated A-19, A-20, A-25, and A-29 by investigators). Most commonly the oxidation products of the methyl group on the aniline ring were not conjugated, however it appears that oxidation of a methyl group between the phthalamide nitrogen and the sulfonyl group frequently was followed by glucuronide conjugation in males. Both sexes were capable of glutathione formation of parent compound, conjugation proposed by investigators to be on the phthalic ring. In females, glutathione conjugates (and downstream derivatives of the conjugation) were the dominant biliary metabolites. A cyclic acetal was observed in bile, particularly in males.|Rat, dog, mouse, and human microsomes (from both sexes in all species) were all able to metabolize flubendiamide to A-16, except for microsomes from female rats. (Human microsomes, but not rat microsomes, additionally produced small amounts of hydroxybenzoic acid metabolite, A-20, however metabolism to A-16 appears to be a valid indicator of overall flubendiamide metabolism.) Antisera to CYP isoforms tested in male rat microsomes found that anti-CYP3A2 sera had no effect on A-16 production, whereas anti-CYP2C11 markedly inhibited A-16 production. In contrast, recombinant microsomes expressing rat CYP3A2 produced A-16, whereas other isoforms including CYP2C11 recombinant microsomes did not. Antibody effects on human liver microsome activities found that anti-rat CYP3A2 and anti-human CYP3A4 caused similar and substantial inhibition in microsomes from male or female human liver (it was noted that anti-rat CYP3A2 was strongly reactive toward CYP3A4). Of 5 recombinant microsomes expressing human liver P450 isoforms evaluated for A-16 production, only CYP3A4 yielded measurable A-16.|F-344 (F344/DuCrj) rats and Crlj: CD1 (ICR) mice (4/species/sex/dosing period) were dosed with 200 mg/kg/day unlabeled flubendiamide, purity 96.7% by gavage in corn oil. Treatments were daily for 1, 7, or 14 days. Animals were sacrificed 24 hr after the final dose. ...Concentrations of flubendiamide and of the iodophthalimide metabolite (A-14) /were determined/ in plasma, liver, and fat. Flubendiamide did not increase in these tissues over time in males. There was a marginal accumulation in females in all studied tissues, reaching steady state by day 7. A-14 appeared to be accumulating in fat in rats of both sexes, reaching steady state by day 7. Flubendiamide was always more concentrated in liver and fat than in plasma, and concentrations were much higher in females than in males. Day 7 concentrations of flubendiamide in liver and fat of male rats at day 7 were 1.3 and 8.9 mg/kg, respectively. Liver and fat concentrations in female rats were 26.7 and 68.0 mg/kg. A-14 concentrations in male and female rats for liver and fat at day 7 were identical at < 1.0 and 2.9 mg/kg, respectively. Flubendiamide concentrations on day 7 in liver and fat of male mice were 2.3 and 3.4 mg/kg, respectively. Corresponding levels in female mice were 2.4 and 1.9 mg/kg (i.e. much unlike the marked accumulation in female rats). A-14 levels were generally below quantification limits in both male and female mice. This study indicates that limited metabolic capacity of female rats toward flubendiamide and tendency to metabolize significant amounts of A-14 do not apply to either sex of mice.

Ryanodine receptors (RyRs) are a distinct class of ligand-gated calcium channels controlling the release of calcium from intracellular stores. They are located on the sarcoplasmic reticulum of muscle and the endoplasmic reticulum of neurons and many other cell types. Ryanodine, a plant alkaloid and an important ligand used to characterize and purify the receptor, has served as a natural botanical insecticide, but attempts to generate synthetic commercial analogues of ryanodine have proved unsuccessful. Recently /the phthalic acid and diamide/ classes of synthetic chemicals have emerged resulting in commercial insecticides that target insect RyRs. ... /This article reviews/ the structure and functions of insect RyRs and addresses the modes of action of phthalic acid diamides and anthranilic diamides on insect ryanodine receptors. Particularly interesting is the inherent selectivity both chemical classes exhibit for insect RyRs over their mammalian counterparts...|Flubendiamide is a benzenedicarboxamide derivative that shows selective insecticidal activity against lepidopterous insects. The specific modulatory effects of flubendiamide on ryanodine binding in insect muscle microsomal membranes suggest that the ryanodine receptor (RyR) Ca(2+) release channel is a primary target of flubendiamide. ... cDNA encoding a novel RyR from the lepidopterous silkworm RyR (sRyR) /was cloned/ and ... the sensitivity to flubendiamide of the recombinant sRyR in HEK293 cells /was tested/. Confocal localization studies and Ca(2+) imaging techniques revealed that sRyRs form Ca(2+) release channels in the endoplasmic reticulum. Importantly, flubendiamide induced release of Ca(2+) through the sRyR, but not through the rabbit RyR isoforms. Photoaffinity labeling of sRyR deletion mutants using a photoreactive derivative revealed that flubendiamide is mainly incorporated into the transmembrane domain (amino acids 4111-5084) of the sRyR. The rabbit cardiac muscle isoform RyR2 (rRyR2) and the RyR mutant carrying a replacement of the transmembrane domain (residues 4084-5084) with its counterpart sequence from rRyR2 (residues 3936-4968) were not labeled by the photoreactive compound. This replacement in the sRyR significantly impaired the responses to flubendiamide but only marginally reduced the sensitivity to caffeine, a general RyR activator. Furthermore, deletion of the N-terminal sequence (residues 183-290) abolished the responses of the sRyR to flubendiamide but not the sensitivity to caffeine. /These/ results suggest that the transmembrane domain plays an important role in the formation of an action site for flubendiamide, while the N-terminus is a structural requirement for flubendiamide-induced activation of the sRyR.|Flubendamide belongs to the phthalic acid diamide class of insecticides for control of adult and larval Lepidoptera. It acts by targeting the ryanodine cell receptor and interfering with the calcium release channel, which is involved in muscle contraction. It is known to stabilize insect ryanodine receptors in an open state in a species-specific manner and to desensitize the calcium dependence of channel activity. Continuous stimulation of muscle contraction by "locking" the calcium channel in an "open" state, leads to muscle paralysis and eventual death of the organism. Whole organism symptoms may include feeding cessation, lethargy, paralysis, and death.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

3-iodo-N-(2-methanesulfonyl-1,1-dmethylethyl)-N'-(2-methyl-4-(1,2,2,2-tetrafluoro-1-trifluoromethylethyl)phenyl)phthalamide

Suspension concentrate (= flowable concentrate); water dispersible granule.|Composition: Technical is greater than or equal to 95.0%.|PREMIX PARTNERS: Buprofezin|Synapse WG Insecticide (Bayer Cropscience LP.) 24% Flubendiamide|For more Formulations/Preparations (Complete) data for Flubendiamide (7 total), please visit the HSDB record page.

Agrochemicals -> Insecticides|PFAS (per- and polyfluoroalkyl substances) -> OECD Category