Absorption, Distribution and Excretion
The intestinal absorption is strongly related to the dosage administered - the higher the dosage, the more is (relatively) excreted unchanged in the feces.
Following oral administration, diflubenzuron is absorbed, extensively metabolized, and almost totally excreted by cattle and sheep ... Trace amounts of the larvicide are excreted in milk following high dosages.
Orechromis niloticus fingerlings were exposed to the insect growth inhibitor diflubenzuron for 21 days. Diflubenzuron was introduced to the aquariums where fish were maintained at the beginning of the experiment, then its level in water, gills and liver was detected after 1, 7, 14 and 21 days. The fish accumulated diflubenzuron 76 and 99 times greater than the water content when kept in an ambient concentration of 2.5 and 5 mg/L, respectively, indicating a low bioaccumulation potential. Some degradation products of diflubenzuron were found mainly in liver and water.
There is limited absorption of diflubenzuron across the skin and intestinal lining of mammals, after which enzymatic hydrolysis and excretion rapidly eliminate the pesticide from tissues.
For more Absorption, Distribution and Excretion (Complete) data for DIFLUBENZURON (16 total), please visit the HSDB record page.

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Metabolism / Metabolites
The mechanisms of detoxification of the benzoylphenylureas, diflubenzuron, and teflubenzuron in the Egyptian cotton leafworm, Spodoptera littoralis, were examined, as were rates of penetration, degradation, and inhibition of benzoyphenylureas hydrolase(s) both in vivo and in vitro. The results were considered in connection with the toxicity of these compounds. Teflubenzuron was 10 times more toxic than diflubenzuron to fourth instar larvae of spodoptera littoralis. Profenofos and S,S,S-tributylphosphorotrithioate synergized both diflubenzuron and teflubenzuron, indicating that the major route of detoxification in spodoptera littoralis was through hydrolysis. Limited synergism by piperonly butoxide indicated that mixed function oxidase enzymes play a relatively small role in benzoyphenylureas detoxification. ... In Spodoptera littoralis, diflubenzuron was metabolized more rapidly than teflubenzuron: based on the relative amount of parent compound present in the larval body, about 58% of extracted radiocarbon was unchanged teflubenzuron compared to only 38% diflubenzuron. In the excreta, unchanged teflubenzuron was excreted more slowly than the metabolites (42% recovered as parent compound), compared to diflubenzuron in which 79% of the total extract was present as parent compound. Pretreatment of the fourth instar with sublethal doses of profenofos resulted in a significant decrease in metabolism, more so with diflubenzuron than with teflubenzuron. A positive correlation was found between in vivo diflubenzuron metabolism inhibition and toxicity. In in vitro assays, diflubenzuron was hydrolyzed more rapidly than teflubenzuron by all tissue extracts. Profenofos was more effective in inhibiting the hydrolysis in vitro of diflubenzuron compared to teflubenzuron, as indicated by a lower I50 value and steeper slope. /The/ results indicate that reduced penetration and fast elimination of unchanged (14)(C)diflubenzuron together with rapid metabolism, which occurs mainly through hydrolysis, are defense mechanisms which contribute to diflubenzuron detoxification in spodoptera littoralis.
After oral treatment of a cow and a castrated sheep with labeled diflubenzuron, urine was collected and analyzed. TLC indicated the presence of eight labeled materials. The major compounds in the sheep urine were identified as 2,6-difluorobenzoic acid and the hippurate analog. In the cow's urine, 2,6-difluoro-3-hydroxydiflubenzuron was the major metabolite. Metabolites N-((4-chloro-2-hydroxyphenyl)aminocarbonyl)-2,6-difluorobenzamide and N-((4-chloro-3-hydroxyphenyl)aminocarbonyl)-2,6-difluorobenzamide were also seen in urine of both cow and sheep but the 4-chlorophenylurea was seen only in the urine of the cow. Feces of both animals contained ... 2,6-difluoro-3-hydroxydiflubenzuron, N-((4-chloro-2-hydroxyphenyl)aminocarbonyl)-2,6-difluorobenzamide, and N-((4-chloro-3-hydroxyphenyl)aminocarbonyl)-2,6-difluorobenzamide. In the bile, ... 2,6-difluoro-3-hydroxydiflubenzuron, N-((4-chloro-2-hydroxyphenyl)aminocarbonyl)-2,6-difluorobenzamide, and N-((4-chloro-3-hydroxyphenyl)aminocarbonyl)-2,6-diflurorbenzamide also appeared in addition to unidentified conjugates. Incubation of bile water-soluble metabolites with b-glucuronidase-aryl sulfatase converted about half the labeled material into organic extractable materials. Although TLC indicated eight radioactive compounds, none were identified. Analysis of milk indicated the presence of unchanged diflubenzuron, 2,6-difluorobenzamide, 2,6-difluorohippuric acid, and an unidentified compound. Digestive fluids of sheep and cattle did not significantly degrade diflubenzuron. When metabolite V /2,6-difluoro-3-hydroxydiflubenzuron/ was orally administered to rats, almost all of the material was excreted within 3 days. Analyses indicated the presence of five additional compounds. None were identified.
After oral admin to rats of 5 mg diflubenzuron labeled with H3 in the benzoyl and with C14 in the aniline moiety, 95% of the H3 and 70-75% of the C14 radioactivity were retrieved in urine and feces. 2,6-DFBA was shown to constitute more than half of the urinary metabolites. Up to 1% of an oral dose of 5 mg C14-diflubenzuron labeled at the benzoyl moiety was recovered in the expired air of rats.
Diflubenzuron was applied topically to adult stable flies and houseflies. Stable flies metabolized only about 2% of the diflubenzuron while in houseflies this amounted to about 10%. Metabolism in the two flies differed qualitatively as well. Extracts of stable flies contained 2,6-difluorobenzamide and 4-chloroacetanilide. Extracts of houseflies did not contain these. Two unidentified metabolites were seen in house flies but not stable flies. In addition to these, 4-chlorophenylurea and one unknown compound were observed in both flies.
For more Metabolism/Metabolites (Complete) data for DIFLUBENZURON (13 total), please visit the HSDB record page.

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Biological Half-Life
... The half life of diflubenzuron appears to be 12 hr in rat and sheep and 18-20 hr in the cow.

Toxicity Summary
One of the metabolites of diflubenzuron, PCA, is a proximate carcinogen. It is conjugated to form the carcinogen that can ionize and reat with DNA to form adducts which result in splenic tumor formation.

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Toxicity Data
LC50 (rat) > 2,490 mg/m3

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Interactions
Although the toxins of Bacillus thuringiensis Berliner (Bt) are frequently used to control lepidopteran pests, the tolerance or resistance of some lepidopteran moth strains may limit Bt applications. In this study, insecticidal cocktails consisting of sublethal doses of Cry1Ab toxin and additive compounds were tested for their suppressive effect on larval relative growth rate (RGR) in Ephestia kuehniella Zeller under laboratory conditions. In the first step, the suppressive effect of diflubenzuron, soybean trypsin inhibitor (STI) and chitinase on RGR was confirmed. In the second step, these compounds were incorporated into a mixture of crushed kernels of Bt maize hybrid MON 810-YieldGard and its isoline with concentrations of Cry1Ab toxin ranging from 0.011 to 0.091 ug/g diet. An additive effect on the suppression of larval RGR in E. kuehniella was found in a combination of diflubenzuron, STI and STI + chitinase as secondary compounds in insecticidal cocktails. Chitinase showed no additive effect on RGR. The highest suppression level was found in cocktails with STI + chitinase as a secondary compound. It is hypothesized that the protease inhibitor (STI) protects both chitinase and Cry1Ab proteins from endogenous proteases in the larval midgut and prolongs their insecticidal activities. The possible application of insecticidal cocktails in the control of E. kuehniella is discussed.
Aedes aegypti mosquito is one of the most notorious vectors of dangerous diseases like dengue hemorrhagic fever and chikangunya. One method of control of the vectors is by the use of semiochemicals or pheromones. The pheromone n-heneicosane (C21) has been proved to be effective in attracting the female Aedes aegypti to lay eggs in the treated water and the growth of the larva is controlled by insect growth regulator diflubenzuron (DB). This study was planned to assess the safety of C21 alone and the combination with DB. Acute toxicity tests were carried out using two doses, viz., 1600 and 3200 mg/kg and two routes of exposure oral and intra-peritoneal. Dermal toxicity test was carried out in both male and female rats at the dose of 3200 mg/kg. Primary skin irritation test was carried out in rabbits. Sub-acute (90 days) dermal toxicity studies in male and female rats at the dose of 1 and 2 mg/kg via the per-cutaneous route were also studied. Sub-acute (90 days) toxicity test through the oral route was carried out, at doses 125, 250 and 500 mg/kg in male and female rats. The calculated LD50 by ip route and dermal route was more than 5 g/kg in mouse and rats of both the sexes. In the primary skin irritation test no significant changes were noted. In the sub-acute toxicity studies even 500 mg/kg dose was not able to produce toxic response in rats when they were dosed daily for 90 days. The established no observed adverse effect level (NOAEL) was more than 500 mg/kg.

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Non-Human Toxicity Values
LD50 Rat oral > 4640 mg/kg
LD50 Mouse oral 4.64 g/kg /Formulation with 50% kaolin/
LD50 Rat oral > 10 g/kg /Formulation with 50% kaolin/
LD50 Rabbit ip 1040 mg/kg
For more Non-Human Toxicity Values (Complete) data for DIFLUBENZURON (15 total), please visit the HSDB record page.

Diflubenzuron appears as colorless to yellow crystals. Used as a selective insecticide.
Diflubenzuron is a benzoylurea insecticide that is urea in which a hydrogen attached to one of the nitrogens is replaced by a 4-chlorophenyl group, and a hydrogen attached to the other nitrogen is replaced bgy a 2,6-difluorobenzoyl group. It has a role as an insect sterilant. It is a benzoylurea insecticide and a member of monochlorobenzenes. It is functionally related to a 1,3-difluorobenzene.
Insecticide, interfering with chitin deposition by oral absorption. Diflubenzuron is used on soya beans, citrus, tea, vegetables and mushrooms. Also used as an insecticide in feed for poultry and pigs and as a controlled release bolus in cattle



Diflubenzuron belongs to the family of N-Phenylureas. These are compounds containing a N-phenylurea moiety, which is structurally characterized by a phenyl group linked to one nitrogen atom of an urea group.
An insect growth regulator which interferes with the formation of the insect cuticle. It is effective in the control of mosquitoes and flies.

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Mechanism of Action
Diflubenzuron has a good inhibitory action on several proteases, including chymotrypsin. ... Proteases such as chymotrypsin are known to activate chitin synthetase. Inhibition of naturally occurring protease (B) should therefore lead to a decrease in chitin synthesis activity. This mechanism, coupled with the effect of diflubenzuron on chitin synthesis, could explain the effectiveness of this compound on cuticular deposition.
Diflubenzuron acts by inhibition of chitin synthesis and so interferes with the formation of the insect cuticle. This action is quite specific; related biochemical processes, such as chitin synthesis in fungi, and biosynthesis of hyaluronic acid and other mucopolysaccharides in chickens, mice and rats are not affected. In insect and rust mites, this mode of action can result larvicidal and ovicidal effects at the time of molting of the larvae or at hatching of the eggs.

C14H9CLF2N2O2

310.68

310.032

35367-38-5

Diflubenzuron-d4;1219795-45-5

37123

Colorless crystals

1.5±0.1 g/cm3

230-232°C

1.618

3.68

2

4

2

21

379

0

FC1=CC=CC(F)=C1C(NC(NC2=CC=C(Cl)C=C2)=O)=O

QQQYTWIFVNKMRW-UHFFFAOYSA-N

InChI=1S/C14H9ClF2N2O2/c15-8-4-6-9(7-5-8)18-14(21)19-13(20)12-10(16)2-1-3-11(12)17/h1-7H,(H2,18,19,20,21)

N-[(4-chlorophenyl)carbamoyl]-2,6-difluorobenzamide

DU112307; DU 112307; Diflubenzuron

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)