Absorption, Distribution and Excretion
In a 1992 study, [aniline-U-14C]flutopril (specific activity: 20 mCi/mmol; radiochemical purity >99%) was suspended in a solvent containing 1% Tween 80 and 0.5% carboxymethyl cellulose and orally administered to three groups of male and three groups of female Sprague-Dawley derived CD rats. Unlabeled flutopril (purity 99.9% or 97.6%) was also used in the solution preparation. Animals received one of four dosing regimens: a single dose of 20 mg/kg body weight of [14C]flutopril; 20 mg/kg body weight of unlabeled flutopril daily for 14 consecutive days, followed by a single dose of [14C]flutopril on day 15; or a single dose of 1000 mg/kg body weight of [14C]flutopril. Urine was collected three times on day 1 after administration, and daily thereafter; feces and cage cleaning fluid were collected daily. After collecting samples on day 7, animals were euthanized, and blood and 12 tissue samples were collected. Radioactivity was determined using liquid scintillation counting after appropriate sample processing. The generation of volatile ¹⁴C was not determined because previous studies indicated that the exhaled dose was less than 0.1%. Overall recovery was acceptable in the low-dose group, but less than 90% in the high-dose group. Most radioactive material was excreted within 24 hours, with approximately half excreted in urine within 12 hours, indicating relatively rapid absorption. The extent of absorption reflected in urinary excretion varied with dose and number of repeated administrations, suggesting that high doses lead to absorption saturation. There is evidence that repeated administration induces the metabolism of flutralabdominalis. Results were similar in male and female animals. At day 7, the concentrations and distribution of radioactivity in blood and tissues were extremely low, less than 0.2% of the dose administered to any animal, indicating no significant bioaccumulation potential. Significant differences in tissue concentrations were observed within the same group of animals. The only tissue with stable concentrations was the liver, with an average concentration approximately 10 times that of blood. In all groups, the radioactivity levels in the livers of female animals were higher than those in male animals (at a dose of 1000 mg/kg body weight, females 2.4 ± 1.1 μg/g, males 0.68 ± 0.38 μg/g; after repeated administration, females 0.23 ± 0.04 μg/g, males 0.12 ± 0.01 μg/g). In one study, researchers added flutralabolic steroids to the diet of Sprague-Dawley rats for 4 weeks. Analysis of the brain, liver, blood, kidneys, and fat showed lower radioactivity concentrations in animals receiving doses >2000 ppm. The highest residual concentrations were found in adipose tissue and liver. Flutralabolic steroid retention was extremely low. The lowest dose of 400 ppm was equivalent to 36 mg/kg body weight/day for males and 41 mg/kg body weight/day for females. Comparing the 400 ppm result with that of another study at 20 mg/kg body weight indicates that flutoprani has no significant tendency to accumulate. The residual concentration increased with increasing dose, suggesting that the absorption saturation observed after gavage administration does not occur after dietary intake. Analysis of tissue samples from repeatedly administered rats showed that flutoprani was only present in fat at low concentrations: 0.2 ppm at 2,000 ppm and 0.6 ppm at 10,000 ppm, similar to the concentrations after a single dose. Because the analytical method only targets the parent compound, any metabolites that may have been produced after a single dose were undetectable. However, due to the relatively high polarity of flutoprani's metabolites and their predominantly urinary excretion, the repeated-dose study results suggest that flutoprani has virtually no potential for bioaccumulation.

Toxicity Summary
Identification and Uses: Flutopranil is a solid fungicide effective against basidiomycetes. It can be used as a foliar fungicide to control barley leafminer and rice sheath blight, and as a seed treatment to control Rhizoctonia solani on potatoes and cucurbitaceous crops. Human Exposure and Toxicity: Flutopranil has estrogenic activity against human breast cancer cells. No results were observed in the human lymphocyte chromosome breakage assay. Animal Studies: Rabbits developed conjunctival congestion after 1 hour, and four rabbits still had congestion after 48 hours. All rabbits' eyes returned to normal after 72 hours. Flutopranil is not carcinogenic to mice, rats, and dogs. In two generations of reproductive toxicity studies in rats, flutopranil did not show specific reproductive toxicity. The only indication of systemic toxicity was increased liver weight, which occurred at a similar frequency in both generations of parents. Flutopranil has been tested for genotoxicity in various in vitro and in vivo mouse bone marrow micronucleus assays. Results for bacterial reversion mutation, bacterial DNA repair, mammalian gene mutation, rat hepatocyte non-programmed DNA synthesis, and in vivo chromosome effects (micronucleus induction) were all negative. Under metabolic activation conditions, the results for the chromosome aberration test in Chinese hamster lung cells were weakly positive. Ecotoxicity studies: In *D. magna*, flutopranil concentrations below half the LC50 (8-day) significantly reduced the number of first-clump larvae. Sublethal effects of flutopranil on zebrafish embryos included growth inhibition, abnormal spontaneous movement, slowed heart rate, complete hatching failure, and morphological deformities. Furthermore, flutopranil may cause notochord deformation and shortened body length in larvae.

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Non-Human Toxicity Values
Oral LD50 in rats: 10 g/kg; Dermal LD50 in rats: >5 g/kg; Intraperitoneal LD50 in rats: >10 g/kg; Subcutaneous LD50 in rats: >10 g/kg. For more complete non-human toxicity data on flutopramide (7 types), please visit the HSDB record page.

[1]. Teng M, et al., Chronic exposure of zebrafish (Danio rerio) to flutolanil leads to endocrine disruption and reproductive disorders. Environ Res. 2020 May;184:109310.

[2]. Mode of antifungal action and selectivity of flutolanil[J]. Agricultural and biological chemistry, 1988, 52(6): 1445-1449.

Flutopranil belongs to the benzamide class of compounds, formed by the condensation of the carboxyl group of 2-(trifluoromethyl)benzoic acid and the amino group of 3-(isopropoxy)aniline. It is a fungicide used to control various pathogens, particularly *Rhizoctonia solani* fungi on rice, lawns, and other crops. It is an EC 1.3.5.1 [succinate dehydrogenase (quinone)] inhibitor and antifungal pesticide. Flutopranil belongs to the benzamide, aromatic ether, (trifluoromethyl)benzene, and benzoylaniline fungicides. Flutopranil is a systemic fungicide. It inhibits the enzyme complexes required for respiration, thereby inhibiting the synthesis of glutamate and aspartic acid. Flutopranil can be used as a powder to disinfect seed potatoes before or during planting to control black scurf. Flutopranil has low acute toxicity to mammals. It is not genotoxic, carcinogenic, or teratogenic.

323.113

66332-96-5

47898

White, crystalline solid Colorless crystals

1.247g/cm3

339.1ºC at 760 mmHg

108 °C ; 100-107 °C

158.9ºC

1.543

4.818

1

5

4

23

398

0

PTCGDEVVHUXTMP-UHFFFAOYSA-N

InChI=1S/C17H16F3NO2/c1-11(2)23-13-7-5-6-12(10-13)21-16(22)14-8-3-4-9-15(14)17(18,19)20/h3-11H,1-2H3,(H,21,22)

N-(3-propan-2-yloxyphenyl)-2-(trifluoromethyl)benzamide

Fluoramide

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.)