Absorption, Distribution and Excretion
This study investigated the absorption and distribution of 14C-trifluralin suspended in 5% sodium carboxymethyl cellulose solution in male and female CD Sprague-Dawley rats. The administration doses were 10 mg/kg body weight (single oral dose) and 1000 mg/kg body weight (single radiolabeled dose). 14C-trifluralin is available in both side-chain and ring-labeled forms, but piperazine ring-labeled 14C-trifluralin was used only in a preliminary study. In this preliminary study, two male and two female rats received a single oral dose of 10 mg/kg body weight. The experimental results showed that the average excretion rate of the administered dose within 120 hours was as follows: urine, 77% in male rats and 82% in female rats; 18% in feces of male rats and 19% in feces of female rats; 3.3% in exhaled air of male rats and 1.5% in exhaled air of female rats; less than 3% remained in the carcass. Most of the radiolabeled substance (73% in male rats and 76% in female rats) was excreted in urine within 0-24 hours. In the primary study, researchers administered a single injection of 10 mg/kg body weight of radiolabeled substance to 5 male rats and 5 female rats. The average excretion rate of the administered dose within 120 hours was as follows: 78% in urine of male rats and 79% in urine of female rats; 12% in feces of male rats and 14% in feces of female rats; 5.2% in exhaled air of male rats and 6.0% in exhaled air of female rats. Less than 3% remained in the carcass. Most of the radiolabeled material (75% in both males and females) was excreted in urine within 0–24 hours. The side-chain labeled 14C-trifluridine was administered orally as a single dose of 1000 mg/kg body weight. The mean excretion percentages of the administered dose over 120 hours were: urine, 11% in males, 19% in females; feces, 85% in males, 77% in females; and exhaled air, 0.9% in males, 1.6% in females. Only about 0.5% remained in the carcass. Most of the radiolabeled material in urine (7.7% in males, 12% in females) was excreted within 6–48 hours. The delayed urinary excretion (compared to other studies) likely reflects a dissolution rate limiting absorption. Of the radiolabeled material recovered from feces within 0–72 hours, over 90% was associated with side-chain labeled 14C-trifluridine, presumably representing unabsorbed material.

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Metabolism/Metabolites
Trifluralin is rapidly metabolized in rats and excreted quickly; only 0-5% of the administered dose remains unmetabolized. A large amount of unmetabolized trifluralin is recovered only from feces. The first metabolite identified was N-[2,2,2-trichloro-1-(piperazin-1-yl)ethyl]-formamide, which is formed through the cleavage of the entire side chain. In subsequent metabolic studies, using ¹⁴C-labeled piperazine rings and aliphatic side chains, results showed that trifluralin is almost completely metabolized after a single oral dose of 10 mg/kg body weight.
In rats receiving [piperazine¹⁴C]-trifluralin, the predominant radiolabeled component in urine was N-[2,2,2-trichloro-1-(piperazine-1-yl)ethyl]formamide, accounting for 46-53% of the administered dose within 0-24 hours; however, in rats receiving side-chain labeled ¹⁴C-trifluralin, this proportion decreased to 24-27% after a single 10 mg/kg body weight dose, and further to 21-24% after repeated administration. This component is excreted as a glucuronide. The side-chain metabolite trichloroethanol and its glucuronide accounted for 18-21% of the administered dose. Another side-chain metabolite appearing in urine was the N-acetylcysteine conjugate of 2,2,2-trichloroethylamine, accounting for 13-15% of the administered dose. In feces collected from female rats within 0–48 hours following administration, 3.6% of the single 10 mg/kg body weight dose and 3.4% of the repeated dose were present as N-[2,2,2-trichloro-1-(piperazin-1-yl)ethyl]formamide. This metabolite was not detected in the feces of rats receiving a 1000 mg/kg body weight dose. Only trace amounts (0–1%) of unmetabolized trifluralin were detected in the feces of low-dose rats, while the unmetabolized trifluralin content in the feces of 1000 mg/kg body weight rats accounted for 70–80% of the administered dose. These results suggest that trifluralin absorption is a saturation process unless significant bile excretion occurs at high doses.

Toxicity Data
LC50 (Rats) > 5,120 mg/m³

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Interactions Twenty or fifty male Swiss mice and twenty or fifty female Swiss mice were placed in drinking water supplemented with 0.05% sodium nitrate, or administered trifluralin suspended in water twice weekly by gavage, or in combination of both drugs, for up to 180 days. Tumor incidence was compared with a control group of 184 male mice and 117 female mice. Trifluralin alone did not increase tumor number; however, combination therapy increased the incidence of lymphoma (including thymoma) as well as epithelial adenomas and carcinomas of the gastrointestinal tract, lungs, and (male) liver. Incubation of trifluralin with 4% acidified sodium nitrite solution for 24 hours produces dinitrosoperpiperazine, which is known to be carcinogenic and suspected of inducing tumors.

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Non-human toxicity values
Rabbit dermal LD50 >10 g/kg
Rats dermal LD50 >10 g/kg
Rats oral LD50 >16 g/kg
Dogs oral LD50 >2 g/kg
For more complete non-human toxicity data for trifluralin (7 in total), please visit the HSDB record page.

According to the U.S. Environmental Protection Agency (EPA), trifluralin may have developmental toxicity. Trifluralin is a colorless, non-corrosive crystal used as a fungicide. It belongs to the N-alkylpiperazine class of compounds, where the two amino groups on the piperazine ring are replaced by 1-formamido-2,2,2-trichloroethyl. It is a fungicide effectively controlling a variety of diseases, including powdery mildew, scab, and rust. It is an EC 1.14.13.70 (sterol 14α-demethylase) inhibitor, sensitizer, and antifungal pesticide. It is an N-alkylpiperazine compound, belonging to the formamide class, an organochlorine compound, and also an amide fungicide.

C10H14CL6N4O2

434.948

431.924

26644-46-2

33565

White to light brown crystals.

1.6±0.1 g/cm3

561.5±50.0 °C at 760 mmHg

155ºC (decomposes)

293.4±30.1 °C

0.0±1.5 mmHg at 25°C

1.571

4.61

2

4

4

22

345

0

ClC(Cl)(Cl)C(NC=O)N1CCN(C(NC=O)C(Cl)(Cl)Cl)CC1

RROQIUMZODEXOR-UHFFFAOYSA-N

InChI=1S/C10H14Cl6N4O2/c11-9(12,13)7(17-5-21)19-1-2-20(4-3-19)8(18-6-22)10(14,15)16/h5-8H,1-4H2,(H,17,21)(H,18,22)

N-[2,2,2-trichloro-1-[4-(2,2,2-trichloro-1-formamidoethyl)piperazin-1-yl]ethyl]formamide

Triforine W-524 W 524

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.)