Co-solvent; Formulation agent

Tumors gavaged with maize oil showed a 54% reduction in growth hormone (GH) levels, and osmotic minipump infusion took the place of GH. In animals that were gavaged with water, there was an increase in in situ MNCL cell proliferation. arrival percentage [1]. Corn oil is frequently employed as a feed additive or as a vehicle for the administration of lipophilic drugs in animal research settings [3]. After intraperitoneal injection, tainted corn oil can turn fatal many days later. It is more advisable to provide corn oil intragastrically [4]. Applying maize oil intraperitoneally results in localized inflammation and peritoneal macrophage depletion [5]. Dosing strategy: four intraperitoneal injections spaced seven days apart, one every 48 hours. Findings: Compared to non-pharmaceutical grade corn oil, pharmaceutical grade (PG) corn oil exhibited considerably greater pathology scores on day 21. There were no other notable distinctions between the groups that used corn oil. It is thought to be safe to inject non-pharmaceutical grade maize oil intraperitoneally into mice as it did not have any negative clinical effects.

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In long-term carcinogenesis studies, oral gavage administration of corn oil to male Fischer rats serving as vehicle controls resulted in approximately 25% lower spontaneous incidence of mononuclear cell leukemia (MNCL), along with extended latency and improved survival, compared to non-gavaged or water-gavaged controls. Using an MNCL transplant model, in situ proliferation assays, and immune competence assessments, researchers found that transplanted MNCL cells grew more slowly in corn oil-gavaged rats. Proliferation rates of cultured MNCL cells in diffusion chambers implanted in these rats were 40% lower than in water-gavaged rats, suggesting that nutrition-sensitive endogenous factors mediate this suppression. Further investigation revealed that corn oil-gavaged rats had 54% lower serum growth hormone (GH) levels, and restoring GH via osmotic minipump infusion normalized MNCL cell proliferation to rates seen in water-gavaged animals. Additionally, corn oil-gavaged rats exhibited enhanced cellular immune competence, as indicated by mitogen stimulation, natural cytotoxicity, and immunofluorescence assays. These findings suggest that corn oil gavage may reduce MNCL development by slowing MNCL cell proliferation—partially through altered GH levels—and/or by enhancing immune function. [1]

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In adult male Buffalo rats, intraperitoneal injection of trace amounts of corn oil before and after transplantation of hepatoma 7777 or 7800 tissue significantly reduced tumor growth rates. The active component was not water-soluble, as exhaustive water extraction of corn oil did not eliminate its effect. In contrast, similar injections of safflower oil or isotonic saline had no impact on tumor growth. Analysis of tissue phospholipid fatty acids indicated that corn oil injection did not alter esterified fatty acids in this lipid fraction, suggesting a mechanism independent of fatty acid composition changes. [2]

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Due to concerns about animal wellbeing, the use of nonpharmaceutical-grade substances in research must be scientifically justified when pharmaceutical-grade alternatives exist. A study in female C57BL/6J mice evaluated intraperitoneal administration of pharmaceutical-grade corn oil, nonpharmaceutical-grade corn oil, and saline every 48 hours for four injections. Clinical assessments—including body weight, body condition score, visual assessment, CBC, and serum chemistries—showed no adverse effects from nonpharmaceutical-grade corn oil. However, at day 21, pharmaceutical-grade corn oil induced significantly higher peritoneal and mesenteric inflammation scores than nonpharmaceutical-grade corn oil, as assessed microscopically. Saline-dosed mice had the lowest pathology scores at both 24 hours and 14 days post-injection. These findings indicate that nonpharmaceutical-grade corn oil is safe for intraperitoneal use in mice, but consistency in the grade of corn oil used within a study is important due to differences in inflammatory responses. [3]

Treatment groups received either pharmaceutical-grade (PG) corn oil, nonpharmaceutical-grade (NPG) corn oil marketed as a vehicle for fat-soluble compounds, or 0.9% normal saline, with 30 mice per group. All compounds were administered via intraperitoneal injection every 48 hours over a 7-day period, totaling four injections per mouse. Injections were performed by a single researcher (JSH) using a standardized technique. Each mouse was manually restrained with its head tilted downward, and a fresh 25-gauge, 5/8-inch needle was inserted into the right caudal abdominal quadrant at approximately a 30° angle. The plunger was withdrawn to confirm negative pressure within the peritoneal cavity and ensure the absence of intestinal contents. A consistent injection volume of 0.1 mL was used across all groups. On day 8, 24 hours after the final injection, half of the mice from each group (n = 15 per group) were euthanized for terminal blood collection and necropsy. The remaining mice were maintained for an additional 14 days and similarly necropsied on day 21.[3]

Absorption: As a lipid, corn oil is absorbed through the lymphatic system. For example, when administered orally in corn oil, compounds like ethchlorvynol were recovered in the lymph .
Distribution: Corn oil and its components can be distributed to various tissues. Following subcutaneous injection, accumulation of the administered substance was observed in the inguinal skin, axillary lymph nodes, and even the alveoli of the lung and bronchus .
Metabolism: Vegetable oils like corn oil are nutrients and are metabolized by the body. They can be taken up by macrophages, leading to the formation of foam cells .
Excretion: The excretion pathways are typical of lipid metabolism. Some compounds delivered in corn oil can also be excreted as metabolites. For instance, ethchlorvynol-glucuronide was recovered in the lymph .

Local Inflammation: Corn oil can cause inflammation at the site of administration. Subcutaneous injection leads to the accumulation of the substance and the formation of granulation tissue . Intraperitoneal injection causes xanthogranulomatous inflammation with depletion of resident peritoneal macrophages and can trigger macrophage pyroptosis, though this inflammatory response is milder than that caused by peanut or mineral oil .
Systemic Effects:
Body and Organ Weights: Repeated administration of corn oil, particularly at higher volumes, can lead to increased body weight in rats. This, in turn, can cause a decrease in some relative organ weights .
Hematology: Slight decreases in red blood cell (RBC) counts have been observed in female rats administered high doses of corn oil subcutaneously .
Neoplasia Modulation: In long-term studies, corn oil gavage has been shown to have a significant impact on tumor incidence. It can increase the incidence of pancreatic proliferative lesions (hyperplasia and adenoma) while simultaneously decreasing the incidence of mononuclear cell leukemia and adrenal medulla pheochromocytomas in male F344/N rats .
Neurobehavioral and Oxidative Stress: Developmental exposure to corn oil can induce behavioral abnormalities, such as decreased locomotor activity and increased anxiety. These changes are accompanied by alterations in brain redox homeostasis, including increased malondialdehyde and superoxide dismutase activity in specific brain regions .

[1]. Inhibition of rat mononuclear cell leukemia by corn oil gavage: in vivo, in situ and immune competence studies. Carcinogenesis. 1994 Feb;15(2):193-9.

[2]. Inhibition of growth of Morris hepatomas 7777 and 7800 by corn oil. Oncology. 1977;34(2):62-4.

[3]. Effects of Repeated Intraperitoneal Injection of Pharmaceutical-grade and Nonpharmaceutical-grade Corn Oil in Female C57BL/6J Mice. J Am Assoc Lab Anim Sci. 2017 Nov 1;56(6):779-785.

[4]. Administration Of Drugs and Experimental Compounds in Mice and Rats.

[5]. Intraperitoneal Oil Application Causes Local Inflammation with Depletion of Resident Peritoneal Macrophages. Mol Cancer Res. 2021 Feb;19(2):288-300.

To our knowledge, this study is the first to evaluate the effects of PG compared with NPG corn oil on animal wellbeing. Unexpectedly, the mice treated with PG corn oil had higher pathology scores than those given NPG corn oil. However, the BCS and VAS did not indicate that the inflammation induced by either corn oil product resulted in pain or distress. Given these findings, there is no benefit to using PG corn oil compared with NPG corn oil. However, the mild differences in inflammation between the 2 groups suggest that the use of either PG or NPG corn oil should be consistent within a study. These findings cannot be extrapolated to other NPG compounds, and the use of NPG products in animals should still be justified and approved on a case-by-case basis. [3]

0

8001-30-7

Colorless to light yellow liquid

0.900 g/mL at 20 °C

254 °C

1.473-1.476

BrC1C=C2C=C(C(=O)O)NC2=CN=1

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)

Ethanol :≥ 100 mg/mL

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.)