The compound has been shown to be a high-affinity and selective metabotropic glutamate receptor (mGluR5) ligand. It inhibits glutamate-induced calcium release from cells expressing human mGlu5 receptors. Additionally, it targets enzymes such as cytochrome P450 monooxygenases, which are involved in the oxidation of organic substances. The compound acts through mechanisms such as induction of detoxifying enzymes and alteration of cytochrome P-450 metabolism.

In vitro, 4-tert-Butyltoluene has been shown to inhibit glutamate‑induced calcium release from L(tk‑) cells expressing human mGlu5 receptors. This indicates a direct antagonistic activity on the mGlu5 receptor, a metabotropic glutamate receptor involved in various neurological processes. It also interacts with cytochrome P450 monooxygenases, altering their activity and impacting the metabolism of other compounds. It is structurally related to toluene and is used in manufacturing.

In vivo, 4-tert-Butyltoluene primarily targets the respiratory system, cardiovascular system, central nervous system, bone marrow, liver, and kidneys. It has been shown to inhibit the action of carcinogens, mutagens, and tumor promoters through mechanisms such as induction of detoxifying enzymes, alteration of cytochrome P-450 metabolism, and antioxidant effects. The compound shows activity in the AR (androgen receptor) agonist pathway.

Non-cell-based experiments for 4-tert-Butyltoluene are primarily analytical. A standard GC-FID or GC-MS method for purity analysis uses a DB-5MS column (30 m × 0.25 mm, 0.25 um) with a temperature program: initial 40degC for 2 min, ramp to 250degC at 10degC/min. The compound has a boiling point of 192degC and a melting point of -54degC. It has a density of 0.857 g/cm3 at 20degC. For cell-free receptor binding assays to determine affinity for mGluR5, membrane preparations from cells expressing the human receptor are incubated with radiolabeled ligand (e.g., [3H]MPEP) in the presence of various concentrations of 4-tert-Butyltoluene. Bound radioactivity is measured by scintillation counting.

Cell-based assays for 4-tert-Butyltoluene are conducted using L(tk‑) cells expressing human mGlu5 receptors. Cells are seeded in 96‑well plates and loaded with a calcium-sensitive dye (e.g., Fluo-4-AM). The cells are pre‑incubated with varying concentrations of the compound (0.1-100 uM) for 10-15 minutes, then stimulated with glutamate (e.g., 100 uM). The increase in intracellular calcium is measured in real time using a fluorescence plate reader (excitation 485 nm, emission 520 nm). The reduction in the fluorescence signal relative to vehicle control indicates antagonism of the mGlu5 receptor. The IC₅0 for inhibition of calcium release is calculated from dose-response curves.

In vivo animal experiments for 4-tert-Butyltoluene are conducted for toxicological safety assessment. A standard 28-day repeated-dose oral toxicity study in rats (OECD TG 407) involves administering the compound by oral gavage at doses of 100, 500, 1000 mg/kg/day for 28 days. Endpoints include clinical observations, body weight, food consumption, hematology, serum chemistry (liver enzymes, kidney function), organ weights (liver, kidneys, adrenals), and histopathology. The compound is a high‑affinity and selective metabotropic glutamate receptor (mGluR5) and inhibits glutamate‑induced calcium release from cells expressing human mGlu5 receptors.

Absorption, Distribution and Excretion
Tributyltin (TBT) can enter the bloodstream through inhaled vapor and oral liquid. Due to its low vapor pressure, only a small amount may be exhaled unchanged, with the majority being metabolized in the liver and excreted in the urine as water-soluble metabolites, alcohols, or carboxylic acids conjugates with glucuronic acid or glycine. In mice exposed to 1000 ppm TBT, high levels of the chemical (2.1 μg/ml) were detected in the blood 15 minutes after the start of inhalation, reaching a plateau level (4.8–5.3 μg/ml) after 4 hours of continuous exposure. TBT can also be absorbed into the bloodstream after oral administration and dermal application. In rats, the excretion rate of radioactive material in urine after intragastric administration of (100 mg/kg) methyl-(14)C)tributyltin (TBT) showed a biphasic curve; the half-life of the first phase was approximately 19 hours, and the half-life of the second phase was approximately 82 hours. This suggests that TBT may accumulate in animals after repeated exposure to the chemical.

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Metabolism / Metabolites
Prior to 1983, information on the metabolism of tributyltin (TBT) was scarce until that year when an extensive study was conducted… Researchers administered TBT to rats and guinea pigs via intragastric instillation at a dose of 100 mg/kg and analyzed the metabolites of TBT in urine treated with glucuronidase-sulfatase using gas chromatography-mass spectrometry. The study found that p-tert-butylbenzoic acid and its alcohol derivative 2-(p-carboxyphenyl)-2-methylprop-1-ol were the major metabolites in rat urine (accounting for 17-22% of the dose), while p-tert-butylbenzoylglycine was the most significant metabolite in guinea pig urine (accounting for 34% of the dose). Trace amounts of metabolites (2-4% of dose) were found in rat urine as 2-methyl-2-p-tolylprop-1-ol and p-tert-butylbenzoylglycine, while metabolites found in guinea pig urine were p-tert-butylbenzoic acid, 2-methyl-2-p-tolylprop-1-ol, and 2-methyl-2-p-tolylpropionic acid, with 2-methyl-2-p-tolylpropionic acid not detected in rat urine. Trace amounts (<0.5%) of p-tert-butylbenzyl alcohol were detected in both rat and guinea pig urine. Trace amounts of 2-(p-carboxyphenyl)-2-methylpropionic acid were detected only in rat urine. Similar TBT metabolism was observed upon inhalation administration. In this case, trace amounts of 2-(p-carboxyphenyl)-2-methylprop-1-ol were detected in guinea pig urine, a substance that was not identified after intragastric administration.

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Pharmacokinetic data for 4-tert-Butyltoluene are limited. As a lipophilic aromatic hydrocarbon (log P ~4.5), it is expected to be well absorbed from the gastrointestinal tract and distributed to fatty tissues. It is likely metabolized by cytochrome P450 enzymes (e.g., CYP2E1, CYP2B) via oxidation of the methyl group and the tert-butyl group, followed by conjugation with glucuronic acid. The metabolites are excreted in urine. The compound is a liquid at room temperature (melting point -54degC) and is stored in a sealed, dry container at room temperature, away from sources of ignition.

Non-Human Toxicity Values
Inhalation LC50 in rats: 165 ppm/8 hours; Inhalation LC50 in rats: 248 ppm/4 hours; Inhalation LC50 in rats: 934 ppm/1 hour; Dermal LD50 in rabbits: 13.8 to 27.8 ml/kg

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Toxicity Data
LC50 (rat) = 165 ppm/8 hours

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The toxicity of 4-tert-Butyltoluene is moderate. It is a skin, eye, and respiratory tract irritant. Prolonged or repeated exposure may cause damage to the liver, kidneys, and central nervous system. It may be harmful if swallowed, inhaled, or absorbed through the skin. The compound is flammable and should be kept away from heat, sparks, and open flames (flash point not listed). Standard safety precautions apply: handle in a well-ventilated area (fume hood) with appropriate PPE.

[1]. Peroxide oxidation of 4-tert-butyltoluene to 4-tert-butylbenzaldehyde over titanium (IV)-functionalized mesostructured silica. Microporous and mesoporous materials, 2007, 104(1-3): 151-158.

4-tert-Butyltoluene is a colorless, transparent liquid with a gasoline-like aromatic odor. (NTP, 1992)

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Additional information: The compound has an EC number of 202-675-9. Its IUPAC name is 1-tert-butyl-4-methylbenzene. It is also known as p-tert-Butyltoluene, 1-methyl-4-tert-butylbenzene, and PTBT. It is used primarily as a chemical intermediate and is not intended for human consumption as a drug. The product is for research and industrial use only.

C11H16

148.24

148.125

98-51-1

7390

Colorless to light yellow liquid

-62 °F (NTP, 1992) ; -52 °C ; -62.5 °C ; -62 °F ; -62 °F

0

1

11

110

0

CC1=CC=C(C=C1)C(C)(C)C

QCWXDVFBZVHKLV-UHFFFAOYSA-N

InChI=1S/C11H16/c1-9-5-7-10(8-6-9)11(2,3)4/h5-8H,1-4H3

1-tert-butyl-4-methylbenzene

p-tert-Butyl toluene; 1-(tert-Butyl)-4-methylbenzene

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.)