Absorption, Distribution and Excretion
A chronic study in rabbits showed that diphenylguanidine (DPG) is absorbed by all body tissues after entering the bloodstream, primarily distributed in the kidneys and liver. 1,3-Diphenylguanidine (DPG) is rapidly absorbed and distributed throughout the body: 30 minutes after intravenous injection of 100 mg/kg body weight of DPG, it is detectable in the blood; after 1 hour, it is detectable in all internal organs; and after 24 hours, it is detectable in the urine. On day 6, DPG is no longer excreted in the urine. Following intravenous injection of 15.15 μmol/kg (14C)-1,3-diphenylguanidine (DPG), radioactivity levels in major organs and tissues were measured at different time points. Initially, the liver had the highest concentration of DPG-derived radioactive material (percentage of total dose/gram of tissue), followed by the kidneys and lungs. The radioactive material concentration in the liver peaked 45 minutes after administration, while the concentrations in other tissues, except for the testes and adipose tissue, showed a decreasing trend. At all detection time points, the concentration of DPG-derived radioactive materials in the liver was higher than in other tissues. 24 hours post-exposure, the concentration of DPG in the liver was 5–10 times higher than in most other tissues. Interestingly, at similar time points, the concentrations of DPG-derived radioactive materials in brain tissue and most lean tissues were similar. This article presents the distribution of radioactive materials in various tissues at different time points following a single intravenous injection of 15.15 μmol/kg (14C)-DPG in rats. DPG-derived radioactive materials are readily cleared from all tissues; therefore, the total radioactive load in tissues within 24 hours post-exposure was approximately 10 times lower than the radioactive load observed at the earliest time point (15 minutes). For more complete data on the absorption, distribution, and excretion of N,N'-diphenylguanidine (9 types), please visit the HSDB record page.

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Metabolism/Metabolites
/After a single intravenous injection of 15.5 μmol/kg (14C)-DPG into rats/…The properties of (14C)-DPG-derived radioactive substances excreted in urine and bile were determined by direct high-performance liquid chromatography. At all detection time points, only trace amounts of the parent compound were present in bile. The majority (95%) of the radioactive substances in bile were present as the major metabolite of DPG (peak II), with trace amounts of another metabolite (peak I). The major metabolite (peak II) excreted in bile was resistant to hydrolysis by arylsulfatase, strong acids, or strong bases. However, incubation with β-glucuronidase resulted in almost complete hydrolysis to metabolite V. This metabolite (peak II) is believed to exist as a glucuronide, but the position of its glucuronidation has not been determined. Following a single intravenous injection of 15.5 μmol/kg (¹⁴C)-DPG into rats, the DPG-derived radioactivity excreted in feces was predominantly (94%) in the form of metabolite V. Therefore, the glucuronide (peak II) present in bile appears to be subsequently hydrolyzed in the intestine, most likely by gut microbiota, releasing metabolite V, which accounts for the majority of the radioactivity excreted in feces. High-performance liquid chromatography (HPLC) analysis of urine showed that approximately 28% of the radioactive material excreted in urine was in the form of the parent compound. The major metabolite in urine (peak II) accounted for approximately 37% of the total radioactivity. Treatment of this metabolite with β-glucuronidase hydrolyzed it to generate metabolite V.
/After a single intravenous injection of 15.5 μmol/kg (¹⁴C)-DPG in rats/…Comparison of bile and fecal excretion showed that up to 30% of the total dose was reabsorbed by the intestine after bile excretion. Since this portion is mostly metabolite V, intestinal reabsorption and reconstitution are likely the source of most of the metabolite II excreted in urine. Two other metabolites were also detected in urine. Metabolite III eluted from the column shortly after peak II, accounting for approximately 32% of the total radioactivity, while unbound metabolite V accounted for only 3% of the total radioactivity.
/After a single intravenous injection of 15.5 μmol/kg (¹⁴C)-DPG in rats/…Radioactivity extracted from lung, skin, and adipose tissue at 45 minutes and 2 hours was present only in the form of the parent compound. Radioactivity extracted from other tissues at the 24-hour time point was insufficient for accurate metabolite determination. This report describes the enzymatic oxidation of N,N'-diphenylguanidine (DPG) to N-(4-hydroxyphenyl)-N'-phenylguanidine (4HPG) at 14C using rat and rabbit liver homogenates (9000 g supernatant and microsomes) as enzyme sources. The enzymatic oxidation reaction is dependent on both O2 and NADPH. NADPH cannot be replaced by hydrogen peroxide. The overall clearance follows a single-component exponential decay law, with a half-life of approximately 9.6 hours.

Interactions
A mathematical design aimed at studying the combined toxic effects of the rubber components thiram and diphenylguanidine derivatives showed that their toxicity was only mild. Non-human Toxicity Values Rats Oral LD50: 375 mg/kg Rats Intraperitoneal LD50: 75 mg/kg Mice Oral LD50: 150 mg/kg Mice Intraperitoneal LD50: 25 mg/kg

1,3-Diphenylguanidine is a white to off-white powder with a bitter taste and a slightly odor. It is a guanidine compound with a phenyl group attached to each of its two amino groups. It is used as an accelerator in the rubber industry and is also an allergen. Diphenylguanidine is a complexing agent used to detect metals and organic bases and is used as an accelerator in rubber vulcanization. It is present in some rubber products. It is also a skin sensitizer and allergen. Sensitivity to diphenylguanidine can be identified through clinical patch testing. Diphenylguanidine is a standardized chemical allergen. The physiological effects of diphenylguanidine are achieved by increasing histamine release and cell-mediated immunity. Drug Indications Diphenylguanidine is approved for use in allergic skin patch testing, which is indicated for the auxiliary diagnosis of allergic contact dermatitis (ACD) in individuals aged 6 years and older.

C13H13N3

211.27

211.11

102-06-7

24245-27-0 (mono-hydrochloride);52392-53-7 (hydrochloride)

7594

Monoclinic needles (crystalized from alcohol and toluene)
White powder

1.1±0.1 g/cm3

321.3±25.0 °C at 760 mmHg

146-148 °C(lit.)

148.1±23.2 °C

0.0±0.7 mmHg at 25°C

1.600

2.36

2

1

3

16

225

0

C1=CC=C(C=C1)NC(=N)NC2=CC=CC=C2

OWRCNXZUPFZXOS-UHFFFAOYSA-N

InChI=1S/C13H13N3/c14-13(15-11-7-3-1-4-8-11)16-12-9-5-2-6-10-12/h1-10H,(H3,14,15,16)

1,2-diphenylguanidine

NSC-3272; NSC 3272; N,N'-Diphenylguanidine

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.)