Absorption, Distribution and Excretion
A chronic experiment with rabbits established that diphenylguanidine after entering the blood is absorbed by all body tissues with its predominant location in the kidneys and liver.
/1,3-Diphenylguanidine/ (DPG) is rapidly absorbed and distributed throughout the body tissues: 30 min after administration of 100 mg DPG/kg bw, the substance was found in the blood; in an hour it was discovered in all the visceral organs; after 24 hours, it was found in the urine. DPG excretion with the urine had ceased on the day 6.
Major organ and tissue volumes were sampled for radioactive content at various time points following iv administration of a 15.15-umol/kg (14C)-/n,n'-diphenylguanidine/ (DPG) dose. Initially the highest concentration (% total dose/g tissue) of DPG-derived radioactivity was observed in liver followed by kidney and lung. The peak concentration in liver was reached in 45 min after administration whereas the DPG-derived radioactivity in other tissues with the possible exception of testes and adipose tissues showed a decline. The concentration of DPG-derived radioactivity in liver was higher than in other tissues at every time point examined. At 24 hr post-exposure the concentration of DPG in liver was 5-10 times higher than in most other tissues. Interestingly, the brain and most lean tissues contained similar concentrations of DPG-derived radioactivity at comparable time points.
The distribution of radioactivity in rat tissues at various time points following a single iv dose of (14C)-DPG of 15.15 umol/kg is presented. DPG-derived radioactivity was readily cleared from all tissues so that within 24 hr after exposure the total tissue burden was approximately 10-fold lower than that observed at the earliest time point, 15 min.
For more Absorption, Distribution and Excretion (Complete) data for N,N'-DIPHENYLGUANIDINE (9 total), please visit the HSDB record page.

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Metabolism / Metabolites
/Following a single iv dose of 15.5 umol/kg (14C)-DPG to rats/ ... the nature of the (14C)-DPG derived radioactivity excreted in urine and bile was examined by direct HPLC analysis. Bile contained only small amounts of parent compound at all time points examined. Most of the radioactivity in bile (95%) was in the form of a major metabolite (Peak II) of DPG with traces of another metabolite (Peak I). The major metabolite (Peak II) excreted in bile was resistant to hydrolysis by arylsulfatase, by strong acid, or by strong base. However, incubation of this metabolite with b-glucuronidase resulted in near complete hydrolysis to yield metabolite V. It is believe that this metabolite (Peak II) is in the form of a glucuronide, the position of glucuronidation has not been determined.
/Following a single iv dose of 15.5 umol/kg (14C)-DPG to rats/ ... DPG-derived radioactivity excreted in feces was primarily (94%) in the form of metabolite V. Therefore, it appears that the glucuronide present in bile (Peak II) was subsequently hydrolysed in the intestine, most probably by intestinal flora, to release metabolite V which accounted for most of the radioactivity excreted in feces. HPLC analysis of urine indicated that around 28% of the radioactivity excreted in urine was in the form of parent compound. The major metabolite (Peak II) in urine accounted for approximately 37% of the total radioactivity. Treatment of this metabolite with b -glucuronidase resulted in its hydrolysis t o yield metabolite V.
/Following a single iv dose of 15.5 umol/kg (14C)-DPG to rats/ ... Comparison of excretion in bile versus feces indicates that as much as 30% of the total dose is reabsorbed from the intestine after excretion in bile. Since most of this material is metabolite V, reabsorption from the intestine and reconjugation may account for most of the metabolite II excreted in urine. Two other metabolites were detected in urine. Metabolite III which eluted from the column shortly after peak II accounted for approximately 32% of the radioactivity while the unconjugated metabolite V accounted only for 3% of the radioactivity.
/Following a single iv dose of 15.5 umol/kg (14C)-DPG to rats/ ... radioactivity extracted from lung, skin, and adipose tissue at the 45-min and 2-hr time points was present only in the form of the parent compound. The radioactivity extracted from other tissues at the 24-hr time point was insufficient for accurate metabolite determination.
The enzymic C-oxygenation of N,N'-diphenylguanidine (DPG) to N-(4-hydroxyphenyl)-N'-phenylguanidine (4HPG)... is reported. ...Rat and rabbit liver homogenates (9000 g supernatant and microsomes) were used as enzyme source. The enzymic oxygenations were both O2 and NADPH dependent. NADPH could not be replaced by hydrogen peroxide.

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Biological Half-Life
Total clearance followed a single component exponential decay with a half-life of approximately 9.6 hr.

Interactions
A mathematical design to study combined toxic effects of rubber ingredients thiram and Diphenylguanidine derivative revealed only mild toxicity.

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Non-Human Toxicity Values
LD50 Rat oral 375 mg/kg
LD50 Rat ip 75 mg/kg
LD50 Mouse oral 150 mg/kg
LD50 Mouse ip 25 mg/kg

1,3-diphenylguanidine is a white to cream-colored chalky powder. Bitter taste and slight odor.
1,3-diphenylguanidine is guanidine carrying a phenyl substituent on each of the two amino groups. It is used as an accelerator in the rubber industry. It has a role as an allergen.
Diphenylguanidine is a complexing agent used in the detection of metals and organic bases and used as an accelerator in the vulcanization of rubber. It is found in some rubber products. It is also a dermatological sensitizer and allergen. Sensitivity to diphenylguanidine may be identified with a clinical patch test.
Diphenylguanidine is a Standardized Chemical Allergen. The physiologic effect of diphenylguanidine is by means of Increased Histamine Release, and Cell-mediated Immunity.

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Drug Indication
Diphenylguanidine is approved for use within allergenic epicutaneous patch tests which are indicated for use as an aid in the diagnosis of allergic contact dermatitis (ACD) in persons 6 years of age 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.)