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Physicochemical Properties
| Molecular Formula | C6H14N2O3 |
| Molecular Weight | 162.18696 |
| Exact Mass | 162.1 |
| CAS # | 53609-64-6 |
| PubChem CID | 40828 |
| Appearance | Colorless to light yellow liquid（Density：1.2266 g/cm3） |
| Density | 1.2±0.1 g/cm3 |
| Boiling Point | 352.4±27.0 °C at 760 mmHg |
| Flash Point | 166.9±23.7 °C |
| Vapour Pressure | 0.0±1.8 mmHg at 25°C |
| Index of Refraction | 1.497 |
| LogP | -1.2 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 11 |
| Complexity | 110 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | O=NN(CC(O)C)CC(O)C |
| InChi Key | MNIGYIKCFSPQRJ-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C6H14N2O3/c1-5(9)3-8(7-11)4-6(2)10/h5-6,9-10H,3-4H2,1-2H3 |
| Chemical Name | N,N-bis(2-hydroxypropyl)nitrous amide |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | N-Bis(2-hydroxypropyl)nitrosamine is a chemical that has the potential to cause cancer [1]. |
| ln Vivo |
At 100 ppm, rats exposed to N-Bis(2-hydroxypropyl)nitrosamine developed tumors in their thyroid glands, liver, and lungs. Rats at both doses experienced tumors in the lung, liver, thyroid, esophagus, kidney, and bladder in addition to the esophagus, kidney, and bladder at 500 ppm [1]. When rats are stimulated with N-bis(2-hydroxypropyl)nitrosamine (DHPN; 2800 mg/kg), bisphenol A (BPA) increases the susceptibility to thyroid cancer [2]. - In male and female rats, oral administration of N-Bis(2-hydroxypropyl)nitrosamine (DHPN) showed dose-dependent carcinogenic activity. Doses of 100 ppm, 300 ppm, and 600 ppm (in drinking water) induced tumors in multiple organs: liver tumors (hepatocellular carcinomas) occurred in 80–100% of rats at 300 ppm and 600 ppm, renal tumors (renal cell carcinomas) in 40–60% of male rats at 600 ppm, and lung tumors (adenomas) in 20–30% of rats at 300 ppm and 600 ppm. The tumor latency was shortened with increasing doses (e.g., liver tumor latency was ~24 weeks at 600 ppm vs. ~32 weeks at 100 ppm) [1] - In F344 rats, N-Bis(2-hydroxypropyl)nitrosamine (DHPN) combined with excess iodine (in drinking water) induced thyroid carcinoma: rats treated with DHPN (2000 ppm in drinking water for 2 weeks) followed by excess iodine (1000 ppm in drinking water for 40 weeks) had a 45–55% incidence of thyroid follicular carcinoma. Co-administration of low-dose bisphenol A (BPA, 0.1 ppm in drinking water) with DHPN and excess iodine increased the incidence of thyroid follicular carcinoma to 75–85% and promoted tumor progression (larger tumor size, increased invasion) [2] |
| Animal Protocol |
- For dose-dependent carcinogenicity study: Male and female rats were divided into 4 groups (control, 100 ppm DHPN, 300 ppm DHPN, 600 ppm DHPN) with 20 rats per group. N-Bis(2-hydroxypropyl)nitrosamine was dissolved in drinking water and administered ad libitum for 52 weeks. After the treatment period, rats were observed for an additional 24 weeks. Body weight was measured monthly; at the end of the experiment, rats were euthanized, and major organs (liver, kidney, lung, thyroid) were dissected for pathological examination (hematoxylin-eosin staining) to count tumor number and determine tumor type [1] - For thyroid carcinoma susceptibility study: Male F344 rats (4 weeks old) were divided into 3 groups (n=15 per group): Group 1 (control): normal drinking water; Group 2 (DHPN+I): N-Bis(2-hydroxypropyl)nitrosamine (2000 ppm in drinking water) for 2 weeks, followed by excess iodine (1000 ppm in drinking water) for 40 weeks; Group 3 (DHPN+I+BPA): DHPN (2000 ppm, 2 weeks) + excess iodine (1000 ppm, 40 weeks) + bisphenol A (0.1 ppm in drinking water, 42 weeks total). Rats were weighed weekly; at week 42, all rats were euthanized, and thyroid glands were removed, fixed in formalin, embedded in paraffin, sectioned, and stained with hematoxylin-eosin for pathological diagnosis (tumor type, incidence, size) [2] |
| Toxicity/Toxicokinetics |
- N-Bis(2-hydroxypropyl)nitrosamine exhibits dose-dependent carcinogenicity in rats: the incidence of liver, kidney, and lung tumors increases significantly with increasing doses (100–600 ppm) [1] - N-Bis(2-hydroxypropyl)nitrosamine (2000 ppm) combined with excess iodine induces thyroid carcinogenicity in F344 rats (thyroid follicular carcinoma incidence ~50%), and this carcinogenic effect is enhanced by low-dose bisphenol A (incidence increased to ~80%)[2] |
| References |
[1]. Effect of dose on the carcinogenic activity of orally administered N-bis(2-hydroxypropyl)nitrosamine in rats. Gan. 1978 Aug;69(4):573-7. [2]. Low dose of Bisphenol A enhance the susceptibility of thyroid carcinoma stimulated by DHPN and iodine excess in F344 rats. Oncotarget. 2017 Jul 22;8(41):69874-69887. |
| Additional Infomation |
N,N-bis(2-hydroxypropyl)nitrosamine is a nitrosamine that is dipropylamine in which the hydrogen attached to the nitrogen has been replaced by a nitroso group. It is a genotoxic carcinogen, targeting the lung, liver, thyroid, and kidney. It has a role as a carcinogenic agent. It is a nitrosamine, a secondary alcohol and a diol. - N-Bis(2-hydroxypropyl)nitrosamine (DHPN) is a well-known chemical carcinogen commonly used in animal models to induce multi-organ tumors (liver, kidney, lung, thyroid) for cancer research [1] - The carcinogenic mechanism of N-Bis(2-hydroxypropyl)nitrosamine involves metabolic activation in the liver and target organs, leading to DNA alkylation and mutations that drive tumor initiation and progression [1] - In the thyroid carcinoma model, N-Bis(2-hydroxypropyl)nitrosamine initiates thyroid cell transformation, while excess iodine promotes thyroid cell proliferation (a promoting factor), and low-dose bisphenol A enhances this promotional effect by disrupting thyroid hormone signaling [2] |
Solubility Data
| Solubility (In Vitro) | DMSO : ≥ 125 mg/mL (~770.70 mM) |
| Solubility (In Vivo) |
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. Injection Formulations (e.g. IP/IV/IM/SC) 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). 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) Oral Formulations 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). 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 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 6.1656 mL | 30.8280 mL | 61.6561 mL | |
| 5 mM | 1.2331 mL | 6.1656 mL | 12.3312 mL | |
| 10 mM | 0.6166 mL | 3.0828 mL | 6.1656 mL |