Nitrosamine impurities in medications: Established acceptable intake limits
Established Acceptable Intake Limits (Excel version - (926.6 Kb))
Health Canada's table of established Acceptable Intake limits (Appendix 1) has been removed from the guidance document and placed in this tab.
- CAS RN
- Chemical Abstracts Service Registry Number
- CPCA
- Carcinogenic Potency Categorization Approach
- AI
- Acceptable Intake
- -
- Not applicable
| Related Drug Substance | N-nitrosamine (and acronym, if available) | Chemical Structure | CAS RN | CPCA Category | AI Limit (ng/day)Table 1 footnote * | Date Most Recently Published (YYYY-MM-DD) |
|---|---|---|---|---|---|---|
| Clozapine | N-nitroso-clozapine EP Impurity C |  |
- | 3 | 400 | 2024-03-28 |
| - | N-nitroso-meglumine |  |
62137-31-9 | - | 1500Table 1 footnote *** | 2024-03-28 |
| Silodosin | N-nitroso-silodosin |  |
- | 4 | 1500 | 2024-03-28 |
| Methylphenidate | N-nitroso-ritalinic acid |  |
- | 4 | 1500 | 2024-03-28 |
| Apixaban | N-nitroso-apixaban EP Impurity B |  |
- | 4 | 1500 | 2024-03-28 |
| Terazosin | N-nitroso-terazosin EP Impurity C |  |
- | 3 | 400 | 2024-03-28 |
| Gliclazide | 2-nitrosooctahydrocyclo-penta[c]pyrrole (Gliclazide EP Impurity B) |  |
54786-86-6 | - | 1700 | 2024-03-28 |
| Indapamide | (2RS)-2-methyl-1-nitroso-2,3-dihydro-1H-indole (Indapamide EP Impurity A) |  |
85440-79-5 | 5 | 1500 | 2024-03-28 |
| - | N-nitroso-piperazine |  |
5632-47-3 | 3 | 400 | 2023-07-24 |
| - | N-nitroso-pyrrolidine (NPYR) |  |
930-55-2 | - | 1700 | 2023-07-24 |
| - | N-nitroso-diethanolamine (NDELA) |  |
1116-54-7 | - | 1900 | 2023-04-17 |
| - | N-nitroso-diphenylamine (NDPh) |  |
86-30-6 | - | 78000 | 2023-04-17 |
| - | 4-(methylnitrosamino)-1-(3-pyridyl)-1-(butanone) (NNK) |  |
64091-91-4 | - | 100 | 2022-09-01 |
| - | N-methyl-N-nitroso-phenethylamine (NMPEA) |  |
13256-11-6 | - | 8 | 2022-05-27 |
| - | N-nitroso-1,2,3,6-tetrahydropyridine (NTHP) |  |
55556-92-8 | - | 37 | 2022-05-27 |
| - | N-nitroso-piperidine (NPIP) |  |
100-75-4 | - | 1300 | 2022-05-27 |
| - | N-nitroso-dipropylamine (NDPA) |  |
621-64-7 | - | 26.5 | 2021-12-06 |
| - | N-nitroso-morpholine (NMOR) |  |
59-89-2 | - | 127 | 2021-12-06 |
| - | N-nitroso-dibutylamine (NDBA) |  |
924-16-3 | - | 26.5 | 2020-12-15 |
| - | N-nitroso-4-(methylamino)butyric acid (NMBA) |  |
61445-55-4 | - | 96 | 2019-10-02 |
| - | N-nitroso-diethylamine (NDEA) |  |
55-18-5 | - | 26.5 | 2019-10-02 |
| - | N-nitroso-diisopropylamine (NDIPA) |  |
601-77-4 | - | 26.5 | 2019-10-02 |
| - | N-nitroso-dimethylamine (NDMA) |  |
62-75-9 | - | 96 | 2019-10-02 |
| - | N-nitroso-ethylisopropylamine (NEIPA) |  |
16339-04-1 | - | 26.5 | 2019-10-02 |
| - | 1-methyl-4-nitrosopiperazine (MNP) |  |
16339-07-4 | 3 | 400 | 2023-07-24 |
| Agomelatine | N-nitroso-2- (7-methoxy-1-naphthyl)- N-[2-(7- methoxy-1 naphthyl)ethyl]ethylamine | ![N-nitroso-2-(7-methoxy-1-naphthyl)-N-[2-(7- methoxy-1-naphthyl)ethyl]ethylamine](/content/dam/hc-sc/images/services/drugs-health-products/compliance-enforcement/information-health-product/drugs/nitrosamine-impurities/established-acceptable-intake-limits/agomelatine.jpg) |
- | 2 | 100 | 2024-03-15 |
| Alogliptin | 3-amino-N-nitrosopiperidine |  |
2819242-71-0 | 3 | 400 | 2023-10-20 |
| Amitriptyline | N-nitroso-nortriptyline (NNORT) |  |
55855-42-0 | - | 8 | 2022-05-27 |
| Aripiprazole | 1-(2,3-dichlorophenyl)-4-nitrosopiperazine |  |
2221987-86-4 | 3 | 400 | 2024-03-15 |
| Atenolol | N-nitroso-atenolol |  |
134720-04-0 | 4 | 1500 | 2023-07-24 |
| Atomoxetine | N-nitroso-atomoxetine |  |
- | - | 100 | 2023-07-24 |
| Azelastine | N-nitroso-desmethylazelastine |  |
- | 2 | 100 | 2024-03-15 |
| Azithromycin | N-nitroso-azaerythromycin |  |
- | - | -Table 1 footnote ** | 2023-07-24 |
| Azithromycin | N-nitroso-N- desmethylazithromycin |  |
- | - | -Table 1 footnote ** | 2023-07-24 |
| Benazepril | N-nitroso-benazepril |  |
- | 5 | 1500 | 2023-07-24 |
| Benzydamine | 2-[benzyl(nitroso)amino] benzoic acid | ![2-[benzyl(nitroso)amino]benzoic acid](/content/dam/hc-sc/images/services/drugs-health-products/compliance-enforcement/information-health-product/drugs/nitrosamine-impurities/established-acceptable-intake-limits/benzydamine.jpg) |
1028-91-7 | 4 | 1500 | 2024-03-15 |
| Betahistine | N-nitroso-betahistine |  |
32635-81-7 | 1 | 18 | 2023-07-24 |
| Betaxolol | N-nitroso-betaxolol |  |
- | 4 | 1500 | 2024-03-15 |
| Bilastine | 1-(2-ethoxyethyl)-2-(1-nitrosopiperidin-4-yl)-1H-benzo[d]imidazole | ![1-(2-ethoxyethyl)-2-(1-nitrosopiperidin-4-yl)-1H-benzo[d]imidazole](/content/dam/hc-sc/images/services/drugs-health-products/compliance-enforcement/information-health-product/drugs/nitrosamine-impurities/established-acceptable-intake-limits/bilastine.jpg) |
- | 3 | 400 | 2024-03-15 |
| Bisoprolol | N-nitroso-bisoprolol |  |
2820170-76-9 | 4 | 1500 | 2023-07-24 |
| Bumetanide | N-nitroso-bumetanide |  |
2490432-02-3 | 4 | 1500 | 2024-03-15 |
| Bupropion | N-nitroso-bupropion |  |
2763780-10-3 | 5 | 1500 | 2023-07-24 |
| Cilazapril | N-nitroso-cilazapril |  |
1053740-92-3 | 5 | 1500 | 2023-07-24 |
| Cinacalcet | N-nitroso-cinacalcet |  |
- | 3 | 400 | 2023-10-20 |
| Ciprofloxacin | N,N'-dinitrosopiperazine |  |
140-79-4 | 3 | 400 | 2023-07-24 |
| Ciprofloxacin | N-nitroso-ciprofloxacin |  |
864443-44-7 | 4 | 1500 | 2023-07-24 |
| Citalopram | N-nitroso-desmethyl-citalopram |  |
- | 1 | 18 | 2023-07-24 |
| Clarithromycin | N-nitroso-N-desmethyl- clarithromycin |  |
- | 4 | 1500 | 2023-07-24 |
| Clozapine | N-nitroso-clozapine |  |
156632-03-0 | 5 | 1500 | 2023-07-24 |
| Dabigatran etexilate | N-nitroso-dabigatran etexilate |  |
- | - | 1500Table 1 footnote *** | 2024-03-15 |
| Daridorexant | 5-chloro-4-methyl-2- [(2S)-2-methyl-1-nitrosopyrrolidin-2-yl]- 1H-benzimidazole | ![5-chloro-4-methyl-2-[(2S)-2-methyl-1-nitrosopyrrolidin-2-yl]-1H-benzimidazole](/content/dam/hc-sc/images/services/drugs-health-products/compliance-enforcement/information-health-product/drugs/nitrosamine-impurities/established-acceptable-intake-limits/daridorexant.jpg) |
- | 5 | 1500 | 2024-03-15 |
| Desloratadine | N-nitroso-desloratadine |  |
1246819-22-6 | 3 | 400 | 2023-07-24 |
| Desvenlafaxine | N-nitroso-N-desmethyl-desvenlafaxine |  |
- | 1 | 18 | 2023-07-24 |
| Dextromethorphan | N-nitroso-N-desmethyl-dextromethorphan |  |
- | 4 | 1500 | 2023-07-24 |
| Diclofenac | N-nitroso-diclofenac |  |
66505-80-4 | 5 | 1500 | 2023-07-24 |
| Diphenhydramine | N-nitroso-N-desmethyl-diphenhydramine |  |
55855-43-1 | 1 | 18 | 2023-07-24 |
| Dorzolamide | N-nitroso-dorzolamide |  |
- | - | 1500Table 1 footnote *** | 2024-03-15 |
| Doxepin | N-nitroso-nordoxepin |  |
- | 1 | 18 | 2023-07-24 |
| Doxycycline | N-nitroso-N-desmethyl-doxycycline |  |
- | 3 | 400 | 2023-07-24 |
| Doxylamine | N-nitroso-N-desmethyl-doxylamine |  |
- | 1 | 18 | 2023-07-24 |
| Doxylamine | N-nitroso-N-methyl-2- [1-phenyl-1-(2-pyridinyl) methoxy]ethanamine | ![N-nitroso-N-methyl-2-[1-phenyl-1-(2-pyridinyl)methoxy]ethanamine](/content/dam/hc-sc/images/services/drugs-health-products/compliance-enforcement/information-health-product/drugs/nitrosamine-impurities/established-acceptable-intake-limits/doxylamine-2.jpg) |
- | 1 | 18 | 2023-07-24 |
| Duloxetine | N-nitroso-duloxetine (NDLX) |  |
- | - | 100 | 2022-05-27 |
| Enalapril | N-nitroso-enalapril |  |
- | 5 | 1500 | 2023-07-24 |
| Felodipine | N-nitroso-felodipine |  |
- | 5 | 1500 | 2023-07-24 |
| Flecainide | N-nitroso-flecainide |  |
- | 4 | 1500 | 2023-07-24 |
| Fluoxetine | N-nitroso-fluoxetine |  |
150494-06-7 | - | 100 | 2023-07-24 |
| Folic acid | N-nitroso-folic acid |  |
26360-21-4 | 4 | 1500 | 2023-07-24 |
| Frovatriptan | N-nitroso-frovatriptan |  |
- | 3 | 400 | 2023-07-24 |
| Furosemide | N-nitroso-furosemide |  |
2708280-93-5 | 4 | 1500 | 2023-07-24 |
| Hydrochlorothiazide | N-nitroso-hydrochlorothiazide |  |
63779-86-2 | - | -Table 1 footnote ** | 2023-07-24 |
| Hydroxyzine | 2-(2-(4-nitrosopiperazin-1-yl) ethoxy)ethan-1-ol |  |
73486-81-4 | 3 | 400 | 2023-07-24 |
| Ketamine | N-nitroso-ketamine |  |
86144-35-6 | 5 | 1500 | 2023-07-24 |
| Labetalol | N-nitroso-labetalol |  |
2820170-74-7 | 4 | 1500 | 2023-07-24 |
| Landiolol | N-nitroso-landiolol |  |
- | 3 | 400 | 2024-03-15 |
| Lapatinib | N-nitroso-lapatinib |  |
- | 1 | 18 | 2023-07-24 |
| Leucovorin | N-nitroso-folinic acid |  |
66505-80-4 | - | -Table 1 footnote ** | 2024-03-15 |
| Levofloxacin | (S)-10-((2-aminoethyl) (nitroso)amino)-9-fluoro- 3-methyl-7-oxo-2,3-dihydro- 7H-[1,4]oxazino[2,3,4-ij] quinoline-6-carboxylic acid | ![(S)-10-((2-aminoethyl)(nitroso)amino)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid](/content/dam/hc-sc/images/services/drugs-health-products/compliance-enforcement/information-health-product/drugs/nitrosamine-impurities/established-acceptable-intake-limits/levofloxacin-1.jpg) |
- | 4 | 1500 | 2023-07-24 |
| Levofloxacin | N-nitroso-N-desmethyl-levofloxacin |  |
1152314-62-9 | 4 | 1500 | 2023-07-24 |
| Lidocaine | N-nitroso-desethyl-lidocaine |  |
- | 2 | 100 | 2023-07-24 |
| Lisinopril | N-nitroso-lisinopril |  |
519175-80-5 | 5 | 1500 | 2023-07-24 |
| Mefenamic acid | N-nitroso-mefenamic acid |  |
2114-63-8 | - | 78000 | 2023-04-17 |
| Meropenem | N-nitroso-meropenem |  |
- | 4 | 1500 | 2023-07-24 |
| Methylphenidate | N-nitroso-methylphenidate (NMPH) |  |
55557-03-4 | - | 1300 | 2022-05-27 |
| Metoprolol | N-nitroso-metoprolol |  |
134720-05-1 | 4 | 1500 | 2023-07-24 |
| Mirabegron | N-nitroso-mirabegron |  |
- | 3 | 400 | 2023-07-24 |
| Mirtazapine | N-nitroso-N-desmethyl- mirtazepine |  |
- | 3 | 400 | 2024-03-15 |
| Moxifloxacin | N-nitroso-moxifloxacin |  |
- | 4 | 1500 | 2023-07-24 |
| Nebivolol | N-nitroso-nebivolol |  |
1391051-68-5 | 4 | 1500 | 2023-07-24 |
| Nortriptyline | N-nitroso-nortriptyline (NNORT) |  |
55855-42-0 | - | 8 | 2022-05-27 |
| Orphenadrine | N-nitroso-N-desmethyl- orphenadrine (NMOA) |  |
- | 1 | 18 | 2023-07-24 |
| Palbociclib | N-nitroso-palbociclib |  |
- | 3 | 400 | 2024-03-15 |
| Paroxetine | N-nitroso-paroxetine |  |
2361294-43-9 | - | 1300 | 2023-04-17 |
| Penicillin G benzathine | N,N'-dinitroso-N,N'- dibenzylethanediamine |  |
- | 1 | 18 | 2023-07-24 |
| Penicillin G benzathine | N-nitroso-N,N'- dibenzylethanediamine |  |
- | 1 | 18 | 2023-07-24 |
| Perindopril | N-nitroso-perindopril |  |
- | 5 | 1500 | 2023-07-24 |
| Phenylephrine | N-nitroso-phenylephrine |  |
78658-64-7 | 2 | 100 | 2023-07-24 |
| Pramipexole | N-nitroso-pramipexole |  |
- | 3 | 400 | 2023-07-24 |
| Propranolol | N-nitroso-propranolol |  |
84418-35-9 | 4 | 1500 | 2023-07-24 |
| Pseudoephedrine | N-nitroso-pseudoephedrine |  |
1850-88-0 | 4 | 1500 | 2023-07-24 |
| Quetiapine | N-nitroso-desalkyl- quetiapine (NDAQ) |  |
- | 3 | 400 | 2023-07-24 |
| Quinapril | N-nitroso-quinapril |  |
158522-79-3 | - | -Table 1 footnote ** | 2023-07-24 |
| Ramipril | N-nitroso-ramipril |  |
- | 5 | 1500 | 2023-07-24 |
| Ranolazine | 1-(2-methoxyphenoxy)- 3-(4-nitrosopiperazin-1-yl) propan-2-ol |  |
- | 3 | 400 | 2024-03-15 |
| Ranolazine | N-(2,6-dimethylphenyl)- 2-(4-nitrosopiperazin-1-yl) acetamide |  |
- | 3 | 400 | 2024-03-15 |
| Rasagiline | N-nitroso-rasagiline |  |
2470278-90-9 | 2 | 100 | 2023-07-24 |
| Ribociclib | N-nitroso-ribociclib |  |
- | 3 | 400 | 2024-03-15 |
| Rifapentine | 1-cyclopentyl-4- nitrosopiperazine (CPNP) |  |
61379-66-6 | 3 | 400 | 2023-07-24 |
| Rivaroxaban | 5-chloro-N-[[(5S)-2-oxo-3- [4-(N-nitroso-2-(carboxymethoxy) ethylamino)phenyl]- 5-oxazolidinyl]methyl]- 2-thiophenecarboxamide | ![5-chloro-N-[[(5S)-2-oxo-3-[4-(N-nitroso-2-(carboxymethoxy)ethylamino)phenyl]-5-oxazolidinyl]methyl]-2-thiophenecarboxamide](/content/dam/hc-sc/images/services/drugs-health-products/compliance-enforcement/information-health-product/drugs/nitrosamine-impurities/established-acceptable-intake-limits/rivaroxaban.jpg) |
- | 4 | 1500 | 2023-10-20 |
| Rivastigmine | N-nitroso-N-desmethyl- rivastigmine |  |
- | 2 | 100 | 2023-07-24 |
| Salbutamol | N-nitroso-salbutamol |  |
- | 5 | 1500 | 2023-07-24 |
| Sertraline | N-nitroso-sertraline |  |
- | - | 1500Table 1 footnote *** | 2023-10-20 |
| Sildenafil | N-nitroso-N-desmethyl- sildenafil |  |
- | 3 | 400 | 2024-03-15 |
| Sitagliptin | 7-nitroso-3-(trifluoromethyl)- 5,6,7,8-tetrahydro[1,2,4] triazolo-[4,3-a]pyrazine (NTTP) | ![7-nitroso-3-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo-[4,3-a]pyrazine (NTTP)](/content/dam/hc-sc/images/services/drugs-health-products/compliance-enforcement/information-health-product/drugs/nitrosamine-impurities/established-acceptable-intake-limits/sitagliptin.jpg) |
2892260-32-9 | - | 37 | 2022-05-27 |
| Sotalol | N-nitroso-sotalol |  |
134720-07-3 | 4 | 1500 | 2023-07-24 |
| Sumatriptan | N-nitroso-N-desmethyl- sumatriptan |  |
- | 1 | 18 | 2023-07-24 |
| Tamsulosin | N-nitroso-tamsulosin |  |
2892260-31-8 | 4 | 1500 | 2023-07-24 |
| Terazosin | (4-nitrosopiperazin-1-yl) (tetrahydrofuran-2-yl)methanone |  |
- | 3 | 400 | 2024-03-15 |
| Terbinafine | N-[(2E)-6,6-dimethyl- 2-hepten-4-yn-1-yl]- N-nitrosomethanamine | ![N-[(2E)-6,6-dimethyl-2-hepten-4-yn-1-yl]-N-nitrosomethanamine](/content/dam/hc-sc/images/services/drugs-health-products/compliance-enforcement/information-health-product/drugs/nitrosamine-impurities/established-acceptable-intake-limits/terbinafine-1.jpg) |
- | 1 | 18 | 2023-07-24 |
| Terbinafine | N-nitroso-N-desmethyl- terbinafine |  |
- | 1 | 18 | 2023-07-24 |
| Terbinafine | N-nitroso-N-methyl-1- naphthylmethylamine |  |
269760-88-8 | 1 | 18 | 2023-07-24 |
| Tigecycline | N-nitroso-tigecycline |  |
- | 5 | 1500 | 2023-07-24 |
| Tofacitinib | N-methyl-N-((3R,4R)- 4-methyl-1-nitrosopiperidin-3-yl) -7H-pyrrolo[2,3-d]pyrimidin-4-amine | ![N-methyl-N-((3R,4R)-4-methyl-1-nitrosopiperidin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine](/content/dam/hc-sc/images/services/drugs-health-products/compliance-enforcement/information-health-product/drugs/nitrosamine-impurities/established-acceptable-intake-limits/tofacitinib.jpg) |
- | 3 | 400 | 2024-03-15 |
| Trimebutine | N-nitroso-N-desmethyl- trimebutine |  |
- | 5 | 1500 | 2023-07-24 |
| Tripelennamine | N-nitroso-N-desmethyl- tripelennamine |  |
- | 1 | 18 | 2023-07-24 |
| Valacyclovir | N-nitroso-N-ethyl-valacyclovir |  |
- | 3 | 400 | 2023-07-24 |
| Valacyclovir | N-nitroso-N-methyl-valacyclovir |  |
- | 3 | 400 | 2023-07-24 |
| Valsartan | (S)-2-(((2'-(1H-tetrazol-5-yl)- [1,1′-biphenyl]-4-yl) methyl)(nitroso)amino)- 3-methylbutanoic acid | ![(S)-2-(((2'-(1H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)(nitroso)amino)-3-methylbutanoic acid](/content/dam/hc-sc/images/services/drugs-health-products/compliance-enforcement/information-health-product/drugs/nitrosamine-impurities/established-acceptable-intake-limits/valsartan.jpg) |
2254485-68-0 | - | -Table 1 footnote ** | 2023-07-24 |
| Varenicline | N-nitroso-varenicline (NNV) |  |
2755871-02-2 | 3 | 400 | 2023-07-24 |
| Vortioxetine | N-nitroso-vortioxetine |  |
- | 3 | 400 | 2023-07-24 |
Table 1 Notes
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