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Record Information
Version2.0
Creation Date2009-06-22 16:08:30 UTC
Update Date2014-12-24 20:24:32 UTC
Accession NumberT3D1724
Identification
Common NameBronopol
ClassSmall Molecule
DescriptionBronopol is a chemical compound of bromine and an antimicrobial substance. It is used as a preservative in pharmaceuticals, as well as numerous consumer products such as shampoos and cosmetics. It is also used as an antimicrobial in many industrial environments such as paper mills, oil exploration and production facilities, as well as cooling water disinfection plants. Its use is declining due to its recognized potential to decompose into carcinogenic nitrosamines. It is also a formaldehyde releaser. (10, 13)
Compound Type
  • Bromide Compound
  • Cosmetic Toxin
  • Household Toxin
  • Industrial/Workplace Toxin
  • Inorganic Compound
  • Organic Compound
  • Organobromide
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
2-Bromo-1-nitro-1,3-propanediol
2-Bromo-2-nitro-1, 3-propanediol
2-Bromo-2-nitro-1,3-propanediol
2-Bromo-2-nitropropan-1,3-diol
2-Bromo-2-nitropropane-1,3-diol
2-Nitro-2-bromo-1, 3-propanediol
2-Nitro-2-bromo-1,3-propanediol
b-bromo-b-nitrotrimethyleneglycol
Beta-bromo-beta-nitrotrimethyleneglycol
Bioban BNPD-40
Bronidiol
Bronocot
Bronopol-boots
Bronopolu
Bronosol
Bronotak
Broponol
C3H6BrNO4
Canguard 409
Epon(r) substitute embedding medium kit
Epoxy embedding medium kit
Lexgard bronopol
Myacide as plus
Myacide S-1, S-2
Onyxide 500
Chemical FormulaC3H6BrNO4
Average Molecular Mass199.988 g/mol
Monoisotopic Mass198.948 g/mol
CAS Registry Number52-51-7
IUPAC Name2-bromo-2-nitropropane-1,3-diol
Traditional Namebronopol
SMILESOCC(Br)(CO)[N+]([O-])=O
InChI IdentifierInChI=1S/C3H6BrNO4/c4-3(1-6,2-7)5(8)9/h6-7H,1-2H2
InChI KeyInChIKey=LVDKZNITIUWNER-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as c-nitro compounds. These are compounds having the nitro group, -NO2 (free valence on nitrogen), which is attached to carbon.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganic 1,3-dipolar compounds
Sub ClassAllyl-type 1,3-dipolar organic compounds
Direct ParentC-nitro compounds
Alternative Parents
Substituents
  • Bromohydrin
  • Halohydrin
  • C-nitro compound
  • Organic oxoazanium
  • Propargyl-type 1,3-dipolar organic compound
  • Alcohol
  • Hydrocarbon derivative
  • Organic zwitterion
  • Primary alcohol
  • Organooxygen compound
  • Organonitrogen compound
  • Organobromide
  • Organic oxide
  • Organohalogen compound
  • Organopnictogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Alkyl halide
  • Alkyl bromide
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite to pale yellow crystals.
Experimental Properties
PropertyValue
Melting Point131.5°C
Boiling Point140°C (decomposes)
Solubility250 mg/mL at 22°C [YALKOWSKY,SH & HE,Y (2003)]
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility12.8 mg/mLALOGPS
logP-0.21ALOGPS
logP-0.2ChemAxon
logS-1.2ALOGPS
pKa (Strongest Acidic)12.94ChemAxon
pKa (Strongest Basic)-3.6ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area86.28 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity32.66 m3·mol-1ChemAxon
Polarizability13.14 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0002-0900000000-ae7a9387ae98df20c0b7View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-001i-0900000000-1726ceff75d5b918516eView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0fsi-1900000000-f0e3840a9d77d1045332View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-0900000000-05837c913cd09c367877View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-001i-1900000000-e42c22307dc905229af1View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0udj-4900000000-e9ccc4cb82ffd0a98572View in MoNA
MSMass Spectrum (Electron Ionization)splash10-057r-9800000000-96a2fa8203c140ebd484View in MoNA
1D NMR1H NMR SpectrumNot Available
1D NMR13C NMR SpectrumNot Available
Toxicity Profile
Route of ExposureOral (4) ; inhalation (4) ; dermal (4)
Mechanism of ToxicityWhile Bronopol is not in itself a nitrosating agent, under conditions where it decomposes (alkaline solution and/or elevated temperatures) it can liberate nitrite and low levels of formaldehyde. These decomposition products can react with any secondary amines or amides (which may contaminate cosmetic products) to produce significant levels of nitrosamines, which are believed to be carcinogenic. Once in the body, nitrosamines are activated by cytochrome P-450 enzymes. They are then believed to induce their carcinogenic effects by forming DNA adducts at the N- and O-atoms. Formaldehyde itself is also carcinogenic. It is likely that formaldehyde toxicity occurs when intracellular levels saturate formaldehyde dehydrogenase activity, allowing the unmetabolized intact molecule to exert its effects. Formaldehyde is known to form cross links between protein and DNA and undergo metabolic incorporation into macromolecules (DNA, RNA, and proteins). (11, 10, 12, 1, 2, 3, 4, 13)
MetabolismNitrosamines can enter the body via ingestion, inhalation, or dermal contact. Once in the body, nitrosamines are metabolized by cytochrome P-450 enzymes, which essentially activates them into carcinogens. Sarcosine is metabolized to glycine by the enzyme sarcosine dehydrogenase. Formaldehyde may be absorbed following inhalation, oral, or dermal exposure. It is an essential metabolic intermediate in all cells and is produced during the normal metabolism of serine, glycine, methionine, and choline and also by the demethylation of N-, S-, and O-methyl compounds. Exogenous formaldehyde is metabolized to formate by the enzyme formaldehyde dehydrogenase at the initial site of contact. After oxidation of formaldehyde to formate, the carbon atom is further oxidized to carbon dioxide or incorporated into purines, thymidine, and amino acids via tetrahydrofolatedependent one-carbon biosynthetic pathways. Formaldehyde is not stored in the body and is excreted in the urine (primarily as formic acid), incorporated into other cellular molecules, or exhaled as carbon dioxide. (1, 2, 14, 11)
Toxicity ValuesLD50: 250 mg/kg (Oral, Dog) (5) LD50: 64-160 mg/kg (Dermal, Rat) (6) LC50: >5 mg/L over 6 hours (Inhalation, Rat) (5)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity (not listed by IARC). (9)
Uses/SourcesBronopol is used as a preservative in pharmaceuticals, as well as numerous consumer products such as shampoos and cosmetics. It is also used as an antimicrobial in many industrial environments such as paper mills, oil exploration and production facilities, as well as cooling water disinfection plants. (10)
Minimum Risk LevelNot Available
Health EffectsBronopol may react to produce nitrosamines, which are believed to be carcinogenic. It also releases formaldehyde, a known human carcinogen. (11, 4)
SymptomsNot Available
TreatmentEYES: irrigate opened eyes for several minutes under running water. INGESTION: do not induce vomiting. Rinse mouth with water (never give anything by mouth to an unconscious person). Seek immediate medical advice. SKIN: should be treated immediately by rinsing the affected parts in cold running water for at least 15 minutes, followed by thorough washing with soap and water. If necessary, the person should shower and change contaminated clothing and shoes, and then must seek medical attention. INHALATION: supply fresh air. If required provide artificial respiration.
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID2450
ChEMBL IDCHEMBL1408862
ChemSpider ID2356
KEGG IDC13034
UniProt IDNot Available
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDC006827
Stitch IDBronopol
PDB IDNot Available
ACToR ID6861
Wikipedia LinkBronopol
References
Synthesis ReferenceNot Available
MSDST3D1724.pdf
General References
  1. Oyama T, Sugio K, Uramoto H, Iwata T, Onitsuka T, Isse T, Nozoe T, Kagawa N, Yasumoto K, Kawamoto T: Increased cytochrome P450 and aryl hydrocarbon receptor in bronchial epithelium of heavy smokers with non-small cell lung carcinoma carries a poor prognosis. Front Biosci. 2007 May 1;12:4497-503. [17485391 ]
  2. Sasaki S, Sata F, Katoh S, Saijo Y, Nakajima S, Washino N, Konishi K, Ban S, Ishizuka M, Kishi R: Adverse birth outcomes associated with maternal smoking and polymorphisms in the N-Nitrosamine-metabolizing enzyme genes NQO1 and CYP2E1. Am J Epidemiol. 2008 Mar 15;167(6):719-26. doi: 10.1093/aje/kwm360. Epub 2008 Jan 23. [18218609 ]
  3. Drablos F, Feyzi E, Aas PA, Vaagbo CB, Kavli B, Bratlie MS, Pena-Diaz J, Otterlei M, Slupphaug G, Krokan HE: Alkylation damage in DNA and RNA--repair mechanisms and medical significance. DNA Repair (Amst). 2004 Nov 2;3(11):1389-407. [15380096 ]
  4. Lanigan RS: Final report on the safety assessment of Cocoyl Sarcosine, Lauroyl Sarcosine, Myristoyl Sarcosine, Oleoyl Sarcosine, Stearoyl Sarcosine, Sodium Cocoyl Sarcosinate, Sodium Lauroyl Sarcosinate, Sodium Myristoyl Sarcosinate, Ammonium Cocoyl Sarcosinate, and Ammonium Lauroyl Sarcosinate. Int J Toxicol. 2001;20 Suppl 1:1-14. [11358107 ]
  5. Yapi HF, Ahiboh H, Ago K, Ake M, Monnet D: [Protein profile and vitamin A in children of school age in Ivory Coast]. Ann Biol Clin (Paris). 2005 May-Jun;63(3):291-5. [15951260 ]
  6. Hinterhuber G, Cauza K, Dingelmaier-Hovorka R, Diem E, Horvat R, Wolff K, Foedinger D: Expression of RPE65, a putative receptor for plasma retinol-binding protein, in nonmelanocytic skin tumours. Br J Dermatol. 2005 Oct;153(4):785-9. [16181461 ]
  7. USEPA/Office of Pesticide Programs (2005). Reregistration Eligibility Decision Document - Bronopol.
  8. Tomlin CDS (ed) (2007). Bronopol (52-51-7). In: The e-Pesticide Manual, Version 2.2. Surrey UK: British Crop Protection Council.
  9. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
  10. Wikipedia. Bronopol. Last Updated 16 May 2009. [Link]
  11. ATSDR - Agency for Toxic Substances and Disease Registry (1999). Toxicological profile for formaldehyde. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  12. Wikipedia. Nitrosamine. Last Updated 16 November 2009. [Link]
  13. Wikipedia. Formaldehyde releaser. Last Updated 25 May 2008. [Link]
  14. Wikipedia. Sarcosine. Last Updated 16 October 2009. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

1. DNA
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
References
  1. Drablos F, Feyzi E, Aas PA, Vaagbo CB, Kavli B, Bratlie MS, Pena-Diaz J, Otterlei M, Slupphaug G, Krokan HE: Alkylation damage in DNA and RNA--repair mechanisms and medical significance. DNA Repair (Amst). 2004 Nov 2;3(11):1389-407. [15380096 ]
  2. Organic Natural Health (1998). Cancer Causing Toxic Chemical Ingredients in Cosmetic and Skin Care Products. [Link]
  3. ATSDR - Agency for Toxic Substances and Disease Registry (1999). Toxicological profile for formaldehyde. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
2. RNA
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (1999). Toxicological profile for formaldehyde. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Zinc ion binding
Specific Function:
Nuclear receptor. Interaction with RXR shifts RXR from its role as a silent DNA-binding partner to an active ligand-binding subunit in mediating retinoid responses through target genes defined by LXRES. LXRES are DR4-type response elements characterized by direct repeats of two similar hexanuclotide half-sites spaced by four nucleotides. Plays an important role in the regulation of cholesterol homeostasis, regulating cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8. Interplays functionally with RORA for the regulation of genes involved in liver metabolism (By similarity). Exhibits a ligand-dependent transcriptional activation activity (PubMed:25661920).
Gene Name:
NR1H3
Uniprot ID:
Q13133
Molecular Weight:
50395.34 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.36 uMATG_LXRa_TRANSAttagene
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Tachykinin receptor activity
Specific Function:
This is a receptor for the tachykinin neuropeptide substance K (neurokinin A). It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of affinity of this receptor to tachykinins is: substance K > neuromedin-K > substance P.
Gene Name:
TACR2
Uniprot ID:
P21452
Molecular Weight:
44441.705 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.92 uMNVS_GPCR_hNK2Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Zinc ion binding
Specific Function:
Binds to an ERR-alpha response element (ERRE) containing a single consensus half-site, 5'-TNAAGGTCA-3'. Can bind to the medium-chain acyl coenzyme A dehydrogenase (MCAD) response element NRRE-1 and may act as an important regulator of MCAD promoter. Binds to the C1 region of the lactoferrin gene promoter. Requires dimerization and the coactivator, PGC-1A, for full activity. The ERRalpha/PGC1alpha complex is a regulator of energy metabolism. Induces the expression of PERM1 in the skeletal muscle.
Gene Name:
ESRRA
Uniprot ID:
P11474
Molecular Weight:
45509.11 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.02 uMATG_ERRa_TRANSAttagene
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular Weight:
55930.545 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.95 uMNVS_ADME_hCYP2C19Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular Weight:
58293.76 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC502.18 uMNVS_ADME_hCYP1A2Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Protein tyrosine kinase activity
Specific Function:
Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including proliferation, scattering, morphogenesis and survival. Ligand binding at the cell surface induces autophosphorylation of MET on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1, SRC, GRB2, STAT3 or the adapter GAB1. Recruitment of these downstream effectors by MET leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. The RAS-ERK activation is associated with the morphogenetic effects while PI3K/AKT coordinates prosurvival effects. During embryonic development, MET signaling plays a role in gastrulation, development and migration of muscles and neuronal precursors, angiogenesis and kidney formation. In adults, participates in wound healing as well as organ regeneration and tissue remodeling. Promotes also differentiation and proliferation of hematopoietic cells.Acts as a receptor for Listeria internalin inlB, mediating entry of the pathogen into cells.
Gene Name:
MET
Uniprot ID:
P08581
Molecular Weight:
155540.035 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC503.17 uMNVS_ENZ_hMetNovascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Steroid hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC503.44 uMNVS_ADME_hCYP2C9Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]