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5-Bromo-2'-deoxyuridine

PubChem CID
6035
Structure
5-Bromo-2'-deoxyuridine_small.png
5-Bromo-2'-deoxyuridine_3D_Structure.png
5-Bromo-2'-deoxyuridine__Crystal_Structure.png
Molecular Formula
Synonyms
  • 5-BROMO-2'-DEOXYURIDINE
  • 59-14-3
  • Broxuridine
  • Bromodeoxyuridine
  • 5-Bromodeoxyuridine
Molecular Weight
307.10 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2005-06-24
  • Modify:
    2025-01-11
Description
5-bromo-2'-deoxyuridine is a white crystalline powder. (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
5-bromo-2'-deoxyuridine is a pyrimidine 2'-deoxyribonucleoside compound having 5-bromouracil as the nucleobase. It has a role as an antineoplastic agent and an antimetabolite.
Broxuridine has been used in trials studying the treatment of Leukemia, Stage I Prostate Cancer, Stage IIB Prostate Cancer, and Stage IIA Prostate Cancer.

1 Structures

1.1 2D Structure

Chemical Structure Depiction
5-Bromo-2'-deoxyuridine.png

1.2 3D Conformer

1.3 Crystal Structures

1 of 2
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CCDC Number
Crystal Structure Data
Crystal Structure Depiction
Crystal Structure Depiction

2 Biologic Description

IUPAC Condensed
br5Ura-dRibf
Sequence
N
HELM
RNA1{[dR]([*n1cc(c(=O)[nH]c1=O)Br |$_R1;;;;;;;;;$|])}$$$$
IUPAC
2'-deoxy-5-bromo-uridine

3 Names and Identifiers

3.1 Computed Descriptors

3.1.1 IUPAC Name

5-bromo-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

3.1.2 InChI

InChI=1S/C9H11BrN2O5/c10-4-2-12(9(16)11-8(4)15)7-1-5(14)6(3-13)17-7/h2,5-7,13-14H,1,3H2,(H,11,15,16)/t5-,6+,7+/m0/s1
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

3.1.3 InChIKey

WOVKYSAHUYNSMH-RRKCRQDMSA-N
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

3.1.4 SMILES

C1[C@@H]([C@H](O[C@H]1N2C=C(C(=O)NC2=O)Br)CO)O
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

3.2 Molecular Formula

C9H11BrN2O5
Computed by PubChem 2.2 (PubChem release 2021.10.14)

3.3 Other Identifiers

3.3.1 CAS

59-14-3

3.3.2 Deprecated CAS

1236362-78-9, 3445-26-9, 723-73-9

3.3.3 European Community (EC) Number

3.3.4 UNII

3.3.5 ChEBI ID

3.3.6 ChEMBL ID

3.3.7 DrugBank ID

3.3.8 DSSTox Substance ID

3.3.9 KEGG ID

3.3.10 Metabolomics Workbench ID

3.3.11 NCI Thesaurus Code

3.3.12 Nikkaji Number

3.3.13 Wikidata

3.3.14 Wikipedia

3.4 Synonyms

3.4.1 MeSH Entry Terms

  • 5 Bromo 2' deoxyuridine
  • 5 Bromodeoxyuridine
  • 5-Bromo-2'-deoxyuridine
  • 5-Bromodeoxyuridine
  • BrdU
  • Bromodeoxyuridine
  • Bromouracil Deoxyriboside
  • Broxuridine
  • BUdR
  • Deoxyriboside, Bromouracil
  • NSC-38297

3.4.2 Depositor-Supplied Synonyms

4 Chemical and Physical Properties

4.1 Computed Properties

Property Name
Molecular Weight
Property Value
307.10 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
XLogP3
Property Value
-0.3
Reference
Computed by XLogP3 3.0 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
3
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Acceptor Count
Property Value
5
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
2
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
305.98513 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
305.98513 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
99.1 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
17
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
386
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Isotope Atom Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Atom Stereocenter Count
Property Value
3
Reference
Computed by PubChem
Property Name
Undefined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Covalently-Bonded Unit Count
Property Value
1
Reference
Computed by PubChem
Property Name
Compound Is Canonicalized
Property Value
Yes
Reference
Computed by PubChem (release 2021.10.14)

4.2 Experimental Properties

4.2.1 Physical Description

5-bromo-2'-deoxyuridine is a white crystalline powder. (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

4.2.2 Color / Form

Crystals from absolute ethanol
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 242

4.2.3 Melting Point

365 to 369 °F (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
187-189 °C
Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 10th ed. Volumes 1-3 New York, NY: John Wiley & Sons Inc., 1999., p. 564

4.2.4 Solubility

10 to 50 mg/mL at 72 °F (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
Water 10 - 20 (mg/mL)
Dimethylacetamide ~ 200 (mg/mL)
1 N NaOH > 400 (mg/mL)
Dimethylsulfoxide ~ 160 (mg/mL)
Acetone ~ 4 (mg/mL)

4.2.5 LogP

log Kow = -0.29
Hansch, C., Leo, A., D. Hoekman. Exploring QSAR - Hydrophobic, Electronic, and Steric Constants. Washington, DC: American Chemical Society., 1995., p. 58

4.2.6 Stability / Shelf Life

Solid BrdU is stable in the dark to heat and humidity for 3 months at temperatures below 60 °C. On exposure to sunlight there is discoloration to grayish-brown. Ultraviolet irritations of frozen aqueous solutions of BrdU results in liberation of bromide ion and formation of a debrominated dimer, while radiolysis of aqueous solutions in the presence of oxygen yields mainly bromide, isodialuric acid deoxyriboside, and smaller amounts of various oxygenated derivatives.
NIH Division of Occupational Health and Safety; Safety Data Sheet for 5-Bromo-2'-deoxyuridine. Accessed through a query of https://www.niehs.nih.gov/odhsb/datasheets/home.htm as of February 20, 2007
Stability
Bulk: The bulk drug should be stored in tightly closed containers at controlled room temperature. Solution: BUdR solutions (0.5 and 25 mg/mL) are stable for at least seven days at room temperature.

4.2.7 Optical Rotation

(c = 1, 0.1 N NaOH) [a]20 D = +31 ± 1°

4.2.8 Decomposition

When heated to decomposition it emits very toxic fumes of /hydrogen bromide and nitrogen oxides/.
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 555

4.2.9 Dissociation Constants

4.3 SpringerMaterials Properties

4.4 Chemical Classes

4.4.1 Drugs

Pharmaceuticals -> Listed in ZINC15
S55 | ZINC15PHARMA | Pharmaceuticals from ZINC15 | DOI:10.5281/zenodo.3247749

5 Spectral Information

5.1 1D NMR Spectra

5.1.1 1H NMR Spectra

Source of Spectrum
Sigma-Aldrich Co. LLC.
Source of Sample
Sigma-Aldrich Co. LLC.
Catalog Number
858811
Copyright
Copyright © 2021-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2021 John Wiley & Sons, Inc. All Rights Reserved.
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5.1.2 13C NMR Spectra

1 of 2
Copyright
Copyright © 2016-2024 W. Robien, Inst. of Org. Chem., Univ. of Vienna. All Rights Reserved.
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2 of 2
Copyright
Copyright © 2016-2024 W. Robien, Inst. of Org. Chem., Univ. of Vienna. All Rights Reserved.
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5.2 UV Spectra

UV max = 280 nm in HCl (epsilon 9.9X10-3); 277 nm in NaOH (epsilon 7.2X10-3)
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 564
(0.1 N HCL) max 280 ± 2 nm E = 8,900 - 9,400

5.2.1 UV-VIS Spectra

Copyright
Copyright © 2008-2024 John Wiley & Sons, Inc. All Rights Reserved.
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5.3 IR Spectra

5.3.1 FTIR Spectra

Technique
KBr WAFER
Source of Sample
P-L Biochemicals Inc., Milwaukee, Wisconsin
Copyright
Copyright © 1980, 1981-2024 John Wiley & Sons, Inc. All Rights Reserved.
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5.3.2 ATR-IR Spectra

Source of Sample
Aldrich
Catalog Number
858811
Copyright
Copyright © 2018-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2018-2024 John Wiley & Sons, Inc. All Rights Reserved.
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5.4 Chromatograms

5.4.1 HPLC

HPLC
Column: 30 cm x 3.2 mm Spherisorb ODS Flow Rate: 1.0 mL /min Detection: UV at 254 nm Mobile Phase: 6% McOH /0.1 M phosphate buffer, pH 5.5 Sample Preparation: 1 mg/2 mL in water or internal standard solution Internal Standard: benzoic acid (0.8 mg/mL in water) Retention Volume: 15.0 mL (NSC - 38297) 7.0 mL (I.S.)

7 Chemical Vendors

8 Drug and Medication Information

8.1 Drug Indication

8.2 Clinical Trials

8.2.1 ClinicalTrials.gov

8.3 Therapeutic Uses

Orphan Drug. Drug Trade name Broxine/Neomark. Used for radiation sensitivity in the treatment of primary brain tumors.
U.S. FDA; Orphan Drug List. (November 20, 2006)
The halogenated pyrimidine analogs, bromodeoxyuridine (BUdR) and iododeoxyuridine (IUdR) have been recognized as potential clinical radiosensitizers for over two decades. In vivo and in vitro experimental studies document that radiosensitization is directly dependent on the amount of thymidine replacement in DNA by these analogs. ...
Kinsella TJ et al; Int J Radiat Oncol Biol Phys 10 (8): 1399-406 (1984)
Carcinogenicity has not been demonstrated; in fact, it is a useful agent in the treatment of neoplasms because it sensitizes tumor cells to the lethal effects of X-rays to a greater degree than normal tissue cells.
NIH Division of Occupational Health and Safety; Safety Data Sheet for 5-Bromo-2'-deoxyuridine. Accessed through a query of https://www.niehs.nih.gov/odhsb/datasheets/home.htm as of February 20, 2007
Antineoplastic adjunct (radiosensitizer); diagnostic aid (tumor cell label for cytokinetic analysis).
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 237
For more Therapeutic Uses (Complete) data for BROMODEOXYURIDINE (9 total), please visit the HSDB record page.

8.4 Drug Warnings

/The authors/ report here the results of a Phase I study conducted to determine the toxicity and serum levels that could be tolerated by patients receiving i.v. bromodeoxyuridine concomitantly with radiation therapy. Because of severe thrombocytopenia and leukopenia that was produced in three patients treated by a 96 hour infusion of bromodeoxyuridine at a dose of 1.5 g/sq m/24 hours, the dose was reduced to 0.8 g/sq m/24 hours in these patients and the remaining 9 patients in the study group. Even at this dosage, myelotoxicity was observed.
Phuphanich S et al; Int J Radiat Oncol Biol Phys 10 (9): 1769-72 (1984)
During a clinical Phase I study of bromodeoxyuridine (BUdR) as a radiation sensitizer ... the normal and malignant cells that incorporated the BUdR /were identified/. BUdR was infused for up to 14 days and the in vivo incorporation of BUdR into DNA was assessed using an immunohistochemical technique and a monoclonal antibody directed against BUdR. BUdR was identified in 50% of breast cancer cells and 10% of cells in a malignant melanoma. BUdR was also found in the basal layer of the normal epidermis and in 50% of cells in the marrow. The incorporation of BUdR into cells in the epidermis and marrow may produce the phototoxicity and myelosuppression observed in patients treated with BUdR. ...
Morstyn G et al; Int J Radiat Oncol Biol Phys 10 (8): 1441-5 (1984)
Twelve patients were treated with continuous intravenous (24-hour) infusions of bromodeoxyuridine (BUdR) at 650 or 1,000 mg/sq m/d for up to two weeks. Myelosuppression, especially thrombocytopenia, was the major systemic toxicity and limited the infusion period to nine to 14 days. However, bone marrow recovery occurred within seven to ten days, allowing for a second infusion in most patients. Local toxicity (within the radiation field) was minimal, with the exception of one of four patients, who underwent abdominal irradiation. Pharmacology studies revealed a steady-state arterial plasma level of 6 X 10-7 mol/L and 1 X 10-6 mol/L during infusion of 650 and 1,000 mg/sq m/d, respectively. In vivo BUdR uptake into normal bone marrow was evaluated in two patients by comparison of preinfusion and postinfusion in vitro radiation survival curves of marrow CFUc with enhancement ratios (D0-pre/D0-post) of 1.8 (with 650 mg/sq m/d) and 2.5 (with 1,000 mg/sq m/d). In vivo BUdR incorporation into normal skin and tumor cells using an anti-BUdR monoclonal antibody and immunohistochemistry was demonstrated in biopsies from three patients revealing substantially less cellular incorporation into normal skin (less than 10%) compared with tumor (up to 50% to 70%). We conclude that local and systemic toxicity of continuous infusion of BUdR at 1,000 mg/sq m/d for approximately two weeks is tolerable. The observed normal tissue toxicity is comparable with our previous clinical experience with intermittent (12 hours every day for two weeks) infusions of BUdR. Theoretically, a constant infusion should allow for greater incorporation of BUdR into cycling tumor cells and thus, for further enhancement of radiosensitization.
Kinsella TJ et al; J Clin Oncol 2 (10): 1144-50 (1984)
... 12 hours of BUdR at a dose of 800-1,000 mg/sq m for five days a week was given to 23 patients with primary and secondary malignant brain tumors during radiation therapy. Radiation therapy was planned at a weekly dose of 10 Gy for five to six weeks. Fifteen patients received 1,000 mg/sq m of BUdR; six of them tolerated more than three weeks of treatment. In eight patients given doses of 800 mg/sq m, five patients tolerated more than three weeks. The most remarkable toxic effects were myelosuppression and stomatitis, which were major obstacles to maintaining the schedule.
Matsutani M et al; Radiat Med 6 (1): 33-9 (1988)
It is cytotoxic, strongly teratogenic, and mutagenic in some test systems.
NIH Division of Occupational Health and Safety; Safety Data Sheet for 5-Bromo-2'-deoxyuridine. Accessed through a query of https://www.niehs.nih.gov/odhsb/datasheets/home.htm as of February 20, 2007

8.5 Reported Fatal Dose

In man, the highest tolerated intravenous infusion dose is 700 mg/sq m/day when given over a period of 12 hr/day.
NIH Division of Occupational Health and Safety; Safety Data Sheet for 5-Bromo-2'-deoxyuridine. Accessed through a query of https://www.niehs.nih.gov/odhsb/datasheets/home.htm as of February 20, 2007

9 Pharmacology and Biochemistry

9.1 MeSH Pharmacological Classification

Antimetabolites
Drugs that are chemically similar to naturally occurring metabolites, but differ enough to interfere with normal metabolic pathways. (From AMA Drug Evaluations Annual, 1994, p2033) (See all compounds classified as Antimetabolites.)
Antiviral Agents
Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. (See all compounds classified as Antiviral Agents.)
Radiation-Sensitizing Agents
Drugs used to potentiate the effectiveness of radiation therapy in destroying unwanted cells. (See all compounds classified as Radiation-Sensitizing Agents.)
Antimetabolites, Antineoplastic
Antimetabolites that are useful in cancer chemotherapy. (See all compounds classified as Antimetabolites, Antineoplastic.)

9.2 Absorption, Distribution and Excretion

Twelve patients were treated with continuous intravenous (24-hour) infusions of bromodeoxyuridine (BUdR) at 650 or 1,000 mg/sq m/d for up to two weeks. ... Pharmacology studies revealed a steady-state arterial plasma level of 6 X 10-7 mol/L and 1 X 10-6 mol/L during infusion of 650 and 1,000 mg/sq m/d, respectively. In vivo BUdR uptake into normal bone marrow was evaluated in two patients by comparison of preinfusion and postinfusion in vitro radiation survival curves of marrow CFUc with enhancement ratios (D0-pre/D0-post) of 1.8 (with 650 mg/sq m/d) and 2.5 (with 1,000 mg/sq m/d). In vivo BUdR incorporation into normal skin and tumor cells using an anti-BUdR monoclonal antibody and immunohistochemistry was demonstrated in biopsies from three patients revealing substantially less cellular incorporation into normal skin (less than 10%) compared with tumor (up to 50% to 70%).
Kinsella TJ et al; J Clin Oncol 2 (10): 1144-50 (1984)
BrdU is absorbed from the gastrointestinal tract following parenteral injection and is presumably absorbed transplacentally (because of its teratogenic effects).
NIH Division of Occupational Health and Safety; Safety Data Sheet for 5-Bromo-2'-deoxyuridine. Accessed through a query of https://www.niehs.nih.gov/odhsb/datasheets/home.htm as of February 20, 2007
Distribution and pharmacokinetics: Intra-arterial injection of BrdU into rodents results in extensive degradation... . Most of the portion which is not so degraded is incorporated into DNA of various tissues, particularly the colon, stomach, bone marrow, and spleen. The label of intraperitoneally injected deuterated BrdU in pregnant mice is also found in the liver of both mothers and embryos.
NIH Division of Occupational Health and Safety; Safety Data Sheet for 5-Bromo-2'-deoxyuridine. Accessed through a query of https://www.niehs.nih.gov/odhsb/datasheets/home.htm as of February 20, 2007
BrdU tablets were implanted subcutaneously in rats, and BrdU concentrations were determined in the serum. Within 5 hr peak concentrations of 10 ug BrdU/mL blood were reached. ... With the use of agar-coated tablets, BrdU concentrations in the blood were reduced by half, and no peak concentration was found. ...
Maier P et al; Environ Mutagen 5 (5): 695-703 (1983)

9.3 Metabolism / Metabolites

BrdU is degraded at a fairly rapid rate in mice and rats upon injection, in at least two metabolic pathways; one is hydrolysis at the glycosyl bond to yield bromouracil and 2-deoxyribose which is presumably then further metabolized. The other is debromination which is evidenced by liberation of bromide ion. The further fate of the remainder of the molecule has not been investigated
Kriss JP, Revesz L; Cancer Res 22: 254-65 (1962) as cited in NIH Division of Occupational Health and Safety; Safety Data Sheet for 5-Bromo-2'-deoxyuridine. Accessed through a query of https://www.niehs.nih.gov/odhsb/datasheets/home.htm as of February 20, 2007
5-bromodeoxyuridine is phosphorylated by thymidine kinase to produce 5-bromodeoxyuridine-phosphate. (L626)
L626: International Programme on Chemical Safety (IPCS) INCHEM (1992). Poison Information Monograph for Bromine. http://www.inchem.org/documents/pims/chemical/pim080.htm

9.4 Mechanism of Action

The principal effects of BrdU in the animal body result from its incorporation into tissue DNA in place of thymidine (the 5-methyl analog of BrdU). Since chromosomal proteins have a greater affinity for BrdU-substituted DNA than for unsubstituted DNA, this results in a variety of chromosomal aberrations including chromosome lengthening, chromatid breakage, and effects on sister chromatid exchange frequency. Effects on meiosis as well as on mitosis have been reported.
NIH Division of Occupational Health and Safety; Safety Data Sheet for 5-Bromo-2'-deoxyuridine. Accessed through a query of https://www.niehs.nih.gov/odhsb/datasheets/home.htm as of February 20, 2007
5-Bromodeoxyuridine induces a senescence-like phenomenon in mammalian cells. This effect was dramatically potentiated by AT-binding ligands such as distamycin A, netropsin, and Hoechst 33258. The genes most remarkably affected by these ligands include the widely used senescence-associated genes and were located on or nearby Giemsa-dark bands of human chromosomes. /The authors/ hypothesize that AT-rich scaffold/nuclear matrix attachment region sequences are involved in this phenomenon. In fact, upon substitution of thymine with 5-bromouracil, a rat S/MAR sequence reduced its degree of bending and became insensitive to cancellation of the bending by distamycin A. The S/MAR sequence containing 5-bromouracil also bound more tightly to nuclear scaffold proteins in vitro and this binding was not inhibited by distamycin A. Under the same conditions, the S/MAR sequence containing thymine easily dissociated from the nuclear scaffold proteins. Taken together, the synergistic induction of the genes may be explained not only by opening of condensed chromatin by distamycin A but also by increase in the binding of 5-bromouracil-containing S/MAR sequences to the nuclear scaffolds.
Suzuki T et al; Exp Cell Res 276 (2): 174-84 (2002)
An ectopic gene integrated in the host genome is occasionally silenced due to a position effect of its adjacent chromatin structure. /The authors/ found that 5-bromodeoxyuridine clearly activated such a transgene in HeLa cells. The transgene was also activated to various degrees by inhibitors of histone deacetylase, DNA topoisomerases, or DNA methyltransferase. The peptide antibiotic distamycin A potentiated markedly the effect of 5-bromodeoxyuridine. Transient expression of an artificial AT-hook protein termed MATH20 also potentiated its effect although significantly activated the transgene alone. Since distamycin A and MATH20 are able to displace histone H1 and other DNA-binding proteins bound to specific AT-rich sequences by a dominant, mutually exclusive fashion, these results suggest that 5-bromodeoxyuridine targets such an AT-rich sequence located adjacent to the silenced transgene, resulting in chromatin accessibility.
Suzuki T et al; Exp Cell Res 266 (1): 53-63 (2001)
5-Bromodeoxyuridine (BrdU) universally induces a senescence-like phenomenon in mammalian cells. To assess this phenomenon at the level of gene expression, /the authors/ constructed a PCR-based subtractive cDNA library enriched for mRNA species that immediately increase by administration of BrdU to HeLa cells. Candidate cDNA clones were isolated by differential colony hybridization, and then positive clones were identified by Northern blot analysis. Sequencing analysis revealed that the identified cDNA species were classified into three groups: widely used senescence-markers, known species whose relevance to senescence is yet to be reported, and known or novel ESTs. As expected, the majority of them showed an increase in expression in senescent human diploid fibroblasts. These results suggest that similar mechanisms operate in the regulation of BrdU-induced genes and senescence-associated genes.
Suzuki T et al; Exp Gerontol 36 (3): 465-74 (2001)
For more Mechanism of Action (Complete) data for BROMODEOXYURIDINE (7 total), please visit the HSDB record page.

10 Use and Manufacturing

10.1 Uses

A drug that makes cancer cells more sensitive to radiation and is also used as a diagnostic agent to determine how fast cancer cells grow.
National Cancer Institute; Dictionary of Cancer Terms. Broxuridine. Available from, as of February 20, 2007: https://cancernet.nci.nih.gov/Templates/db_alpha.aspx?CdrID=45179
A nucleoside that substitutes for thymidine in DNA and thus acts as an antimetabolite. It causes breaks in chromosomes and has been proposed as an antiviral and antineoplastic agent. It has been given orphan drug status for use in the treatment of primary brain tumors.
National Toxicology Program/NIEHS; CAS Registry Number: 59-14-3. Available from, as of February 20, 2007: https://ntp.niehs.nih.gov/index.cfm?objectid=E8812980-BDB5-82F8-FD8CB12B786663F9
A thymidine analog that incorporates /into/ DNA of dividing cells during the S-phase of the cell cycle. ... However, BrdU is not a marker of the S-phase of the cell cycle. As a thymidine analog, it is a marker of DNA synthesis. BrdU immunohistochemistry has been instrumental for the study of the development of the nervous system, and to confirm that neurogenesis occurs in the adult mammalian brain, including in human. ... BrdU labeling is currently the most used technique for studying adult neurogenesis in situ.
Taupin P; Brain Res Brain Res Rev 53 (1): 198-214 (2007)
The standard method for assessment of cell proliferation in paraffin-embedded tissue sections is 5-bromodeoxyuridine (BrdU) immunohistochemistry (IHC). BrdU can be administered to laboratory animals via IP injections, is readily incorporated into nuclei during the DNA synthetic phase of the cell cycle, and is detected with an anti-BrdU antibody. ...
Muskhelishvili L et al; J Histochem Cytochem 51 (12): 1681-8 (2003)
Laboratory chemical used as a mutagen in mutagenesis experiments. It is more commonly used in the detection of proliferating cells in living tissues.

10.2 Methods of Manufacturing

Nucleosides are manufactured by base exchange reaction of inosine and/or deoxyinosine with pyrimidine bases by thermostable purine nucleoside phosphorylase and thermostable pyrimidine nucleoside phosphorylase in aqueous solutions containing /phosphoric acid/ or phosphate salts and conversion of the resulting hypoxanthine into uric acid by thermostable xanthine dehydrogenase in the presence of electron receptors. Alternatively, nucleosides are manufactured by base exchange reaction of inosine and/or deoxyinosine with purine bases by thermostable purine nucleoside phosphorylase in aqueous solutions containing /phosphoric acid/ or phosphate salts and conversion of the resulting hypoxanthine into uric acid by thermostable xanthine dehydrogenase in the presence of electron receptors.
Mikami Y, Matsumoto S; Jpn Kokai Tokkyo Koho, JP 09215498, Yuki Gosei Kogyo Co Ltd, Japan 7pp. (1997)
Treatment of an aqueous solution of /deoxyuridine/ with saturated bromine water at 0 °C followed by removal of excess /bromine/ by suction, concentration at 30 °C, refluxing with /ethanol/, concentration at <35 °C, and crystallization from absolute /ethanol/ gave 60% /5-bromodeoxyuridine/ (purity 99%).
Huang Y, Lu Y; Shengwu Huaxue Yu Shengwu Wuli Jinzhan 48: 70-3 (1982)

10.3 General Manufacturing Information

EPA TSCA Commercial Activity Status
Uridine, 5-bromo-2'-deoxy-: ACTIVE

11 Identification

11.1 Clinical Laboratory Methods

Analyte: broxuridine; matrix: blood, cerebrospinal fluid, urine; procedure: high-performance liquid chromatography
Agarwal RP et al; J Chromatogr 231(2): 418-24 (1982)
Analyte: broxuridine; matrix: plasma; procedure: high-performance liquid chromatography
Ganes DA, Wagner JG; J Chromatogr 432: 233-42 (1988)
Montaldo PG, D'Incalci M; J. Chromatogr 491(1): 129-38 (1989)
Analysis: The method of choice is high-performance liquid chromatography which allows for the separation of BrdU from its metabolites and their separate quantitation.
NIH Division of Occupational Health and Safety; Safety Data Sheet for 5-Bromo-2'-deoxyuridine. Accessed through a query of https://www.niehs.nih.gov/odhsb/datasheets/home.htm as of February 20, 2007
Analyte: bromouracil; matrix: biological fluid (blood, urine); procedure: high-performance liquid chromatography
Stetson PL et al; J Chromatogr 341(1): 217-22 (1985)

12 Safety and Hazards

12.1 Hazards Identification

12.1.1 GHS Classification

Pictogram(s)
Health Hazard
Signal
Danger
GHS Hazard Statements

H340 (83.3%): May cause genetic defects [Danger Germ cell mutagenicity]

H341 (13%): Suspected of causing genetic defects [Warning Germ cell mutagenicity]

H361 (79.6%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]

Precautionary Statement Codes

P203, P280, P318, P405, and P501

(The corresponding statement to each P-code can be found at the GHS Classification page.)

ECHA C&L Notifications Summary

Aggregated GHS information provided per 54 reports by companies from 10 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.

12.1.2 Hazard Classes and Categories

Muta. 1B (83.3%)

Muta. 2 (13%)

Repr. 2 (79.6%)

12.1.3 Health Hazards

ACUTE/CHRONIC HAZARDS: When heated to decomposition this compound emits very toxic fumes of bromide ion and NOx. (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

12.1.4 Fire Hazards

Flash point data for this chemical are not available; however, it is probably combustible. (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

12.2 First Aid Measures

12.2.1 First Aid

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment.

INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing.

INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

12.3 Fire Fighting

Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

12.3.1 Fire Fighting Procedures

Fire, Explosion and Reactivity Hazard Data 1. BrdU does not require special fire-fighting procedures or equipment and does not present unusual fire and explosion hazards. 2. The presence of strong alkali, acid, and/or oxidant probably contributes to instability of BrdU. 3. No incompatibilities are known. 4. BrdU does not require non-spark equipment.
NIH Division of Occupational Health and Safety; Safety Data Sheet for 5-Bromo-2'-deoxyuridine. Accessed through a query of https://www.niehs.nih.gov/odhsb/datasheets/home.htm as of February 20, 2007

12.4 Accidental Release Measures

12.4.1 Cleanup Methods

Decontamination: Turn off equipment that could be affected by BrdU or the materials used for cleanup. ... Wipe off surfaces with water, then wash with copious quantities of water. Glassware should be rinsed in a hood with soap and water. Animal cages should be washed with water.
NIH Division of Occupational Health and Safety; Safety Data Sheet for 5-Bromo-2'-deoxyuridine. Accessed through a query of https://www.niehs.nih.gov/odhsb/datasheets/home.htm as of February 20, 2007

12.4.2 Disposal Methods

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.
Disposal: No waste streams containing BrdU /should/ be disposed of in sinks or general refuse. Surplus BrdU or chemical waste streams contaminated with BrdU /should/ be handled as hazardous chemical waste ... . Nonchemical waste (e.g., animal carcasses and bedding) containing BrdU /should/ be handled and packaged for incineration ... . Potentially infectious waste (e.g., tissue cultures) containing BrdU /should/ be disinfected by heat using a standard autoclave treatment and packaged for incineration, as above. Burnable waste (e.g., absorbent bench top liners) minimally contaminated with BrdU /should/ be handled as potentially infectious waste and packaged for incineration, as above. Absorbent materials (e.g., associated with spill cleanup) grossly contaminated /should/ be handled in accordance with the chemical waste disposal system.
NIH Division of Occupational Health and Safety; Safety Data Sheet for 5-Bromo-2'-deoxyuridine. Accessed through a query of https://www.niehs.nih.gov/odhsb/datasheets/home.htm as of February 20, 2007
The limited available research has not concluded how extensively BrDu is metabolized making it imperative that all potentially contaminated carcasses, bedding, and other nonsharps materials be disposed of as regulated medical waste through incineration. All contaminated sharps waste materials must be placed in proper sharps container and disposed of as regulated medical waste.
Virginia Commonwealth University; Working with Bromo-Deoxyuridine (BrDu) (April 26, 2005). Available from, as of February 20, 2007: https://www.vcu.edu/oehs/chemical/biosafe/brdu.pdf

12.4.3 Preventive Measures

Principal investigators /should/ develop and implement standard operating procedures (SOPs) by which laboratory staff will prepare/administer BrDu with minimal potential for exposure. All tasks having potential for occupational BrDu exposure (mixing of doses, dose preparation, administering of injections, etc.) /should/ only be conducted by competent staff whom have received appropriate training (OSHA: "Worker Right to Know") regarding the specific BrDu-related health and safety risks, SOPs, and procedures to be followed in event of an exposure incident.
Virginia Commonwealth University; Working with Bromo-Deoxyuridine (BrDu) (April 26, 2005). Available from, as of February 20, 2007: https://www.vcu.edu/oehs/chemical/biosafe/brdu.pdf
Avoid formation and breathing of aerosols. Laboratory operations should be conducted in a fume hood, glove box, or ventilated cabinet.
NIH Division of Occupational Health and Safety; Safety Data Sheet for 5-Bromo-2'-deoxyuridine. Accessed through a query of https://www.niehs.nih.gov/odhsb/datasheets/home.htm as of February 20, 2007
Avoid skin contact. If exposed, wash with soap and cold water. Avoid washing with solvents and exposure to UV light. Avoid rubbing of skin or increasing its temperature. For eye exposure, irrigate immediately with large amounts of water. ...
NIH Division of Occupational Health and Safety; Safety Data Sheet for 5-Bromo-2'-deoxyuridine. Accessed through a query of https://www.niehs.nih.gov/odhsb/datasheets/home.htm as of February 20, 2007
In case of laboratory spill, wear protective clothing during cleanup. Avoid skin contact or breathing of aerosols. Use water to dissolve compound. Use absorbent paper to mop up spill. Wash down area with soap and water.
NIH Division of Occupational Health and Safety; Safety Data Sheet for 5-Bromo-2'-deoxyuridine. Accessed through a query of https://www.niehs.nih.gov/odhsb/datasheets/home.htm as of February 20, 2007

12.5 Handling and Storage

12.5.1 Nonfire Spill Response

SMALL SPILLS AND LEAKAGE: If you spill this chemical, you should dampen the solid spill material with water, then transfer the dampened material to a suitable container. Use absorbent paper dampened with water to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Wash all contaminated surfaces with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

STORAGE PRECAUTIONS: You should protect this chemical from exposure to light, and store it in a freezer. (NTP, 1992)

National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

12.5.2 Storage Conditions

Store solid BrdU and its solutions in dark-colored, tightly closed containers, preferably under refrigeration. Avoid exposure to light and moisture. Store working quantities of BrdU and its solutions in an explosion-safe refrigerator in the work area.
NIH Division of Occupational Health and Safety; Safety Data Sheet for 5-Bromo-2'-deoxyuridine. Accessed through a query of https://www.niehs.nih.gov/odhsb/datasheets/home.htm as of February 20, 2007

12.6 Exposure Control and Personal Protection

12.6.1 Personal Protective Equipment (PPE)

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
Staff involved with any tasks where potential for BrDu exposure exists must don the following PPE: (a) examination gloves, (b) safety glasses or safety goggles (ANSI Z-87 approved, (c) lab coat, (d) appropriate laboratory attire, (e) if aerosol exposure threat exists suitable respiratory protection must be provided. Whenever feasible, procedures with the potential for producing BrDu aerosols should be conducted with a certified biosafety cabinet.
Virginia Commonwealth University; Working with Bromo-Deoxyuridine (BrDu) (April 26, 2005). Available from, as of February 20, 2007: https://www.vcu.edu/oehs/chemical/biosafe/brdu.pdf

12.7 Stability and Reactivity

12.7.1 Air and Water Reactions

Water soluble.

12.7.2 Reactive Group

Alcohols and Polyols

Amides and Imides

Amines, Phosphines, and Pyridines

Halogenated Organic Compounds

12.7.3 Reactivity Profile

5-BROMO-2'-DEOXYURIDINE may be heat and light sensitive. (NTP, 1992).
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.

12.7.4 Hazardous Reactivities and Incompatibilities

Chemical reactivity: BrdU is hydrolyzed at the N-glycosyl bond, yielding bromouracil and 2-deoxyribose. The pH dependency of this reaction varies with the experimental conditions. The rate of hydrolysis increases sharply at alkaline pH.
NIH Division of Occupational Health and Safety; Safety Data Sheet for 5-Bromo-2'-deoxyuridine. Accessed through a query of https://www.niehs.nih.gov/odhsb/datasheets/home.htm as of February 20, 2007

13 Toxicity

13.1 Toxicological Information

13.1.1 Toxicity Summary

5-bromodeoxyuridine acts on DNA. It induces a random DNA point mutation via base substitution. The base pair will change from an A-T to a G-C or from a G-C to an A-T after a number of replication cycles. As a thymine analog, 5-bromodeoxyuridine normally pairs with adenine.

13.1.2 Carcinogen Classification

Carcinogen Classification
Not listed by IARC. May cause heritable genetic damage.

13.1.3 Health Effects

5-bromodeoxyuridine is a mutagen (causes mutations), a cytotoxin, a teratogen and a weak carcinogen. The primary harmful effects are genetic mutation, anemia, reproductive disorders (fetal death or abnormality), cataracts, and skin irritation. It can cause respiratory tract irritation if inhaled, skin irritation if it contacts the skin and eye irritation if it contacts the eyes. As a reproductive toxin BrDU would be considered a “particularly hazardous substance” under the OSHA lab standard.

13.1.4 Exposure Routes

Oral (L626) ; inhalation (L626) ; dermal (L626)
L626: International Programme on Chemical Safety (IPCS) INCHEM (1992). Poison Information Monograph for Bromine. http://www.inchem.org/documents/pims/chemical/pim080.htm

13.1.5 Symptoms

5-bromodeoxyuridine can cause hypermotility, diarrhea, weight loss and possibly death if large amounts are repeatedly ingested.

13.1.6 Acute Effects

13.1.7 Toxicity Data

ToxicityData
Rat(po): LD50: 8400 mg/kg
Iyakuhin Kenkyu, 4,467,(1973)
ToxicityData
Rat(ip): LD50: 1500 mg/kg
Advances in Teratology, 3,181,(1968)
ToxicityData
Rat(sc): LD50: 3900 mg/kg
Takeda Kenkyusho Ho, 30,530,(1971)
ToxicityData
Rat(iv): LD50: 2320 mg/kg
Takeda Kenkyusho Ho, 30,735,(1971)
ToxicityData
Mouse(po): LD50: 9100 mg/kg
Takeda Kenkyusho Ho, 30,530,(1971)
ToxicityData
Mouse(ip): LD50: 3050 mg/kg
Takeda Kenkyusho Ho, 30,530,(1971)
ToxicityData
Mouse(sc): LD50: 3500 mg/kg
Takeda Kenkyusho Ho, 30,530,(1971)
ToxicityData
Mouse(iv): LD50: 2500 mg/kg
Takeda Kenkyusho Ho, 30,530,(1971)
LD50: 2500 mg/kg (Intravenous, Mouse) (T14) LD50: 3500 mg/kg (Subcutaneous, Mouse) (T14) LD50: 3050 mg/kg (Intraperitoneal, Mouse) (T14) LD50: 9100 mg/kg (Oral, Mouse) (T14)
T14: Lewis RJ (1996). Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold.

13.1.8 Treatment

EYES: 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.

13.1.9 Interactions

5-Bromo-2'-deoxyuridine (BrdUrd) was found to increase the cytotoxicity induced by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and cisplatin in human glioma cells. At a fixed concentration of BrdUrd and BCNU, the greatest cell loss was observed in exponentially growing cells. As cells approached plateau growth, cytotoxicity was reduced as indicated by greater cell viability. Under varying growth conditions the percentage of thymine replacement by bromouracil in DNA, as determined by gas chromatography/mass spectrometry analysis, declined as cultures approached maximum density. These data indicate BrdUrd must be incorporated into DNA for the enhanced effect to be observed. In exponentially growing cells, sensitization was dependent upon both the concentration of BrdUrd and alkylating agent. Using regression analysis (at 95% CL), a relationship between the level of bromouracil in DNA and the extent of enhanced cytotoxicity was observed at two concentrations of BCNU (r2 = 0.99, 0.96). Although it is known that bifunctional alkylating agents exert cytotoxicity by forming cross-links between cDNA strands, increased cross-link formation was not observed in BrdUrd substituted DNA as determined by alkaline elution. The data suggest that DNA damage induced by halogenated pyrimidines may not involve interstrand cross-links and that these agents may be useful in the treatment of glioma in combination with alkylating agents.
Mancini WR et al; J Pharmacol Exp Ther 289 (3): 1404-9 (1999)

13.1.10 Antidote and Emergency Treatment

Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 160
Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 160-1

13.1.11 Human Toxicity Excerpts

/HUMAN EXPOSURE STUDIES/ /The authors/ report here the results of a Phase I study conducted to determine the toxicity and serum levels that could be tolerated by patients receiving i.v. bromodeoxyuridine concomitantly with radiation therapy. Because of severe thrombocytopenia and leukopenia that was produced in three patients treated by a 96 hour infusion of bromodeoxyuridine at a dose of 1.5 g/sq m/24 hours, the dose was reduced to 0.8 g/sq m/24 hours in these patients and the remaining 9 patients in the study group. Even at this dosage, myelotoxicity was observed.
Phuphanich S et al; Int J Radiat Oncol Biol Phys 10 (9): 1769-72 (1984)
/SIGNS AND SYMPTOMS/ Twelve patients were treated with continuous intravenous (24-hour) infusions of bromodeoxyuridine (BUdR) at 650 or 1,000 mg/sq m/d for up to two weeks. Myelosuppression, especially thrombocytopenia, was the major systemic toxicity and limited the infusion period to nine to 14 days. However, bone marrow recovery occurred within seven to ten days, allowing for a second infusion in most patients.
Kinsella TJ et al; J Clin Oncol 2 (10): 1144-50 (1984)
/ALTERNATIVE and IN VITRO TESTS/ /The authors/ identified genes that immediately respond to 5-bromodeoxyuridine (BrdU) in SUSM-1, an immortal fibroblastic line, with DNA microarray and Northern blot analysis. At least 29 genes were found to alter gene expression greater than twice more or less than controls within 36 h after addition of BrdU. They took several different expression patterns upon addition of BrdU, and the majority showed a significant alteration within 12 hr. When compared among SUSM-1, HeLa, and TIG-7 normal human fibroblasts, 19 genes behaved similarly upon addition of BrdU. In addition, 14 genes, 9 of which are novel as regards senescence, behaved similarly in senescent TIG-7 cells. The genes do not seem to have a role in proliferation or cell cycle progression. These results suggest that the early BrdU-responsive genes represent early signs of cellular senescence and can be its new biomarkers.
Minagawa S et al; Exp Cell Res 304 (2): 552-8 (2005)
/GENOTOXICITY/ The existence of a high frequency of spontaneous sister-chromatid exchanges (SCEs) in Bloom syndrome (BS) has thus far been supported by data on a small number of BS cell lines. To examine the cause of baseline SCEs more broadly, the frequencies of SCEs, as well as chromosomal aberrations (CAs) in 4 additional BS fibroblast strains were compared, under different assay and cell culture conditions, with those of normal cells in the range of approximately 0.9-90% 5-bromodeoxyuridine (BrdUrd) substitution into template DNA. SCEs at low levels of BrdUrd substitution were detected by an extremely sensitive immunofluorescent technique. From approximately 0.9% to 4.5% BrdUrd substitution, the SCE frequency in BS cells remained constant, at a level (40/cell) 8 times higher than that of normal cells. As BrdUrd substitution increased further, the SCE frequency in BS cells increased almost linearly, reaching 70-100 per cell at approximately 90% substitution, while the SCE increment in control fibroblasts was less than 5 per cell. Analysis of SCEs in 3 successive replication cycles similarly revealed that the SCE increment in BS cells depended on BrdUrd only at a high BrdUrd substitution level. In contrast to data on SCEs, CA induction by incorporated BrdUrd in BS cells was only slightly higher than that in normal cells. Thus, BS cells are extremely sensitive to BrdUrd for SCE induction, but much less so for CA induction.
Tsuji H et al; Mutat Res 198 (1): 241-53 (1988)
For more Human Toxicity Excerpts (Complete) data for BROMODEOXYURIDINE (9 total), please visit the HSDB record page.

13.1.12 Non-Human Toxicity Excerpts

/LABORATORY ANIMALS: Acute Exposure/ The acute toxicity of BrdU appears to be quite low in rodents; various authors list acute LD50a by various parenteral routes in mice and rats to be in the range of 1.5-4 g/kg, and by the oral route 8.4 g/kg.
NIH Division of Occupational Health and Safety; Safety Data Sheet for 5-Bromo-2'-deoxyuridine. Accessed through a query of https://www.niehs.nih.gov/odhsb/datasheets/home.htm as of February 20, 2007
/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ No clinical or hematological signs of acute toxicity were noticed in rats receiving up to 500 mg/kg/day for 28 days in their drinking water.
NIH Division of Occupational Health and Safety; Safety Data Sheet for 5-Bromo-2'-deoxyuridine. Accessed through a query of https://www.niehs.nih.gov/odhsb/datasheets/home.htm as of February 20, 2007
/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Subacute effects in rodents include inflammatory skin lesions, decreased weight and hair growth, and hematological effects (anemia, leukocytopenia, thrombocytopenia).
NIH Division of Occupational Health and Safety; Safety Data Sheet for 5-Bromo-2'-deoxyuridine. Accessed through a query of https://www.niehs.nih.gov/odhsb/datasheets/home.htm as of February 20, 2007
/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ This study was designed to examine the pathogenesis of bromodeoxyuridine-induced (BrdU) clefts of the secondary palate in mice. Intraperitoneal injections of BrdU (500 mg/kg body weight) were given on days 11 and 12 to some pregnant mice and on days 12 and 13, and days 11, 12 and 13 to others. Evaluation of craniofacial relations and palate development in BrdU-treated mice revealed inhibition of vertical development of the palatal shelves, mandibular hypoplasia which led to failure of downward displacement of the tongue and the creation of an obstacle to reorientation of the palatal shelves. The results of this study demonstrate a strong correlation between induction of cleft palate and the presence of structural alterations in the mandible, and the mechanism of BrdU-induced cleft palate resembles the defect in the Pierre Robin anomaly.
Antoniades K et al; J Cranio-Maxillofacial Surg 23 (4): 252-5 (1995)
For more Non-Human Toxicity Excerpts (Complete) data for BROMODEOXYURIDINE (15 total), please visit the HSDB record page.

13.1.13 Non-Human Toxicity Values

LD50 Mouse iv 2500 mg/kg
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 555
LD50 Mouse sc 3500 mg/kg
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 555
LD50 Mouse ip 3050 mg/kg
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 555
LD50 Mouse oral 9100 mg/kg
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 555
For more Non-Human Toxicity Values (Complete) data for BROMODEOXYURIDINE (8 total), please visit the HSDB record page.

14 Associated Disorders and Diseases

15 Literature

15.1 Consolidated References

15.2 NLM Curated PubMed Citations

15.3 Springer Nature References

15.4 Wiley References

15.5 Nature Journal References

15.6 Chemical Co-Occurrences in Literature

15.7 Chemical-Gene Co-Occurrences in Literature

15.8 Chemical-Disease Co-Occurrences in Literature

16 Patents

16.1 Depositor-Supplied Patent Identifiers

16.2 WIPO PATENTSCOPE

16.3 Chemical Co-Occurrences in Patents

16.4 Chemical-Disease Co-Occurrences in Patents

16.5 Chemical-Gene Co-Occurrences in Patents

17 Interactions and Pathways

17.1 Protein Bound 3D Structures

17.1.1 Ligands from Protein Bound 3D Structures

PDBe Ligand Code
PDBe Conformer

17.2 Chemical-Target Interactions

17.3 Drug-Drug Interactions

18 Biological Test Results

18.1 BioAssay Results

19 Classification

19.1 MeSH Tree

19.2 NCI Thesaurus Tree

19.3 ChEBI Ontology

19.4 ChemIDplus

19.5 CAMEO Chemicals

19.6 ChEMBL Target Tree

19.7 UN GHS Classification

19.8 NORMAN Suspect List Exchange Classification

19.9 EPA DSSTox Classification

19.10 EPA TSCA and CDR Classification

19.11 MolGenie Organic Chemistry Ontology

20 Information Sources

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    https://creativecommons.org/licenses/by-nc/4.0/
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    https://pubchem.ncbi.nlm.nih.gov/source/ChemIDplus
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    https://www.drugbank.ca/legal/terms_of_use
  5. EPA Chemicals under the TSCA
    EPA TSCA Classification
    https://www.epa.gov/tsca-inventory
  6. EPA DSSTox
    CompTox Chemicals Dashboard Chemical Lists
    https://comptox.epa.gov/dashboard/chemical-lists/
  7. European Chemicals Agency (ECHA)
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  11. NCI Thesaurus (NCIt)
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  13. Toxin and Toxin Target Database (T3DB)
    LICENSE
    T3DB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (T3DB) and the original publication.
    http://www.t3db.ca/downloads
  14. NCI Investigational Drugs
  15. ChEMBL
    LICENSE
    Access to the web interface of ChEMBL is made under the EBI's Terms of Use (http://www.ebi.ac.uk/Information/termsofuse.html). The ChEMBL data is made available on a Creative Commons Attribution-Share Alike 3.0 Unported License (http://creativecommons.org/licenses/by-sa/3.0/).
    http://www.ebi.ac.uk/Information/termsofuse.html
  16. ClinicalTrials.gov
    LICENSE
    The ClinicalTrials.gov data carry an international copyright outside the United States and its Territories or Possessions. Some ClinicalTrials.gov data may be subject to the copyright of third parties; you should consult these entities for any additional terms of use.
    https://clinicaltrials.gov/ct2/about-site/terms-conditions#Use
  17. Comparative Toxicogenomics Database (CTD)
    LICENSE
    It is to be used only for research and educational purposes. Any reproduction or use for commercial purpose is prohibited without the prior express written permission of NC State University.
    http://ctdbase.org/about/legal.jsp
  18. Drug Gene Interaction database (DGIdb)
    LICENSE
    The data used in DGIdb is all open access and where possible made available as raw data dumps in the downloads section.
    http://www.dgidb.org/downloads
  19. Therapeutic Target Database (TTD)
  20. Crystallography Open Database (COD)
    LICENSE
    All data in the COD and the database itself are dedicated to the public domain and licensed under the CC0 License. Users of the data should acknowledge the original authors of the structural data.
    https://creativecommons.org/publicdomain/zero/1.0/
  21. The Cambridge Structural Database
  22. IUPAC Digitized pKa Dataset
  23. Japan Chemical Substance Dictionary (Nikkaji)
  24. KEGG
    LICENSE
    Academic users may freely use the KEGG website. Non-academic use of KEGG generally requires a commercial license
    https://www.kegg.jp/kegg/legal.html
  25. Metabolomics Workbench
  26. Nature Chemical Biology
  27. NORMAN Suspect List Exchange
    LICENSE
    Data: CC-BY 4.0; Code (hosted by ECI, LCSB): Artistic-2.0
    https://creativecommons.org/licenses/by/4.0/
    5-Bromo-2'-deoxyuridine
    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
  28. Protein Data Bank in Europe (PDBe)
  29. SpectraBase
  30. Springer Nature
  31. SpringerMaterials
  32. Wikidata
  33. Wikipedia
  34. Wiley
  35. Medical Subject Headings (MeSH)
    LICENSE
    Works produced by the U.S. government are not subject to copyright protection in the United States. Any such works found on National Library of Medicine (NLM) Web sites may be freely used or reproduced without permission in the U.S.
    https://www.nlm.nih.gov/copyright.html
    Radiation-Sensitizing Agents
    https://www.ncbi.nlm.nih.gov/mesh/68011838
    Antimetabolites, Antineoplastic
    https://www.ncbi.nlm.nih.gov/mesh/68000964
  36. PubChem
  37. GHS Classification (UNECE)
  38. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
  39. PATENTSCOPE (WIPO)
  40. NCBI
CONTENTS