An official website of the United States government

(6R,7R)-7-((E)-2-(2-Aminothiazol-4-yl)-2-(methoxyimino)acetamido)-3-((furan-2-carbonylthio)methyl)-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid

PubChem CID
5484735
Structure
(6R,7R)-7-((E)-2-(2-Aminothiazol-4-yl)-2-(methoxyimino)acetamido)-3-((furan-2-carbonylthio)methyl)-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid_small.png
(6R,7R)-7-((E)-2-(2-Aminothiazol-4-yl)-2-(methoxyimino)acetamido)-3-((furan-2-carbonylthio)methyl)-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid_3D_Structure.png
Molecular Formula
Synonyms
  • Ceftiofur
  • Ceftiofur E-isomer
  • Excenel
  • MAN163YXK8
  • 120882-20-4
Molecular Weight
523.6 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2005-08-08
  • Modify:
    2025-02-01
Description
Ceftiofur is a third generation cephalosporin antibiotic, first described in 1987, and now used in veterinary medicine. It is marketed by pharmaceutical company Zoetis as Excenel, and is the active ingredient in that company's Specramast LC (lactating cow formula) product. It is resistant to hydrolysis by beta-lactamase, and has activity against both Gram-positive and Gram-negative bacteria. E. coli strains resistant to ceftiofur have been reported. The metabolite desfurolyceftiofur also has antibiotic activity, consequently the two compounds are measured together to monitor for antibiotic activity in the milk.
Ceftiofur is a semisynthetic, beta-lactamase-stable, broad-spectrum, third-generation cephalosporin with antibacterial activity. Ceftiofur binds to and inactivates penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall. PBPs are enzymes involved in the terminal stages of assembling the bacterial cell wall and in reshaping the cell wall during growth and division. Inactivation of PBPs interferes with the cross-linkage of peptidoglycan chains necessary for bacterial cell wall strength and rigidity. This results in the weakening of the bacterial cell wall and causes cell lysis.
See also: Ceftiofur (annotation moved to).

1 Structures

1.1 2D Structure

Chemical Structure Depiction
(6R,7R)-7-((E)-2-(2-Aminothiazol-4-yl)-2-(methoxyimino)acetamido)-3-((furan-2-carbonylthio)methyl)-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid.png

1.2 3D Conformer

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

(6R,7R)-7-[[(2E)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-3-(furan-2-carbonylsulfanylmethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

2.1.2 InChI

InChI=1S/C19H17N5O7S3/c1-30-23-11(9-7-34-19(20)21-9)14(25)22-12-15(26)24-13(17(27)28)8(5-32-16(12)24)6-33-18(29)10-3-2-4-31-10/h2-4,7,12,16H,5-6H2,1H3,(H2,20,21)(H,22,25)(H,27,28)/b23-11+/t12-,16-/m1/s1
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.3 InChIKey

ZBHXIWJRIFEVQY-HURQQZHVSA-N
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.4 SMILES

CO/N=C(\C1=CSC(=N1)N)/C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)CSC(=O)C4=CC=CO4)C(=O)O
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C19H17N5O7S3
Computed by PubChem 2.2 (PubChem release 2021.10.14)

2.3 Other Identifiers

2.3.1 CAS

120882-20-4
80370-57-6

2.3.2 European Community (EC) Number

2.3.3 UNII

2.3.4 DrugBank ID

2.3.5 DSSTox Substance ID

2.3.6 KEGG ID

2.3.7 Metabolomics Workbench ID

2.3.8 NCI Thesaurus Code

2.3.9 Nikkaji Number

2.3.10 RXCUI

2.3.11 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • ceftiofur
  • ceftiofur hydrochloride
  • ceftiofur sodium
  • Naxcel
  • U 64279A
  • U-64279E

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
523.6 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
XLogP3
Property Value
0.2
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
13
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
9
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
523.02901142 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
523.02901142 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
256 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
34
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
945
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
2
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
1
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)

3.2 Experimental Properties

3.2.1 Collision Cross Section

211.2 Ų [M+Na]+ [CCS Type: TW; Method: calibrated with Waters Major Mix]

215 Ų [M+H]+ [CCS Type: TW; Method: calibrated with Waters Major Mix]

3.2.2 Other Experimental Properties

Mol wt: 545.55 /Monosodium salt/
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. 334
Mol wt: 560.03 /Monohydrochloride/
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. 334

3.3 Chemical Classes

3.3.1 Drugs

3.3.1.1 Animal Drugs
Veterinary drugs -> Antibacterials for systemic use -> Veterinary pharmacotherapeutic group -> EMA Drug Category

4 Spectral Information

4.1 Mass Spectrometry

4.1.1 LC-MS

Authors
Nikiforos Alygizakis, Anna Bletsou, Nikolaos Thomaidis, University of Athens
Instrument
Bruker maXis Impact
Instrument Type
LC-ESI-QTOF
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
Ramp 26.1-39.2 eV
Fragmentation Mode
CID
Column Name
Acclaim RSLC C18 2.2um, 2.1x100mm, Thermo
Retention Time
5.5 min
Precursor m/z
524.0363
Precursor Adduct
[M+H]+
Top 5 Peaks

241.0403 999

210.0207 697

167.0278 568

126.0119 538

156.023 517

Thumbnail
Thumbnail
License
CC BY

6 Chemical Vendors

7 Drug and Medication Information

7.1 Drug Indication

PigsTreatment of bacterial respiratory disease associated with Actinobacillus pleuropneumoniae, Pasteurella multocida, Haemophilus parasuis and Streptococcus suis. Treatment of septicaemia, polyarthritis or polyserositis associated with Streptococcus suis infection. CattleTreatment of acute interdigital necrobacillosis in cattle also known as Panaritium or foot rot. Treatment of acute post-partum (puerperal) metritis in cattle, in cases where treatment with another antimicrobial has failed.

7.2 Drug Labels

Drug and label
Active ingredient and drug

7.3 EMA Drug Information

Medicine
Category
Veterinary drugs
Active Substance
ceftiofur
INN/Common name
ceftiofur
Pharmacotherapeutic Classes
Antibacterials for systemic use
Status
This medicine is authorized for use in the European Union
Company
Zoetis Belgium SA
Market Date
2005-05-19

7.4 Therapeutic Uses

MEDICATION (VET): Ceftiofur is used in the treatment of respiratory infections in cattle and pigs.
Joint FAO/WHO Expert Committee on Food Additives; WHO Food Additive Series 36: Toxicological Evaluation of Certain Veterinary Drug Residues in Food: Ceftiofur (1996). Available from, as of July 17, 2006: https://www.inchem.org/documents/jecfa/jecmono/v36je01.htm
THERAP CAT (VET): Antibacterial
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. 334
MEDICATION (VET): Ceftiofur is an injectable cephalosporin approved for respiratory disease in horses and cattle and for treatment of canine bacterial urinary tract infections caused by E coli and Proteus.
Kahn, C.M. (Ed.); The Merck Veterinary Manual 9th ed. Merck & Co. Whitehouse Station, NJ. 2005, p. 2042
MEDICATION (VET): Dogs: ... Ceftiofur sodium for injection are indicated in the treatment of urinary tract infections caused by susceptible organisms, including E. coli, P. mirabilis, and S. aureus. /Ceftiofur sodium/
Thomson/Micromedex. USP Veterinary Pharmaceutical Information Monographs: Cephalolsporins (2003). Available from, as of July 26, 2006: https://www.usp.org/audiences/veterinary/monographs/main.html
For more Therapeutic Uses (Complete) data for CEFTIOFUR (13 total), please visit the HSDB record page.

7.5 Drug Warnings

The cephalosporins are relatively nontoxic, ... . IM injections can be painful, and repeated IV administration may lead to local phlebitis. Nausea, vomiting, and diarrhea may occasionally be seen. Hypersensitivity reactions of several forms have been seen, particularly in animals with a history of acute penicillin allergy. Superinfection may arise with the use of cephalosporins, and Pseudomonas or Candida spp are likely opportunistic pathogens. /Cephalosporins/
Kahn, C.M. (Ed.); The Merck Veterinary Manual 9th ed. Merck & Co. Whitehouse Station, NJ. 2005, p. 2065
Ceftiofur is associated with a duration and dose-related thrombocytopenia and anemia in dogs, which would not be expected with the recommended dosage regimen.
Kahn, C.M. (Ed.); The Merck Veterinary Manual 9th ed. Merck & Co. Whitehouse Station, NJ. 2005, p. 2042
Ceftiofur concentrations in an infected and uninfected environment were compared and the efficacy of locally administered ceftiofur was evaluated in an experimental infection with Staphylococcus aureus in tissue cages. Eight ponies had tissue cages (TCs) implanted sc on each side of the neck. Into one of the cages 150 mg of ceftiofur was administered and fluid samples were taken to determine ceftiofur concentrations. After 1 week the other TC was infected with S. aureus and subsequently treated with 150 mg ceftiofur administered locally into the TC once daily for 21 days. Samples of fluid were taken to determine ceftiofur concentrations and for bacterial counts. Ceftiofur concentrations did not differ significantly in the infected and uninfected environments after single dose of 150 mg of ceftiofur. Concentrations were considerably in excess of the minimum inhibitory concentration (MIC) of the S. aureus strain used. A marked decrease of viable bacteria in tissue cage fluid (TCF) occurred. In five of seven ponies; however, the infection was not eliminated and abscess formation occurred. Therefore, local application of ceftiofur alone is not advisable for infections with S. aureus in secluded sites in horses, but should be used only with adjunctive therapy.
Bosch G et al; J Vet Pharmacol Ther 29 (1): 31-6 (2006)
Horses: Diarrhea with ceftiofur.
Thomson/Micromedex. USP Veterinary Pharmaceutical Information Monographs: Cephalolsporins (2003). Available from, as of July 26, 2006: https://www.usp.org/audiences/veterinary/monographs/main.html
Anemia and thrombocytopenia have been seen in dogs given ceftiofur at high doses (three to five times the labeled dose) or for long periods of time (5 to 6 weeks). These side effects appear to be reversible when treatment is discontinued.
Thomson/Micromedex. USP Veterinary Pharmaceutical Information Monographs: Cephalolsporins (2003). Available from, as of July 26, 2006: https://www.usp.org/audiences/veterinary/monographs/main.html

8 Food Additives and Ingredients

8.1 Food Additive Classes

JECFA Functional Classes
Veterinary Drug -> ANTIMICROBIAL_AGENT;

8.2 Evaluations of the Joint FAO / WHO Expert Committee on Food Additives - JECFA

Chemical Name
CEFTIOFUR
Evaluation Year
1998
ADI
Upper limit temporary value: 0-0.05 mg/kg bw/d
Comments
The Committee's evaluation of concluded that ceftiofur was of no concern for carcinogenicity, due to the following factors: no evidence of genotoxicity in a variety of assays, no chemical relation of the drug or its metabolites to known carcinogens, rapid metabolism of drug, and lack of neoplastic nor preneoplastic lesions in 90-day feeding studies in rats, dogs, monkeys, or in reproductive toxicity studies involving exposure for periods of up to 160 days. No reproductive or developmental toxicity was observed in rodents. The Committee concluded that most sensitive endpoint is toxicity to gut flora. Therefore, an ADI of 0-50 µg/kg bw/d (3000 µg/p/d for a 60-kg adult) was established, based on the lowest MIC50 value for desfuroylceftiofur cysteine disulfide of 2 µg/ml for Clostridium and Escherichia species, converted to an upper-limit temporary ADI value using the following formula: ADI (µg/kg bw) = Concentration without effect on gut flora (2 µg/ml) X Daily fecal bolus (150 g)/(Fraction of oral dose bioavailable (0.1) × Safety factor (1) × Weight of human (60 kg)). The total safety factor of 1 accounted for the following factors: the range of MICs needed to account for sensitive bacteria, anaerobic environment, bacterial density and pH; the fraction of the dose available to the gut microflora from PK studies of ceftiofur in humans; and variability among exposed individuals. On the basis of residue studies, the Committee recommended the following MRLs: 1000 µg/kg (muscle), 6000 µg/kg (kidney), and 2000 µg/kg (fat) in cattle & pigs. The Committee reaffirmed the MRL values of 2000 µg/kg (liver, cattle & pigs) & 100 µg/L (cow's milk). These MRLs would result in a maximum daily intake of 1050 µg/p/d.
Tox Monograph

9 Pharmacology and Biochemistry

9.1 MeSH Pharmacological Classification

Anti-Bacterial Agents
Substances that inhibit the growth or reproduction of BACTERIA. (See all compounds classified as Anti-Bacterial Agents.)

9.2 ATC Code

QJ01DD90

9.3 Absorption, Distribution and Excretion

A study of 4 male and 4 female Sprague-Dawley rats treated intramuscularly with (14)C-ceftiofur (2 mg/kg bw) revealed that 55% of the administered dose was excreted in the urine and about 30% in the GI tract and feces. The major urinary metabolite was desfuroylceftiofur (DFC). The metabolism of ceftiofur was similar in calves administered (14)C-ceftiofur (2 mg/kg bw) via the i.m. route. Unmetabolized ceftiofur was also present in the urine (4.4-21% of total radioactivity).
Joint FAO/WHO Expert Committee on Food Additives; WHO Food Additive Series 36: Toxicological Evaluation of Certain Veterinary Drug Residues in Food: Ceftiofur (1996). Available from, as of July 17, 2006: https://www.inchem.org/documents/jecfa/jecmono/v36je01.htm
A group of Sprague-Dawley rats (7/sex) received single oral doses of (14)C-ceftiofur (200 mg/kg bw) in a comparative study with calves. Approximately 55% of the total dose was recovered in the urine and the rest was present in the feces and GI tract. Plasma concentration at 6 hr was 1 mg/kg and trace amounts of ceftiofur were present in all tissues (i.e. liver, muscle and fat). The highest residue levels (0.7 mg/kg) were present in kidney.
Joint FAO/WHO Expert Committee on Food Additives; WHO Food Additive Series 36: Toxicological Evaluation of Certain Veterinary Drug Residues in Food: Ceftiofur (1996). Available from, as of July 17, 2006: https://www.inchem.org/documents/jecfa/jecmono/v36je01.htm
A study of lactating cows treated with (14)C-ceftiofur (2.3 mg/kg bw/day for 5 days) revealed that 32-38% of the radioactivity was present in the milk as free metabolites. The major metabolite was desfuroylceftiofur cysteine disulfide representing 7-9% of the total radioactivity. No parent compound was detected in the milk.
Joint FAO/WHO Expert Committee on Food Additives; WHO Food Additive Series 36: Toxicological Evaluation of Certain Veterinary Drug Residues in Food: Ceftiofur (1996). Available from, as of July 17, 2006: https://www.inchem.org/documents/jecfa/jecmono/v36je01.htm
A study of im administration of (14)C-ceftiofur in a bull revealed that 55% of the administered dose was excreted in the urine and approximately 30% in the GI tract and feces. The initial metabolite in both urine and plasma was desfuroylceftiofur. HPLC analysis of radioactive metabolites was similar to the results found in the rat studies. A number of metabolites were produced, the major metabolite (87% of total urinary metabolites) being desfuroylceftiofur acetamide conjugates. No parent compound was observed in the urine.
Joint FAO/WHO Expert Committee on Food Additives; WHO Food Additive Series 36: Toxicological Evaluation of Certain Veterinary Drug Residues in Food: Ceftiofur (1996). Available from, as of July 17, 2006: https://www.inchem.org/documents/jecfa/jecmono/v36je01.htm
For more Absorption, Distribution and Excretion (Complete) data for CEFTIOFUR (13 total), please visit the HSDB record page.

9.4 Metabolism / Metabolites

A study of 4 male and 4 female Sprague-Dawley rats treated intramuscularly with (14)C-ceftiofur (2 mg/kg bw) revealed that 55% of the administered dose was excreted in the urine and about 30% in the GI tract and faeces. The major urinary metabolite was desfuroylceftiofur (DFC). The metabolism of ceftiofur was similar in calves administered (14)C-ceftiofur (2 mg/kg bw) via the i.m. route. Unmetabolized ceftiofur was also present in the urine (4.4-21% of total radioactivity).
Joint FAO/WHO Expert Committee on Food Additives; WHO Food Additive Series 36: Toxicological Evaluation of Certain Veterinary Drug Residues in Food: Ceftiofur (1996). Available from, as of July 17, 2006: https://www.inchem.org/documents/jecfa/jecmono/v36je01.htm
A group of Sprague-Dawley rats (7/sex) received single oral doses of (14)C-ceftiofur (200 mg/kg bw) in a comparative study with calves. Approximately 55% of the total dose was recovered in the urine and the rest was present in the feces and GI tract. ... The major urinary metabolite was ceftiofursulfoxide cysteine thioester.
Joint FAO/WHO Expert Committee on Food Additives; WHO Food Additive Series 36: Toxicological Evaluation of Certain Veterinary Drug Residues in Food: Ceftiofur (1996). Available from, as of July 17, 2006: https://www.inchem.org/documents/jecfa/jecmono/v36je01.htm
HPLC analysis of metabolites of (14)C-ceftiofur formed by arochlor-induced rat liver S-9 fractions in vitro revealed that desfuroylceftiofur was the major metabolite. Low doses (119 mg/kg bw) of ceftiofur were completely metabolized within 15 minutes. Higher doses (857 mg/kg bw) were converted to desfuroylceftiofur after 60 minutes of incubation.
Joint FAO/WHO Expert Committee on Food Additives; WHO Food Additive Series 36: Toxicological Evaluation of Certain Veterinary Drug Residues in Food: Ceftiofur (1996). Available from, as of July 17, 2006: https://www.inchem.org/documents/jecfa/jecmono/v36je01.htm
A study in 8-week old Sprague-Dawley rats (7/sex) treated with (14)C-ceftiofur (800 mg/kg bw/day) by oral gavage for 5 days revealed several urinary metabolites, including desfuroylceftiofur, ceftiofur sulfoxide, and cysteine disulfide.
Joint FAO/WHO Expert Committee on Food Additives; WHO Food Additive Series 36: Toxicological Evaluation of Certain Veterinary Drug Residues in Food: Ceftiofur (1996). Available from, as of July 17, 2006: https://www.inchem.org/documents/jecfa/jecmono/v36je01.htm
For more Metabolism/Metabolites (Complete) data for CEFTIOFUR (15 total), please visit the HSDB record page.

9.5 Biological Half-Life

Six Friesian calves (3/sex) were treated with ceftiofur according to different protocols including one single im and iv injection at 1 mg/kg bw, and 5 i.m. injections at 1 mg/kg bw at 24 hr intervals. ... The half life (0.07 hr) was short due to rapid metabolism to desfuroylceftiofur. The t1/2 of desfuroylceftiofur after im and iv administration were similar (9.7 and 8.6 hr, respectively).
Joint FAO/WHO Expert Committee on Food Additives; WHO Food Additive Series 36: Toxicological Evaluation of Certain Veterinary Drug Residues in Food: Ceftiofur (1996). Available from, as of July 17, 2006: https://www.inchem.org/documents/jecfa/jecmono/v36je01.htm
A study of 4 calves (sex and breed unspecified) administered ceftiofur intramuscularly daily for 4 days at 2 dose levels (2.2 or 4.4 mg/kg bw/day) demonstrated a plasma half life of 3.5 hr. ... Plasma half life of the metabolite desfuroylceftiofur was 9.7 h after im administration.
Joint FAO/WHO Expert Committee on Food Additives; WHO Food Additive Series 36: Toxicological Evaluation of Certain Veterinary Drug Residues in Food: Ceftiofur (1996). Available from, as of July 17, 2006: https://www.inchem.org/documents/jecfa/jecmono/v36je01.htm
A study of 4- to 5-month old Yorkshire-Hampshire pigs (6/sex) treated with 3 daily im injections of (14)C-ceftiofur (5.2 mg/kg bw) produced similar results to those observed in rats and cattle. ... The half life of desfuroylceftiofur was 13.5 hr after im treatment and 12.2 hr after iv treatment. /Desfuroylceftiofur/
Joint FAO/WHO Expert Committee on Food Additives; WHO Food Additive Series 36: Toxicological Evaluation of Certain Veterinary Drug Residues in Food: Ceftiofur (1996). Available from, as of July 17, 2006: https://www.inchem.org/documents/jecfa/jecmono/v36je01.htm

9.6 Mechanism of Action

Ceftiofur sodium is a third generation broad-spectrum cephalosporin, formulated as an intramuscular injection, which is used to treat respiratory diseases in swine, ruminants and horses. The thioester bond on ceftiofur is rapidly cleaved to give desfuroylceftiofur which is further metabolized to a disulfide dimer and various desfuroylceftiofur-protein and amino acid conjugates.
Jacobson GA; Journal of Pharmaceutical and Biomedical Analysis 40 (5): 1249-1252 (2006)
Cephalosporins ... bind to penicillin-binding proteins located beneath the cell wall and thereby interfere with the action of transpeptidase and other cell-wall enzymes. A residual antibacterial effect is also evident with the cephalosporins. /Cephalosporins/
Kahn, C.M. (Ed.); The Merck Veterinary Manual 9th ed. Merck & Co. Whitehouse Station, NJ. 2005, p. 2063

10 Use and Manufacturing

10.1 Uses

Vet: Antibacterial ... moderatley active against gram-positive bacteria ... are active against gram-negative bacteria ... highly resistant to beta-lactamase enzymes /Third-generation cephalosporins/
Aiello, S.E. (ed). The Merck Veterinary Manual. 8th ed. Merck & Co., Inc., National Publishing Inc., Philadelphia, PA. 1998., p. 1751
Mesh Heading: anti-bacterial agents
National Library of Medicine, SIS; ChemIDplus Record for Ceftiofur (80370-57-6). Available from, as of July 21, 2006: https://chem.sis.nlm.nih.gov/chemidplus/chemidlite.jsp

10.1.1 Use Classification

Veterinary drugs -> Antibacterials for systemic use -> Veterinary pharmacotherapeutic group -> EMA Drug Category
Veterinary Drug -> ANTIMICROBIAL_AGENT; -> JECFA Functional Classes

10.2 Methods of Manufacturing

... B. Labeeuw, A. Salhi, European patent 36812; ... US patent 4464367 (1981, 1984 both to Sanofi).
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. 334

10.3 Formulations / Preparations

Veterinary-labeled product(s): 50 mg per mL (Rx) (Naxcel). /Ceftiofur sodium for injection/
Thomson/Micromedex. USP Veterinary Pharmaceutical Information Monographs: Cephalolsporins (2003). Available from, as of July 26, 2006: https://www.usp.org/audiences/veterinary/monographs/main.html
Veterinary-labeled product(s): 50 mg per mL (Rx) (Excenel RTU). /Ceftiofur hydrochloride injection/
Thomson/Micromedex. USP Veterinary Pharmaceutical Information Monographs: Cephalolsporins (2003). Available from, as of July 26, 2006: https://www.usp.org/audiences/veterinary/monographs/main.html

10.4 General Manufacturing Information

... approved for use in cows and dogs
Aiello, S.E. (ed). The Merck Veterinary Manual. 8th ed. Merck & Co., Inc., National Publishing Inc., Philadelphia, PA. 1998., p. 1751

11 Identification

11.1 Clinical Laboratory Methods

Analyte: ceftiofur; matrix: milk; procedure: high-performance liquid chromatography with ultraviolet detection at 295 nm; limit of quantitation: 2-5 ppb
Moats WA, Harik-Khan R; J AOAC Int 78: 49-54 (1995). As cited in: Lunn G; HPLC Methods for Pharmaceutical Analysis. Volumes 2-4. New York, NY: John Wiley & Sons, 2000., p.1162
Analyte: ceftiofur; matrix: milk; procedure: high-performance liquid chromatography with ultraviolet detection at 210 nm
Zomer E et al; J AOAC Int 78: 1165-1172 (1995). As cited in: Lunn G, Schmuff N; HPLC Methods for Pharmaceutical Analysis. New York, NY: John Wiley & Sons, 1997., p.270
Analyte: ceftiofur; matrix: blood, milk; procedure: high-performance liquid chromatography with ultraviolet detection at 265.8 nm; limit of detection: 50 ppb
Tyczkowska KL et al; J Chromatogr 614: 123-134 (1993). As cited in: Lunn G; HPLC Methods for Pharmaceutical Analysis. Volumes 2-4. New York, NY: John Wiley & Sons, 2000., p.1160
Analyte: ceftiofur; matrix: milk; procedure: high-performance liquid chromatography with ultraviolet detection at 293 nm; limit of detection: 4 ppb
McNeilly PJ et al; J AOAC Int 79: 844-847 (1996). As cited in: Lunn G; HPLC Methods for Pharmaceutical Analysis. Volumes 2-4. New York, NY: John Wiley & Sons, 2000., p.1160
For more Clinical Laboratory Methods (Complete) data for CEFTIOFUR (7 total), please visit the HSDB record page.

12 Safety and Hazards

12.1 Hazards Identification

12.1.1 GHS Classification

Note
This chemical does not meet GHS hazard criteria for 100% (2 of 2) of all reports. Pictograms displayed are for < 0.1% (0 of 2) of reports that indicate hazard statements.
GHS Hazard Statements

Not Classified

Reported as not meeting GHS hazard criteria by 2 of 2 companies. For more detailed information, please visit ECHA C&L website.

ECHA C&L Notifications Summary

Aggregated GHS information provided per 2 reports by companies from 1 notifications to the ECHA C&L Inventory.

Reported as not meeting GHS hazard criteria per 2 of 2 reports by companies. For more detailed information, please visit ECHA C&L website.

There are 0 notifications provided by 0 of 2 reports by companies with hazard statement code(s).

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

Not Classified

12.2 Accidental Release Measures

12.2.1 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.

12.3 Handling and Storage

12.3.1 Storage Conditions

Store unreconstituted product at controlled room temperature, 20 to 25 °C (68 to 77 °F), unless otherwise specified by manufacturer. Store reconstituted product either in a refrigerator at 2 to 8 °C (36 to 46 °F) for up to seven days or at controlled room temperature, 20 to 25 °C (68 to 77 °F), for up to twelve hours, unless otherwise specified by manufacturer. Protect from light. /Ceftiofur sodium for injection/
Thomson/Micromedex. USP Veterinary Pharmaceutical Information Monographs: Cephalolsporins (2003). Available from, as of July 26, 2006: https://www.usp.org/audiences/veterinary/monographs/main.html
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from freezing. /Ceftiofur hydrochloride injection/
Thomson/Micromedex. USP Veterinary Pharmaceutical Information Monographs: Cephalolsporins (2003). Available from, as of July 26, 2006: https://www.usp.org/audiences/veterinary/monographs/main.html

12.4 Exposure Control and Personal Protection

12.4.1 Acceptable Daily Intakes

Acceptable daily intake and acceptable single-dose intake-(1) Acceptable daily intake (ADI). The ADI for total residues of ceftiofur is 30 micrograms per kilogram of body weight per day. (2) Acceptable single-dose intake (ASDI). The ASDI total residues of ceftiofur is 0.830 milligrams per kilogram of body weight. The ASDI is the amount of total residues of ceftiofur that may safely be consumed in a single meal. The ASDI is used to derive the tolerance for residues of desfuroylceftiofur at the injection site.
21 CFR 556.113; U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of June 21, 2006: https://www.ecfr.gov

12.4.2 Allowable Tolerances

Tolerances-(1) Poultry, and sheep. A tolerance for residues of ceftiofur in edible tissue is not required. (2) Swine. The tolerances for desfuroylceftiofur (marker residue) are: (i) Kidney (target tissue). 0.25 parts per million (ppm). (ii)Liver. 3 ppm. (iii) Muscle. 2 ppm. (3) Cattle. The tolerances for desfuroylceftiofur (marker residue) are: (i) Kidney (target tissue). 0.4 ppm. (ii) Liver. 2 ppm. (iii)Muscle. 1 ppm. (iv) Milk. 0.1 ppm.
21 CFR 556.113; U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of June 21, 2006: https://www.ecfr.gov

12.5 Regulatory Information

New Zealand EPA Inventory of Chemical Status
Ceftiofur: Does not have an individual approval but may be used under an appropriate group standard

12.5.1 FDA Requirements

Implantation or injectable dosage form new animal drugs. Ceftiofur crystalline free acid. ... (1) Swine. Indications for use: For the treatment of swine respiratory disease (SRD) associated with Actinobacillus pleuropneumoniae, Pasteurella multocida, Haemophilus parasuis, and Streptococcus suis. ... (2) Cattle. Indications for use. For the treatment of bovine respiratory disease (BRD, shipping fever, pneumonia) associated with Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni in beef, non-lactating dairy, and lactating dairy cattle. For the control of respiratory disease in beef and non-lactating dairy cattle which are at high risk of developing BRD associated with M. haemolytica, P. multocida, and H. somni. /Ceftiofur crystalline free acid/
21 CFR 552.313a; U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of June 21, 2006: https://www.ecfr.gov
Implantation or injectable dosage form new animal drugs. Ceftiofur hydrochloride. ... (1) Swine. Indications for use: For treatment and control of swine bacterial respiratory disease (swine bacterial pneumonia) associated with Actinobacillus pleuropneumoniae, Pasteurella multocida, Salmonella choleraesuis, and Streptococcus suis. ... (2) Cattle. Indications for use: For treatment of bovine respiratory disease (BRD, shipping fever, pneumonia) associated with Mannheimia haemolytica, P. multocida, and Histophilus somni; acute bovine interdigital necrobacillosis (foot rot, pododermatitis) associated with Fusobacterium necrophorum and Bacteroides melaninogenicus; and acute metritis (0 to 14 days post-partum) associated with bacteria susceptible to ceftiofur. /Ceftiofur hydrochloride/
21 CFR 552.313b; U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of June 21, 2006: https://www.ecfr.gov
Implantation or injectable dosage form new animal drugs. Ceftiofur sodium. ... (1) Swine. Indications for use: For treatment and control of swine bacterial respiratory disease (swine bacterial pneumonia) associated with Actinobacillus pleuropneumoniae, Pasteurella multocida, Salmonella choleraesuis, and Streptococcus suis. ... (2) Cattle. Indications for use: For treatment of bovine respiratory disease (shipping fever, pneumonia) associated with Mannheimia haemolytica, P. multocida, and Histophilus somni in beef and dairy cattle; and for treatment of acute bovine interdigital necrobacillosis (foot rot, pododermatitis) associated with Fusobacterium necrophorum and Bacteroides melaninogenicus. ... (3) Sheep. Indications for use: For treatment of sheep respiratory disease (pneumonia) associated with M. haemolytica and P. multocida. ... (4) Goats. Indications for use: For treatment of caprine respiratory disease (goat pneumonia) associated with M. haemolytica and P. multocida. ... (5) Chickens. Indications for use: For control of early mortality associated with Escherichia coli organisms susceptible to ceftiofur in day-old chicks. ... (6) Turkeys. Indications for use: For control of early mortality associated with E. coli organisms susceptible to ceftiofur in day-old poults. ... (7) Horses. Indications for use: For treatment of respiratory infections in horses associated with Streptococcus zooepidemicus. ... (8) Dogs. Indications for use: For treatment of canine urinary tract infections associated with E. coli and Proteus mirabilis. /Ceftiofur sodium/
21 CFR 552.313c; U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of June 21, 2006: https://www.ecfr.gov
Intramammary dosage forms. Ceftiofur. ... (1) Lactating cows. Indications for use. For the treatment of clinical mastitis in lactating dairy cattle associated with coagulase-negative staphylococci, Streptococcus dysgalactiae, and Escherichia coli. ... (2) Dry cows. For the treatment of subclinical mastitis in dairy cattle at the time of dry off associated with Staphylococcus aureus, Streptococcus dysgalactiae, and Streptococcus uberis.
21 CFR 313; U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of June 21, 2006: https://www.ecfr.gov
For more FDA Requirements (Complete) data for CEFTIOFUR (6 total), please visit the HSDB record page.

13 Toxicity

13.1 Toxicological Information

13.1.1 Antidote and Emergency Treatment

/SRP:/ 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
/SRP:/ 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

13.1.2 Non-Human Toxicity Excerpts

/LABORATORY ANIMALS: Acute Exposure/ In an inhalation study, ceftiofur was administered at an aerosol concentration of 8.3 mg/L to a group of 5 male and 5 female Sprague-Dawley rats for a 4-hr exposure period. During exposure, rats exhibited salivation, nasal discharge and dyspnea; these signs virtually disappeared within 1 hr after exposure. Post-exposure signs included diarrhea in 6 rats, and 1 rat exhibited a red encrusted material around the nares. Both gross and microscopic examination did not reveal any treatment-related changes.[Joint FAO/WHO Expert Committee on Food Additives; WHO Food Additive Series 36: Toxicological Evaluation of Certain Veterinary Drug Residues in Food: Ceftiofur (1996). Available from, as of July 17, 2006: http://www.inchem.org/documents/jecfa/jecmono/v36je01.htm]
/LABORATORY ANIMALS: Acute Exposure/ In an acute oral study, ceftiofur was administered as a single dose of up to 7800 mg/kg bw to groups of Sprague-Dawley rats (10/sex). Treatment-related diarrhea was noted at the 2 highest dose levels. No other treatment-related signs were observed.[Joint FAO/WHO Expert Committee on Food Additives; WHO Food Additive Series 36: Toxicological Evaluation of Certain Veterinary Drug Residues in Food: Ceftiofur (1996). Available from, as of July 17, 2006: http://www.inchem.org/documents/jecfa/jecmono/v36je01.htm]
/LABORATORY ANIMALS: Acute Exposure/ In studies in which cattle were given daily intramuscular injections of up to 55 mg/kg bw/day for 5 days and pigs were given dally intramuscular injections of up to 125 mg/kg bw/day for 5 days, transient injection site reactions were the most notable findings.[European Medicines Agency (EMEA), The European Agency for the Evaluation of Medicinal Products, Veterinary Medicines Evaluation Unit, Committee for Veterinary Medicinal Products; Ceftiofur, Summary Report (2). EMEA/MRL/498/98-Final (July 1999). Available from, as of July 21, 2006: http://www.ema.europa.eu/ema/index.jsp?curl=pages/document_library/landing/document_library_search.jsp&murl=menus/document_library/document_library.jsp&mid]
/LABORATORY ANIMALS: Acute Exposure/ The acute toxicity of ceftiofur was studied in groups of 5 female mice per dose, which were treated via the iv and im routes. In the iv study, convulsions preceded death while in the im study, mild prostration was noted.[Joint FAO/WHO Expert Committee on Food Additives; WHO Food Additive Series 36: Toxicological Evaluation of Certain Veterinary Drug Residues in Food: Ceftiofur (1996). Available from, as of July 17, 2006: http://www.inchem.org/documents/jecfa/jecmono/v36je01.htm]
For more Non-Human Toxicity Excerpts (Complete) data for CEFTIOFUR (20 total), please visit the HSDB record page.

13.1.3 Non-Human Toxicity Values

LD50 Mouse (female) im approximately 3400 mg/kg bw
Joint FAO/WHO Expert Committee on Food Additives; WHO Food Additive Series 36: Toxicological Evaluation of Certain Veterinary Drug Residues in Food: Ceftiofur (1996). Available from, as of July 17, 2006: https://www.inchem.org/documents/jecfa/jecmono/v36je01.htm
LD50 Mouse (female) iv approximately 2000 mg/kg bw
Joint FAO/WHO Expert Committee on Food Additives; WHO Food Additive Series 36: Toxicological Evaluation of Certain Veterinary Drug Residues in Food: Ceftiofur (1996). Available from, as of July 17, 2006: https://www.inchem.org/documents/jecfa/jecmono/v36je01.htm
LD50 Rat (female) 2200 mg/kg bw
Joint FAO/WHO Expert Committee on Food Additives; WHO Food Additive Series 36: Toxicological Evaluation of Certain Veterinary Drug Residues in Food: Ceftiofur (1996). Available from, as of July 17, 2006: https://www.inchem.org/documents/jecfa/jecmono/v36je01.htm
LD50 Rat (female) im 1250 mg/kg bw
Joint FAO/WHO Expert Committee on Food Additives; WHO Food Additive Series 36: Toxicological Evaluation of Certain Veterinary Drug Residues in Food: Ceftiofur (1996). Available from, as of July 17, 2006: https://www.inchem.org/documents/jecfa/jecmono/v36je01.htm
LC50 Rat inhalation > 8.3 mg/L/4 hr
Joint FAO/WHO Expert Committee on Food Additives; WHO Food Additive Series 36: Toxicological Evaluation of Certain Veterinary Drug Residues in Food: Ceftiofur (1996). Available from, as of July 17, 2006: https://www.inchem.org/documents/jecfa/jecmono/v36je01.htm

13.2 Ecological Information

13.2.1 Environmental Fate / Exposure Summary

Ceftiofur's production and use as a veterinary antibacterial medicine may result in its release to the environment through various waste streams. If released to air, an estimated vapor pressure of 6X10-20 mm Hg at 25 °C indicates ceftiofur will exist solely in the particulate phase in the atmosphere. Particulate-phase ceftiofur will be removed from the atmosphere by wet or dry deposition. Ceftiofur contains chromophores that absorb at wavelengths >290 nm indicating that this substance may be susceptible to direct photolysis by sunlight; however photodegradation of centiofur sodium has been reported to be minimal. If released to soil, ceftiofur is expected to have slight mobility based upon an estimated Koc of 3,700. An estimated pKa of 3.7 (carboxylic acid) indicates that this compound will exist primarily as an anion in the environment and anions generally have higher mobility in soils than their neutral counterparts. Volatilization from moist soil surfaces is not expected to be an important fate process because anions do not volatilize. Volatilization from dry soil surfaces is not expected based on the estimated vapor pressure. Half-lives reported for the aerobic biodegradation of cefiofur sodium in clay loam at pH 5, and at pH 7, and silty clay loam at pH 9 were 22.2, 49, and 41.1 days, respectively. If released into water, ceftiofur is expected to adsorb to suspended solids and sediment based upon the estimated Koc; however, adsorption may be less than this Koc indicates since ceftiofur exists primarily as an anion in the environment and anions generally do not adsorb to sediments as strongly as their neutral counterparts. Volatilization is not expected to be an important fate process in water since anions do not volatilize. An estimated BCF of 3 suggests the potential for bioconcentration in aquatic organisms is low. Half-lives reported for the aqueous hydrolysis of ceftiofur sodium were 22.2 days at pH 5, 49 days at pH 7, and 41.1 days at pH 9. Occupational exposure to ceftiofur may occur through dermal contact with this compound at workplaces where ceftiofur is produced or used. Exposure of the general population is expected to be limited to those who administer this substance to animals and those who eat foods made from animals containing residues of this substance. (SRC)

13.2.2 Artificial Pollution Sources

Ceftiofur's production and use as a veterinary antibacterial medicine(1,2) may result in its release to the environment through various waste streams(SRC).
(1) O'Neil MJ ed; The Merck Index. 13th ed. Whitehouse Station, NJ: Merck and Co., Inc. p 334 (2001)
(2) Aiello SE, Mays A; The Merck Veterinary Manual. 8th. Whitehouse Station, N.J.: Merck & Co., in cooperation with Merial Limited. p.1752 (1998)

13.2.3 Environmental Fate

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 3,700(SRC), determined from a structure estimation method(2), indicates that ceftiofur is expected to have slight mobility in soil(SRC). An estimated pKa of 3.7 (carboxylic acid)(SRC), calculated using a method based on linear free energy relationships and perturbed molecular orbital theory(3), indicates that this compound will exist primarily as an anion in the environment and anions generally have higher mobility in soils than their neutral counterparts(4). Volatilization of ceftiofur from moist soil surfaces is not expected to be an important fate process(SRC) since anions do not volatilize. Ceftiofur is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 6X10-20 mm Hg(SRC), determined from a fragment constant method(6). Half-lives reported for the aerobic biodegradation of cefiofur sodium in clay loam at pH 5, sand at pH 7, and silty clay loam at pH 9 were 22.2, 49, and 41.1 days, respectively(7-9).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) Meylan WM et al; Environ Sci Technol 26: 1560-67 (1992)
(3) SPARC; pKa/property server. Ver 3. Jan, 2006. Available at https://ibmlc2.chem.uga.edu/sparc/ as of Apr 20, 2006.
(4) Doucette WJ; pp. 141-188 in Handbook of Property Estimation Methods for Chemicals. Boethling RS, Mackay D, eds. Boca Raton, FL: Lewis Publ (2000)
(5) Meylan WM, Howard PH; Environ Toxicol Chem 10: 1283-93 (1991)
(6) Lyman WJ; p. 31 in Environmental Exposure From Chemicals Vol I, Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985)
(7) Boxall ABA et al; Rev Environ Contam Toxicol 180: 1-91
(8) Halling-Sorensen B et al; Chemosphere 36: 357-93 (1998)
(9) Thiele-Bruhn S; J Plant Nutr Soil Sci 166: 145-167 (2003)
AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 3,700(SRC), determined from a structure estimation method(2), indicates that ceftiofur is expected to adsorb to suspended solids and sediment(SRC). However, an estimated pKa of 3.7 (carboxylic acid)(SRC), calculated using a method based on linear free energy relationships and perturbed molecular orbital theory(3), indicates that this compound will exist primarily as an anion in the environment, and anions do not adsorb to sediment as strongly as their neutral counterparts(4). Volatilization from water surfaces is not expected because anions do not volatilize. According to a classification scheme(5), an estimated BCF of 3(SRC), from an estimated log Kow of 1.6(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Half-lives reported for the aqueous hydrolysis of ceftiofur sodium were 22.2 days at pH 5, 49 days at pH 7, and 41.1 days at pH 9(8,9). Half-lives reported for the aerobic biodegradation of ceftiofur sodium in clay loam at pH 5, sand at pH 7, and silty clay loam at pH 9 were 22.2, 49, and 41.1 days, respectively(8-10).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) Meylan WM et al; Environ Sci Technol 26: 1560-67 (1992)
(3) SPARC; pKa/property server. Ver 3. Jan, 2006. Available at https://ibmlc2.chem.uga.edu/sparc/ as of Apr 20, 2006.
(4) Doucette WJ; pp. 141-188 in Handbook of Property Estimation Methods for Chemicals. Boethling RS, Mackay D, eds. Boca Raton, FL: Lewis Publ (2000)
(5) Franke C et al; Chemosphere 29: 1501-14 (1994)
(6) Meylan WM, Howard PH; J Pharm Sci 84: 83-92 (1995)
(7) Meylan WM et al; Environ Toxicol Chem 18: 664-72 (1999)
(8) Boxall ABA et al; Rev Environ Contam Toxicol 180: 1-91
(9) Halling-Sorensen B et al; Chemosphere 36: 357-93 (1998)
(10) Thiele-Bruhn S; J Plant Nutr Soil Sci 166: 145-167 (2003)
ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), ceftiofur, which has an estimated vapor pressure of 6X10-20 mm Hg(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase ceftiofur may be removed from the air by wet or dry deposition(SRC). Ceftiofur contains chromophores that absorb at wavelengths >290 nm indicating that this substance may be susceptible to direct photolysis by sunlight(3); however photodegradation of ceftiofur sodium has been reported to be minimal(4).
(1) Bidleman TF; Environ Sci Technol 22: 361-367 (1988)
(2) Lyman WJ; p. 31 in Environmental Exposure From Chemicals Vol I, Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985)
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 8-12 (1990)
(4) Halling-Sorensen B et al; Chemosphere 36: 357-93 (1998)

13.2.4 Environmental Biodegradation

AEROBIC: Half-lives reported for the aerobic biodegradation of cefiofur sodium in clay loam at pH 5, sand at pH 7, and silty clay loam at pH 9 were 22.2, 49, and 41.1 days, respectively(1-3).
(1) Boxall ABA et al; Rev Environ Contam Toxicol 180: 1-91
(2) Halling-Sorensen B et al; Chemosphere 36: 357-93 (1998)
(3) Thiele-Bruhn S; J Plant Nutr Soil Sci 166: 145-167 (2003)

13.2.5 Environmental Abiotic Degradation

Half-lives reported for the aqueous hydrolysis of cefiofur sodium were 22.2 days at pH 5, 49 days at pH 7, and 41.1 days at pH 9(1,2). Ceftiofur contains chromophores that absorb at wavelengths >290 nm indicating that this substance may be susceptible to direct photolysis by sunlight(3); however photodegradation of ceftiofur sodium has been reported to be minimal(4); data supporting this conclusion were not provided by the authors.
(1) Boxall ABA et al; Rev Environ Contam Toxicol 180: 1-91 (2004)
(2) Halling-Sorensen et al; Chemosphere 36: 357-93 (1998)
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 8-12 (1990)
(4) Halling-Sorensen B et al; Chemosphere 36: 357-93 (1998)

13.2.6 Environmental Bioconcentration

An estimated BCF of 3 was calculated for ceftiofur(SRC), using an estimated log Kow of 1.6(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).
(1) Meylan WM, Howard PH; J Pharm Sci 84: 83-92 (1995)
(2) Meylan WM et al; Environ Toxicol Chem 18: 664-72 (1999)
(3) Franke C et al; Chemosphere 29: 1501-14 (1994)

13.2.7 Soil Adsorption / Mobility

Using a structure estimation method based on molecular connectivity indices(1), the Koc of ceftiofur can be estimated to be 3,700(SRC). According to a classification scheme(2), this estimated Koc value suggests that ceftiofur is expected to have slight mobility in soil. However, an estimated pKa of 3.7 (carboxylic acid)(SRC), calculated using a method based on linear free energy relationships and perturbed molecular orbital theory(3), indicates that this compound will exist primarily as an anion in the environment and anions generally have higher mobility in soils than their neutral counterparts(4).
(1) Meylan WM et al; Environ Sci Technol 26: 1560-67 (1992)
(2) Swann RL et al; Res Rev 85: 17-28 (1983)
(3) SPARC; pKa/property server. Ver 3. Jan, 2006. Available at https://ibmlc2.chem.uga.edu/sparc/ as of Apr 20, 2006.
(4) Doucette WJ; pp. 141-188 in Handbook of Property Estimation Methods for Chemicals. Boethling RS, Mackay D, eds. Boca Raton, FL: Lewis Publ (2000)

13.2.8 Volatilization from Water / Soil

An estimated pKa of 3.7 (carboxylic acid)(1), calculated using a method based on linear free energy relationships and perturbed molecular orbital theory(2), indicates that this compound will exist primarily as an anion in the environment. Volatilization from moist soil or water surfaces is not expected(SRC) since anions do not volatilize. Ceftiofur is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 6X10-20 mm Hg(SRC), determined from a fragment constant method(3).
(1) SPARC; pKa/property server. Ver 3. Jan, 2006. Available at https://ibmlc2.chem.uga.edu/sparc/ as of Apr 20, 2006.
(2) Hilal SH et al; pp. 291-353 in Quantitative Treatments of Solute/Solvent Interactions: Theoretical and Computational Chemistry Vol. 1 NY, NY: Elsevier (1994)
(3) Lyman WJ; p. 31 in Environmental Exposure From Chemicals Vol I, Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985)

13.2.9 Probable Routes of Human Exposure

Occupational exposure to ceftiofur may occur through dermal contact with this compound at workplaces where ceftiofur is produced or used. Exposure of the general population is expected to be limited to those who administer this substance to animals and those who eat foods made from animals containing residues of this substance. (SRC)

14 Literature

14.1 Consolidated References

14.2 NLM Curated PubMed Citations

14.3 Chemical Co-Occurrences in Literature

14.4 Chemical-Gene Co-Occurrences in Literature

14.5 Chemical-Disease Co-Occurrences in Literature

15 Patents

15.1 Depositor-Supplied Patent Identifiers

16 Interactions and Pathways

16.1 Drug-Drug Interactions

17 Biological Test Results

17.1 BioAssay Results

18 Classification

18.1 MeSH Tree

18.2 ChemIDplus

18.3 ChEMBL Target Tree

18.4 UN GHS Classification

18.5 NORMAN Suspect List Exchange Classification

18.6 CCSBase Classification

18.7 EPA DSSTox Classification

18.8 MolGenie Organic Chemistry Ontology

19 Information Sources

  1. CCSbase
    CCSbase Classification
    https://ccsbase.net/
  2. ChemIDplus
    (6R,7R)-7-((E)-2-(2-Aminothiazol-4-yl)-2-(methoxyimino)acetamido)-3-((furan-2-carbonylthio)methyl)-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid
    https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0120882204
    ChemIDplus Chemical Information Classification
    https://pubchem.ncbi.nlm.nih.gov/source/ChemIDplus
  3. DrugBank
    LICENSE
    Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode)
    https://www.drugbank.ca/legal/terms_of_use
  4. EPA DSSTox
    CompTox Chemicals Dashboard Chemical Lists
    https://comptox.epa.gov/dashboard/chemical-lists/
  5. European Chemicals Agency (ECHA)
    LICENSE
    Use of the information, documents and data from the ECHA website is subject to the terms and conditions of this Legal Notice, and subject to other binding limitations provided for under applicable law, the information, documents and data made available on the ECHA website may be reproduced, distributed and/or used, totally or in part, for non-commercial purposes provided that ECHA is acknowledged as the source: "Source: European Chemicals Agency, http://echa.europa.eu/". Such acknowledgement must be included in each copy of the material. ECHA permits and encourages organisations and individuals to create links to the ECHA website under the following cumulative conditions: Links can only be made to webpages that provide a link to the Legal Notice page.
    https://echa.europa.eu/web/guest/legal-notice
    (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-3-(furan-2-carbonylsulfanylmethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
    https://echa.europa.eu/substance-information/-/substanceinfo/100.214.921
    (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-3-(furan-2-carbonylsulfanylmethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid (EC: 688-302-4)
    https://echa.europa.eu/information-on-chemicals/cl-inventory-database/-/discli/details/220112
  6. FDA Global Substance Registration System (GSRS)
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
    (6R,7R)-7-((E)-2-(2-AMINOTHIAZOL-4-YL)-2-(METHOXYIMINO)ACETAMIDO)-3-((FURAN-2-CARBONYLTHIO)METHYL)-8-OXO-5-THIA-1-AZABICYCLO(4.2.0)OCT-2-ENE-2-CARBOXYLIC ACID
    https://gsrs.ncats.nih.gov/ginas/app/beta/substances/MAN163YXK8
  7. Hazardous Substances Data Bank (HSDB)
  8. New Zealand Environmental Protection Authority (EPA)
    LICENSE
    This work is licensed under the Creative Commons Attribution-ShareAlike 4.0 International licence.
    https://www.epa.govt.nz/about-this-site/general-copyright-statement/
  9. DailyMed
  10. NCI Thesaurus (NCIt)
    LICENSE
    Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source.
    https://www.cancer.gov/policies/copyright-reuse
  11. European Medicines Agency (EMA)
    LICENSE
    Information on the European Medicines Agency's (EMA) website is subject to a disclaimer and copyright and limited reproduction notices.
    https://www.ema.europa.eu/en/about-us/legal-notice
  12. Joint FAO/WHO Expert Committee on Food Additives (JECFA)
    LICENSE
    Permission from WHO is not required for the use of WHO materials issued under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Intergovernmental Organization (CC BY-NC-SA 3.0 IGO) licence.
    https://www.who.int/about/policies/publishing/copyright
  13. Japan Chemical Substance Dictionary (Nikkaji)
  14. 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
  15. MassBank Europe
  16. Metabolomics Workbench
  17. NLM RxNorm Terminology
    LICENSE
    The RxNorm Terminology is created by the National Library of Medicine (NLM) and is in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from NLM. Credit to the U.S. National Library of Medicine as the source is appreciated but not required. The full RxNorm dataset requires a free license.
    https://www.nlm.nih.gov/research/umls/rxnorm/docs/termsofservice.html
  18. Wikipedia
  19. PubChem
  20. 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
  21. GHS Classification (UNECE)
  22. 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
  23. 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/
    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
  24. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
CONTENTS