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Beta-Carotene

PubChem CID
5280489
Structure
Beta-Carotene_small.png
Beta-Carotene_3D_Structure.png
Beta-Carotene__Crystal_Structure.png
Molecular Formula
Synonyms
  • beta-carotene
  • 7235-40-7
  • beta Carotene
  • beta,beta-Carotene
  • Solatene
Molecular Weight
536.9 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2004-09-16
  • Modify:
    2025-01-18
Description
Beta-carotene is a cyclic carotene obtained by dimerisation of all-trans-retinol. A strongly-coloured red-orange pigment abundant in plants and fruit and the most active and important provitamin A carotenoid. It has a role as a biological pigment, a provitamin A, a plant metabolite, a human metabolite, a mouse metabolite, a cofactor, a ferroptosis inhibitor and an antioxidant. It is a cyclic carotene and a carotenoid beta-end derivative.
Beta-carotene, with the molecular formula C40H56, belongs to the group of carotenoids consisting of isoprene units. The presence of long chains of conjugated double bonds donates beta-carotene with specific colors. It is the most abundant form of carotenoid and it is a precursor of the vitamin A. Beta-carotene is composed of two retinyl groups. It is an antioxidant that can be found in yellow, orange and green leafy vegetables and fruits. Under the FDA, beta-carotene is considered as a generally recognized as safe substance (GRAS).
Beta-Carotene has been reported in Planktothrix rubescens, Mauritia flexuosa, and other organisms with data available.
See also: Lycopene (part of); Broccoli (part of); Lycium barbarum fruit (part of).

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Beta-Carotene.png

1.2 3D Conformer

1.3 Crystal Structures

CCDC Number
Crystal Structure Data
Crystal Structure Depiction
Crystal Structure Depiction

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

1,3,3-trimethyl-2-[(1E,3E,5E,7E,9E,11E,13E,15E,17E)-3,7,12,16-tetramethyl-18-(2,6,6-trimethylcyclohexen-1-yl)octadeca-1,3,5,7,9,11,13,15,17-nonaenyl]cyclohexene
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

2.1.2 InChI

InChI=1S/C40H56/c1-31(19-13-21-33(3)25-27-37-35(5)23-15-29-39(37,7)8)17-11-12-18-32(2)20-14-22-34(4)26-28-38-36(6)24-16-30-40(38,9)10/h11-14,17-22,25-28H,15-16,23-24,29-30H2,1-10H3/b12-11+,19-13+,20-14+,27-25+,28-26+,31-17+,32-18+,33-21+,34-22+
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.3 InChIKey

OENHQHLEOONYIE-JLTXGRSLSA-N
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.4 SMILES

CC1=C(C(CCC1)(C)C)/C=C/C(=C/C=C/C(=C/C=C/C=C(/C=C/C=C(/C=C/C2=C(CCCC2(C)C)C)\C)\C)/C)/C
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C40H56
Computed by PubChem 2.2 (PubChem release 2021.10.14)

2.3 Other Identifiers

2.3.1 CAS

7235-40-7

2.3.2 Deprecated CAS

116-32-5, 2321332-51-6, 31797-85-0
116-32-5, 2321332-51-6, 2519474-91-8, 31797-85-0
116-32-5

2.3.3 European Community (EC) Number

230-636-6

2.3.4 UNII

2.3.5 ChEBI ID

2.3.6 ChEMBL ID

2.3.7 DrugBank ID

2.3.8 DSSTox Substance ID

2.3.9 HMDB ID

2.3.10 KEGG ID

2.3.11 Lipid Maps ID (LM_ID)

2.3.12 Metabolomics Workbench ID

2.3.13 NCI Thesaurus Code

2.3.14 Nikkaji Number

2.3.15 NSC Number

2.3.16 Pharos Ligand ID

2.3.17 RXCUI

2.3.18 Wikidata

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • BellaCarotin
  • beta Carotene
  • beta-Carotene
  • Betacarotene
  • Carotaben
  • Carotene, beta
  • Max Caro
  • Max-Caro
  • MaxCaro
  • Provatene
  • Solatene
  • Vetoron

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
536.9 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
XLogP3
Property Value
13.5
Reference
Computed by XLogP3 3.0 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
0
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Acceptor Count
Property Value
0
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
10
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
536.438201786 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
536.438201786 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
0 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
40
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
1120
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
0
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
9
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 Physical Description

Red to brownish-red crystals or crystalline powder
Red, brownish-red or purple-violet crystals or crystalline powder (colour varies according to extraction solvent used and conditions of crystallisation)
Deep purple or red solid; [Merck Index]
Solid

3.2.2 Color / Form

Deep purple, hexagonal prisms from benzene and methanol
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. 313
Red, rhombic, almost square leaflets from petroleum ether; dil soln are yellow
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. 313
CRYSTALLINE FORM APPEARS DEEP ORANGE OR COPPER-COLORED
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 939
Red-brown hexagonal prisms from benzene and methanol
Lide, D.R. CRC Handbook of Chemistry and Physics 86TH Edition 2005-2006. CRC Press, Taylor & Francis, Boca Raton, FL 2005, p. 3-88

3.2.3 Boiling Point

633-577ºC
UCSD
654.00 to 657.00 °C. @ 760.00 mm Hg
The Good Scents Company Information System

3.2.4 Melting Point

176-184ºC
'MSDS'
183 °C (evacuated tube)
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. 313
183 °C

3.2.5 Solubility

0.0006 g/l at 25ºC
'MSDS'
Sol in benzene, chloroform, carbon disulfide; moderately sol in ether, petroleum ether, oils; 100 ml hexane dissolve 109 mg at 0 °C; very sparingly sol in methanol and ethanol; practically insol in water, acids, alkalies
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. 313
SOL IN FAT SOLVENTS
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 939
Soluble in acetone
Lide, D.R. CRC Handbook of Chemistry and Physics 86TH Edition 2005-2006. CRC Press, Taylor & Francis, Boca Raton, FL 2005, p. 3-88
Soluble in vegetable oils
Ashford, R.D. Ashford's Dictionary of Industrial Chemicals. London, England: Wavelength Publications Ltd., 1994., p. 179
For more Solubility (Complete) data for BETA-CAROTENE (7 total), please visit the HSDB record page.
0.6 mg/mL

3.2.6 Density

1.00 at 20 °C/20 °C
Lide, D.R. CRC Handbook of Chemistry and Physics 86TH Edition 2005-2006. CRC Press, Taylor & Francis, Boca Raton, FL 2005, p. 3-88

3.2.7 LogP

17.62
US EPA

3.2.8 Stability / Shelf Life

ABSORBS OXYGEN FROM AIR GIVING RISE TO INACTIVE, COLORLESS OXIDATION PRODUCTS
Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989., p. 282

3.2.9 Other Experimental Properties

Sensitive to alkali and very sensitive to air and light, particularly at high temperatures.
Kirk-Othmer Encyclopedia of Chemical Technology. 4th ed. Volumes 1: New York, NY. John Wiley and Sons, 1991-Present., p. V6: 927 (1993)
UV: 7-1258 (Organic Electronic Spectral Data, Phillips et al, John Wiley & Sons, New York) /Alpha-carotene/
Weast, R.C. and M.J. Astle. CRC Handbook of Data on Organic Compounds. Volumes I and II. Boca Raton, FL: CRC Press Inc. 1985., p. V1 403
UV: 7-1258 (Organic Electronic Spectral Data, Phillips et al, John Wiley & Sons, New York) /Gamma-carotene/
Weast, R.C. and M.J. Astle. CRC Handbook of Data on Organic Compounds. Volumes I and II. Boca Raton, FL: CRC Press Inc. 1985., p. V1 403

3.3 SpringerMaterials Properties

3.4 Chemical Classes

Biological Agents -> Vitamins and Derivatives
pigment
S75 | CyanoMetDB | Comprehensive database of secondary metabolites from cyanobacteria | DOI:10.5281/zenodo.4551528 | DOI:10.1093/pcp/pcw143 PMID:27519311

3.4.1 Drugs

Pharmaceuticals -> Listed in ZINC15
S55 | ZINC15PHARMA | Pharmaceuticals from ZINC15 | DOI:10.5281/zenodo.3247749
3.4.1.1 Human Drugs
Breast Feeding; Lactation; Milk, Human; Complementary Therapies; Carotenoids; Food; Vitamins
Human drug -> Discontinued
Human drug -> Active ingredient (BETA CAROTENE)

3.4.2 Cosmetics

Skin conditioning; Cosmetic colorant
S13 | EUCOSMETICS | Combined Inventory of Ingredients Employed in Cosmetic Products (2000) and Revised Inventory (2006) | DOI:10.5281/zenodo.2624118

3.4.3 Food Additives

Foods, Drugs, Cosmetics -> FDA Regulatory Status of Color Additives
ANTIOXIDANT, COLOR OR COLORING ADJUNCT, FLAVOR ENHANCER, FLAVORING AGENT OR ADJUVANT, NUTRIENT SUPPLEMENT, PROCESSING AID, SURFACE-FINISHING AGENT -> FDA Substance added to food

3.4.4 Fragrances

Fragrance Ingredient (.beta.,.beta.-Carotene) -> IFRA transparency List

3.4.5 Lipids

Lipids -> Prenol Lipids [PR] -> Isoprenoids [PR01] -> C40 isoprenoids (tetraterpenes) [PR0107]

4 Spectral Information

4.1 1D NMR Spectra

4.1.1 1H NMR Spectra

1 of 2
Instrument Name
Varian CFT-20
Copyright
Copyright © 2009-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Source of Spectrum
Sigma-Aldrich Co. LLC.
Source of Sample
Sigma-Aldrich Co. LLC.
Catalog Number
855553
Copyright
Copyright © 2021-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2021 John Wiley & Sons, Inc. All Rights Reserved.
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4.1.2 13C NMR Spectra

1 of 2
Instrument Name
BRUKER HX-90
Copyright
Copyright © 2002-2024 Wiley-VCH Verlag GmbH & Co. KGaA. All Rights Reserved.
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2 of 2
Instrument Name
Bruker WH-90
Copyright
Copyright © 2002-2024 Wiley-VCH Verlag GmbH & Co. KGaA. All Rights Reserved.
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4.2 2D NMR Spectra

4.2.1 1H-13C NMR Spectra

2D NMR Spectra Type
1H-13C HSQC
Spectra ID
Instrument Type
Bruker
Frequency
600 MHz
Solvent
CDCl3
pH
7.00
Shifts [ppm] (F2:F1):Intensity
6.65:125.04:0.07, 6.63:130.02:0.07, 1.47:39.62:0.21, 6.15:126.68:0.06, 2.02:33.18:0.25, 1.97:12.83:0.16, 6.34:137.24:0.11, 6.37:137.27:0.10, 1.03:29.02:1.00, 1.62:19.27:0.14, 1.72:21.78:0.41, 6.15:137.79:0.12, 6.15:130.88:0.10, 6.25:132.45:0.15
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4.3 Mass Spectrometry

4.3.1 GC-MS

1 of 7
View All
NIST Number
68285
Library
Main library
Total Peaks
235
m/z Top Peak
43
m/z 2nd Highest
536
m/z 3rd Highest
69
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2 of 7
View All
NIST Number
68287
Library
Main library
Total Peaks
298
m/z Top Peak
536
m/z 2nd Highest
43
m/z 3rd Highest
69
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4.3.2 MS-MS

1 of 6
View All
Spectra ID
Instrument Type
FAB-EBEB (JMS-HX/HX 110A, JEOL)
Ionization Mode
Positive
Top 5 Peaks

536.5316 1

105.0893 1

119.0738 0.90

91.068 0.81

69.0671 0.69

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2 of 6
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Spectra ID
Ionization Mode
positive
Top 5 Peaks

444.388519 100

445.342072 30.19

281.320251 6

399.321381 5.60

255.197662 5.06

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Notes
instrument=Ion Trap

4.3.3 LC-MS

1 of 9
View All
Authors
da Silva KM, Iturrospe E, van de Lavoir M, Robeyns R, University of Antwerp, Belgium
Instrument
Agilent 6560 QTOF
Instrument Type
LC-ESI-QTOF
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
20 eV
Fragmentation Mode
CID
Column Name
Direct injection
Retention Time
0.325 min
Precursor m/z
536.4377
Precursor Adduct
[M]+
Top 5 Peaks

444.3765 999

105.0709 624

171.1159 550

107.0871 541

237.1633 519

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License
CC BY
2 of 9
View All
Authors
da Silva KM, Iturrospe E, van de Lavoir M, Robeyns R, University of Antwerp, Belgium
Instrument
Agilent 6560 QTOF
Instrument Type
LC-ESI-QTOF
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
10 eV
Fragmentation Mode
CID
Column Name
Direct injection
Retention Time
0.324 min
Precursor m/z
536.4377
Precursor Adduct
[M]+
Top 5 Peaks

536.4366 999

444.3743 836

161.1307 199

119.0857 194

445.3763 144

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License
CC BY

4.3.4 Other MS

1 of 5
View All
Other MS
MASS: 280 (Aldermaston, Eight Peak Index of Mass Spectra, UK) /Alpha-carotene/
Other MS
MASS: 280 (Aldermaston, Eight Peak Index of Mass Spectra, UK) /Gamma-carotene/
Other MS
MASS: 280 (Aldermaston, Eight Peak Index of Mass Spectra, UK); 68285 (NIST/EPA/MSDC Mass Spectral database, 1990 version
2 of 5
View All
Authors
Akimoto N, Graduate School of Pharmaceutical Sciences, Kyoto University and Maoka T, Research Institute for Production Development
Instrument
JMS-HX/HX 110A, JEOL
Instrument Type
FAB-EBEB
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
FAB
Collision Energy
3 kV
Precursor m/z
536.44
Precursor Adduct
[M]+*
Top 5 Peaks

536.5316 999

105.0893 999

119.0738 901

91.068 805

69.0671 689

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License
CC BY-SA
Reference
Akimoto, N.; Takashi, M.; Fujiwara, Y.; Hashimoto, K.; Analysis of carotenoids by FAB CID-MS2 (in Japanese). J. Mass Spectrom. Soc. Jpn. 2000, 48, 32-41. doi:10.5702/massspec.48.32

4.4 UV Spectra

Maximum in cyclohexane at 453 nm to 456 nm
Maximum in cyclohexane at 440 nm to 457 nm and 470 nm to 486 nm
Maximum in cyclohexane at 440 nm to 457 nm and 474 nm to 486 nm
Max absorption (chloroform): 497, 466 nm
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. 313
MAX ABSORPTION (BENZENE): 278 NM (LOG E= 4.30), 364 NM (LOG E= 4.62), 463 NM (LOG E= 5.10), 494 NM (LOG E= 4.77)
Weast, R.C. (ed.). Handbook of Chemistry and Physics. 60th ed. Boca Raton, Florida: CRC Press Inc., 1979., p. C-241
Max Absorption: 456, 484 nm (E=2500, 2200)(in ethanol)
Gerhartz, W. (exec ed.). Ullmann's Encyclopedia of Industrial Chemistry. 5th ed.Vol A1: Deerfield Beach, FL: VCH Publishers, 1985 to Present., p. VA27: 455 (1996)
UV: 7-1258 (Organic Electronic Spectral Data, Phillips et al, John Wiley & Sons, New York)
Lide, D.R., G.W.A. Milne (eds.). Handbook of Data on Organic Compounds. Volume I. 3rd ed. CRC Press, Inc. Boca Raton ,FL. 1994., p. 2072

4.5 IR Spectra

IR Spectra
IR: 21933 (Sadtler Research Laboratories Prism Collection) /Alpha-carotene/
IR Spectra
IR: 11591 (Sadtler Research Laboratories Prism Collection)

4.5.1 FTIR Spectra

1 of 2
Technique
KBr WAFER
Source of Sample
EASTMAN ORGANIC CHEMICALS, ROCHESTER, NEW YORK
Catalog Number
3702
Copyright
Copyright © 1980, 1981-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Instrument Name
Bruker IFS 85
Technique
KBr-Pellet
Copyright
Copyright © 1989, 1990-2024 Wiley-VCH Verlag GmbH & Co. KGaA. All Rights Reserved.
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4.5.2 ATR-IR Spectra

1 of 2
Instrument Name
Bio-Rad FTS
Technique
ATR-Neat (DuraSamplIR II)
Source of Spectrum
Forensic Spectral Research
Source of Sample
Spectrum Chemical Manufacturing Corp.
Catalog Number
CA200
Lot Number
XK0119
Copyright
Copyright © 2009-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Source of Sample
Aldrich
Catalog Number
855553
Copyright
Copyright © 2018-2024 Sigma-Aldrich Co. LLC. - Database Compilation Copyright © 2018-2024 John Wiley & Sons, Inc. All Rights Reserved.
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6 Chemical Vendors

7 Drug and Medication Information

7.1 Drug Indication

Beta-carotene is FDA approved to be used as a nutrient supplement and to be even added in infant formula as a source of vitamin A. It is also approved to be used as a color additive for food products, drugs (with the label of "only as a color additive") and cosmetics. It is used commonly for the reduction of photosensitivity in patients with erythropoietic protoporphyria and other photosensitivity diseases.

7.2 Drug Classes

Breast Feeding; Lactation; Milk, Human; Complementary Therapies; Carotenoids; Food; Vitamins

7.3 FDA Approved Drugs

7.4 FDA Orange Book

7.5 FDA National Drug Code Directory

7.6 Drug Labels

Active ingredient and drug
Active ingredient and drug

7.7 Clinical Trials

7.7.1 ClinicalTrials.gov

7.8 Therapeutic Uses

Antioxidants
National Library of Medicine's Medical Subject Headings online file (MeSH, 1999)
THERAPY WITH ORAL BETA-CAROTENE IN PATIENT WITH POLYMORPHOUS LIGHT ERUPTION; COMPLETE REMISSION OCCURRED IN 32% (6/19) TREATED WITH BETA-CAROTENE.
PARRISH JA ET AL; BR J DERMATOL 100 (2): 187 (1979)
MEDICATION (VET): VITAMIN A PRECURSOR FOR ALL SPECIES EXCEPT CATS.
Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989., p. 282
The effects of chronic oral administration of beta-carotene, a carotenoid partially metabolized to retinol, on plasma lipid concentrations have not been well studied; therefore, 61 subjects were studied over 12 mo while they were enrolled in a skin cancer prevention study in which patients were randomly assigned to receive either placebo (n = 30) or 50 mg beta-carotene/day orally (n = 31). At study entry and 1 yr later, fasting blood samples were obtained for measurement of triglycerides, total cholesterol, high density lipoprotein cholesterol, retinol, and beta-carotene. Retinol concentrations changed minimally in both groups; beta-carotene concentration increased an average of 12.1 + or - 47 nmol/L in the placebo group and 4279 + or - 657 nmol/l in the active treatment group. Both groups experienced similar small increases in triglyceride and total cholesterol concentrations and small decreases in high density lipoprotein cholesterol. Daily oral administration of 50 mg beta-carotene/day did not affect plasma lipid concentrations.
Nierenberg DW et al; Am J Clin Nutr 53 (3): 652-4 (1991)
For more Therapeutic Uses (Complete) data for BETA-CAROTENE (10 total), please visit the HSDB record page.

7.9 Drug Warnings

NOT EFFECTIVE AS SUNSCREEN IN NORMAL INDIVIDUALS & SHOULD NOT BE USED FOR THAT PURPOSE ... USED WITH CAUTION IN PT WITH IMPAIRED RENAL OR HEPATIC FUNCTION BECAUSE SAFE USE ... HAS NOT BEEN ESTABLISHED.
American Society of Hospital Pharmacists. Data supplied on contract from American Hospital Formulary Service and other current ASHP sources., p. 1976
Beta carotene is well tolerated. Carotenodermia is usually the only adverse effect. Patients should be forewarned that carotenodermia will develop after 2-6 weeks of therapy, usually first noticed as yellowness of the palms of the hands or soles of the feet and to a lesser extent of the face. Some patients may experience loose stools during beta carotene therapy, but this is sporadic and may not require discontinuance of therapy. Ecchymoses and arthralgia have been reported rarely
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 3555
Beta carotene should be used with caution in patients with impaired renal or hepatic function because safe use of the drug in the presence of these conditions has not been established. Although abnormally high blood concentrations of vitamin A do not occur during beta carotene therapy, patients receiving beta carotene should be advised against taking supplementary vitamin A because beta carotene will fulfill normal vitamin A requirements. Patients should be cautioned that large quantities of green or yellow vegetables or their juices or extracts are not suitable substitutes for crystalline beta carotene because consumption of excessive quantities of these vegetables may cause adverse effects such as leukopenia or menstrual disorders. Patients should be warned that the protective effect of beta carotene is not total and that they may still develop considerable burning and edema after sufficient exposure to sunlight. Each patient must establish his own time limit of exposure.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 3556
There are no adequate and controlled studies to date in humans. Beta carotene should be used during pregnancy only when the potential benefits justify the possible risks to the fetus. The effect of beta carotene on fertility in humans is not known.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 3556
For more Drug Warnings (Complete) data for BETA-CAROTENE (11 total), please visit the HSDB record page.

7.10 Biomarker Information

8 Food Additives and Ingredients

8.1 Food Additive Classes

JECFA Functional Classes
Food Additives -> COLOUR;

8.2 Food Additive Definition

EU Food Additive Definition
These specifications apply predominantly to all trans isomer of beta-carotene together with minor amounts of other carotenoids. Diluted and stabilised preparations may have different trans-cis isomer ratios.
EU Food Additive Definition
Plant carotenes are obtained by solvent extraction of strains of edible plants, carrots, vegetable oils, grass, alfalfa (lucerne) and nettle.; The main colouring principle consists of carotenoids of which beta-carotene accounts for the major part. Alpha, gamma-carotene and other pigments may be present. Besides the colour pigments, this substance may contain oils, fats and waxes naturally occurring in the source material.; Only the following solvents may be used in the extraction: acetone, methyl ethyl ketone, methanol, ethanol, propan-2-ol, hexane(9), dichloromethane and carbon dioxide.
EU Food Additive Definition
Obtained by a fermentation process using a mixed culture of the two sexual mating types (+) and (–) of strains of the fungusBlakeslea trispora. The beta-carotene is extracted from the biomass with ethyl acetate or isobutyl acetate followed by propan-2-ol and crystallised. The crystallised product consists mainly of trans beta-carotene. Because of the natural process approximately 3 % of the product consists of mixed carotenoids, which is specific for the product.
EU Food Additive Definition
Mixed carotenes may also be produced from strains of the algaeDunaliella salina, grown in large saline lakes located in Whyalla, South Australia. Beta-carotene is extracted using an essential oil. The preparation is a 20 to 30 % suspension in edible oil. The ratio of trans-cis isomers is in the range of 50/50 to 71/29.; The main colouring principle consists of carotenoids of which beta-carotene accounts for the major part. Alpha-carotene, lutein, zeaxanthin and beta-cryptoxanthin may be present. Besides the colour pigments, this substance may contain oils, fats and waxes naturally occurring in the source material.

8.3 FDA Substances Added to Food

Used for (Technical Effect)
ANTIOXIDANT, COLOR OR COLORING ADJUNCT, FLAVOR ENHANCER, FLAVORING AGENT OR ADJUVANT, NUTRIENT SUPPLEMENT, PROCESSING AID, SURFACE-FINISHING AGENT

8.4 Color Additive Status

Color Additive
Use
Foods, Drugs, Cosmetics
Restrictions
Foods generally. Ingested drugs generally. Externally applied drugs including eye area use. Cosmetics generally including eye area use.
End Note
2 - The year approved is based on the date listed in the "Confirmation of Effective Date" notice for the action as published in the Federal Register.
Color additive regulations in 21 eCFR
Other regulations in 21 eCFR

8.5 Associated Foods

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

1 of 2
Chemical Name
beta,beta-CAROTENE
Evaluation Year
2019
ADI
WITHDRAWN
Comments
The Committee reaffirmed the conclusion from the eighty-fourth meeting that rats are not an appropriate model for deriving an ADI for β-carotene due to the relatively low bioavailability of β-carotene in rats compared with humans. Therefore, the Committee withdrew the two group ADIs of 0–5 mg/kg bw for (1) the sum of the synthetic carotenoids β-carotene, β-apo-8′-carotenal and β-apo-8′-carotenoic acid methyl and ethyl esters and (2) synthetic β-carotene and β-carotene derived from Blakeslea trisporae, which were based on a no-observed-adverse-effect level (NOAEL) from a rat study. The Committee was unable to establish a group ADI for synthetic βcarotene, β-carotene derived from B. trispora, β-carotene-rich extract from D. salina, and β-apo-8′-carotenoic acid methyl and ethyl esters because a group ADI is applicable to the general population, which includes heavy smokers. The Committee noted that it is very unlikely that it will ever be possible to establish a group ADI because further data from the population of heavy smokers cannot be gathered ethically.
Tox Monograph
2 of 2
Chemical Name
CAROTENES (natural)
Evaluation Year
1989
ADI
NO ADI ALLOCATED
Tox Monograph

9 Pharmacology and Biochemistry

9.1 Pharmacodynamics

Oral administration of beta-carotene increases the serum concentration of beta-carotene by 60% but it does not change the concentration found in the heart, liver or kidneys. In vitro studies in hepatocytes have shown that beta-carotene ameliorates oxidative stress, enhances antioxidant activity and decreases apoptosis. Other than the antioxidant activities, some other actions have been correlated to beta-carotene. It is thought to have detoxifying properties, as well as to help increase resistance to inflammation and infection and increase immune response and enhance RNA production.

9.2 MeSH Pharmacological Classification

Provitamins
Precursor forms of vitamins. (See all compounds classified as Provitamins.)

9.3 ATC Code

S76 | LUXPHARMA | Pharmaceuticals Marketed in Luxembourg | Pharmaceuticals marketed in Luxembourg, as published by d'Gesondheetskeess (CNS, la caisse nationale de sante, www.cns.lu), mapped by name to structures using CompTox by R. Singh et al. (in prep.). List downloaded from https://cns.public.lu/en/legislations/textes-coordonnes/liste-med-comm.html. Dataset DOI:10.5281/zenodo.4587355

A - Alimentary tract and metabolism

A11 - Vitamins

A11C - Vitamin a and d, incl. combinations of the two

A11CA - Vitamin a, plain

A11CA02 - Betacarotene

D - Dermatologicals

D02 - Emollients and protectives

D02B - Protectives against uv-radiation

D02BB - Protectives against uv-radiation for systemic use

D02BB01 - Betacarotene

9.4 Bionecessity

Beta-carotene is a precursor to vitamin A, which is essential for normal function of the retina; in the form of retinal, it combines with opsin (red pigment in the retina) to form rhodopsin (visual purple), which is necessary for visual adaptation to darkness. It is also necessary for growth of bone, testicular and ovarian function, and embryonic development, and for regulation of growth and differentiation of epithelial tissues.
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2006.
Of 600 carotenoids from natural sources that have been characterized, fewer than 10% serve as precursors of vitamin A. Many dietary carotenoids, both with and without provitamin A activity, are found in the blood and tissues of humans. beta-Carotene, the most nutritionally active carotenoid, comprises 15-30% of total serum carotenoids. Vitamin A is formed primarily by the oxygen-dependent central cleavage of beta-carotene and other provitamin A carotenoids.
Bendich A, Olson JA; FASEB J 3 (8): 1927-32 (1989)

9.5 Absorption, Distribution and Excretion

Absorption
After administration of beta-carotene, some of the administered dose is absorbed into the circulatory system unchanged and stored in the fat tissue. The coadministration of beta-carotene and a high-fat content diet is correlated to a better absorption of beta-carotene. The absorption is also dependent on the isomeric form of the molecule where the cis conformation seems to present a higher bioavailability. The absorption of beta-carotene is thought to be performed in 6-7 hours. The reported AUC of beta-carotene when administered orally from 0 to 440 hours after initial administration was reported to be 26.3 mcg.h/L. The maximal concentration of beta-carotene is attained in a dual pharmacokinetic profile after 6 hours and again after 32 hours with a concentration of 0.58 micromol/L.
Route of Elimination
The unabsorbed carotene is excreted in feces. It is also excreted in feces and urine as metabolites. The consumption of dietary fiber can increase the fecal excretion of fats and other fat-soluble compounds such as beta-carotene.
Volume of Distribution
No pharmacokinetic studies have been performed regarding the volume of distribution of beta-carotene.
Clearance
The clearance rate of beta-carotene administered orally is 0.68 nmol/L each hour.
Carotenoids are absorbed and transported via lymphatics to the liver. They circulate in association with lipoproteins, and are found in liver, adrenal, testes, and adipose tissue, and can be converted to vitamin A in numerous tissues, including the liver. Some beta carotene is absorbed as such and circulates in association with lipoproteins; it apparently partitions into body lipids and can be converted to vitamin A in numerous tissues, including the liver.
Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001., p. 1781
Absorption of beta-carotene depends on the presence of dietary fat and bile in the intestinal tract.
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2006.
Unchanged beta-carotene is found in various tissues, primarily fat tissues, adrenal glands, and ovaries. Small concentrations are found in the liver.
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2006.
Only about one-third of beta-carotene or other carotenoids is absorbed by human beings. The absorption of carotenoids takes place in a relatively nonspecific fashion and depends upon the presence of bile and absorbable fat in the intestinal tract; it is greatly decreased by steatorrhea, chronic diarrhea, and very-low-fat diets.
Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001., p. 1781
For more Absorption, Distribution and Excretion (Complete) data for BETA-CAROTENE (9 total), please visit the HSDB record page.

9.6 Metabolism / Metabolites

Beta-carotene is broken down in the mucosa of the small intestine and liver by beta-carotene dioxygenase to retinal which is a form of vitamin A. The function of this enzyme is vital as it decides if the beta-carotene is transformed to vitamin A or if it circulates in the plasma as beta-carotene. Less than a quarter of the ingested beta-carotene from root vegetables and about half of the beta-carotene from leafy green vegetables are converted to vitamin A.
A portion of the beta-carotene is converted to retinol in the wall of the small intestine, principally by its initial cleavage at the 15,15' double bond to form two molecules of retinal. Some of the retinal is further oxidized to retinoic acid; only one-half is reduced to retinol, which is then esterified and transported in the lymph. ...
Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001., p. 1781
Approximately 20 to 60% of beta-carotene is metabolized to retinaldehyde and then converted to retinol, primarily in the intestinal wall. A small amount of beta-carotene is converted to vitamin A in the liver. The proportion of beta-carotene converted to vitamin A diminishes inversely to the intake of beta-carotene, as long as the dosages are higher than one to two times the daily requirements. High doses of beta-carotene do not lead to abnormally high serum concentrations of vitamin A.
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2006.
Beta carotene may be converted to 2 molecules of retinal by cleavage at the 15-15' double bond in the center of the molecule. Most of the retinal is reduced to retinol which is then conjugated with glucuronic acid and excreted in urine and feces. Some retinal may be further oxidized to retinoic acid which can be decarboxylated and further metabolized, secreted into bile, and excreted in feces as the glucuronide.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 3556
Two pathways have been suggested for the conversion of carotenoids to vitamin A in mammals, central cleavage and excentric cleavage. An enzyme, beta-carotenoid-15,15'-dioxygenase, has been partly purified from the intestines of several species and has been identified in several other organs and species. The enzyme, which converts beta-carotene into two molecules of retinal in good yield, requires molecular oxygen and is inhibited by sulfhydryl binding reagents and iron binding reagents. Most provitamin A carotenoids, including the beta-apo-carotenals, are cleaved to retinal by this enzyme. Its maximal activity in the rabbit is approximately 200 times that required to meet nutritional needs but is less than 50% of that expected to produce signs of vitamin A toxicity. Excentric cleavage unquestionably occurs in plants and some microorganisms and might occur in mammals. Thus far, however, carotenoid dioxygenase with excentric bond specificity has been identified in mammals, the yield of beta-apo-carotenals from beta-carotene in vivo and in vitro is very low, and beta-apo-carotenals are formed nonbiologically from beta-carotene.
Olson JA; J Nutr 119 (1): 105-8 (1989)
The carotenes are not converted to retinol very rapidly, so that overdoses of the carotenes do not cause vitamin A toxicity. /Carotenes/
Shoden & Griffin; Fundamentals of Clinical Nutrition: 77 (1980)

9.7 Biological Half-Life

The apparent half-life of beta-carotene is of 6-11 days after initial administration.

9.8 Mechanism of Action

Beta-carotene is an antioxidant that presents significant efficacy against the reactive oxygen species singlet oxygen. Beta-carotene acts as a scavenger of lipophilic radicals within the membranes of every cell compartments. It also presents an oxidative modification of LDL. The presence of long chains of conjugated double bonds is responsible for its antioxidative properties by allowing beta-carotene to chelate oxygen-free radicals and dissipate their energy. The chelation of free radicals inhibits the peroxidation of lipids. The effect of beta-carotene in the immune response is thought to be related to the direct effect on the thymus which increases the production of immune cells.
IN HEMATOPORPHYRIN PHOTOSENSITIZED MICE BETA-CAROTENE SHOWED PHOTOPROTECTION WAS DUE TO FREE RADICAL SCAVENGING OR SINGLET O QUENCHING BUT ALSO A POSSIBLE ROLE OF 400 NM LIGHT ABSORPTION, A PROPERTY OF BETA-CAROTENE.
MOSHELL AN, BJORNSON L; J INVEST DERMATOL 68 (3): 157 (1977)
Beta carotene protects patients with erythropoietic protoporphyria against severe photosensitivity reactions (burning sensation, edema, erythema, pruritus, and/or cutaneous lesions). The drug has no effect on the basic biochemical abnormality of erythropoietic protoporphyria (eg, erythrocyte, plasma, and stool concentrations of protoporphyrins are not altered by the drug). The precise mechanism by which the drug exerts photoprotection has not been established. There is some evidence that photosensitizers may act through the formation of singlet excited oxygen and/or free radicals. Since in vitro studies indicate that beta carotene can quench free radicals and singlet excited oxygen, this may be the mechanism by which the drug acts. It is unlikely that beta carotene acts simply as a filter for the wavelengths of light that induce phototoxic effects.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 3556
beta-Carotene inhibits UV-B carcinogenesis. beta-Carotene is an excellent quencher of singlet oxygen, and can quench free radicals. beta-Carotene has been shown to quench singlet oxygen/free radical reactions in the skin of porphyric mice, and has been found to quench excited species formed on irradiation of mouse skin by UV-B.
Black HS, Mathews-Roth MM; Photochem Photobiol 53 (5): 707-16 (1991)

9.9 Human Metabolite Information

9.9.1 Tissue Locations

  • Adipose Tissue
  • Adrenal Gland
  • Epidermis
  • Erythrocyte
  • Fibroblasts
  • Intestine
  • Liver
  • Placenta
  • Platelet
  • Prostate
  • Spleen

9.9.2 Cellular Locations

  • Cytoplasm
  • Extracellular
  • Membrane

9.9.3 Metabolite Pathways

9.10 Biochemical Reactions

10 Use and Manufacturing

10.1 Uses

EPA CPDat Chemical and Product Categories
The Chemical and Products Database, a resource for exposure-relevant data on chemicals in consumer products, Scientific Data, volume 5, Article number: 180125 (2018), DOI:10.1038/sdata.2018.125
Sources/Uses
The most important provitamin A; Found in plants and animals and used to color foods yellow, as an ultraviolet screen, and as a vitamin A precursor; [Merck Index] Used as flavoring agent, antioxidant, color, nutritional supplement, processing aid, and surface-finishing agent for foods; [FDA]
Merck Index - O'Neil MJ, Heckelman PE, Dobbelaar PH, Roman KJ (eds). The Merck Index, An Encyclopedia of Chemicals, Drugs, and Biologicals, 15th Ed. Cambridge, UK: The Royal Society of Chemistry, 2013.
Yellow coloring agent for foods.
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. 313
MEDICATION
Therapeutic Category: Vitamine A precursor. Ultraviolet screen.
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. 313
Therapeutic Category (Vet): Vitamin A precursor for all species except cats.
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. 313

Use (kg; approx.) in Germany (2009): >50

Consumption (g per capita; approx.) in Germany (2009): 0.000611

Calculated removal (%): 94

10.1.1 Use Classification

Food additives
Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients
Fragrance Ingredients
Food Additives -> COLOUR; -> JECFA Functional Classes
Cosmetics -> Skin conditioning; Cosmetic colorant
S13 | EUCOSMETICS | Combined Inventory of Ingredients Employed in Cosmetic Products (2000) and Revised Inventory (2006) | DOI:10.5281/zenodo.2624118

10.1.2 Household Products

Household & Commercial/Institutional Products

Information on 35 consumer products that contain beta-Carotene in the following categories is provided:

• Personal Care

10.2 Methods of Manufacturing

beta-Carotene is ... made by a microbial fermentation process from corn and soybean oil.
Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 12th ed. New York, NY: Van Nostrand Rheinhold Co., 1993, p. 226

10.3 Formulations / Preparations

Beta-carotene supplements are available as synthetic beta-carotene and natural beta-carotene. Synthetic beta-carotene is comprised mainly of all-trans beta-carotene with small amounts of 13-cis beta-carotene and even smaller amounts of 9-cis beta-carotene. Natural beta-carotene is principally derived from the algae Dunaliella salina and is comprised of all-trans beta-carotene and 9-cis beta-carotene. Three mg of beta-carotene is equal to 5,000 UIs. Supplemental intake of beta-carotene ranges from 3-15 mg/day.
Physicians Desk Reference (PDR) for Nutritional Supplements 1st ed, Medical Economics, Thomson Healthcare; Montvale, NJ (2001) p.42
GRADES: ACCORDING TO USP, UNITS OF VIT A, SOLD AS PURE CRYSTALS, AS SOLN IN VARIOUS OILS, AS COLLOIDAL DISPERSION. ALSO 'FOOD CHEMICAL CODEX' /CAROTENE/
Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 12th ed. New York, NY: Van Nostrand Rheinhold Co., 1993, p. 226
Oral: Capsules: 15 mg, 60 mg (available by nonproprietary name).
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 3556

10.4 General Manufacturing Information

EPA TSCA Commercial Activity Status
.beta.,.beta.-Carotene: ACTIVE
MOST IMPORTANT OF PROVITAMINS A. WIDELY DISTRIBUTED IN PLANT & ANIMAL KINGDOM. IN PLANTS IT OCCURS ALMOST ALWAYS TOGETHER WITH CHLOROPHYLL. ... COMMERCIAL CRYSTALLINE BETA-CAROTENE HAS A VIT A ACTIVITY OF 1.67 MILLION USP UNITS/G. THE IU OF 0.6 UG BETA-CAROTENE IS ALMOST EXACTLY EQUIV TO 0.3 UG VIT A.
Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989., p. 282
ONE IU OF VITMIN A IS SPECIFIC BIOLOGICAL ACTIVITY OF 0.3 UG OF ALL-TRANS-RETINOL OR 0.6 UG OF BETA-CAROTENE. BECAUSE OF RELATIVELY INEFFICIENT DIETARY UTILIZATION OF BETA-CAROTENE COMPARED WITH RETINOL, NOMENCLATURE IS IN THE TERMS OF RETINOL EQUIVALENTS, WHICH REPRESENTS 1 UG OF ALL-TRANS-RETINOL, 6 UG OF DIETARY BETA-CAROTENE, OR 12 UG OF OTHER PROVITAMIN A CAROTENOIDS.
Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001., p. 1782
... CONSISTS OF 3 ISOMERS, APPROX 15% ALPHA, 85% BETA, & 0.1% GAMMA. /CAROTENE/
Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 12th ed. New York, NY: Van Nostrand Rheinhold Co., 1993, p. 226
THEORETICALLY ONE MOLECULE OF BETA-CAROTENE SHOULD YIELD TWO MOLECULES OF VIT A1; HOWEVER, AVAILABILITY OF CAROTENE IN FOODS AS SOURCES OF VIT A FOR HUMANS IS LOW & EXTREMELY VARIABLE. ... UTILIZATION EFFICIENCY OF CAROTENE IS GENERALLY CONSIDERED TO BE 1/6 FOR HUMANS ... .
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 939
For more General Manufacturing Information (Complete) data for BETA-CAROTENE (6 total), please visit the HSDB record page.

11 Identification

11.1 Analytic Laboratory Methods

CHROMATOGRAPHY TO DETECT CAROTENOIDS ADDED FOR COLORING PURPOSES, IN MACARONI, NOODLES, FLOUR, SEMOLINA, & EGG YOLK. /CAROTENES/
Association of Official Analytical Chemists. Official Methods of Analysis. 10th ed. and supplements. Washington, DC: Association of Official Analytical Chemists, 1965. New editions through 13th ed. plus supplements, 1982., p. 13/230 14.156
Method: AOAC 941.15; Procedure: spectrophotometric method; Analyte: carotene; Matrix: fresh plant materials and silages; Detection Limit: not provided.
Horwitz W, ed.; Official Methods of Analysis of AOAC International 17th ed. (2003). CD-ROM, AOAC International, Gaithersburg, MD
Determination of alpha- and beta-carotene in some raw fruits and vegetables by HPLC.
Bushway RJ; J Agric Food Chem 34 (3): 409-12 (1986)
Analyte: beta-carotene; matrix: blood (serum); procedure: high-performance liquid chromatography with ultraviolet detection at 450 nm; limit of detection: 10 ng/mL
Steghens JR et al; J Chromatogr B 694: 71-81 (1997). As cited in: Lunn G; HPLC Methods for Pharmaceutical Analysis. Volumes 2-4. New York, NY: John Wiley & Sons, 2000, p.705
For more Analytic Laboratory Methods (Complete) data for BETA-CAROTENE (15 total), please visit the HSDB record page.

11.2 Clinical Laboratory Methods

Simultaneous quantitation and separation of carotenoids and retinol in human milk by HPLC.
Giuliano AR et al; Methods Enzymol 213 (ISS Carotenoids, Pt. A): 391-9 (1992)
Determination of retinol, alpha-tocopherol, and beta-carotene in serum by liquid chromatography.
MacCrehan WA; Methods Enzymol 189 (Retinoids, Pt. A): 172-81 (1990)

12 Safety and Hazards

12.1 Hazards Identification

12.1.1 GHS Classification

GHS Hazard Statements

Not Classified

Reported as not meeting GHS hazard criteria by 294 of 350 companies

ECHA C&L Notifications Summary

Aggregated GHS information provided per 350 reports by companies from 7 notifications to the ECHA C&L Inventory.

Reported as not meeting GHS hazard criteria per 294 of 350 reports by companies. For more detailed information, please visit ECHA C&L website.

There are 6 notifications provided by 56 of 350 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

12.1.3 Hazards Summary

No evidence of reproductive toxicity, embryotoxicity, or teratogenicity in experimental animals; [REPROTOX] Acceptable daily intake (ADI) of 0-5 mg/kg (applies to use as a coloring agent but not to use as a food supplement); [JECFA] May cause irritation; [Sigma-Aldrich MSDS] See Vitamin A.
REPROTOX - Scialli AR, Lione A, Boyle Padgett GK. Reproductive Effects of Chemical, Physical, and Biological Agents. Baltimore: The Johns Hopkins University Press, 1995.

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 below 40 °C (104 °F), preferably between 15 and 30 °C 59 and 86 °F), unless otherwise specified by manufacturer.
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2006.

12.4 Regulatory Information

The Australian Inventory of Industrial Chemicals
Chemical: .beta.,.beta.-Carotene
REACH Registered Substance
New Zealand EPA Inventory of Chemical Status
Beta Carotene: Does not have an individual approval but may be used under an appropriate group standard

12.4.1 FDA Requirements

Certification of this color additive when used as a food is not necessary for the protection of the public health and therefore batches thereof are exempt from the requirements of section 706(c) of the Federal Food, Drug, and Cosmetic Act.
21 CFR 73.95; U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of August 30, 2006: https://www.ecfr.gov
Certification of this color additive when used as a drug is not necessary for the protection of the public health and therefore batches thereof are exempt from the requirements of section 706(c) of the Federal Food, Drug, and Cosmetic Act.
21 CFR 73.1095; U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of August 30, 2006: https://www.ecfr.gov
Certification of this color additive when used as a cosmetic is not necessary for the protection of the public health and therefore batches thereof are exempt from the requirements of section 706(c) of the Federal Food, Drug, and Cosmetic Act.
21 CFR 73.2095; U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of August 30, 2006: https://www.ecfr.gov
Substance added directly to human food affirmed as generally recognized as safe (GRAS).
21 CFR 184.1245; U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of August 30, 2006: https://www.ecfr.gov
For more FDA Requirements (Complete) data for BETA-CAROTENE (7 total), please visit the HSDB record page.

12.5 Other Safety Information

12.5.1 Special Reports

Bendich A; The Safety of beta-Carotene. Nutr Cancer 11 (4): 207-14 (1988). Epidemiological studies have associated low dietary and/or plasma level of carotenoids with higher incidences of certain cancers. This evidence has led the NCI to initiate more than a dozen prospective clinical trials in which supplements of beta-carotene alone, or in combination with other micronutrients, are being taken.
WHO/IPCS; Toxicological Evaluation of Certain Food Additives and Contaminants WHO Food Additives Series 32 (1993)

13 Toxicity

13.1 Toxicological Information

13.1.1 Effects During Pregnancy and Lactation

◉ Summary of Use during Lactation

Beta-carotene is a plant pigment that is converted into vitamin A in the body. Maternal vitamin A requirements are increased during lactation, but there are no specific guidelines for increased beta-carotene intake or indications for high-dose supplementation in nursing mothers. Typical beta-carotene intake in a Western diet is 6 to 8 mg daily. Beta-carotene is a normal component of human colostrum and mature milk, where it contributes to antioxidant defenses in the neonate. A systematic review found that in infants younger than 6 months, those fed primarily human milk have greater blood carotenoid concentrations than those fed formula. Some evidence suggests that there is a correlation between beta-carotene and infant motor development in exclusively breastfed infants, but not in overall psychomotor performance. Beta-carotene supplementation during pregnancy and for 6 months postpartum in nursing mothers with poor diets in a resource-poor setting reduced the number of days of illness in the mothers, but does not reduce infant morbidity or mortality according to another study. The bioavailability of beta-carotene is dependent on the fat content of the meal and the form in which it is administered, with synthetic pharmaceutical forms having the best bioavailability. High-dose beta-carotene supplements lead to a slow increase in breastmilk beta-carotene concentrations, with an accumulation half-life of about 9 days. Levels drop towards baseline slowly over several weeks after discontinuation. In general, beta-carotene is well tolerated, although excessive maternal intake of beta-carotene can lead to a harmless, reversible discoloration of the breastfed infant's skin. In HIV-infected women, high-dose beta-carotene plus vitamin A supplementation increases the rate of HIV viral shedding into breastmilk and increases HIV infection in breastfed infants, although the mortality rate over the first 2 years of life is not increased. The viral shedding may be a result of an increase in subclinical mastitis caused by beta-carotene. Beta-carotene concentration in breastmilk is not affected by refrigeration, freezing, or low-temperature microwaving. The concentration does decrease when milk passes through a tube feeding system, regardless of light exposure.

Dietary supplements do not require extensive pre-marketing approval from the U.S. Food and Drug Administration. Manufacturers are responsible to ensure the safety, but do not need to prove the safety and effectiveness of dietary supplements before they are marketed. Dietary supplements may contain multiple ingredients, and differences are often found between labeled and actual ingredients or their amounts. A manufacturer may contract with an independent organization to verify the quality of a product or its ingredients, but that does not certify the safety or effectiveness of a product. Because of the above issues, clinical testing results on one product may not be applicable to other products. More detailed information about dietary supplements is available elsewhere on the LactMed Web site.

◉ Effects in Breastfed Infants

A nursing mother was eating 2 to 3 pounds of carrots a week as raw and cooked carrots. The mother's skin was yellow in color, but her sclera were clear. At 2 months of age, her breastfed infant was diagnosed as having jaundice because of a yellow coloration of the skin. Breastfeeding was discontinued and the infant's skin returned to a normal color. The mother continued her diet and examination of the maternal serum found elevated levels of beta-carotene which was probably the cause of her infant's skin discoloration.

HIV-infected women in Tanzania received 1 of 4 supplements during pregnancy and lactation in a series of studies. Groups received either multivitamins (thiamine, riboflavin, vitamin B6, niacin, vitamin B12, vitamin C, vitamin E, and folic acid), multivitamins plus vitamin A and beta-carotene, vitamin A and beta-carotene alone, or placebo daily. The beta-carotene dose was 30 mg. At 24 months of age, the multivitamin-supplemented group's infants had significantly better growth parameters than the other groups. One study found that the infants of mothers supplemented with vitamin A and beta-carotene had a higher rate of HIV transmission than those supplemented with multivitamins alone or placebo. After 6 months postpartum, women who received vitamin A plus beta-carotene had greater shedding of the HIV virus into breastmilk than women who had not; multivitamins without vitamin A and beta-carotene did not increase viral shedding. Beta-carotene appeared to have a shedding effect that was independent of vitamin A. One possible explanation comes from another similar study in which those who received vitamin A plus beta-carotene alone had a 45% increased risk of severe subclinical mastitis and those who received multivitamins plus vitamin A and beta-carotene had a 29% increased risk of severe subclinical mastitis.

Breastmilk samples were collected at the first, third and sixth months postpartum from 39 mother-infant pairs of exclusively breastfed infants. Psychomotor testing found a correlation between beta-carotene intake in breastmilk during the first 3 months of life and infant motor development, but not overall psychomotor development, at 6 months of life. Some long-chain polyunsaturated fatty acids, DHA, alpha-linolenic acid and total n-3 PUFAs, also correlated with motor development.

◉ Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

13.1.2 Interactions

Cigarette smoking is associated with decreased plasma levels of ascorbate and beta-carotene, which indicates that the smoking related chronic inflammatory response leads to an imbalance of oxidant/antioxidant homeostasis and possible predisposition to oxidant inflicted tissue damage and disease.
Anderson R; Am J Clin Nutr 53 (1): 358S-61S (1991)
Weanling male Sprague-Dawley rats were pair-fed beta-carotene (56.5 mg/L of diet) for 8 weeks, with and without ethanol. As expected, ethanol increased CYP2E1 (measured by Western blots) from 67 + or - 8 to 317 + or - 27 densitometric units (p < 0.001). Furthermore, beta-carotene potentiated the ethanol induction to 442 + or - 38 densitometric units (p < 0.01) with a significant interaction (p = 0.012). The rise was confirmed by a corresponding increase in the hydroxylation of p-nitrophenol, a specific substrate for CYP2E1, and by the inhibition with diethyl dithiocarbamate (50 microM). Beta-carotene alone also significantly induced CYP4A1 protein (328 + or - 49 vs. 158 + or - 17 densitometric units, p < 0.05). The corresponding CYP4A1 mRNA (measured by Northern blots) was also increased (p < 0.05) and there was a significant interaction of the two treatments (p = 0.015). The combination of ethanol and beta-carotene had no significant effect on either total cytochrome P-450 or CYP1A1/2, CYP2B, CYP3A, and CYP4A2/3 contents. Beta-carotene potentiates the CYP2E1 induction by ethanol in rat liver and also increases CYP4A1, which may, at least in part, explain the associated hepatotoxicity.
Kessova IG et al; Alcohol Clin Exp Res 25 (9): 1368-72 (2001)
AFLATOXIN B1 (4 MG/KG/DAY, ORALLY) ADMIN TO RATS FOR 26 DAYS INHIBITED THE FORMATION OF VITAMIN A FROM BETA-CAROTENE IN THE INTESTINAL MUCOSA.
HIKARAISHI S; KANAGAWA KENRITSU EIYO TANKI DAIGAKU KIYO 9: 20 (1977)
SULFITE-MEDIATED BETA-CAROTENE DESTRUCTION WAS INVESTIGATED; IT WAS INHIBITED BY ALPHA-TOCOPHEROL, 1,2-DIHYDROXYBENZENE-3,5-DISULFONIC ACID & BUTYLATED HYDROXYTOLUENE
PEISER GD, YANG SF; J AGRIC FOOD CHEM 27 (2): 446 (1979)
For more Interactions (Complete) data for BETA-CAROTENE (25 total), please visit the HSDB record page.

13.1.3 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

13.1.4 Human Toxicity Excerpts

/SIGNS AND SYMPTOMS/ Two large studies have found an increased incidence in lung cancers when beta-carotene supplements were given to individuals with a history of smoking and/or asbestos exposure. One study of 29,000 males with a history of smoking found an 18% increase in the incidence of lung cancer in the group receiving 20 mg of beta-carotene a day for 5 to 8 years as compared with those receiving placebo . Another study of 18,000 individuals found 28% more lung cancers in individuals with a history of smoking and/or asbestos exposure who took 30 mg of beta-carotene in addition to 25,000 Units of retinol a day for 4 years as compared with those receiving placebo . However, one study of 22,000 male physicians, some of them smokers and former smokers, found no increased risk of lung cancer at doses of 50 mg of beta-carotene every other day for 12 years .
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2006.
/EPIDEMIOLOGY STUDIES/ Epidemiological studies have suggested a protective effect of vegetables and fruits on urinary tract cancer but the possible protective nutrients are unknown. We studied the effect of alpha-tocopherol (a form of vitamin E) and beta-carotene supplementation on urinary tract cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. A total of 29,133 male smokers aged 50-69 years from southwestern Finland were randomly assigned to receive alpha-tocopherol (50 mg), beta-carotene (20 mg), both agents, or a placebo daily for 5-8 years (median 6.1 years). Incident urothelial cancers (bladder, ureter, and renal pelvis; n = 169) and renal cell cancers (n = 102) were identified through the nationwide cancer registry. The diagnoses were centrally confirmed by review of medical records and pathology specimens. The supplementation effects were estimated using a proportional hazards model. Neither alpha-tocopherol nor beta-carotene affected the incidence of urothelial cancer, relative risk 1.1 (95% confidence interval (CI) 0.8-1.5) and 1.0 (95% CI 0.7-1.3), respectively, or the incidence of renal cell cancer, relative risk 1.1 (95% CI 0.7-1.6) and 0.8 95% CI 0.6-1.3), respectively. Long-term supplementation with alpha-tocopherol and beta-carotene has no preventive effect on urinary tract cancers in middle-aged male smokers.
Virtamo J et la; Cancer Causes Control 11 (10): 933-9 (2000)
/EPIDEMIOLOGY STUDIES/ The Beta-Carotene and Retinol Efficacy Trial (CARET) was terminated 21 months ahead of schedule due to an excess of lung cancers. Deaths from cardiovascular disease also increased (relative risk=1.26 (95% confidence interval (CI) 0.99-1.61)) in the group assigned to a combination of 30 mg beta-carotene and 25 000 IU retinyl palmitate (vitamin A) daily. The basis for increased cardiovascular mortality is unexplained. Data on serum lipids, available for 1474 CARET Vanguard participants who were enrolled in the two CARET pilot studies and transitioned to the Vanguard study /were analyzed/. Total cholesterol and triglycerides were measured 2 months prior to, 4 and 12 months following randomization, and annually thereafter for up to 7 y. In the asbestos-exposed pilot (N = 816), participants were assigned to beta-carotene and retinol or to placebo; in the smokers pilot (N = 1029), participants were assigned to beta-carotene, retinol, a combination, or placebo. Serum cholesterol showed a decline over time in both arms; serum triglycerides had a continuous decline over time in the placebo arm, but an initial increase that persisted in the active arm. Both serum cholesterol concentrations (P < 0.0003) and serum triglycerides (P < 0.0001) were significantly higher in the participants receiving vitamin A and/or a combination of vitamin A and beta-carotene (n = 863) as compared to the placebo group (n = 611). Those in this active intervention group had an average cholesterol concentration 5.3 mg/dl (0.137 mmol/l) higher than those in the placebo arm. /It was concluded/ the differences in cholesterol and triglyceride concentrations between the groups following randomization may account in part for the unexpected excess in cardiovascular deaths seen in the active intervention arm of CARET.
Cartmel B et al; Eur J Clin Nutr 59 (10): 1173-80 (2005)
/EPIDEMIOLOGY STUDIES/ The Physicians' Health Study (PHS) was a randomized trial of beta-carotene (50 mg, alternate days) and aspirin in primary prevention of cancer and cardiovascular disease among 22,071 US male physicians. This report updates results for beta-carotene and examines effect modification by baseline characteristics. Beta-carotene's effect on cancer over nearly 13 years was examined overall and within subgroups defined by baseline characteristics using proportional-hazards models. 2667 incident cancers were confirmed, with 1117 prostate, 267 colon, and 178 lung cancers. There were no significant differences with supplementation in total (relative risk (RR) = 1.0, 95% confidence interval (CI) = 0.9-1.0); prostate (RR = 1.0, 95% CI = 0.9-1.1); colon (RR = 0.9, 95% CI = 0.7-1.2); or lung (RR = 0.9, 95% CI = 0.7-1.2) cancer, and no differences over time. In subgroup analyses, total cancer was modestly reduced with supplementation among those aged 70+ years (RR = 0.8, 95% CI = 0.7-1.0), daily drinkers of alcohol (RR = 0.9, 95% CI = 0.8-1.0), and those in the highest BMI quartile (RR = 0.9, 95% CI = 0.7-1.0). Prostate cancer was reduced with supplementation among those in the highest BMI quartile (RR = 0.8, 95% CI = 0.6-1.0), and colon cancer was reduced among daily drinkers of alcohol (RR = 0.5, 95% CI = 0.3-0.8). The PHS found no overall effect of beta-carotene on total cancer, or the three most common site-specific cancers. The possibility of risk reduction within specific subgroups remains.
Cook NR et al; Cancer Causes Control 11 (7): 617-26 (2000)
For more Human Toxicity Excerpts (Complete) data for BETA-CAROTENE (15 total), please visit the HSDB record page.

13.1.5 Non-Human Toxicity Excerpts

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ The inhibitory effects of beta-carotene on preneoplastic lesions induced in male Wistar rats by the resistant hepatocyte model was investigated. Rats were divided into six groups. Initiation was performed in all animals by a single injection of diethylnitrosamine. During the selection/promotion period five doses of 2-acetylaminofluorene were administered to the rats and a partial hepatectomy was performed. To three different groups beta-carotene was given by gavage throughout the experiment, before the initiation or during the selection/promotion period respectively. Three other groups served as controls and received corn oil instead of the carotenoid. At the end of the study (8 weeks), beta- carotene administration throughout the experiment reduced the incidence (p< 0.005), multiplicity as well as the total number and size of hepatocyte nodules. Furthermore, it significantly decreased the number of foci per sq cm (p< 0.05), the average focal area (p< 0.01) and the percentage of liver parenchyma occupied (p< 0.01). Similar results were observed when beta-carotene was given only before the initiation. However, the administration of the carotenoid during the selection/promotion period did not result in significant decreases of these parameters. These results suggest that the inhibitory effects of beta-carotene are primarily exerted on the initiation phase of the hepatocarcinogenic process. Nevertheless, continuous long term exposure to the carotenoid would confer a greater degree of protection. In addition, by means of an analysis of correlation a positive relationship was found between the number of hepatocyte nodules and the hepatic concentration of beta-carotene. In contrast, an inverse relationship was observed between the number of nodules and the hepatic concentration of total vitamin A.
Moreno FS et al; Carcinogenesis 12 (10): 1817-22 (1991)
/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ In this study, the inhibitory effect of natural alpha-carotene, obtained from palm oil was compared with that of beta-carotene on spontaneous liver carcinogenesis in C3H/He male mice. The mean number of hepatomas per mouse was significantly decreased by alpha-carotene supplementation (oral administration in drinking water at a concentration of 0.05%, at pleasure) as compared with that in the control group (p< 0.001, Student's t test). On the other hand, beta-carotene, at the same dose as alpha-carotene, did not show any such significant difference from the control group.
Murakoshi M et al; Cancer Res 52 (23): 6583-7 (1992)
/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ The effects of beta-carotene (BC) on ventricular remodeling after myocardial infarction /were studied/. Myocardial infarction was induced in Wistar rats that were then treated with a BC diet (500 mg/kg of diet per day; MI-BC; n = 27) or a regular diet (MI; n = 27). Hearts were analyzed in vivo and in vitro after 6 mo. BC caused decreased left ventricular wall thickness (MI = 1.49 + or - 0.3 mm, MI-BC = 1.23 + or - 0.2 mm, P = 0.027) and increased diastolic (MI = 0.83 + or - 0.15 cm2, MI-BC = 0.98 + or - 0.14 cm2, P = 0.020) and systolic (MI = 0.56 + or - 0.12 cm2, MI-BC = 0.75 + or - 0.13 cm2, P = 0.002) left ventricular chamber areas. With respect to systolic function, the BC group presented less change in fractional area than did controls (MI = 32.35 + or - 6.67, MI-BC = 23.77 + or - 6.06, P = 0.004). There was no difference in transmitral diastolic flow velocities between groups. In vitro results showed decreased maximal isovolumetric systolic pressure (MI = 125.5 + or - 24.1 mm Hg, MI-BC = 95.2 + or - 28.4 mmHg, P = 0.019) and increased interstitial myocardial collagen concentration (MI = 3.3 + or - 1.2%, MI-BC = 5.8 + or - 1.7%, P = 0.004) in BC-treated animals. Infarct sizes were similar between groups (MI = 45.0 + or - 6.6%, MI-BC = 48.0 + or - 5.8%, P = 0.246). Taken together, these data suggest that BC has adverse effects on ventricular remodeling after myocardial infarction.
Zornoff LA et al; Nutrition 22 (2): 146-51 (2006)
/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ A 3 generation reproduction study in rats receiving beta carotene at a dietary concentration of 0.1% has revealed no evidence of harm to the fetus.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 3556
For more Non-Human Toxicity Excerpts (Complete) data for BETA-CAROTENE (12 total), please visit the HSDB record page.

13.1.6 Populations at Special Risk

Two large studies have found an increased incidence in lung cancers when beta-carotene supplements were given to individuals with a history of smoking and/or asbestos exposure. One study of 29,000 males with a history of smoking found an 18% increase in the incidence of lung cancer in the group receiving 20 mg of beta-carotene a day for 5 to 8 years as compared with those receiving placebo . Another study of 18,000 individuals found 28% more lung cancers in individuals with a history of smoking and/or asbestos exposure who took 30 mg of beta-carotene in addition to 25,000 Units of retinol a day for 4 years as compared with those receiving placebo . However, one study of 22,000 male physicians, some of them smokers and former smokers, found no increased risk of lung cancer at doses of 50 mg of beta-carotene every other day for 12 years .
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2006.

13.1.7 Protein Binding

Beta-carotene is thought to be highly bound to plasma proteins. It is registered to be retained by the chylomicron and transported in VLDL. After absorption, beta-carotene is rapidly transformed to retinol which is highly bound to a high number of plasma proteins.

13.2 Ecological Information

13.2.1 Natural Pollution Sources

ORANGE-YELLOW PIGMENT IN PLANTS, ALGAE, & SOME MARINE ANIMALS, ESP IN LEAVES, VEGETATION, & ROOT CROPS, IN TRACE CONCN. NOTABLY PRESENT IN BUTTER & CARROTS. /CAROTENE/
Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 12th ed. New York, NY: Van Nostrand Rheinhold Co., 1993, p. 226
RICHEST SOURCES OF CAROTENE ARE YELLOW & GREEN (LEAFY) VEGETABLES & YELLOW FRUITS.
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 940

13.2.2 Milk Concentrations

EXPERIMENTAL: This study investigated milk carotenoid concentrations during days 4-32 postpartum and assessed the effects of maternal beta-carotene supplementation. Subjects (n = 21; aged 19-39 y) were randomly assigned to receive beta-carotene (30 mg/d) or placebo from days 4 to 32 postpartum. Each subject provided 8 diet records and 8 milk samples during the study. Diet records were analyzed for energy, macronutrients, vitamins A and E, and carotenoids. Milk samples were analyzed with HPLC for concentrations of carotenoids, retinol, and alpha-tocopherol. Data were analyzed by using repeated-measures analysis and orthogonal contrasts. No significant differences in average dietary intakes, body mass index, age, or parity were found between groups at baseline or after supplementation. Milk carotenoid concentrations decreased over time (P < 0.01), as did retinol and alpha-tocopherol concentrations (P < 0.003). Concentrations of most carotenoids decreased to those reported for mature milk by day 32 postpartum. Milk lutein concentrations remained elevated throughout the study compared with values reported for mature milk, whereas plasma lutein concentrations decreased significantly over time. beta-carotene supplementation did not significantly change the milk concentrations of beta-carotene, the other carotenoids, retinol, or alpha-tocopherol. CONCLUSIONS: The lack of increase in milk beta-carotene despite supplementation suggests that transitional milk may be already nearly saturated with beta-carotene. The elevated milk lutein concentration and simultaneous decrease in plasma lutein suggest that lutein metabolism may be altered during early lactation.
Gossage CP et al; Am J Clin Nutr 76 (1): 193-7 (2002)

14 Associated Disorders and Diseases

Disease
Diabetes mellitus type 1
References

PubMed: 12067838, 22279428, 16452910

Lorena Ivona ŞTEFAN, Alina NICOLESCU, Simona POPA, Maria MOŢA, Eugenia KOVACS and Calin DELEANU. 1H-NMR URINE METABOLIC PROFILING IN TYPE 1 DIABETES MELLITUS. Rev. Roum. Chim., 2010, 55(11-12), 1033-1037

Disease
Obesity
References

PubMed: 15899597, 17264178, 16253646, 2401584, 1783639, 26505825, 17408529, 18997681, 24740590, 23108202, 26910390

Metabolomics reveals determinants of weight loss during lifestyle intervention in obese children

Disease
Endometrial cancer
References
PubMed: 19235557

15 Literature

15.1 Consolidated References

15.2 NLM Curated PubMed Citations

15.3 Springer Nature References

15.4 Thieme References

15.5 Wiley References

15.6 Nature Journal References

15.7 Chemical Co-Occurrences in Literature

15.8 Chemical-Gene Co-Occurrences in Literature

15.9 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 Structure Code
PDBe Conformer

17.2 Chemical-Target Interactions

17.3 Drug-Drug Interactions

17.4 Pathways

18 Biological Test Results

18.1 BioAssay Results

19 Taxonomy

WormJam Metabolites Local CSV for MetFrag | DOI:10.5281/zenodo.3403364
WormJam: A consensus C. elegans Metabolic Reconstruction and Metabolomics Community and Workshop Series, Worm, 6:2, e1373939, DOI:10.1080/21624054.2017.1373939
The LOTUS Initiative for Open Natural Products Research: frozen dataset union wikidata (with metadata) | DOI:10.5281/zenodo.5794106

20 Classification

20.1 MeSH Tree

20.2 NCI Thesaurus Tree

20.3 ChEBI Ontology

20.4 LIPID MAPS Classification

20.5 KEGG: Lipid

20.6 KEGG: Phytochemical Compounds

20.7 KEGG: ATC

20.8 WHO ATC Classification System

20.9 ChemIDplus

20.10 ChEMBL Target Tree

20.11 UN GHS Classification

20.12 EPA CPDat Classification

20.13 NORMAN Suspect List Exchange Classification

20.14 EPA DSSTox Classification

20.15 Consumer Product Information Database Classification

20.16 EPA TSCA and CDR Classification

20.17 LOTUS Tree

20.18 EPA Substance Registry Services Tree

20.19 MolGenie Organic Chemistry Ontology

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    https://creativecommons.org/licenses/by/4.0/
    BETACAROTENE
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    https://www.norman-network.com/nds/SLE/
  34. FDA Orange Book
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  35. Joint FAO/WHO Expert Committee on Food Additives (JECFA)
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  36. FDA Regulatory Status of Color Additives
  37. FDA Substances Added to Food
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  38. FooDB
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    https://foodb.ca/about
  39. MassBank Europe
  40. MassBank of North America (MoNA)
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    https://mona.fiehnlab.ucdavis.edu/documentation/license
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  42. KEGG
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  43. LIPID MAPS
    Lipid Classification
    https://www.lipidmaps.org/
  44. MarkerDB
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    https://markerdb.ca/
  45. Metabolomics Workbench
  46. National Drug Code (NDC) Directory
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  47. Nature Chemical Biology
  48. NIST Mass Spectrometry Data Center
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  49. SpectraBase
  50. NLM RxNorm Terminology
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  51. WHO Anatomical Therapeutic Chemical (ATC) Classification
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  52. Pharos
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  55. Rhea - Annotated Reactions Database
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  56. Springer Nature
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  59. Thieme Chemistry
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  60. Wikidata
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  63. PubChem
  64. GHS Classification (UNECE)
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  66. MolGenie
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  67. PATENTSCOPE (WIPO)
CONTENTS