EFSA Compendium of Botanicals

Draft - work in progress

Lemon (as plant) // Citrus limon (L.) Osbeck // Citrus limon Burm. F.

Family:: Rutaceae
Approval state:: Approved
Number of articles retrieved:: 7244
Number of processed references:: 9

Compositions

#1: xanthyletin #2: Coumarins (wakayamalimonol A-D) #3: Furanocoumarins (wakayamalimonol E, apaensin, cnidilin, byakangelicin and derivatives, oxypeucedanin and derivatives, (+)-pangelin, (+)- 2a,3a-dihydroxyimperatorin, (+)-Omethylheraclenol, and 8-geranyloxypsoralen) #4: Limonoids (limonin and nomilin) #5: Bergamottin #6: Citropten #7: Oxypeucedanin #8: 5-Geranyloxy-7-methoxycoumarin #9: 8-Geranyloxypsoralen #10: Byakangelicol #11: Bergapten #12: Isopimpellin #13: Bergamottin #14: synephrin - leaves #15: synephrin - fruit #16: Piperitone #17: scopoletin #18: scoparone #19: seselin

Endpoint Studies

#1: acute antifertility, but no longterm #2: reproduction toxicity

Genotoxicity

#1: lemon juice and limonene mutagenic at highest concentrations (50% v/v and 0.73 mM, respectively)

Composition #1: Banerji, J., Ghoshal, N., Sarkar, S., Kumar, M. Studies on Rutaceae. Part II. Chemical investigations of the constituents of Atalantia wightii, Limonia crenulata, Feronia limonia, Citrus limon and synthesis of luvangetin, xanthyletin, and marmin. indian journal of chemistry, section b: organic chemistry including medicinal chemistry, 1982, vol. 21B, no. 5, p. 496–8. .

Language:

English (en)
Plant part:

Roots and other underground parts (as part-nature) (A067M)
Additional extraction description:

unspecified
Substance:

xanthyletin (RF-00010982-PAR)
Analytical method code:

Unspecified (F598A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

xanthyletin

Composition #2: Matsumoto, Takahiro., Takahashi, Kazuki., Kanayama, Sumire., Nakano, Yuka., Imai, Hiromi., Kibi, Masumi., Imahori, Daisuke., Hasei, Tomohiro., Watanabe, Tetsushi. Structures of antimutagenic constituents in the peels of Citrus limon.. journal of natural medicines, 2017 . DOI: 10.1007/s11418-017-1108-3. [DOI link]

Language:

English (en)
Plant part:

Fruit peel (as part-nature) (A067G)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

MeOH
Substance:

coumarins (RF-00004351-PAR)
Additional substance description:

wakayamalimonol A-D
Analytical method code:

Nuclear Magnetic Resonance (NMR) (F061A)
Analytical method - additional description:

IR, EIMS
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

Coumarins (wakayamalimonol A-D)

Composition #3: Matsumoto, Takahiro., Takahashi, Kazuki., Kanayama, Sumire., Nakano, Yuka., Imai, Hiromi., Kibi, Masumi., Imahori, Daisuke., Hasei, Tomohiro., Watanabe, Tetsushi. Structures of antimutagenic constituents in the peels of Citrus limon.. journal of natural medicines, 2017 . DOI: 10.1007/s11418-017-1108-3. [DOI link]

Language:

English (en)
Plant part:

Fruit peel (as part-nature) (A067G)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

MeOH
Substance:

Furanocoumarins (RF-00004381-PAR)
Additional substance description:

(wakayamalimonol E, apaensin, cnidilin, byakangelicin and derivatives, oxypeucedanin and derivatives, (+)-pangelin, (+)- 2a,3a-dihydroxyimperatorin, (+)-Omethylheraclenol, and 8-geranyloxypsoralen
Analytical method code:

Nuclear Magnetic Resonance (NMR) (F061A)
Analytical method - additional description:

IR, EIMS
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

Furanocoumarins (wakayamalimonol E, apaensin, cnidilin, byakangelicin and derivatives, oxypeucedanin and derivatives, (+)-pangelin, (+)- 2a,3a-dihydroxyimperatorin, (+)-Omethylheraclenol, and 8-geranyloxypsoralen)

Composition #4: Matsumoto, Takahiro., Takahashi, Kazuki., Kanayama, Sumire., Nakano, Yuka., Imai, Hiromi., Kibi, Masumi., Imahori, Daisuke., Hasei, Tomohiro., Watanabe, Tetsushi. Structures of antimutagenic constituents in the peels of Citrus limon.. journal of natural medicines, 2017 . DOI: 10.1007/s11418-017-1108-3. [DOI link]

Language:

English (en)
Plant part:

Fruit peel (as part-nature) (A067G)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

MeOH
Substance:

limonoids limonoids (RF-00004362-PAR)
Additional substance description:

limonin and nomilin
Analytical method code:

Nuclear Magnetic Resonance (NMR) (F061A)
Analytical method - additional description:

IR, EIMS
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

Limonoids (limonin and nomilin)

Composition #5: Dugo, P., Mondello, L., Cogliandro, E., Cavazza, A., Dugo, G. On the genuineness of citrus essential oils. Part LIII. Determination of the composition of the oxygen heterocyclic fraction of lemon essential oils (Citrus limon (L.) Burm. f.) by normal-phase high performance liquid chromatography . flavour and fragrance journal, 1998, vol. 13, no. 5, p. 329–334. DOI: 10.1002/(SICI)1099-1026(1998090)13:5<329::AID-FFJ754>3.0.CO;2-1. [DOI link]

Language:

English (en)
Plant part:

Fruit peel (as part-nature) (A067G)
Extraction/Preparation method:

Essential oil (as part-nature) (A166Q)
Additional extraction description:

cold-pressed
Substance:

Bergamottin (RF-00003800-PAR)
Analytical method code:

HPLC-DAD (F587A)
Result unit:

Milligram/100 gram (G057A)
Result expression:

Whole weight (B001A)
Result type:

Numerical Value (VAL)
Value (concentration, content):

160- 291
Internal remarks:

Bergamottin

Composition #6: Dugo, P., Mondello, L., Cogliandro, E., Cavazza, A., Dugo, G. On the genuineness of citrus essential oils. Part LIII. Determination of the composition of the oxygen heterocyclic fraction of lemon essential oils (Citrus limon (L.) Burm. f.) by normal-phase high performance liquid chromatography . flavour and fragrance journal, 1998, vol. 13, no. 5, p. 329–334. DOI: 10.1002/(SICI)1099-1026(1998090)13:5<329::AID-FFJ754>3.0.CO;2-1. [DOI link]

Language:

English (en)
Plant part:

Fruit peel (as part-nature) (A067G)
Extraction/Preparation method:

Essential oil (as part-nature) (A166Q)
Additional extraction description:

cold-pressed
Substance:

limettin (RF-00011371-PAR)
Additional substance description:

citropten
Analytical method code:

HPLC-DAD (F587A)
Result unit:

Milligram/100 gram (G057A)
Result expression:

Whole weight (B001A)
Result type:

Numerical Value (VAL)
Value (concentration, content):

52- 142
Internal remarks:

Citropten

Composition #7: Dugo, P., Mondello, L., Cogliandro, E., Cavazza, A., Dugo, G. On the genuineness of citrus essential oils. Part LIII. Determination of the composition of the oxygen heterocyclic fraction of lemon essential oils (Citrus limon (L.) Burm. f.) by normal-phase high performance liquid chromatography . flavour and fragrance journal, 1998, vol. 13, no. 5, p. 329–334. DOI: 10.1002/(SICI)1099-1026(1998090)13:5<329::AID-FFJ754>3.0.CO;2-1. [DOI link]

Language:

English (en)
Plant part:

Fruit peel (as part-nature) (A067G)
Extraction/Preparation method:

Essential oil (as part-nature) (A166Q)
Additional extraction description:

cold-pressed
Substance:

oxypeucedanin (RF-00003968-PAR)
Analytical method code:

HPLC-DAD (F587A)
Result unit:

Milligram/100 gram (G057A)
Result expression:

Whole weight (B001A)
Result type:

Numerical Value (VAL)
Value (concentration, content):

89- 157
Internal remarks:

Oxypeucedanin

Composition #8: Dugo, P., Mondello, L., Cogliandro, E., Cavazza, A., Dugo, G. On the genuineness of citrus essential oils. Part LIII. Determination of the composition of the oxygen heterocyclic fraction of lemon essential oils (Citrus limon (L.) Burm. f.) by normal-phase high performance liquid chromatography . flavour and fragrance journal, 1998, vol. 13, no. 5, p. 329–334. DOI: 10.1002/(SICI)1099-1026(1998090)13:5<329::AID-FFJ754>3.0.CO;2-1. [DOI link]

Language:

English (en)
Plant part:

Fruit peel (as part-nature) (A067G)
Extraction/Preparation method:

Essential oil (as part-nature) (A166Q)
Additional extraction description:

cold-pressed
Substance:

coumarins (RF-00004351-PAR)
Additional substance description:

5-Geranyloxy-7-methoxycoumarin
Analytical method code:

HPLC-DAD (F587A)
Result unit:

Milligram/100 gram (G057A)
Result expression:

Whole weight (B001A)
Result type:

Numerical Value (VAL)
Value (concentration, content):

180- 250
Internal remarks:

5-Geranyloxy-7-methoxycoumarin

Composition #9: Dugo, P., Mondello, L., Cogliandro, E., Cavazza, A., Dugo, G. On the genuineness of citrus essential oils. Part LIII. Determination of the composition of the oxygen heterocyclic fraction of lemon essential oils (Citrus limon (L.) Burm. f.) by normal-phase high performance liquid chromatography . flavour and fragrance journal, 1998, vol. 13, no. 5, p. 329–334. DOI: 10.1002/(SICI)1099-1026(1998090)13:5<329::AID-FFJ754>3.0.CO;2-1. [DOI link]

Language:

English (en)
Plant part:

Fruit peel (as part-nature) (A067G)
Extraction/Preparation method:

Essential oil (as part-nature) (A166Q)
Additional extraction description:

cold-pressed
Substance:

8-geranoxypsoralen (RF-00003845-PAR)
Analytical method code:

HPLC-DAD (F587A)
Result unit:

Milligram/100 gram (G057A)
Result expression:

Whole weight (B001A)
Result type:

Numerical Value (VAL)
Value (concentration, content):

19- 36
Internal remarks:

8-Geranyloxypsoralen

Composition #10: Dugo, P., Mondello, L., Cogliandro, E., Cavazza, A., Dugo, G. On the genuineness of citrus essential oils. Part LIII. Determination of the composition of the oxygen heterocyclic fraction of lemon essential oils (Citrus limon (L.) Burm. f.) by normal-phase high performance liquid chromatography . flavour and fragrance journal, 1998, vol. 13, no. 5, p. 329–334. DOI: 10.1002/(SICI)1099-1026(1998090)13:5<329::AID-FFJ754>3.0.CO;2-1. [DOI link]

Language:

English (en)
Plant part:

Fruit peel (as part-nature) (A067G)
Extraction/Preparation method:

Essential oil (as part-nature) (A166Q)
Additional extraction description:

cold-pressed
Substance:

Byakangelicol (RF-00011117-PAR)
Analytical method code:

HPLC-DAD (F587A)
Result unit:

Milligram/100 gram (G057A)
Result expression:

Whole weight (B001A)
Result type:

Numerical Value (VAL)
Value (concentration, content):

66- 123
Internal remarks:

Byakangelicol

Composition #11: Peroutka, Radek., Schulzova, Vera., Botek, Petr., Hajslova, Jana. Analysis of furanocoumarins in vegetables (Apiaceae) anal citrus fruits (Rutaceae) . journal of the science of food and agriculture, 2007, vol. 87, no. 11, p. 2152–2163. DOI: 10.1002/jsfa.2979. [DOI link]

Language:

English (en)
Plant part:

Fruit peel (as part-nature) (A067G)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

MeOH
Substance:

Bergapten (RF-00003837-PAR)
Analytical method code:

GC-MS (F046A)
Analytical method - additional description:

LC-MS/MS
Result unit:

Microgram/gram (G049A)
Result expression:

Whole weight (B001A)
Result type:

Numerical Value (VAL)
Value (concentration, content):

2.57
Internal remarks:

Bergapten

Composition #12: Peroutka, Radek., Schulzova, Vera., Botek, Petr., Hajslova, Jana. Analysis of furanocoumarins in vegetables (Apiaceae) anal citrus fruits (Rutaceae) . journal of the science of food and agriculture, 2007, vol. 87, no. 11, p. 2152–2163. DOI: 10.1002/jsfa.2979. [DOI link]

Language:

English (en)
Plant part:

Fruit peel (as part-nature) (A067G)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

MeOH
Substance:

Isopimpinellin (RF-00003784-PAR)
Analytical method code:

GC-MS (F046A)
Analytical method - additional description:

LC-MS/MS
Result unit:

Microgram/gram (G049A)
Result expression:

Whole weight (B001A)
Result type:

Numerical Value (VAL)
Value (concentration, content):

0.14
Internal remarks:

Isopimpellin

Composition #13: Peroutka, Radek., Schulzova, Vera., Botek, Petr., Hajslova, Jana. Analysis of furanocoumarins in vegetables (Apiaceae) anal citrus fruits (Rutaceae) . journal of the science of food and agriculture, 2007, vol. 87, no. 11, p. 2152–2163. DOI: 10.1002/jsfa.2979. [DOI link]

Language:

English (en)
Plant part:

Fruit peel (as part-nature) (A067G)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

MeOH
Substance:

Bergamottin (RF-00003800-PAR)
Analytical method code:

GC-MS (F046A)
Analytical method - additional description:

LC-MS/MS
Result unit:

Microgram/gram (G049A)
Result expression:

Whole weight (B001A)
Result type:

Numerical Value (VAL)
Value (concentration, content):

72.27
Internal remarks:

Bergamottin

Composition #14: Arbo, M. D., Larentis, E. R., Linck, V. M., Aboy, A. L., Pimentel, A. L., Henriques, A. T., Dallegrave, E., Garcia, S. C., Leal, M. B., Limberger, R. P. Concentrations of p-synephrine in fruits and leaves of Citrus species (Rutaceae) and the acute toxicity testing of Citrus aurantium extract and p-synephrine . food and chemical toxicology, 2008, vol. 46, no. 8, p. 2770–2775. DOI: 10.1016/j.fct.2008.04.037. [DOI link]

Language:

English (en)
Plant part:

Leaves (as part-nature) (A0EKT)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

MeOH
Substance:

synephrine (RF-00004068-PAR)
Analytical method code:

High Performance Liquid Chromatography (HPLC)/Liquid Chromatography (LC) (F018A)
Result unit:

Percent (G138A)
Result expression:

Dry matter (B002A)
Result type:

Numerical Value (VAL)
Value (concentration, content):

0.01
Internal remarks:

synephrin - leaves

Composition #15: Arbo, M. D., Larentis, E. R., Linck, V. M., Aboy, A. L., Pimentel, A. L., Henriques, A. T., Dallegrave, E., Garcia, S. C., Leal, M. B., Limberger, R. P. Concentrations of p-synephrine in fruits and leaves of Citrus species (Rutaceae) and the acute toxicity testing of Citrus aurantium extract and p-synephrine . food and chemical toxicology, 2008, vol. 46, no. 8, p. 2770–2775. DOI: 10.1016/j.fct.2008.04.037. [DOI link]

Language:

English (en)
Plant part:

Fruit unspecified (as part-nature) (A067D)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

MeOH
Substance:

synephrine (RF-00004068-PAR)
Analytical method code:

High Performance Liquid Chromatography (HPLC)/Liquid Chromatography (LC) (F018A)
Result unit:

Percent (G138A)
Result expression:

Dry matter (B002A)
Result type:

Numerical Value (VAL)
Value (concentration, content):

0.037-0.045
Internal remarks:

synephrin - fruit

Composition #16: Karaborklu, Salih., Ayvaz, Abdurrahman., Yilmaz, Semih., Akbulut, Mikail. Chemical Composition and Fumigant Toxicity of Some Essential Oils Against Ephestia kuehniella . journal of economic entomology, 2011, vol. 104, no. 4, p. 1212–1219. DOI: 10.1603/EC10284. [DOI link]

Language:

English (en)
Plant part:

Leaves (as part-nature) (A0EKT)
Extraction/Preparation method:

Essential oil (as part-nature) (A166Q)
Additional extraction description:

steam distillation
Substance:

p-Menth-1-en-3-one (RF-00009951-PAR)
Analytical method code:

GC-MS (F046A)
Result unit:

Percent (G138A)
Result type:

Numerical Value (VAL)
Value (concentration, content):

2.29
Internal remarks:

Piperitone

Composition #17: ZOBEL, AM., WANG, JY., MARCH, RE., BROWN, SA. IDENTIFICATION OF 8 COUMARINS OCCURRING WITH PSORALEN, XANTHOTOXIN, AND BERGAPTEN ON LEAF SURFACES . journal of chemical ecology, 1991, vol. 17, no. 9, p. 1859–1870. DOI: 10.1007/BF00993733. [DOI link]

Language:

English (en)
Plant part:

Leaves (as part-nature) (A0EKT)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

boiling water
Substance:

scopoletin (RF-00004048-PAR)
Analytical method code:

HPLC with standard detection methods (F019A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

scopoletin

Composition #18: ZOBEL, AM., WANG, JY., MARCH, RE., BROWN, SA. IDENTIFICATION OF 8 COUMARINS OCCURRING WITH PSORALEN, XANTHOTOXIN, AND BERGAPTEN ON LEAF SURFACES . journal of chemical ecology, 1991, vol. 17, no. 9, p. 1859–1870. DOI: 10.1007/BF00993733. [DOI link]

Language:

English (en)
Plant part:

Leaves (as part-nature) (A0EKT)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

boiling water
Substance:

scoparone (RF-00004047-PAR)
Analytical method code:

HPLC with standard detection methods (F019A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

scoparone

Composition #19: ZOBEL, AM., WANG, JY., MARCH, RE., BROWN, SA. IDENTIFICATION OF 8 COUMARINS OCCURRING WITH PSORALEN, XANTHOTOXIN, AND BERGAPTEN ON LEAF SURFACES . journal of chemical ecology, 1991, vol. 17, no. 9, p. 1859–1870. DOI: 10.1007/BF00993733. [DOI link]

Language:

English (en)
Plant part:

Leaves (as part-nature) (A0EKT)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

boiling water
Substance:

Seselin (RF-00010993-PAR)
Analytical method code:

HPLC with standard detection methods (F019A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

seselin

Endpoint study #1: Singh, Nidhi., Singh, Shio Kumar. Citrus limon extract: possible inhibitory mechanisms affecting testicular functions and fertility in male mice . systems biology in reproductive medicine, 2016, vol. 62, no. 1, p. 39–48. DOI: 10.3109/19396368.2015.1078422. [DOI link]

Study relevance:

Human health
Plant part:

Leaves (as part-nature) (A0EKT)
Preparation/Extraction method:

Solvent extraction (A0BZR)
Additional plant/substance description:

50% ethanol
Type of toxicological test:

reproduction toxicity (CHD009TT)
Tested organism:

House mouse (as animal) (A0CNT)
Sex:

Male
Route of exposure:

ORAL: GAVAGE (OECD2231PL)
Exposure duration:

24.0
Unit of exposure duration:

Hour (G099A)
Number of organisms dosed:

5
Control groups used:

yes
Endpoint measured:

Concentration level (CHD013EP)
Concentration unit:

Milligrams per kilogram body weight per day (G211A)
Effect concentration:

1000
Critical effect:

REPRODUCTIVE (TOX05A)
Target tissue:

urogenital: Testes (TT050A)
Effect description:

Fertility of Citrus-treated males was adversely affected at 24 hours post-withdrawal, as none of the females mated to these males showed live implants
Effect or parameter linked to the endpoint:

reproduction (CHD014BE)
Internal remarks:

acute antifertility, but no longterm

Endpoint study #2: Singh, Nidhi., Singh, Shio Kumar. Citrus limon extract: possible inhibitory mechanisms affecting testicular functions and fertility in male mice . systems biology in reproductive medicine, 2016, vol. 62, no. 1, p. 39–48. DOI: 10.3109/19396368.2015.1078422. [DOI link]

Study relevance:

Human health
Plant part:

Leaves (as part-nature) (A0EKT)
Preparation/Extraction method:

Solvent extraction (A0BZR)
Additional plant/substance description:

50% ethanol
Type of toxicological test:

reproduction toxicity (CHD009TT)
Tested organism:

House mouse (as animal) (A0CNT)
Sex:

Male
Route of exposure:

ORAL: GAVAGE (OECD2231PL)
Exposure duration:

35.0
Unit of exposure duration:

Day (G134A)
Number of organisms dosed:

5
Control groups used:

yes
Endpoint measured:

Concentration level (CHD013EP)
Concentration unit:

Milligrams per kilogram body weight per day (G211A)
Effect concentration:

500
Critical effect:

REPRODUCTIVE (TOX05A)
Target tissue:

urogenital: Testes (TT050A)
Effect description:

changes of reproductive organ weight (Testis, Epididymis, Seminal vesicle), decrease in motility, viability, and number of spermatozoa
Effect or parameter linked to the endpoint:

reproduction (CHD014BE)
Internal remarks:

reproduction toxicity

Genotox #1: Fernandez-Bedmar, Zahira., Anter, Jaouad., de La Cruz-Ares, Silvia., Munoz-Serrano, Andres., Alonso-Moraga, Angeles., Perez-Guisado, Joaquin. ROLE OF CITRUS JUICES AND DISTINCTIVE COMPONENTS IN THE MODULATION OF DEGENERATIVE PROCESSES: GENOTOXICITY, ANTIGENOTOXICITY, CYTOTOXICITY, AND LONGEVITY IN DROSOPHILA . journal of toxicology and environmental health-part a-current issues, 2011, vol. 74, no. 15-16, p. 1052–1066. DOI: 10.1080/15287394.2011.582306. [DOI link]

Study category:

Mutagenicity
Type of toxicological test:

somatic mutation assay in Drosophila (CHD045TT)
Method type:

in vivo
Tested organism:

Drosophila melanogaster (as animal) (A0CMC)
Sex:

Male/Female
Exogenous metabolic activation applied:

not applicable
Route of exposure:

OTHER (OECD0PL)
Control groups used:

yes
Endpoint measured:

gene mutation
Is genotoxic:

Positive
Remarks on genotox study:

lemon juice and limonene were mutagenic (0.325 spots/wing) in the SMART at the highest concentration (50% v/v and 0.73 mM, respectively)
Internal remarks:

lemon juice and limonene mutagenic at highest concentrations (50% v/v and 0.73 mM, respectively)
Internal ID:

WOS:000294904400010