EFSA Compendium of Botanicals

Draft - work in progress

Chinotto (as plant) // Citrus x aurantium L. // Citrus x aurantium L. var. myrtifolia Ker Gawl. // Citrus x myrtifolia (Ker Gawl.) Raf.

Family:: Rutaceae
Approval state:: Approved
Number of articles retrieved:: 5863
Number of processed references:: 5

Compositions

#1: Myrcene (leaves) #2: Myrcene (trunk) #3: synephrine #4: synephrine

Endpoint Studies

#1: LD50 = 20 mg/kg for a 6% synephrine standardised extract #2: cardiac effects #3: LD50 = 476.94 mg/kg #4: neurotoxic effect

Genotoxicity

#1: C. aurantium extracts exhibited mutagenic activities with the TA98 strain and in the absence of metabolic activation (2–2.5 fold).

Composition #1: Ortiz, J. M., Kumamoto, J., Scora, R. W. Possible relationships among sour oranges by analysis of their essential oils. international flavours and food additives, 1978, p. 224–226. .

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:

myrcene (RF-00003503-PAR)
Analytical method code:

GC-MS (F046A)
Result unit:

Percent (G138A)
Result type:

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

0.7- 4.3
Internal remarks:

Myrcene (leaves)

Composition #2: Ortiz, J. M., Kumamoto, J., Scora, R. W. Possible relationships among sour oranges by analysis of their essential oils. international flavours and food additives, 1978, p. 224–226. .

Language:

English (en)
Plant part:

Trunk (as part-nature) (A166N)
Extraction/Preparation method:

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

steam distillation
Substance:

myrcene (RF-00003503-PAR)
Analytical method code:

GC-MS (F046A)
Result unit:

Percent (G138A)
Result type:

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

1.5- 2.1
Internal remarks:

Myrcene (trunk)

Composition #3: 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:

methanol
Substance:

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

HPLC-UV (F021A)
Analytical method - additional description:

HPLC
Result unit:

Percent (G138A)
Result type:

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

0.041-0.048
Internal remarks:

synephrine

Composition #4: 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:

methanol
Substance:

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

HPLC-UV (F021A)
Result unit:

Percent (G138A)
Result type:

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

0.007
Internal remarks:

synephrine

Endpoint study #1: Calapai, G., Firenzuoli, F., Saitta, A., Squadrito, F., Arlotta, MR., Costantino, G., Inferrera, G. Antiobesity and cardiovascular toxic effects of Citrus aurantium extracts in the rat: a preliminary report. FITOTERAPIA, 1999, vol. 70, no. 6, p. 586–592. DOI: 10.1016/S0367-326X(99)00093-3. [DOI link]

Study relevance:

Human health
Substance:

synephrine (RF-00004068-PAR)
Plant part:

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

Solvent extraction (A0BZR)
Additional plant/substance description:

hydroalcoholic standardised at 6% synephrine
Type of toxicological test:

short-term toxicity (CHD017TT)
Tested organism:

Rat (as animal) (A0CNV)
Strain of test organism:

Sprague-Dawley (CHD012ST)
Sex:

Male
Route of exposure:

ORAL: FEED (OECD2230PL)
Exposure duration:

15.0
Unit of exposure duration:

Day (G134A)
Number of organisms dosed:

10
Control groups used:

yes
Endpoint measured:

Lethal dose rate in 50% of experimental organisms (CHD029EP)
Concentration unit:

Milligram/kilogram (G061A)
Effect concentration:

20
Critical effect:

NONE (TOX14A)
Effect description:

LD50 = 20 mg/kg for a 6% synephrine standardised extract
Effect or parameter linked to the endpoint:

mortality (CHD010BE)
Internal remarks:

LD50 = 20 mg/kg for a 6% synephrine standardised extract

Endpoint study #2: Calapai, G., Firenzuoli, F., Saitta, A., Squadrito, F., Arlotta, MR., Costantino, G., Inferrera, G. Antiobesity and cardiovascular toxic effects of Citrus aurantium extracts in the rat: a preliminary report. FITOTERAPIA, 1999, vol. 70, no. 6, p. 586–592. DOI: 10.1016/S0367-326X(99)00093-3. [DOI link]

Study relevance:

Human health
Substance:

synephrine (RF-00004068-PAR)
Plant part:

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

Solvent extraction (A0BZR)
Additional plant/substance description:

hydroalcoholic standardised at 4 and 6% synephrine
Type of toxicological test:

short-term toxicity (CHD017TT)
Tested organism:

Rat (as animal) (A0CNV)
Strain of test organism:

Sprague-Dawley (CHD012ST)
Sex:

Male
Route of exposure:

ORAL: FEED (OECD2230PL)
Exposure duration:

15.0
Unit of exposure duration:

Day (G134A)
Number of organisms dosed:

10
Control groups used:

yes
Endpoint measured:

Concentration level (CHD013EP)
Concentration unit:

Milligram/kilogram (G061A)
Effect concentration:

20
Critical effect:

PULMONARY AND CARDIAC (TOX08A)
Target tissue:

cardiovascular / haematological: Heart (TT011A)
Effect description:

ECG alterations such as ventricular arhythmias with enlargement of QRS complex starting from 10 days of treatment and still evident after 15 days of treatment
Effect or parameter linked to the endpoint:

gross pathology (CHD022BE)
Internal remarks:

cardiac effects

Endpoint study #3: Parra, AL., Yhebra, RS., Sardinas, IG., Buela, LI. Comparative study of the assay of Artemia salina L. and the estimate of the medium lethal dose (LD50 value) in mice, to determine oral acute toxicity of plant extracts. PHYTOMEDICINE, 2001, vol. 8, no. 5, p. 395–400. .

Study relevance:

Human health
Plant part:

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

Solvent extraction (A0BZR)
Additional plant/substance description:

Tinctures
Type of toxicological test:

acute toxicity (CHD016TT)
Tested organism:

House mouse (as animal) (A0CNT)
Strain of test organism:

Swiss (CHD005ST)
Sex:

No data
Route of exposure:

ORAL: GAVAGE (OECD2231PL)
Control groups used:

yes
Endpoint measured:

Lethal dose rate in 50% of experimental organisms (CHD029EP)
Concentration unit:

Milligram/kilogram (G061A)
Effect concentration:

476.94
Critical effect:

NONE (TOX14A)
Effect description:

LD50 = 476.94 mg/kg
Effect or parameter linked to the endpoint:

mortality (CHD010BE)
Internal remarks:

LD50 = 476.94 mg/kg

Endpoint study #4: 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]

Study relevance:

Human health
Substance:

synephrine (RF-00004068-PAR)
Plant part:

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

Solvent extraction (A0BZR)
Additional plant/substance description:

methanol extract from unripe fruits, standardised at 2.5% of synephrine
Type of toxicological test:

acute toxicity (CHD016TT)
Limit test:

No data
Tested organism:

House mouse (as animal) (A0CNT)
Strain of test organism:

CF-1 (CHD062ST)
Sex:

Male
Route of exposure:

ORAL: GAVAGE (OECD2231PL)
Exposure duration:

1.0
Unit of exposure duration:

Meal (G109A)
Number of organisms dosed:

8
Control groups used:

yes, concurrent no treatment
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Milligram/kilogram (G061A)
Effect concentration:

1000
Critical effect:

NEUROTOXICITY (TOX04A)
Target tissue:

Neurologic (TT004A)
Effect description:

reduction in locomotor activity, which. was evident 15 min after administration of 1000–5000 mg/kg and persisted for 2 h.
Effect or parameter linked to the endpoint:

mobility (CHD011BE)
Internal remarks:

neurotoxic effect

Genotox #1: Abudayyak, Mahmoud., Ozdemir Nath, Ebru., Ozhan, Gul. Toxic potentials of ten herbs commonly used for aphrodisiac effect in Turkey. TURKISH JOURNAL OF MEDICAL SCIENCES, 2015, vol. 45, no. 3, p. 496–506. DOI: 10.3906/sag-1401-153. [DOI link]

Study category:

Genotoxicity
Type of toxicological test:

bacterial reverse mutation assay (CHD028TT)
Method type:

in vitro
Tested organism:

Salmonella typhimurium (as organism) (A0CPZ)
Strain of test organism:

TA 98 (CHD029ST)
Sex:

No data
Exogenous metabolic activation applied:

with
Route of exposure:

OTHER (OECD0PL)
Control groups used:

yes
Endpoint measured:

gene mutation
Is genotoxic:

Positive
Remarks on genotox study:

C. aurantium extracts exhibited mutagenic activities with the TA98 strain and in the absence of metabolic activation (2–2.5 fold).
Internal remarks:

C. aurantium extracts exhibited mutagenic activities with the TA98 strain and in the absence of metabolic activation (2–2.5 fold).
Internal ID:

WOS:000356357800005