EFSA Compendium of Botanicals

Draft - work in progress

Teucrium chamaedrys L.

Family:: Lamiaceae
Approval state:: Approved
Number of articles retrieved:: 326
Number of processed references:: 12

Compositions

#1: podophyllotoxin in aerial parts #2: teucrin A in aerial parts #3: saponins in unspecified part #4: Dihydroteugin in aerial parts #5: teucrin A in aerial parts #6: Chamaedroxide in aerial parts #7: Teucroxide in aerial parts #8: Teuflin in aerial parts #9: Teugin in aerial parts #10: teucrioside in aerial parts #11: syspirensins A and B in aerial parts #12: Teucrioside in aerial parts #13: Chamaedryoside B, Chamaedryoside A, 6b-Hydroxyteucridin, Teuflin, Teucrin (A,E,F,G), Teuflidin in leaves and roots #14: Teucrin A in aerial parts #15: teuchamaedryn A in aerial parts

Endpoint Studies

#1: Hepatotoxicity in humans #2: hepatotoxicity in humans #3: Hepatotoxicity in rats #4: A lethal case of hepatotoxicity in human #5: Hepatitis in humans #6: Hepatotoxicity in humans #7: Hepatotoxicity in mice

Genotoxicity

Composition #1: Konuklugil, Belma. Investigation of podophyllotoxin in some plants in Lamiaceae using HPLC. ankara universitesi eczacilik fakultesi dergisi, 1996, vol. 25, no. 1, p. 23–27. .

Language:

English (en)
Plant part:

Aerial part of plants (as part-nature) (A166F)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

dichlorometan
Substance:

podophyllotoxin (RF-00004001-PAR)
Analytical method code:

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

Percent (G138A)
Result type:

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

0.14
Internal remarks:

podophyllotoxin in aerial parts

Composition #2: Ravichandiran, V., Satish, P.V. A review on hepatotoxicity of phytomedicines. international journal of pharmacognosy and phytochemical research, 2013, vol. 5, no. 3, p. 186–191. .

Language:

English (en)
Plant part:

Aerial part of plants (as part-nature) (A166F)
Additional extraction description:

unspecified
Substance:

teucrin A (RF-00004076-PAR)
Analytical method code:

High Performance Liquid Chromatography (HPLC)/Liquid Chromatography (LC) (F018A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

teucrin A in aerial parts

Composition #3: Stedman, C. Herbal hepatotoxicity. seminars in liver disease, 2002, vol. 22, no. 2, p. 195–206. DOI: 10.1055/s-2002-30104. [DOI link]

Language:

English (en)
Plant part:

Unspecified (A07XD)
Additional extraction description:

unspecified
Substance:

Saponins (RF-00004333-PAR)
Analytical method code:

Unspecified (F598A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

saponins in unspecified part

Composition #4: Bosisio, E., Giavarini, F., Dell'Agli, M., Galli, G., Galli, CL. Analysis by high-performance liquid chromatography of teucrin A in beverages flavoured with an extract of Teucrium chamaedrys L. . food additives and contaminants, 2004, vol. 21, no. 5, p. 407–414. DOI: 10.1080/02652030410001670157. [DOI link]

Language:

English (en)
Plant part:

Aerial part of plants (as part-nature) (A166F)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

Water, Ethanol
Substance:

furan derivatives (RF-00004396-PAR)
Additional substance description:

Dihydroteugin
Analytical method code:

LC-MS (F026A)
Result unit:

ppm (G288A)
Result type:

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

91
Internal remarks:

Dihydroteugin in aerial parts

Composition #5: Bosisio, E., Giavarini, F., Dell'Agli, M., Galli, G., Galli, CL. Analysis by high-performance liquid chromatography of teucrin A in beverages flavoured with an extract of Teucrium chamaedrys L. . food additives and contaminants, 2004, vol. 21, no. 5, p. 407–414. DOI: 10.1080/02652030410001670157. [DOI link]

Language:

English (en)
Plant part:

Aerial part of plants (as part-nature) (A166F)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

Water, Ethanol
Substance:

teucrin A (RF-00004076-PAR)
Analytical method code:

LC-MS (F026A)
Result unit:

ppm (G288A)
Result type:

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

2251
Internal remarks:

teucrin A in aerial parts

Composition #6: Bosisio, E., Giavarini, F., Dell'Agli, M., Galli, G., Galli, CL. Analysis by high-performance liquid chromatography of teucrin A in beverages flavoured with an extract of Teucrium chamaedrys L. . food additives and contaminants, 2004, vol. 21, no. 5, p. 407–414. DOI: 10.1080/02652030410001670157. [DOI link]

Language:

English (en)
Plant part:

Aerial part of plants (as part-nature) (A166F)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

Water, Ethanol
Substance:

furan derivatives (RF-00004396-PAR)
Additional substance description:

Chamaedroxide
Analytical method code:

LC-MS (F026A)
Result unit:

ppm (G288A)
Result type:

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

144
Internal remarks:

Chamaedroxide in aerial parts

Composition #7: Bosisio, E., Giavarini, F., Dell'Agli, M., Galli, G., Galli, CL. Analysis by high-performance liquid chromatography of teucrin A in beverages flavoured with an extract of Teucrium chamaedrys L. . food additives and contaminants, 2004, vol. 21, no. 5, p. 407–414. DOI: 10.1080/02652030410001670157. [DOI link]

Language:

English (en)
Plant part:

Aerial part of plants (as part-nature) (A166F)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

Water, Ethanol
Substance:

furan derivatives (RF-00004396-PAR)
Additional substance description:

Teucroxide
Analytical method code:

LC-MS (F026A)
Result unit:

ppm (G288A)
Result type:

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

122
Internal remarks:

Teucroxide in aerial parts

Composition #8: Bosisio, E., Giavarini, F., Dell'Agli, M., Galli, G., Galli, CL. Analysis by high-performance liquid chromatography of teucrin A in beverages flavoured with an extract of Teucrium chamaedrys L. . food additives and contaminants, 2004, vol. 21, no. 5, p. 407–414. DOI: 10.1080/02652030410001670157. [DOI link]

Language:

English (en)
Plant part:

Aerial part of plants (as part-nature) (A166F)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

Water, Ethanol
Substance:

furan derivatives (RF-00004396-PAR)
Additional substance description:

Teuflin
Analytical method code:

LC-MS (F026A)
Result unit:

ppm (G288A)
Result type:

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

711
Internal remarks:

Teuflin in aerial parts

Composition #9: Bosisio, E., Giavarini, F., Dell'Agli, M., Galli, G., Galli, CL. Analysis by high-performance liquid chromatography of teucrin A in beverages flavoured with an extract of Teucrium chamaedrys L. . food additives and contaminants, 2004, vol. 21, no. 5, p. 407–414. DOI: 10.1080/02652030410001670157. [DOI link]

Language:

English (en)
Plant part:

Aerial part of plants (as part-nature) (A166F)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

Water, Ethanol
Substance:

furan derivatives (RF-00004396-PAR)
Additional substance description:

Teugin
Analytical method code:

LC-MS (F026A)
Result unit:

ppm (G288A)
Result type:

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

87
Internal remarks:

Teugin in aerial parts

Composition #10: Rader, Jeanne I., Delmonte, Pierluigi., Trucksess, Mary W. Recent studies on selected botanical dietary supplement ingredients. analytical and bioanalytical chemistry, 2007, vol. 389, no. 1, p. 27–35. DOI: 10.1007/s00216-007-1254-7. [DOI link]

Language:

English (en)
Plant part:

Aerial part of plants (as part-nature) (A166F)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

unspecified
Substance:

phenylpropanoids (RF-00004367-PAR)
Additional substance description:

teucrioside
Analytical method code:

High Performance Liquid Chromatography (HPLC)/Liquid Chromatography (LC) (F018A)
Analytical method - additional description:

GC, TLC
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

teucrioside in aerial parts

Composition #11: Rader, Jeanne I., Delmonte, Pierluigi., Trucksess, Mary W. Recent studies on selected botanical dietary supplement ingredients. analytical and bioanalytical chemistry, 2007, vol. 389, no. 1, p. 27–35. DOI: 10.1007/s00216-007-1254-7. [DOI link]

Language:

English (en)
Plant part:

Aerial part of plants (as part-nature) (A166F)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

unspecified
Substance:

clerodane-type diterpenes (RF-00004350-PAR)
Additional substance description:

syspirensins A and B
Analytical method code:

High Performance Liquid Chromatography (HPLC)/Liquid Chromatography (LC) (F018A)
Analytical method - additional description:

GC, TLC
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

syspirensins A and B in aerial parts

Composition #12: Lin, Long-Ze., Harnly, James M., Upton, Roy. Comparison of the Phenolic Component Profiles of Skullcap (Scutellaria lateriflora) and Germander (Teucrium canadense and T. chamaedrys), a Potentially Hepatotoxic Adulterant . phytochemical analysis, 2009, vol. 20, no. 4, p. 298–306. DOI: 10.1002/pca.1127. [DOI link]

Language:

English (en)
Plant part:

Aerial part of plants (as part-nature) (A166F)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

ethanol + methanol + water
Substance:

teucrin A (RF-00004076-PAR)
Additional substance description:

Teucrioside (Teucrin G, Teucrin A, isoteuflidin, teuflidin, Teuflin)
Analytical method code:

LC-MS (F026A)
Result unit:

Percent (G138A)
Result type:

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

0.45 - 2.30
Internal remarks:

Teucrioside in aerial parts

Composition #13: Ricci, Andreina., Piccolella, Simona., Fiorentino, Antonio., Pepi, Federico., D'Abrosca, Brigida., Monaco, Pietro. A tandem mass spectrometric investigation of the low-energy collision-activated fragmentation of neo-clerodane diterpenes . rapid communications in mass spectrometry, 2010, vol. 24, no. 11, p. 1543–1556. DOI: 10.1002/rcm.4545. [DOI link]

Language:

English (en)
Plant part:

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

Solvent extraction (A0BZR)
Additional extraction description:

Methanol and acetonitrile (from leaves and roots)
Substance:

clerodane-type diterpenes (RF-00004350-PAR)
Additional substance description:

Chamaedryoside B, Chamaedryoside A, 6b-Hydroxyteucridin, Teuflin, Teucrin (A,E,F,G), Teuflidin
Analytical method code:

Mass Spectroscopy and hyphenated methods without chromatography (F063A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

Chamaedryoside B, Chamaedryoside A, 6b-Hydroxyteucridin, Teuflin, Teucrin (A,E,F,G), Teuflidin in leaves and roots

Composition #14: KOUZI, SA., MCMURTRY, RJ., NELSON, SD. HEPATOTOXICITY OF GERMANDER (TEUCRIUM-CHAMAEDRYS L) AND ONE OF ITS CONSTITUENT NEOCLERODANE DITERPENES TEUCRIN-A IN THE MOUSE . chemical research in toxicology, 1994, vol. 7, no. 6, p. 850–856. DOI: 10.1021/tx00042a020. [DOI link]

Language:

English (en)
Plant part:

Aerial part of plants (as part-nature) (A166F)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

acetone
Substance:

teucrin A (RF-00004076-PAR)
Analytical method code:

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

Percent (G138A)
Result type:

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

1.09 - 1.58
Internal remarks:

Teucrin A in aerial parts

Composition #15: Lekehal, M., Pessayre, D., Lereau, JM., Moulis, C., Fouraste, I., Fau, D. Hepatotoxicity of the herbal medicine germander: Metabolic activation of its furano diterpenoids by cytochrome P450 3A depletes cytoskeleton-associated protein thiols and forms plasma membrane blebs in rat hepatocytes . hepatology, 1996, vol. 24, no. 1, p. 212–218. DOI: 10.1002/hep.510240134. [DOI link]

Language:

English (en)
Plant part:

Aerial part of plants (as part-nature) (A166F)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

CH2CL2 / Methanol
Substance:

clerodane-type diterpenes (RF-00004350-PAR)
Additional substance description:

teuchamaedryn A
Analytical method code:

Standard Chromatographic tests (paper- thin layer- and column chromatography) (F016A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

teuchamaedryn A in aerial parts

Endpoint study #1: Ravichandiran, V., Satish, P.V. A review on hepatotoxicity of phytomedicines. international journal of pharmacognosy and phytochemical research, 2013, vol. 5, no. 3, p. 186–191. .

Study relevance:

Human health
Plant part:

Aerial part of plants (as part-nature) (A166F)
Type of toxicological test:

case report (CHD060TT)
Limit test:

Not applicable
Tested organism:

Human (as organism) (A056J)
Sex:

Female
Route of exposure:

ORAL: UNSPECIFIED (OECD2234PL)
Exposure duration:

6.0
Unit of exposure duration:

Month (G206A)
Number of organisms dosed:

1
Control groups used:

no
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Milligrams per day (G209A)
Effect concentration:

1600
Critical effect:

HEPATOTOXICITY (TOX02A)
Target tissue:

digestive: Liver (TT023A)
Effect description:

a case of 55-year-old woman taking 1600 mg per day of germander became jaundiced after six months.
Effect or parameter linked to the endpoint:

histopathology non neoplastic (CHD025BE)
Internal remarks:

Hepatotoxicity in humans

Endpoint study #2: Stedman, C. Herbal hepatotoxicity. seminars in liver disease, 2002, vol. 22, no. 2, p. 195–206. DOI: 10.1055/s-2002-30104. [DOI link]

Study relevance:

Human health
Plant part:

Unspecified (A07XD)
Type of toxicological test:

other (CHD008TT)
Limit test:

Not applicable
Tested organism:

Human (as organism) (A056J)
Sex:

No data
Route of exposure:

ORAL: UNSPECIFIED (OECD2234PL)
Exposure duration:

2.0
Unit of exposure duration:

Month (G206A)
Number of organisms dosed:

30
Control groups used:

no
Endpoint measured:

Dose not reported (CHD066EP)
Critical effect:

HEPATOTOXICITY (TOX02A)
Target tissue:

digestive: Liver (TT023A)
Effect description:

Hepatitis developed after about 2 months of medication use and was typically characterized by mild to moderate cytolytic hepatitis, necrosis; fibrosis; cirrhosis
Effect or parameter linked to the endpoint:

histopathology non neoplastic (CHD025BE)
Internal remarks:

hepatotoxicity in humans

Endpoint study #3: De Vincenzi, M., Maialetti, F., Silano, M. Constituents of aromatic plants: teucrin A. fitoterapia, 2003, vol. 74, no. 7-8, p. 746–749. DOI: 10.1016/S0367-326X(03)00145-X. [DOI link]

Study relevance:

Human health
Plant part:

Aerial part of plants (as part-nature) (A166F)
Additional plant/substance description:

unspecified
Type of toxicological test:

subchronic (CHD013TT)
Limit test:

Yes
Tested organism:

Rat (as animal) (A0CNV)
Sex:

Male/Female
Route of exposure:

ORAL: FEED (OECD2230PL)
Exposure duration:

13.0
Unit of exposure duration:

Week (G205A)
Endpoint measured:

Lowest observed adverse effect level (CHD026EP)
Concentration unit:

Grams per kilogram body weight per day (G212A)
Effect concentration:

0.056
Critical effect:

HEPATOTOXICITY (TOX02A)
Target tissue:

digestive: Liver (TT023A)
Effect description:

At 0.056 g/kg/day, the compound induced a slight hepatocellular hypertrophy in the female group.
Effect or parameter linked to the endpoint:

histopathology non neoplastic (CHD025BE)
Internal remarks:

Hepatotoxicity in rats

Endpoint study #4: De Vincenzi, M., Maialetti, F., Silano, M. Constituents of aromatic plants: teucrin A. fitoterapia, 2003, vol. 74, no. 7-8, p. 746–749. DOI: 10.1016/S0367-326X(03)00145-X. [DOI link]

Study relevance:

Human health
Plant part:

Aerial part of plants (as part-nature) (A166F)
Type of toxicological test:

case report (CHD060TT)
Limit test:

Not applicable
Tested organism:

Human (as organism) (A056J)
Sex:

Female
Route of exposure:

ORAL: UNSPECIFIED (OECD2234PL)
Exposure duration:

2.0
Unit of exposure duration:

Week (G205A)
Number of organisms dosed:

1
Control groups used:

no
Endpoint measured:

Lowest lethal dose (CHD025EP)
Concentration unit:

Milligrams per person per day (G232A)
Effect concentration:

450
Critical effect:

HEPATOTOXICITY (TOX02A)
Effect description:

a lethal case (massive hepatic necrosis), after ingestion of 450 mg/day of wild germander for 2 weeks, repeated after 6 months
Effect or parameter linked to the endpoint:

mortality (CHD010BE)
Internal remarks:

A lethal case of hepatotoxicity in human

Endpoint study #5: Furbee, RB., Barlotta, KS., Allen, MK., Holstege, CP. Hepatotoxicity associated with herbal products. clinics in laboratory medicine, 2006, vol. 26, no. 1, p. 227–+. DOI: 10.1016/j.cll.2006.02.005. [DOI link]

Study relevance:

Human health
Plant part:

Unspecified (A07XD)
Type of toxicological test:

case report (CHD060TT)
Limit test:

Not applicable
Tested organism:

Human (as organism) (A056J)
Sex:

Female
Route of exposure:

ORAL: CAPSULE (OECD2228PL)
Exposure duration:

2.0
Unit of exposure duration:

Month (G206A)
Number of organisms dosed:

26
Control groups used:

no
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Milligrams per day (G209A)
Effect concentration:

600 - 1600
Critical effect:

HEPATOTOXICITY (TOX02A)
Target tissue:

digestive: Liver (TT023A)
Effect description:

Several reports of hepatitis. Most cases involved women taking the product for weight loss in doses of 600 to 1600 mg per day for 2 or more months. 12 of 26 patients re-exposed to Germander redeveloped evidence of hepatitis.
Effect or parameter linked to the endpoint:

histopathology non neoplastic (CHD025BE)
Internal remarks:

Hepatitis in humans

Endpoint study #6: Haslan, Haszianaliza., Suhaimi, Farihah Haji., Das, Srijit. Herbal Supplements and Hepatotoxicity: A Short Review. natural product communications, 2015, vol. 10, no. 10, p. 1779–1784. .

Study relevance:

Human health
Plant part:

Unspecified (A07XD)
Type of toxicological test:

other (CHD008TT)
Limit test:

Not applicable
Tested organism:

Human (as organism) (A056J)
Sex:

No data
Route of exposure:

ORAL: UNSPECIFIED (OECD2234PL)
Number of organisms dosed:

26
Control groups used:

no
Endpoint measured:

Dose not reported (CHD066EP)
Critical effect:

HEPATOTOXICITY (TOX02A)
Target tissue:

digestive: Liver (TT023A)
Effect description:

twenty-six patients developed acute hepatitis and presented with jaundice and elevated liver enzymes. Liver biopsy showed hepatocytes necrosis with few cases leading to chronic hepatitis and cirrhosis
Effect or parameter linked to the endpoint:

histopathology non neoplastic (CHD025BE)
Internal remarks:

Hepatotoxicity in humans

Endpoint study #7: KOUZI, SA., MCMURTRY, RJ., NELSON, SD. HEPATOTOXICITY OF GERMANDER (TEUCRIUM-CHAMAEDRYS L) AND ONE OF ITS CONSTITUENT NEOCLERODANE DITERPENES TEUCRIN-A IN THE MOUSE . chemical research in toxicology, 1994, vol. 7, no. 6, p. 850–856. DOI: 10.1021/tx00042a020. [DOI link]

Study relevance:

Human health
Substance:

teucrin A (RF-00004076-PAR)
Plant part:

Aerial part of plants (as part-nature) (A166F)
Preparation/Extraction method:

Solvent extraction (A0BZR)
Additional plant/substance description:

acetone / ethanol
Type of toxicological test:

acute toxicity (CHD016TT)
Tested organism:

House mouse (as animal) (A0CNT)
Sex:

Male
Route of exposure:

ORAL: GAVAGE (OECD2231PL)
Number of organisms dosed:

11
Control groups used:

no
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Gram/kilogram (G015A)
Effect concentration:

0.5 - 4
Critical effect:

HEPATOTOXICITY (TOX02A)
Target tissue:

digestive: Liver (TT023A)
Effect description:

Administration of an ethanol extract of germander caused midzonal necrosis in mice, and midzonal necrosis extending to centrilobular necrosis of the livers at the highest dose
Effect or parameter linked to the endpoint:

histopathology non neoplastic (CHD025BE)
Internal remarks:

Hepatotoxicity in mice