EFSA Compendium of Botanicals

Draft - work in progress

Daphne mezereum L.

Family:: Thymelaeaceae
Approval state:: Approved
Number of articles retrieved:: 134
Number of processed references:: 8

Compositions

#1: Daphnin (bark) #2: Daphnoretin (berries) #3: Daphnin (flower) #4: Daphnetoxin in bark. #5: Daphnetoxin (seeds) #6: Mezerein (seeds) #7: Diterpene esters (gniditrin in bark) #8: Mezerein (fruit) #9: Coumarin glycosides #10: Diterpene esters #11: Lignans in bark

Endpoint Studies

#1: Fatal poisoning by berries or bark #2: Co-carcinogeicity of "mecerein" = mezerein in mice. #3: Poisoning of pigs by berries #4: Mortality in a herd of cows after grazing - showing salivation, blindness, ataxia, impaired parenchymatous and circulatory organs, spasms, paresis, paralysis, and coma.

Genotoxicity

Composition #1: Tschesche, Rudolf., Schacht, Ulrich., Legler, Guenter. Daphnoretin, a naturally occurring derivative of 3,7'-dicoumaryl ether. annalen der chemie, justus liebigs, 1963, vol. 662, p. 113–25. .

Language:

English (en)
Plant part:

Bark (as part-nature) (A066X)
Substance:

daphnin (RF-00004251-PAR)
Additional substance description:

7,8-Dihydroxycoumarin-7-beta-glucoside
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

Daphnin (bark)

Composition #2: Tschesche, Rudolf., Schacht, Ulrich., Legler, Guenter. Daphnoretin, a naturally occurring derivative of 3,7'-dicoumaryl ether. annalen der chemie, justus liebigs, 1963, vol. 662, p. 113–25. .

Language:

English (en)
Plant part:

Fruit unspecified (as part-nature) (A067D)
Substance:

daphnoretin (RF-00004252-PAR)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

Daphnoretin (berries)

Composition #3: Tschesche, Rudolf., Schacht, Ulrich., Legler, Guenter. Daphnoretin, a naturally occurring derivative of 3,7'-dicoumaryl ether. annalen der chemie, justus liebigs, 1963, vol. 662, p. 113–25. .

Language:

English (en)
Plant part:

Flower (as part-nature) (A067B)
Substance:

daphnin (RF-00004251-PAR)
Additional substance description:

7,8-Dihydroxycoumarin-7-beta-glucoside
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

Daphnin (flower)

Composition #4: Stout, George H., Balkenhol, Wayne J., Poling, Mitchell., Hickernell, Gary L. Isolation and structure of daphnetoxin, the poisonous principle of Daphne species. journal of the american chemical society, 1970, vol. 92, no. 4, p. 1070–1. .

Language:

English (en)
Plant part:

Bark (as part-nature) (A066X)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

Dichloromethane; isolation and crystallisation from ethanol
Substance:

daphnetoxin (RF-00004250-PAR)
Result unit:

Percent (G138A)
Result expression:

Whole weight (B001A)
Result type:

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

0.02
Internal remarks:

Daphnetoxin in bark.

Composition #5: Ronlan, Alvin., Wickberg, Borje. Structure of mezerein, a major toxic principle of Daphne mezereum. tetrahedron letters, 1970, vol. (49), p. 4261–4. .

Language:

English (en)
Plant part:

Seed (as part-nature) (A066P)
Substance:

daphnetoxin (RF-00004250-PAR)
Result unit:

Percent (G138A)
Result type:

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

0.02
Internal remarks:

Daphnetoxin (seeds)

Composition #6: Ronlan, Alvin., Wickberg, Borje. Structure of mezerein, a major toxic principle of Daphne mezereum. tetrahedron letters, 1970, vol. (49), p. 4261–4. .

Language:

English (en)
Plant part:

Seed (as part-nature) (A066P)
Substance:

mezerein (RF-00003496-PAR)
Result unit:

Percent (G138A)
Result type:

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

0.1
Internal remarks:

Mezerein (seeds)

Composition #7: Goerick, C., Melzig, M. F. Gniditrin is the main diterpenoid constituent in the bark of Daphne mezereum L. . pharmazie, 2013, vol. 68, no. 7, p. 640–642. DOI: 10.1692/ph.2013.6522. [DOI link]

Language:

English (en)
Plant part:

Bark (as part-nature) (A066X)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

96% ethanol
Substance:

Diterpene esters (RF-00010831-PAR)
Additional substance description:

gniditrine
Analytical method code:

HPLC-MS/MS (F698A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

Diterpene esters (gniditrin in bark)

Composition #8: Goerick, C., Melzig, M. F. Gniditrin is the main diterpenoid constituent in the bark of Daphne mezereum L. . pharmazie, 2013, vol. 68, no. 7, p. 640–642. DOI: 10.1692/ph.2013.6522. [DOI link]

Language:

English (en)
Plant part:

Fruit unspecified (as part-nature) (A067D)
Substance:

mezerein (RF-00003496-PAR)
Analytical method code:

HPLC-MS/MS (F698A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

Mezerein (fruit)

Composition #9: KREHER, B., NESZMELYI, A., WAGNER, H. TRIUMBELLIN, A TRICOUMARIN RHAMNOPYRANOSIDE FROM DAPHNE-MEZEREUM. phytochemistry, 1990, vol. 29, no. 11, p. 3633–3637. DOI: 10.1016/0031-9422(90)85290-V. [DOI link]

Language:

English (en)
Plant part:

Bark (as part-nature) (A066X)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

chloroform
Substance:

Coumarin glycosides Coumarin glycosides (RF-00000810-VET)
Additional substance description:

TRIUMBELLIN (A TRICOUMARIN RHAMNOPYRANOSIDE)
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:

Coumarin glycosides

Composition #10: KREHER, B., NESZMELYI, A., WAGNER, H. TRIUMBELLIN, A TRICOUMARIN RHAMNOPYRANOSIDE FROM DAPHNE-MEZEREUM. phytochemistry, 1990, vol. 29, no. 11, p. 3633–3637. DOI: 10.1016/0031-9422(90)85290-V. [DOI link]

Language:

English (en)
Plant part:

Bark (as part-nature) (A066X)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

chloroform
Substance:

Diterpene esters (RF-00010831-PAR)
Additional substance description:

gniditrin
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:

Diterpene esters

Composition #11: KREHER, B., NESZMELYI, A., WAGNER, H. TRIUMBELLIN, A TRICOUMARIN RHAMNOPYRANOSIDE FROM DAPHNE-MEZEREUM. phytochemistry, 1990, vol. 29, no. 11, p. 3633–3637. DOI: 10.1016/0031-9422(90)85290-V. [DOI link]

Language:

English (en)
Plant part:

Bark (as part-nature) (A066X)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

chloroform
Substance:

lignans (RF-00004361-PAR)
Additional substance description:

dihydrosesamin, lariciresinol, syringaresinol, pinoresinol,,and ooumarolignan daphneticin,
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:

Lignans in bark

Endpoint study #1: Stout, George H., Balkenhol, Wayne J., Poling, Mitchell., Hickernell, Gary L. Isolation and structure of daphnetoxin, the poisonous principle of Daphne species. journal of the american chemical society, 1970, vol. 92, no. 4, p. 1070–1. .

Study relevance:

Human health
Plant part:

Bark (as part-nature) (A066X)
Preparation/Extraction method:

Raw, no heat treatment (A07HS)
Type of toxicological test:

case report (CHD060TT)
Limit test:

No
Tested organism:

Human (as organism) (A056J)
Sex:

No data
Route of exposure:

ORAL: UNSPECIFIED (OECD2234PL)
Control groups used:

no
Endpoint measured:

Dose not reported (CHD066EP)
Critical effect:

NOT REPORTED (TOX17A)
Effect description:

Fatal poisoning in humans, horse and dog by ingestion of a few berries or few grams of bark
Effect or parameter linked to the endpoint:

mortality (CHD010BE)
Internal remarks:

Fatal poisoning by berries or bark

Endpoint study #2: Hecker, E. Cocarcinogens from Euphorbiaceae and Thymeleaceae. pharmacogn. phytochem., int. congr., 1st, 1971, p. 147–65. .

Study relevance:

Human health
Substance:

mezerein (RF-00003496-PAR)
Plant part:

Fruit unspecified (as part-nature) (A067D)
Additional plant/substance description:

"mecerein" = mezerein
Type of toxicological test:

subchronic (CHD013TT)
Limit test:

No
Tested organism:

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

NMRI (CHD004ST)
Sex:

No data
Route of exposure:

ORAL: UNSPECIFIED (OECD2234PL)
Exposure duration:

12.0
Unit of exposure duration:

Week (G205A)
Control groups used:

no data
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Millimole (G115A)
Effect concentration:

0.0002
Effect description:

Tumour rate 9 %; co-carcinogenicity using 0.1 uM DMBA (7,12-dimethylbeno(a)anthracene ?) as a tumour initiator
Effect or parameter linked to the endpoint:

Co-carcinogenic (CHD037BE)
Internal remarks:

Co-carcinogeicity of "mecerein" = mezerein in mice.

Endpoint study #3: Duncanson, Graham R. Poisons and Causes of Sudden Death. veterinary treatment of pigs, 2013, p. 131–140. .

Study relevance:

Animal (target species) health
Plant part:

Fruit unspecified (as part-nature) (A067D)
Type of toxicological test:

case report (CHD060TT)
Limit test:

No
Tested organism:

Pig (as animal) (A057F)
Sex:

No data
Control groups used:

no
Endpoint measured:

Dose not reported (CHD066EP)
Critical effect:

Digestive (TOX18A)
Target tissue:

digestive: Stomach (TT027A)
Effect description:

Death
Effect or parameter linked to the endpoint:

mortality (CHD010BE)
Internal remarks:

Poisoning of pigs by berries

Endpoint study #4: PERNTHANER, A., LANGER, T. POISONING WITH DAPHNE-MEZEREUM IN CATTLE. wiener tierarztliche monatsschrift, 1993, vol. 80, no. 5, p. 138–142. .

Study relevance:

Animal (target species) health
Plant part:

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

plant as whole grazed by cows
Type of toxicological test:

case report (CHD060TT)
Tested organism:

Cattle (as animal) (A057E)
Sex:

No data
Route of exposure:

ORAL: UNSPECIFIED (OECD2234PL)
Control groups used:

no data
Endpoint measured:

Dose not reported (CHD066EP)
Critical effect:

PULMONARY AND CARDIAC (TOX08A)
Effect description:

Mortality in a herd of cows after grazing - showing salivation, blindness, ataxia, impaired parenchymatous and circulatory organs, spasms, paresis, paralysis, and coma..
Effect or parameter linked to the endpoint:

mortality (CHD010BE)
Internal remarks:

Mortality in a herd of cows after grazing - showing salivation, blindness, ataxia, impaired parenchymatous and circulatory organs, spasms, paresis, paralysis, and coma.