EFSA Compendium of Botanicals

Draft - work in progress

Veratrum californicum Durand

Family:: Melanthiaceae
Approval state:: Approved
Number of articles retrieved:: 220
Number of processed references:: 6

Compositions

#1: Cyclopamine in roots #2: veratrosine and veratramine in roots #3: cyclopamine in roots #4: cycloposine in roots #5: cycloposine contaminated with veratramine and veratrosine in unspecified part

Endpoint Studies

#1: teratogenicity in cattles #2: Teratogenicity in hamsters #3: Teratogenic toxicity in sheeps #4: embryotoxic in ewes

Genotoxicity

Composition #1: Welch, K. D., Panter, K. E., Lee, S. T., Gardner, D. R., Stegelmeier, B. L., Cook, D. Cyclopamine-induced synophthalmia in sheep: defining a critical window and toxicokinetic evaluation . journal of applied toxicology, 2009, vol. 29, no. 5, p. 414–421. DOI: 10.1002/jat.1427. [DOI link]

Language:

English (en)
Plant part:

Roots and other underground parts (as part-nature) (A067M)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

CH2CL2 / NH4OH
Substance:

cyclopamine (RF-00004245-PAR)
Analytical method code:

UHPLC-MS-MS (F608A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

Cyclopamine in roots

Composition #2: Chandler, Christopher M., Habig, Jeffrey W., Fisher, Ashley A., Ambrose, Katherine V., Jimenez, Susana T., McDougal, Owen M. Improved Extraction and Complete Mass Spectral Characterization of Steroidal Alkaloids from Veratrum californicum . natural product communications, 2013, vol. 8, no. 8, p. 1059–1064. .

Language:

English (en)
Plant part:

Roots and other underground parts (as part-nature) (A067M)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

98.3:1.7 EtOH:NH4OH (v/v)
Substance:

Steroidal alkaloids (RF-00004336-PAR)
Additional substance description:

veratrosine and veratramine
Analytical method code:

UHPLC-MS-MS (F608A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

veratrosine and veratramine in roots

Composition #3: Chandler, Christopher M., Habig, Jeffrey W., Fisher, Ashley A., Ambrose, Katherine V., Jimenez, Susana T., McDougal, Owen M. Improved Extraction and Complete Mass Spectral Characterization of Steroidal Alkaloids from Veratrum californicum . natural product communications, 2013, vol. 8, no. 8, p. 1059–1064. .

Language:

English (en)
Plant part:

Roots and other underground parts (as part-nature) (A067M)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

98.3:1.7 EtOH:NH4OH (v/v)
Substance:

cyclopamine (RF-00004245-PAR)
Analytical method code:

UHPLC-MS-MS (F608A)
Result unit:

Gram/kilogram (G015A)
Result type:

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

6
Internal remarks:

cyclopamine in roots

Composition #4: Chandler, Christopher M., Habig, Jeffrey W., Fisher, Ashley A., Ambrose, Katherine V., Jimenez, Susana T., McDougal, Owen M. Improved Extraction and Complete Mass Spectral Characterization of Steroidal Alkaloids from Veratrum californicum . natural product communications, 2013, vol. 8, no. 8, p. 1059–1064. .

Language:

English (en)
Plant part:

Roots and other underground parts (as part-nature) (A067M)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

98.3:1.7 EtOH:NH4OH (v/v)
Substance:

cycloposine (RF-00004246-PAR)
Analytical method code:

UHPLC-MS-MS (F608A)
Result unit:

Gram/kilogram (G015A)
Result type:

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

6
Internal remarks:

cycloposine in roots

Composition #5: KEELER, RF. TERATOGENIC COMPOUNDS OF VERATRUM CALIFORNICUM (DURAND) .7. STRUCTURE OF GLYCOSIDIC ALKALOID CYCLOPOSINE . steroids, 1969, vol. 13, no. 5, p. 579–&. DOI: 10.1016/S0039-128X(69)80012-7. [DOI link]

Language:

English (en)
Plant part:

Unspecified (A07XD)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

Methanol
Substance:

cycloposine (RF-00004246-PAR)
Additional substance description:

cycloposine contaminated with veratramine and veratrosine
Analytical method code:

Standard Chromatographic tests (paper- thin layer- and column chromatography) (F016A)
Analytical method - additional description:

TLC
Result unit:

Percent (G138A)
Result type:

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

4
Internal remarks:

cycloposine contaminated with veratramine and veratrosine in unspecified part

Endpoint study #1: Leipold, H.W., Husby, F., Brundage, A.L., Shupe, J.L. Congenital defects of calves on Kodiak Island. journal of the american veterinary medical association, 1977, vol. 170, no. 12, p. 1408–1410. .

Study relevance:

Human health
Plant part:

Unspecified (A07XD)
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:

TERATOGENIC (TOX06A)
Target tissue:

neurologic: Spinal Cord (TT039A)
Effect description:

cyclopia in fetal calves and spinal dysraphia has been reported only in calves affected with arthrogryposis
Effect or parameter linked to the endpoint:

reproduction (CHD014BE)
Internal remarks:

teratogenicity in cattles

Endpoint study #2: Coventry-, S., Kapur, R.P., Siebert, J.R. Holoprosencephalic facies induced in golden hamsters by the teratogen cyclopamine. pediatric pathology and laboratory medicine, 1996, vol. 16, no. 2, p. 351–352. .

Study relevance:

Human health
Substance:

cyclopamine (RF-00004245-PAR)
Additional plant/substance description:

isolated from Veratrum californicum
Type of toxicological test:

reproduction toxicity (CHD009TT)
Tested organism:

Hamster (as animal) (A0CNX)
Sex:

Female
Route of exposure:

ORAL: GAVAGE (OECD2231PL)
Exposure duration:

1.0
Unit of exposure duration:

single (food/feed) (G203A)
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Milligram (G155A)
Effect concentration:

30
Critical effect:

TERATOGENIC (TOX06A)
Target tissue:

Muscle, Skeletal (TT055A)
Effect description:

Approximately 75% of fetuses collected 1 day prior to term (El 5) showed a spectrum of craniofacial abnormalities ranging from premaxillary dysgenesis to cebocephaly.
Effect or parameter linked to the endpoint:

reproduction (CHD014BE)
Internal remarks:

Teratogenicity in hamsters

Endpoint study #3: Welch, K. D., Panter, K. E., Lee, S. T., Gardner, D. R., Stegelmeier, B. L., Cook, D. Cyclopamine-induced synophthalmia in sheep: defining a critical window and toxicokinetic evaluation . journal of applied toxicology, 2009, vol. 29, no. 5, p. 414–421. DOI: 10.1002/jat.1427. [DOI link]

Study relevance:

Animal (target species) health
Substance:

cyclopamine (RF-00004245-PAR)
Plant part:

Roots and other underground parts (as part-nature) (A067M)
Preparation/Extraction method:

Solvent extraction (A0BZR)
Additional plant/substance description:

CH2CL2 - NH4OH extract containing 0.88 mg cyclopamine kg−1 BW
Type of toxicological test:

reproduction toxicity (CHD009TT)
Tested organism:

Sheep (as animal) (A057G)
Sex:

Female
Route of exposure:

ORAL: UNSPECIFIED (OECD2234PL)
Exposure duration:

3.0
Unit of exposure duration:

Day (G134A)
Number of organisms dosed:

20
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Grams per kilogram body weight (G226A)
Effect concentration:

0.88
Critical effect:

TERATOGENIC (TOX06A)
Target tissue:

Muscle, Skeletal (TT055A)
Effect description:

The malformations consisted of many craniofacial malformations ranging from mild maxillary hypoplasia to severe cranial doming, abnormal proboscis formation, to cyclopia and maxillary aplasia
Effect or parameter linked to the endpoint:

reproduction (CHD014BE)
Internal remarks:

Teratogenic toxicity in sheeps

Endpoint study #4: JAMES, LF., PANTER, KE., NIELSEN, DB., MOLYNEUX, RJ. THE EFFECT OF NATURAL TOXINS ON REPRODUCTION IN LIVESTOCK. journal of animal science, 1992, vol. 70, no. 5, p. 1573–1579. .

Study relevance:

Animal (target species) health
Substance:

Steroidal alkaloids (RF-00004336-PAR)
Additional plant/substance description:

Jervine and cyclopamine
Type of toxicological test:

case report (CHD060TT)
Limit test:

Not applicable
Tested organism:

Sheep (as animal) (A057G)
Sex:

No data
Control groups used:

no data
Endpoint measured:

Dose not reported (CHD066EP)
Critical effect:

TERATOGENIC (TOX06A)
Target tissue:

Muscle, Skeletal (TT055A)
Effect description:

Facial defects, skeletal defects, tracheal stenosis Skeletal defects, cleft palate
Effect or parameter linked to the endpoint:

reproduction (CHD014BE)
Internal remarks:

embryotoxic in ewes