EFSA Compendium of Botanicals

Draft - work in progress

Heliotropium europaeum L.

Family:: Boraginaceae
Approval state:: Approved
Number of articles retrieved:: 226
Number of processed references:: 10

Compositions

#1: Lasiocarpine and derivatives in whole plants #2: Heleurine (a pyrrolizidine alkaloid) in seeds #3: Europine (a pyrrolizidine alkaloid) in seeds #4: Lasiocarpine (a pyrrolizidine alkaloid) in seeds #5: Supinine (a pyrrolizidine alkaloid) in seeds #6: Heliotrine and 7-angelylheliotrine (pyrrolizidine alkaloids) in seeds #7: Lasiocarpine in plant #8: Pyrollizidine alkaloids in seeds #9: Pyrrolizidine alkaloids in aerial parts #10: Europine-N-oxide #11: Heliotrine-N-oxide #12: Lasiocarpine-N-oxide

Endpoint Studies

#1: Hepatotoxicity and mortality in cows #2: Hepatotoxicity and liver DNA-adducts in cattle fed pyrrolizidine alkaloids in contaminated feed #3: Mortality, preceded by neurologic effects, and digestive effects (loss of appetite, diarrhea) in cattle #4: Liver and kidney effects in chickens #5: Liver and kidney effects and mortality in pigs #6: Mortality and liver lesions

Genotoxicity

#1: calf thymus DNA adduct formation in presence of lasiocarpine during metabolism in vitro by rat liver microsomes

Composition #1: Yassa, N., Farsam, H., Rustaiyan, A., Shafiee, A. Alkaloids of boraginaceae II 1, pyrrolizidine alkaloids of Heliotropium europaeum L. population garmsar. journal of sciences, islamic republic of iran, 1999, vol. 10, no. 1, p. 39–42. .

Language:

English (en)
Plant part:

Live plants (as part-nature) (A0BA0)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

methanol
Substance:

Lasiocarpine-N-oxide (RF-00000289-TOX)
Additional substance description:

also, lasiocarpine and a derivative: acetyllasiocarpine-N-oxide
Analytical method code:

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

Also: IR, NMR, MS
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

Lasiocarpine and derivatives in whole plants

Composition #2: Tosun, F., Tamer, U. Determination of pyrrolizidine alkaloids in the seeds of Heliotropium europaeum by GC-MS. ankara universitesi eczacilik fakultesi dergisi, 2004, vol. 33, no. 1, p. 7–9. .

Language:

English (en)
Plant part:

Seed (as part-nature) (A066P)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

hexane and H2SO4
Substance:

Heleurine (RF-00009189-PAR)
Additional substance description:

a pyrrolizidine alkaloid
Analytical method code:

GC-MS (F046A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

Heleurine (a pyrrolizidine alkaloid) in seeds

Composition #3: Tosun, F., Tamer, U. Determination of pyrrolizidine alkaloids in the seeds of Heliotropium europaeum by GC-MS. ankara universitesi eczacilik fakultesi dergisi, 2004, vol. 33, no. 1, p. 7–9. .

Language:

English (en)
Plant part:

Seed (as part-nature) (A066P)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

hexane and H2SO4
Substance:

Europine (RF-00000390-TOX)
Additional substance description:

a pyrrolizidine alkaloid
Analytical method code:

GC-MS (F046A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

Europine (a pyrrolizidine alkaloid) in seeds

Composition #4: Tosun, F., Tamer, U. Determination of pyrrolizidine alkaloids in the seeds of Heliotropium europaeum by GC-MS. ankara universitesi eczacilik fakultesi dergisi, 2004, vol. 33, no. 1, p. 7–9. .

Language:

English (en)
Plant part:

Seed (as part-nature) (A066P)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

hexane and H2SO4
Substance:

Lasiocarpine (RF-00000241-TOX)
Additional substance description:

a pyrrolizidine alkaloid
Analytical method code:

GC-MS (F046A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

Lasiocarpine (a pyrrolizidine alkaloid) in seeds

Composition #5: Tosun, F., Tamer, U. Determination of pyrrolizidine alkaloids in the seeds of Heliotropium europaeum by GC-MS. ankara universitesi eczacilik fakultesi dergisi, 2004, vol. 33, no. 1, p. 7–9. .

Language:

English (en)
Plant part:

Seed (as part-nature) (A066P)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

hexane and H2SO4
Substance:

Supinine (RF-00000302-TOX)
Additional substance description:

a pyrrolizidine alkaloid
Analytical method code:

GC-MS (F046A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

Supinine (a pyrrolizidine alkaloid) in seeds

Composition #6: Tosun, F., Tamer, U. Determination of pyrrolizidine alkaloids in the seeds of Heliotropium europaeum by GC-MS. ankara universitesi eczacilik fakultesi dergisi, 2004, vol. 33, no. 1, p. 7–9. .

Language:

English (en)
Plant part:

Seed (as part-nature) (A066P)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

hexane and H2SO4
Substance:

Heliotrine (RF-00000240-TOX)
Additional substance description:

also 7-angelylheliotrine, both pyrrolizidine alkaloids
Analytical method code:

GC-MS (F046A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

Heliotrine and 7-angelylheliotrine (pyrrolizidine alkaloids) in seeds

Composition #7: Xia, QS., Chou, MW., Edgar, JA., Doerge, DR., Fu, PP. Formation of DHP-derived DNA adducts from metabolic activation of the prototype heliotridine-type pyrrolizidine alkaloid, lasiocarpine . cancer letters, 2006, vol. 231, no. 1, p. 138–145. DOI: 10.1016/j.canlet.2005.01.023. [DOI link]

Language:

English (en)
Plant part:

Unspecified (A07XD)
Substance:

Lasiocarpine (RF-00000241-TOX)
Additional substance description:

isolated from the plant with 99% purity
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:

Lasiocarpine in plant

Composition #8: These, Anja., Bodi, Dorina., Ronczka, Stefan., Lahrssen-Wiederholt, Monika., Preiss-Weigert, Angelika. Structural screening by multiple reaction monitoring as a new approach for tandem mass spectrometry: presented for the determination of pyrrolizidine alkaloids in plants . analytical and bioanalytical chemistry, 2013, vol. 405, no. 29, p. 9375–9383. DOI: 10.1007/s00216-013-7365-4. [DOI link]

Language:

English (en)
Plant part:

Seed (as part-nature) (A066P)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

25% methanol in 2% formic acid
Substance:

Pyrrolizidine alkaloids (RF-00000230-TOX)
Analytical method code:

HPLC with standard detection methods (F019A)
Analytical method - additional description:

HPLC-ESI-MS/MS (tandem mass spec)
Result unit:

Percent (G138A)
Result type:

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

3.68
Internal remarks:

Pyrollizidine alkaloids in seeds

Composition #9: Shimshoni, Jakob Avi., Mulder, Patrick P. J., Bouznach, Arieli., Edery, Nir., Pasval, Israel., Barel, Shimon., Khaliq, Mohammed Abd-El., Perl, Samuel. Heliotropium europaeum Poisoning in Cattle and Analysis of Its Pyrrolizidine Alkaloid Profile . journal of agricultural and food chemistry, 2015, vol. 63, no. 5, p. 1664–1672. DOI: 10.1021/jf5052199. [DOI link]

Language:

English (en)
Plant part:

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

Solvent extraction (A0BZR)
Additional extraction description:

2% formic acid solution in a 1:100 (w/v) ratio
Substance:

Pyrrolizidine alkaloids (RF-00000230-TOX)
Additional substance description:

Heliotrine and lasiocarpine-type PAs constituted 80% and 18% of the total PAs, respectively
Analytical method code:

LC-MS/MS (F027A)
Result unit:

Milligram/gram (G060A)
Result expression:

Dry matter (B002A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

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

27.7
Internal remarks:

Pyrrolizidine alkaloids in aerial parts

Composition #10: Fu, Peter P., Xia, Qingsu., He, Xiaobo., Barel, Shimon., Edery, Nir., Beland, Frederick A., Shimshoni, Jakob A. Detection of Pyrrolizidine Alkaloid DNA Adducts in Livers of Cattle Poisoned with Heliotropium europaeum . chemical research in toxicology, 2017, vol. 30, no. 3, p. 851–858. DOI: 10.1021/acs.chemrestox.6b00456. [DOI link]

Language:

English (en)
Plant part:

Unspecified (A07XD)
Substance:

Europine-N-oxide (RF-00000391-TOX)
Analytical method code:

Unspecified (F598A)
Result expression:

Dry matter (B002A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

Europine-N-oxide

Composition #11: Fu, Peter P., Xia, Qingsu., He, Xiaobo., Barel, Shimon., Edery, Nir., Beland, Frederick A., Shimshoni, Jakob A. Detection of Pyrrolizidine Alkaloid DNA Adducts in Livers of Cattle Poisoned with Heliotropium europaeum . chemical research in toxicology, 2017, vol. 30, no. 3, p. 851–858. DOI: 10.1021/acs.chemrestox.6b00456. [DOI link]

Language:

English (en)
Plant part:

Unspecified (A07XD)
Substance:

Heliotrine-N-oxide (RF-00000363-TOX)
Analytical method code:

Unspecified (F598A)
Result expression:

Dry matter (B002A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

Heliotrine-N-oxide

Composition #12: Fu, Peter P., Xia, Qingsu., He, Xiaobo., Barel, Shimon., Edery, Nir., Beland, Frederick A., Shimshoni, Jakob A. Detection of Pyrrolizidine Alkaloid DNA Adducts in Livers of Cattle Poisoned with Heliotropium europaeum . chemical research in toxicology, 2017, vol. 30, no. 3, p. 851–858. DOI: 10.1021/acs.chemrestox.6b00456. [DOI link]

Language:

English (en)
Plant part:

Unspecified (A07XD)
Substance:

Lasiocarpine-N-oxide (RF-00000289-TOX)
Analytical method code:

Unspecified (F598A)
Result expression:

Dry matter (B002A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

Lasiocarpine-N-oxide

Endpoint study #1: Shimshoni, Jakob Avi., Mulder, Patrick P. J., Bouznach, Arieli., Edery, Nir., Pasval, Israel., Barel, Shimon., Khaliq, Mohammed Abd-El., Perl, Samuel. Heliotropium europaeum Poisoning in Cattle and Analysis of Its Pyrrolizidine Alkaloid Profile . journal of agricultural and food chemistry, 2015, vol. 63, no. 5, p. 1664–1672. DOI: 10.1021/jf5052199. [DOI link]

Study relevance:

Animal (target species) health
Plant part:

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

Drying (dehydration) (A07KG)
Additional plant/substance description:

Dried green plant material accidentally contaminated feed hay
Type of toxicological test:

case report (CHD060TT)
Tested organism:

Cattle (as animal) (A057E)
Sex:

No data
Route of exposure:

ORAL: FEED (OECD2230PL)
Exposure duration:

42.0
Unit of exposure duration:

Day (G134A)
Number of organisms dosed:

73
Control groups used:

no
Endpoint measured:

Dose not reported (CHD066EP)
Critical effect:

HEPATOTOXICITY (TOX02A)
Target tissue:

digestive: Liver (TT023A)
Effect description:

33% of cattle died within 68 days after exposure. Mostly liver lesions: hyperplasias and cirrhosis.
Effect or parameter linked to the endpoint:

mortality (CHD010BE)
Internal remarks:

Hepatotoxicity and mortality in cows

Endpoint study #2: Fu, Peter P., Xia, Qingsu., He, Xiaobo., Barel, Shimon., Edery, Nir., Beland, Frederick A., Shimshoni, Jakob A. Detection of Pyrrolizidine Alkaloid DNA Adducts in Livers of Cattle Poisoned with Heliotropium europaeum . chemical research in toxicology, 2017, vol. 30, no. 3, p. 851–858. DOI: 10.1021/acs.chemrestox.6b00456. [DOI link]

Study relevance:

Human health
Substance:

Pyrrolizidine alkaloids (RF-00000230-TOX)
Plant part:

Unspecified (A07XD)
Additional plant/substance description:

Hay feed contaminated with ~15% H. europaeum. Dose level below is amount of total PAs from plant in ingested from feed daily.
Type of toxicological test:

short-term toxicity (CHD017TT)
Tested organism:

Cattle (as animal) (A057E)
Sex:

No data
Route of exposure:

ORAL: FEED (OECD2230PL)
Exposure duration:

6.0
Unit of exposure duration:

Week (G205A)
Number of organisms dosed:

73
Control groups used:

yes
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

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

34
Critical effect:

HEPATOTOXICITY (TOX02A)
Target tissue:

digestive: Liver (TT023A)
Effect description:

Histopathology of livers revealed: bile duct hyperplasia, periportal fibrosis, and megalocytosis. DNA adducts observed in liver also.
Effect or parameter linked to the endpoint:

histopathology non neoplastic (CHD025BE)
Internal remarks:

Hepatotoxicity and liver DNA-adducts in cattle fed pyrrolizidine alkaloids in contaminated feed

Endpoint study #3: MCLENNAN, MW., DODSON, ME., RAC, R. HELIOTROPIUM POISONING IN CATTLE. australian veterinary journal, 1972, vol. 48, no. 8, p. 480–&. DOI: 10.1111/j.1751-0813.1972.tb02302.x. [DOI link]

Study relevance:

Animal (target species) health
Plant part:

Unspecified (A07XD)
Additional plant/substance description:

consumed from fresh grazing
Type of toxicological test:

case report (CHD060TT)
Tested organism:

Cattle (as animal) (A057E)
Sex:

Female
Route of exposure:

ORAL: FEED (OECD2230PL)
Number of organisms dosed:

13
Control groups used:

no
Endpoint measured:

Dose not reported (CHD066EP)
Critical effect:

SYSTEMIC (TOX01A)
Target tissue:

Neurologic (TT004A)
Effect description:

Death, depression, ascites, diarrhea, photosensitisation, oedema, toxic effect on liver.
Effect or parameter linked to the endpoint:

mortality (CHD010BE)
Internal remarks:

Mortality, preceded by neurologic effects, and digestive effects (loss of appetite, diarrhea) in cattle

Endpoint study #4: PASSLL, DA., HOGG, GG., RUSSELL, RG., EDGAR, JA., TENCE, IM., RIKARDBELL, L. POISONING OF CHICKENS AND DUCKS BY PYRROLIZIDINE ALKALOIDS OF HELIOTROPIUM-EUROPAEUM . australian veterinary journal, 1979, vol. 55, no. 6, p. 284–288. DOI: 10.1111/j.1751-0813.1979.tb00397.x. [DOI link]

Study relevance:

Animal (target species) health
Plant part:

Unspecified (A07XD)
Additional plant/substance description:

mixed with 50% lucerne feed pellets
Type of toxicological test:

short-term toxicity (CHD017TT)
Tested organism:

Gallus gallus (chicken) (as animal) (A057Z)
Route of exposure:

ORAL: FEED (OECD2230PL)
Exposure duration:

13.0
Unit of exposure duration:

Day (G134A)
Number of organisms dosed:

8
Control groups used:

yes, plain diet
Endpoint measured:

Dose not reported (CHD066EP)
Critical effect:

HEPATOTOXICITY (TOX02A)
Target tissue:

urogenital: Kidneys (TT046A)
Effect description:

Microscopic changes in the liver: periacinar fatty change, enlarged pale nuclei in many hepatocytes, distortion and widening of sinusoids and foci of dissociated hepatocytes and haemorrhage. Also renal lesions.
Effect or parameter linked to the endpoint:

histopathology non neoplastic (CHD025BE)
Internal remarks:

Liver and kidney effects in chickens

Endpoint study #5: JONES, RT., DRUMMOND, GR., CHATHAM, RO. HELIOTROPIUM-EUROPAEUM POISONING OF PIGS. australian veterinary journal, 1981, vol. 57, no. 8, p. 396–396. DOI: 10.1111/j.1751-0813.1981.tb00537.x. [DOI link]

Study relevance:

Animal (target species) health
Plant part:

Seed (as part-nature) (A066P)
Additional plant/substance description:

seeds mixed in/contaminated feed. Total pyrrolizidine alkaloid content : 117 ppm
Type of toxicological test:

case report (CHD060TT)
Tested organism:

Pig (as animal) (A057F)
Sex:

Female
Route of exposure:

ORAL: FEED (OECD2230PL)
Number of organisms dosed:

100
Control groups used:

no
Endpoint measured:

Dose not reported (CHD066EP)
Critical effect:

HEPATOTOXICITY (TOX02A)
Target tissue:

digestive: Liver (TT023A)
Effect description:

Death and lesions in liver megalocytosis, periportal fibrosis, and periacinar necrosis. Renal megalocytosis.
Effect or parameter linked to the endpoint:

mortality (CHD010BE)
Internal remarks:

Liver and kidney effects and mortality in pigs

Endpoint study #6: PETERSON, JE., PAYNE, AL., CULVENOR, CCJ. HELIOTROPIUM-EUROPEAUM POISONING OF SHEEP WITH LOW LIVER COPPER CONCENTRATIONS AND THE PREVENTIVE EFFICACY OF COBALT AND ANTIMETHANOGEN . australian veterinary journal, 1992, vol. 69, no. 3, p. 51–56. DOI: 10.1111/j.1751-0813.1992.tb07448.x. [DOI link]

Study relevance:

Animal (target species) health
Plant part:

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

Fresh (A166Y)
Additional plant/substance description:

Total pyrrolizidine alkaloid content: 0.36-1.46%
Type of toxicological test:

subchronic (CHD013TT)
Tested organism:

Sheep (as animal) (A057G)
Sex:

Male/Female
Route of exposure:

ORAL: FEED (OECD2230PL)
Exposure duration:

4.0
Unit of exposure duration:

Month (G206A)
Number of organisms dosed:

30
Control groups used:

yes
Endpoint measured:

Concentration level (CHD013EP)
Concentration unit:

Percent (G138A)
Effect concentration:

0.36-1.46
Critical effect:

HEPATOTOXICITY (TOX02A)
Target tissue:

digestive: Liver (TT023A)
Effect description:

Estimated that H.p. contributed to 23-37% of deaths. The principal lesions in livers were parenchymal megalocytosis, proliferation of biliary tissue, fibrosis and nodular regeneration.
Effect or parameter linked to the endpoint:

mortality (CHD010BE)
Internal remarks:

Mortality and liver lesions

Genotox #1: Xia, QS., Chou, MW., Edgar, JA., Doerge, DR., Fu, PP. Formation of DHP-derived DNA adducts from metabolic activation of the prototype heliotridine-type pyrrolizidine alkaloid, lasiocarpine . cancer letters, 2006, vol. 231, no. 1, p. 138–145. DOI: 10.1016/j.canlet.2005.01.023. [DOI link]

Study category:

Genotoxicity
Type of toxicological test:

DNA damage and repair assay, unscheduled DNA synthesis in mammalian cells in vitro (CHD038TT)
Method type:

in vitro
Tested organism:

Other (A07XE)
Control groups used:

yes
Endpoint measured:

DNA damage and/or repair
Is genotoxic:

Positive
Remarks on genotox study:

Lasiocarpine extracted from the plant caused DHP-DNA adducts to form in calf thymus DNA when metabolized by rat liver microsomes in vitro
Internal remarks:

calf thymus DNA adduct formation in presence of lasiocarpine during metabolism in vitro by rat liver microsomes
Internal ID:

WOS:000234622600016