EFSA Compendium of Botanicals

Draft - work in progress

Nerium oleander L.

Family:: Apocynaceae
Approval state:: Approved
Number of articles retrieved:: 2212
Number of processed references:: 12

Compositions

#1: digitoxigenin #2: oleandrin #3: Cardiac glycosides: folineriin, adynerin #4: neriantin, adynerin, deacetyloeandrin in leaves #5: cardiac glycosides in leaves #6: oleandrin in leaves

Endpoint Studies

#1: case report: vomiting, GIT distress, cardiac symptoms, mortality #2: case report: vomiting, lightheadedness, heart block #3: case report: vomiting, slowness, drowsiness, bradycardia #4: case reports: acute cattle toxicity, mortality #5: camelids case report: renal, gastrointestinal, and cardiovascular dysfunction #6: poisoning by Nerium oleander in cattle #7: case report: high potassium concentration, cardiac dysrhythmia, acute gastrointestinal complains #8: gastrointestinal and cardiovascular toxicity, arrhythmias, decreased blood pressure #9: hepatotoxicity and nephrotoxicity in mice #10: hepatotoxicity and nephrotoxicity in rats #11: acute toxicity in mice #12: acute toxicity in rats

Genotoxicity

Composition #1: Roberts, Darren M., Gallapatthy, Gamini., Dunuwille, Asunga., Chan, Betty S. Pharmacological treatment of cardiac glycoside poisoning. british journal of clinical pharmacology, 2016, vol. 81, no. 3, p. 488–495. .

Language:

English (en)
Plant part:

Unspecified (A07XD)
Substance:

digitoxigenin (RF-00004273-PAR)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

digitoxigenin

Composition #2: Roberts, Darren M., Gallapatthy, Gamini., Dunuwille, Asunga., Chan, Betty S. Pharmacological treatment of cardiac glycoside poisoning. british journal of clinical pharmacology, 2016, vol. 81, no. 3, p. 488–495. .

Language:

English (en)
Plant part:

Unspecified (A07XD)
Substance:

oleandrin (RF-00003524-PAR)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

oleandrin

Composition #3: Roberts, Darren M., Gallapatthy, Gamini., Dunuwille, Asunga., Chan, Betty S. Pharmacological treatment of cardiac glycoside poisoning. british journal of clinical pharmacology, 2016, vol. 81, no. 3, p. 488–495. .

Language:

English (en)
Plant part:

Unspecified (A07XD)
Substance:

cardiac glycosides (RF-00010823-PAR)
Additional substance description:

folineriin, adynerin
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

Cardiac glycosides: folineriin, adynerin

Composition #4: Dai, Lingpeng., Wang, Wanxian., Dong, Xinjiao., Hu, Renyong., Nan, Xuyang. Molluscicidal activity of cardiac glycosides from Nerium indicum against Pomacea canaliculata and its implications for the mechanisms of toxicity . environmental toxicology and pharmacology, 2011, vol. 32, no. 2, p. 226–232. DOI: 10.1016/j.etap.2011.05.007. [DOI link]

Language:

English (en)
Plant part:

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

Solvent extraction (A0BZR)
Additional extraction description:

ethanol 80%
Substance:

cardiac glycosides (RF-00010823-PAR)
Additional substance description:

neriantin, adynerin, deacetyloeandrin
Analytical method code:

Nuclear Magnetic Resonance (NMR) (F061A)
Analytical method - additional description:

MS
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

neriantin, adynerin, deacetyloeandrin in leaves

Composition #5: Dai, Lingpeng., Wang, Wanxian., Dong, Xinjiao., Hu, Renyong., Nan, Xuyang. Molluscicidal activity of cardiac glycosides from Nerium indicum against Pomacea canaliculata and its implications for the mechanisms of toxicity . environmental toxicology and pharmacology, 2011, vol. 32, no. 2, p. 226–232. DOI: 10.1016/j.etap.2011.05.007. [DOI link]

Language:

English (en)
Plant part:

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

Solvent extraction (A0BZR)
Additional extraction description:

ethanol 80%
Substance:

cardiac glycosides (RF-00010823-PAR)
Analytical method code:

Nuclear Magnetic Resonance (NMR) (F061A)
Analytical method - additional description:

MS
Result unit:

Gram (G148A)
Result expression:

Whole weight (B001A)
Result type:

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

0.0402
Internal remarks:

cardiac glycosides in leaves

Composition #6: Turkmen, Zeynep., Mercan, Selda., Cengiz, Salih. An HPTLC Method for the Determination of Oleandrin in Nerium Plant Extracts and Its Application to Forensic Toxicology . jpc-journal of planar chromatography-modern tlc, 2013, vol. 26, no. 3, p. 279–283. DOI: 10.1556/JPC.26.2013.3.13. [DOI link]

Language:

English (en)
Plant part:

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

Solvent extraction (A0BZR)
Additional extraction description:

ethanol-water (9:1)
Substance:

oleandrin (RF-00003524-PAR)
Analytical method code:

Gelpermeation, High Performance Thin Layer Chromatography (HPTLC) (F017A)
Analytical method - additional description:

MS
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

oleandrin in leaves

Endpoint study #1: Wasfi, Ibrahim A., Zorob, Omar., Al Katheeri, Nawal A., Al Awadhi, Anwar M. A fatal case of oleandrin poisoning. forensic science international, 2008, vol. 179(2-3), p. e31–e36. .

Study relevance:

Human health
Plant part:

Leaves (as part-nature) (A0EKT)
Type of toxicological test:

case report (CHD060TT)
Limit test:

Not applicable
Tested organism:

Human (as organism) (A056J)
Sex:

Male
Exposure duration:

1.0
Unit of exposure duration:

single (food/feed) (G203A)
Number of organisms dosed:

1
Control groups used:

no
Endpoint measured:

Dose not reported (CHD066EP)
Critical effect:

Digestive (TOX18A)
Target tissue:

Cardiovascular / Haematological (TT001A)
Effect description:

vomiting, GIT distress, complete heart block, cardiac arrest, ventricular fibrillation and multiple organ failure, mortality
Effect or parameter linked to the endpoint:

mortality (CHD010BE)
Internal remarks:

case report: vomiting, GIT distress, cardiac symptoms, mortality

Endpoint study #2: Khan, Ibraheem., Kant, Chandra., Sanwaria, Anil., Meena, Lokesh. Acute cardiac toxicity of nerium oleander/indicum poisoning (kaner) poisoning. . heart views : the official journal of the gulf heart association, 2010, vol. 11, no. 3, p. 115–6. DOI: 10.4103/1995-705X.76803. [DOI link]

Study relevance:

Human health
Plant part:

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

Solvent extraction (A0BZR)
Additional plant/substance description:

boiled water
Type of toxicological test:

case report (CHD060TT)
Limit test:

Not applicable
Tested organism:

Human (as organism) (A056J)
Sex:

Female
Route of exposure:

ORAL: DRINKING WATER (OECD2229PL)
Unit of exposure duration:

single (food/feed) (G203A)
Number of organisms dosed:

1
Control groups used:

no
Endpoint measured:

Dose not reported (CHD066EP)
Critical effect:

Digestive (TOX18A)
Target tissue:

neurologic: Central Nervous System (TT035A)
Effect description:

vomiting, lightheadedness, heart block
Effect or parameter linked to the endpoint:

neurology (CHD027BE)
Internal remarks:

case report: vomiting, lightheadedness, heart block

Endpoint study #3: Pietsch, J., Oertel, R., Trautmann, S., Schulz, K., Kopp, B., Dressler, J. A non-fatal oleander poisoning. international journal of legal medicine, 2005, vol. 119, no. 4, p. 236–240. DOI: 10.1007/s00414-005-0548-6. [DOI link]

Study relevance:

Human health
Plant part:

Flower (as part-nature) (A067B)
Type of toxicological test:

case report (CHD060TT)
Tested organism:

Human (as organism) (A056J)
Sex:

Female
Route of exposure:

ORAL: UNSPECIFIED (OECD2234PL)
Exposure duration:

1.0
Unit of exposure duration:

single (food/feed) (G203A)
Number of organisms dosed:

1
Endpoint measured:

Dose not reported (CHD066EP)
Critical effect:

NEUROTOXICITY (TOX04A)
Target tissue:

neurologic: Central Nervous System (TT035A)
Effect description:

vomiting, slowness, drowsiness, bradycardia,
Effect or parameter linked to the endpoint:

neurology (CHD027BE)
Internal remarks:

case report: vomiting, slowness, drowsiness, bradycardia

Endpoint study #4: Soto-Blanco, B., Fontenele-Neto, J. D., Silva, D. M., Reis, P. F. C. C., Nobrega, J. E. Acute cattle intoxication from Nerium oleander pods. tropical animal health and production, 2006, vol. 38, no. 6, p. 451–454. DOI: 10.1007/s11250-006-4400-x. [DOI link]

Study relevance:

Animal (target species) health
Plant part:

Seed (as part-nature) (A066P)
Type of toxicological test:

case report (CHD060TT)
Tested organism:

Cattle (as animal) (A057E)
Sex:

No data
Route of exposure:

ORAL: FEED (OECD2230PL)
Number of organisms dosed:

92
Endpoint measured:

Dose not reported (CHD066EP)
Critical effect:

Digestive (TOX18A)
Target tissue:

neurologic: Central Nervous System (TT035A)
Effect description:

widespread haemorrhagemortality, petechiae, locomotion disturbances, diarrhoea, depression, salivation, tachycardia, rapid breathing, atyxia
Effect or parameter linked to the endpoint:

mortality (CHD010BE)
Internal remarks:

case reports: acute cattle toxicity, mortality

Endpoint study #5: Kozikowski, Tania A., Magdesian, K. Gary., Puschner, Birgit. Oleander intoxication in New World camelids: 12 cases (1995-2006). javma-journal of the american veterinary medical association, 2009, vol. 235, no. 3, p. 305–310. .

Study relevance:

Human health
Plant part:

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

case report (CHD060TT)
Tested organism:

Animals (as animal) (A04SF)
Sex:

No data
Route of exposure:

ORAL: FEED (OECD2230PL)
Number of organisms dosed:

12
Control groups used:

no
Endpoint measured:

Dose not reported (CHD066EP)
Critical effect:

NEPHROTOXICITY (TOX03A)
Target tissue:

Digestive (TT002A)
Effect description:

renal, gastrointestinal, and cardiovascular dysfunction
Effect or parameter linked to the endpoint:

other (CHD003BE)
Internal remarks:

camelids case report: renal, gastrointestinal, and cardiovascular dysfunction

Endpoint study #6: Pedroso, Pedro M. O., Bandarra, Paulo M., Bezerra Junior, Pedro S., Raymundo, Djeison L., Borba, Mauro R., Leal, Juliano S., Driemeier, David. Natural and experimental poisoning by Nerium oleander (Apocynaceae) in cattle in Rio Grande do Sul . pesquisa veterinaria brasileira, 2009, vol. 29, no. 5, p. 404–408. .

Study relevance:

Animal (target species) health
Plant part:

Leaves (as part-nature) (A0EKT)
Type of toxicological test:

case report (CHD060TT)
Sex:

Male/Female
Route of exposure:

ORAL: FEED (OECD2230PL)
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Gram/kilogram (G015A)
Effect concentration:

0.5-1.0
Critical effect:

PULMONARY AND CARDIAC (TOX08A)
Target tissue:

cardiovascular / haematological: Heart (TT011A)
Effect description:

petechiae and ecchymosis in the left atrium, clots and hemorrhages in the left ventricle endocardium, slightly pale areas in the interventricular septum and in some portions of the myocardium of the ventricles
Effect or parameter linked to the endpoint:

mortality (CHD010BE)
Internal remarks:

poisoning by Nerium oleander in cattle

Endpoint study #7: Bavunoglu, Isil., Balta, Musa., Turkmen, Zeynep. Oleander Poisoning as an Example of Self-Medication Attempt. balkan medical journal, 2016, vol. 33, no. 5, p. 559–562. DOI: 10.5152/balkanmedj.2016.150307. [DOI link]

Study relevance:

Human health
Plant part:

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

Solvent extraction (A0BZR)
Additional plant/substance description:

boiled water
Type of toxicological test:

case report (CHD060TT)
Tested organism:

Human (as organism) (A056J)
Sex:

Female
Exposure duration:

2.0
Unit of exposure duration:

Events per day (G236A)
Number of organisms dosed:

1
Control groups used:

no
Endpoint measured:

Dose not reported (CHD066EP)
Critical effect:

Digestive (TOX18A)
Target tissue:

cardiovascular / haematological: Heart (TT011A)
Effect description:

high potassium concentration, cardiac dysrhythmia, diarrhea, vomiting, abdominal pain
Effect or parameter linked to the endpoint:

haematology (CHD023BE)
Internal remarks:

case report: high potassium concentration, cardiac dysrhythmia, acute gastrointestinal complains

Endpoint study #8: Camplesi, Annelise Carla., Bellodi, Carolina., Mesa Socha, Jose Javier., Hatayde, Mario Roberto., da Rosa Sobreira, Marcia Ferreira., Marques Araujo, Gustavo Henrique., Moya Araujo, Carla Fredrichsen. Dogs poisoned with Nerium oleander fresh leaves: clinical and electrocardiographic findings . ciencia rural, 2017, vol. 47, no. 6 . DOI: 10.1590/0103-8478cr20160970. [DOI link]

Study relevance:

Human health
Plant part:

Leaves (as part-nature) (A0EKT)
Type of toxicological test:

acute toxicity (CHD016TT)
Tested organism:

Dog (as animal) (A0CNL)
Sex:

No data
Route of exposure:

ORAL: FEED (OECD2230PL)
Unit of exposure duration:

single (food/feed) (G203A)
Control groups used:

no
Endpoint measured:

Dietary dose producing lethality in 50% of experimental organisms (CHD004EP)
Concentration unit:

Grams per kilogram body weight (G226A)
Effect concentration:

0.25
Critical effect:

Digestive (TOX18A)
Target tissue:

neurologic: Central Nervous System (TT035A)
Effect description:

vomiting, sialorrhea, nausea, apathy, conjunctiva congestion, dehydration, abdominal pain, tremors, diarrhea, loss of appetite, and tenesmus, arrhytmias, decreased systolic blood prssure,
Effect or parameter linked to the endpoint:

mortality (CHD010BE)
Internal remarks:

gastrointestinal and cardiovascular toxicity, arrhythmias, decreased blood pressure

Endpoint study #9: Khordadmehr, Monire., Nazifi, Saeed., Mansourian, Maryam., Basiri, Sara., Kolahian, Saeed. Experimental Nerium oleander poisoning in Balb/c mice and Wistar rat: comparative hepatotoxicity and nephrotoxicity effects based on biochemical and pathological studies . turkish journal of biochemistry-turk biyokimya dergisi, 2017, vol. 42, no. 4, p. 427–434. DOI: 10.1515/tjb-2016-0285. [DOI link]

Study relevance:

Human health
Plant part:

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

Solvent extraction (A0BZR)
Additional plant/substance description:

water 100°C
Type of toxicological test:

short-term toxicity (CHD017TT)
Tested organism:

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

Balb/c (CHD002ST)
Sex:

Male
Route of exposure:

ORAL: GAVAGE (OECD2231PL)
Exposure duration:

4.0
Unit of exposure duration:

Day (G134A)
Number of organisms dosed:

10
Control groups used:

yes, concurrent vehicle
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Milligrams per kilogram body weight (G225A)
Effect concentration:

10
Critical effect:

HEPATOTOXICITY (TOX02A)
Target tissue:

urogenital: Kidneys (TT046A)
Effect description:

increased AST, ALT, BUN, decreased creatinine, hyperemia, hemorrhage, cosgulative necrosis and interstitial nephritis, inflammatory cell infiltration in kidneys, hyperemia, hemorrhage, coagulative necrosis, hepatitis in liver
Effect or parameter linked to the endpoint:

histopathology non neoplastic (CHD025BE)
Internal remarks:

hepatotoxicity and nephrotoxicity in mice

Endpoint study #10: Khordadmehr, Monire., Nazifi, Saeed., Mansourian, Maryam., Basiri, Sara., Kolahian, Saeed. Experimental Nerium oleander poisoning in Balb/c mice and Wistar rat: comparative hepatotoxicity and nephrotoxicity effects based on biochemical and pathological studies . turkish journal of biochemistry-turk biyokimya dergisi, 2017, vol. 42, no. 4, p. 427–434. DOI: 10.1515/tjb-2016-0285. [DOI link]

Study relevance:

Human health
Plant part:

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

Solvent extraction (A0BZR)
Additional plant/substance description:

water 100°C
Type of toxicological test:

short-term toxicity (CHD017TT)
Tested organism:

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

Wistar (CHD013ST)
Sex:

Male
Route of exposure:

ORAL: GAVAGE (OECD2231PL)
Exposure duration:

4.0
Unit of exposure duration:

Day (G134A)
Number of organisms dosed:

10
Control groups used:

yes, concurrent vehicle
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Milligrams per kilogram body weight (G225A)
Effect concentration:

10
Critical effect:

HEPATOTOXICITY (TOX02A)
Target tissue:

urogenital: Kidneys (TT046A)
Effect description:

increased AST, ALT, BUN, decreased creatinine, hyperemia, hemorrhage, cosgulative necrosis and interstitial nephritis, inflammatory cell infiltration in kidneys, hyperemia, hemorrhage, coagulative necrosis, hepatitis in liver
Effect or parameter linked to the endpoint:

histopathology non neoplastic (CHD025BE)
Internal remarks:

hepatotoxicity and nephrotoxicity in rats

Endpoint study #11: Khordadmehr, Monire., Nazifi, Saeed., Mansourian, Maryam., Basiri, Sara., Kolahian, Saeed. Experimental Nerium oleander poisoning in Balb/c mice and Wistar rat: comparative hepatotoxicity and nephrotoxicity effects based on biochemical and pathological studies . turkish journal of biochemistry-turk biyokimya dergisi, 2017, vol. 42, no. 4, p. 427–434. DOI: 10.1515/tjb-2016-0285. [DOI link]

Study relevance:

Human health
Plant part:

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

Solvent extraction (A0BZR)
Additional plant/substance description:

water 100°C
Type of toxicological test:

acute toxicity (CHD016TT)
Tested organism:

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

Balb/c (CHD002ST)
Sex:

Male
Route of exposure:

ORAL: GAVAGE (OECD2231PL)
Exposure duration:

12.0
Unit of exposure duration:

Hour (G099A)
Number of organisms dosed:

10
Control groups used:

yes, concurrent vehicle
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Milligrams per kilogram body weight (G225A)
Effect concentration:

20
Critical effect:

SYSTEMIC (TOX01A)
Target tissue:

neurologic: Central Nervous System (TT035A)
Effect description:

anorexia, nervous signs, depression, restlessness, crying, ataxia, pawing of the ground, convulsion, falling and turning of the head backward
Effect or parameter linked to the endpoint:

behaviour (CHD001BE)
Internal remarks:

acute toxicity in mice

Endpoint study #12: Khordadmehr, Monire., Nazifi, Saeed., Mansourian, Maryam., Basiri, Sara., Kolahian, Saeed. Experimental Nerium oleander poisoning in Balb/c mice and Wistar rat: comparative hepatotoxicity and nephrotoxicity effects based on biochemical and pathological studies . turkish journal of biochemistry-turk biyokimya dergisi, 2017, vol. 42, no. 4, p. 427–434. DOI: 10.1515/tjb-2016-0285. [DOI link]

Study relevance:

Human health
Plant part:

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

Solvent extraction (A0BZR)
Additional plant/substance description:

water 100°C
Type of toxicological test:

acute toxicity (CHD016TT)
Tested organism:

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

Wistar (CHD013ST)
Sex:

Male
Route of exposure:

ORAL: GAVAGE (OECD2231PL)
Exposure duration:

12.0
Unit of exposure duration:

Hour (G099A)
Number of organisms dosed:

10
Control groups used:

yes, concurrent vehicle
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Milligrams per kilogram body weight (G225A)
Effect concentration:

20
Critical effect:

SYSTEMIC (TOX01A)
Target tissue:

neurologic: Central Nervous System (TT035A)
Effect description:

anorexia, nervous signs, depression, restlessness, crying, ataxia, pawing of the ground, convulsion, falling and turning of the head backward
Effect or parameter linked to the endpoint:

behaviour (CHD001BE)
Internal remarks:

acute toxicity in rats