Ilex aquifolium L.
| 1. NAME |
| 1.1 Scientific name |
| 1.2 Family |
| 1.3 Common name(s) |
| 2. SUMMARY |
| 2.1 Main risks and target organs |
| 2.2 Summary of clinical effects |
| 2.3 Diagnosis |
| 2.4 First-aid measures and management principles |
| 2.5 Poisonous parts |
| 2.6 Main toxins |
| 3. CHARACTERISTICS |
| 3.1 Description of the plant |
| 3.1.1 Special identification features |
| 3.1.2 Habitat |
| 3.1.3 Distribution |
| 3.2 Poisonous parts of the plant |
| 3.3 The toxin(s) |
| 3.3.1 Name(s) |
| 3.3.2 Description, chemical structure, stability |
| 3.3.3 Other physico-chemical characteristics |
| 3.4 Other chemical contents of the plant |
| 4. USES/CIRCUMSTANCES OF POISONING |
| 4.1 Uses |
| 4.2 High risk circumstances |
| 4.3 High risk geographical areas |
| 5. ROUTES OF ENTRY |
| 5.1 Oral |
| 5.2 Inhalation |
| 5.3 Dermal |
| 5.4 Eye |
| 5.5 Parenteral |
| 5.6 Others |
| 6. KINETICS |
| 6.1 Absorption by route of exposure |
| 6.2 Distribution by route of exposure |
| 6.3 Biological half-life by route of exposure |
| 6.4 Metabolism |
| 6.5 Elimination by route of exposure |
| 7. TOXICOLOGY/TOXINOLOGY/PHARMACOLOGY |
| 7.1 Mode of action |
| 7.2 Toxicity |
| 7.2.1 Human data |
| 7.2.1.1 Adults |
| 7.2.1.2 Children |
| 7.2.2 Animal data |
| 7.2.3 Relevant vitro data |
| 7.3 Carcinogenicity |
| 7.4 Teratogenicity |
| 7.5 Mutagenicity |
| 7.6 Interactions |
| 8. TOXICOLOGICAL/TOXINOLOGICAL ANALYSIS |
| 9. CLINICAL EFFECTS |
| 9.1 Acute poisoning by: |
| 9.1.1 Ingestion |
| 9.1.2 Inhalation |
| 9.1.3 Skin exposure |
| 9.1.4 Eye contact |
| 9.1.5 Parenteral exposure |
| 9.1.6 Other |
| 9.2 Chronic poisoning by: |
| 9.2.1 Ingestion |
| 9.2.2 Inhalation |
| 9.2.3 Skin exposure |
| 9.2.4 Eye contact |
| 9.2.5 Parenteral exposure |
| 9.2.6 Other |
| 9.3 Course, prognosis, cause of death |
| 9.4 Systematic description of clinical effects |
| 9.4.1 Cardiovascular |
| 9.4.2 Respiratory |
| 9.4.3 Neurological |
| 9.4.3.1 CNS |
| 9.4.3.2 Peripheral nervous system |
| 9.4.3.3 Autonomic nervous system |
| 9.4.3.4 Skeletal and smooth muscle |
| 9.4.4 Gastrointestinal |
| 9.4.5 Hepatic |
| 9.4.6 Urinary |
| 9.4.6.1 Renal |
| 9.4.6.2 Others |
| 9.4.7 Endocrine and reproductive system |
| 9.4.8 Dermatological |
| 9.4.9 Eyes, ear, nose, throat : local effects |
| 9.4.10 Haematological |
| 9.4.11 Immunological |
| 9.4.12 Metabolic |
| 9.4.12.1 Acid base disturbances |
| 9.4.12.2 Fluid and electrolyte disturbances |
| 9.4.12.3 Others |
| 9.4.13 Allergic reactions |
| 9.4.14 Other clinical effects |
| 9.4.15 Special risks: pregnancy, breast feeding, enzyme |
| 9.5 Others |
| 10. MANAGEMENT |
| 10.1 General principles |
| 10.2 Relevant laboratory analyses and other investigations |
| 10.2.1 Sample collection |
| 10.2.2 Biomedical analysis |
| 10.2.3 Toxicological/Toxinological analysis |
| 10.2.4 Other investigations |
| 10.3 Life supportive procedures and symptomatic treatment |
| 10.4 Decontamination |
| 10.5 Elimination |
| 10.6 Antidote treatment |
| 10.6.1 Adults |
| 10.6.2 Children |
| 10.7 Management discussion: alternatives and controversies, research |
| 11. ILLUSTRATIVE CASES |
| 11.1 Case reports from literature |
| 11.2 Internally extracted data on cases |
| 11.3 Internal cases (added by the PC using monograph). |
| 12. ADDITIONAL INFORMATION |
| 12.1 Availability of antidotes and antisera |
| 12.2 Specific preventive measures |
| 12.3 Other |
| 13. REFERENCES |
| 13.1 Clinical and toxicological |
| 13.2 Botanical |
| 14. AUTHOR(S), REVIEWER(S), DATES, COMPLETE ADDRESSES |
1. NAME
1.1 Scientific name
Ilex aquifolium
1.2 Family
Aquifoliaceae
1.3 Common name(s)
UK: European Holly, English Holly, Oregon Holly, Sparked Holly,
Christmas Holly, Crocodile Holly, Prick Holly, Holly,
Common Holly, Holly Green.
France: Houx, Houx Epineux, Housson, Grand Pardon, Bois Franc,
Greou, Agrifous, Agriou, Grifeuil, Agabousse, Alquiroux.
Spain: Acebo Comun.
Germany: Stechpalme, Hulst, Hülse.
Italy: Aquifolio Comune, Alloro Spinoso, Leccio Spinoso.
2. SUMMARY
2.1 Main risks and target organs
Poisoning by ilex aquifolium is due to the ingestion of
berries, which may induce gastrointestinal symptoms.
2.2 Summary of clinical effects
Ingestion of berries may cause nausea, vomiting, abdominal pain
and diarrhoea. Stupor and drowsiness have been seen in children
after ingestion of large quantities of berries. Although lethal
cases have been reported in older literature there are no
recent reports of severe poisonings. Ingestion of Ilex
aquifolium berries is mostly associated with gastrointestinal
symptoms.
Mechanical damage to the eye may occur due to the thorny
leaves.
2.3 Diagnosis
There are no specific laboratory analyses. Identification of
the plant and berries is easy.
2.4 First-aid measures and management principles
Emesis or gastric lavage may be indicated in recent ingestion
of more than 5-10 berries in a child.
Hospitalization is indicated if large amounts have been
ingested.
Symptomatic treatment of gastrointestinal symptoms.
2.5 Poisonous parts
All parts of the plant contain active principles (Aliharidis,
1987).
2.6 Main toxins
Ilex aquifolium contains several toxins: saponin, phenolic
compounds, terpenoides, sterols, alkaloids, anthocyanines
(Thomas, 1980, Alikaridis 1987).
3. CHARACTERISTICS
3.1 Description of the plant
3.1.1 Special identification features
Ilex aquifolium is an evergreen tree 1-20 metres high.
Leaves: dark green, shining, hard, thorny on the young
branches.
Flowers: small, white, rosy, fragrant; situated at the
base of the leaves (from April to July).
Fruits: globulose, red berries of 8 mm diameter. Each
berry contains 4 seeds (from August to October-December).
3.1.2 Habitat
Ilex aquifolium grows in forests, parks, gardens and in
plains and mountain areas.
3.1.3 Distribution
Native plant of Europe. It is also cultivated as an
ornamental tree in North America and North Africa.
3.2 Poisonous parts of the plant
Leaves, bark, berries contain active principles; no information
available on roots.
3.3 The toxin(s)
3.3.1 Name(s)
Several active principles have been identified:
Phenolic derivatives: vanillic acid, p-hydroxybenzoic
acid (fruit);
Anthocyanines: cyanidin-3-xylosylglucoside (fruit);
pelargonidin-3-glucoside (fruit);
Flavonoids: quercetin-3-rutinoside (leaves)
Terpenoids: alpha-amyrin (bark, leaves, fruit); ursolic
acid (leaves, fruit); oleanolic acid (leaves); ilex
lactone (fruit);
Sterols: ergosterol (leaves); beta-sitosterol (fruit);
Alkaloids: theobromine
Fatty acids: pentadecanoic acid (leaves); palmitic acid
(leaves); stearic acid (leaves); arachidic acid (leaves);
oleic acid (leaves); linolenic acid (leaves);
Alkanes: (leaves, fruit)
Cyanogenic glucosides:
2 beta-D-glucopyranosyloxy-p-hydroxy-6,7-dihydromande-
lonitrile (fruit, leaves, bark).
(Alkaridis, 1987; Budzikiewicz, 1979; Willems, 1988)
3.3.2 Description, chemical structure, stability
The chemical structure of only some principles is known
in detail.
Ilex lactone: 3-(3'-Hydroxycyclopent-1-enyl-Z-propenic
acid-1,5'-lactone (Thomas & Budzikiewicz, 1980).
Cyanogenic glucoside: 2 beta-D-glucopyranosyloxy-p-
hydroxy-6,7 dihydromandelonitrile (Willems, 1988).
Triterpenester: 27,p-cumaroxy ursolic acid (Budzikiewicz
& Thomas, 1980).
3.3.3 Other physico-chemical characteristics
3.4 Other chemical contents of the plant
4. USES/CIRCUMSTANCES OF POISONING
4.1 Uses
In folk medicine, Ilex aquifolium (infusion or decoction of
dried leaves) is traditionally used for intermittent fevers and
rheumatism; for its antipyretic properties; and for its
astringent, diuretic and expectorant effects (Alikaridis,
1987). Ilex aquifolium is also occasionally used in homeopathic
medicine.
4.2 High risk circumstances
Intoxications are almost exclusively seen in children after
ingestion of berries from Ilex aquifolium cultivated in parks,
gardens, or when branches with berries are used ornamentally in
homes.
4.3 High risk geographical areas
The plant is native to Europe but is also cultivated in North
America and North Africa.
5. ROUTES OF ENTRY
5.1 Oral
The only route of poisoning.
5.2 Inhalation
No data available.
5.3 Dermal
No data available.
5.4 Eye
No data available.
5.5 Parenteral
No data available.
5.6 Others
No data available.
6. KINETICS
6.1 Absorption by route of exposure
No data available.
6.2 Distribution by route of exposure
No data available.
6.3 Biological half-life by route of exposure
No data available.
6.4 Metabolism
No data available.
6.5 Elimination by route of exposure
No data available.
7. TOXICOLOGY/TOXINOLOGY/PHARMACOLOGY
7.1 Mode of action
The exact mode of action is unknown. The gastrointestinal
symptoms may be due to the saponin. (West et al. 1977).
However, no specific toxin responsible for the symptoms has
been identified.
7.2 Toxicity
7.2.1 Human data
7.2.1.1 Adults
No data available.
7.2.1.2 Children
3 - 5 berries may cause gastrointestinal symptoms.
Although 20 to 30 berries are estimated to be a
"lethal dose" no recent references or cases confirm
this data.
7.2.2 Animal data
No data available.
7.2.3 Relevant vitro data
No data available.
7.3 Carcinogenicity
No data available.
7.4 Teratogenicity
No data available.
7.5 Mutagenicity
No data available.
7.6 Interactions
No data available.
8. TOXICOLOGICAL/TOXINOLOGICAL ANALYSIS
9. CLINICAL EFFECTS
9.1 Acute poisoning by:
9.1.1 Ingestion
Vomiting, diarrhoea, abdominal pain are the most common
symptoms after ingestion of berries.
9.1.2 Inhalation
No data available.
9.1.3 Skin exposure
No data available.
9.1.4 Eye contact
No data available.
9.1.5 Parenteral exposure
No data available.
9.1.6 Other
No data available.
9.2 Chronic poisoning by:
9.2.1 Ingestion
No data available.
9.2.2 Inhalation
No data available.
9.2.3 Skin exposure
No data available.
9.2.4 Eye contact
No data available.
9.2.5 Parenteral exposure
No data available.
9.2.6 Other
No data available.
9.3 Course, prognosis, cause of death
Gastrointestinal symptoms appear within hours after the
ingestion of berries and may last for 24 h. Severe symptoms
may be observed after ingestion of a large number of berries.
Death has been reported in the older literature (Lewin, 1929),
but has not been confirmed by more recent reports.
9.4 Systematic description of clinical effects
9.4.1 Cardiovascular
No cardiac disturbances reported in humans.
Experimental studies performed on frog and rabbit hearts,
showed that extracts of fruits and seeds are similar in
toxicity to digitalis (Waud, 1931-1932).
9.4.2 Respiratory
No data available.
9.4.3 Neurological
9.4.3.1 CNS
Drowsiness and stupor have been observed in cases
with severe gastrointestinal symptoms (Arena 1979;
Rodriguez et al. 1984).
9.4.3.2 Peripheral nervous system
No data available.
9.4.3.3 Autonomic nervous system
No data available.
9.4.3.4 Skeletal and smooth muscle
No data available.
9.4.4 Gastrointestinal
Vomiting, diarrhoea, abdominal cramps are the common
symptoms after ingestion of berries especially in
children.
9.4.5 Hepatic
No data available.
9.4.6 Urinary
9.4.6.1 Renal
No data available.
9.4.6.2 Others
No data available.
9.4.7 Endocrine and reproductive system
No data available.
9.4.8 Dermatological
No data available.
9.4.9 Eyes, ear, nose, throat : local effects
No data available.
9.4.10 Haematological
A haemolytic principle has been isolated from the leaves
(Balansard and Flandrin, 1951). However, no haemolysis
has been reported in human poisoning.
9.4.11 Immunological
No data available.
9.4.12 Metabolic
9.4.12.1 Acid base disturbances
No data available.
9.4.12.2 Fluid and electrolyte disturbances
May be seen in patients with severe
gastrointestinal disturbances
9.4.12.3 Others
No data available.
9.4.13 Allergic reactions
No data available.
9.4.14 Other clinical effects
No data available.
9.4.15 Special risks: pregnancy, breast feeding, enzyme
deficiencies
No data available.
9.5 Others
No data available.
10. MANAGEMENT
10.1 General principles
Emesis or gastric lavage is indicated, especially in children
if more than 3 -5 berries have been ingested. Treatment is
supportive in the symptomatic patient. A sample of the berries
and leaves is useful for identification.
10.2 Relevant laboratory analyses and other investigations
10.2.1 Sample collection
Sample of vomitus or gastric lavage fluid may be useful
for identification of the berries.
10.2.2 Biomedical analysis
Control fluid balance and blood electrolytes.
10.2.3 Toxicological/Toxinological analysis
Not relevant.
10.2.4 Other investigations
No data available.
10.3 Life supportive procedures and symptomatic treatment
Treatment is symptomatic and supportive : replacement of fluid
and electrolyte losses in the case of vomiting and diarrhoea.
10.4 Decontamination
Emesis or gastric lavage followed by activated charcoal may be
indicated in children. When more than 3 to 5 berries have been
ingested.
10.5 Elimination
No data available.
10.6 Antidote treatment
10.6.1 Adults
No data available.
10.6.2 Children
No data available.
10.7 Management discussion: alternatives and controversies, research
needs
No data available.
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
No data available.
11.2 Internally extracted data on cases
Among 46 children who had ingested berries of Ilex aquifolium,
only three showed symptoms:
10 month-old child hypersalivation
17 month-old child vomiting and diarrhoea
2 year-old child vomiting and abdominal cramps
Abdominal movements and mydriasis have been reported following
ingestion by a dog.
11.3 Internal cases (added by the PC using monograph).
12. ADDITIONAL INFORMATION
12.1 Availability of antidotes and antisera
No data available.
12.2 Specific preventive measures
No data available.
12.3 Other
No data available.
13. REFERENCES
13.1 Clinical and toxicological
13.2 Botanical
Alikaridis F (1987). Natural constituents of ilex species. J
Ethnopharmacol 20: 121-144.
Arena JM (1979). Are holly berries toxic? (letter). J Am Med
Assoc 242: 2341.
Balansard J & Flandrin P (1951). Heterosides of the leaves of
the holly tree (Ilex aquifolium). Chem Abst 45: 7307.
Bate-Smith EC (1962). The phenolic constituents of plants of
their taxonomic significance I. Dicotyledons. J Linnean Soc
(Botany) 58: 95-173.
Bohnic P (1959). Contribution to the knowledge of the
chemistry of holly (Ilex aquifolium). Farm Vestn (L. Jubljana)
10: 57-58.
Bohnic P (1967). Determination of theobromine in Ilex
aquifolium. Farmacevtski Vestnik 18: 9-20.
Budzikiewicz H, Thomas H (1980). p-cumaroxy-ursolsaure, ein
neuer inhaltstoff von Ilex aquifolium. L Z Naturforsch 35b:
230-231.
Catalano S, Marsili A, Morell I, Pistelli L, Scartoni V.
Constituents of the leaves of Ilex aquifolium. Planta Medica
33: 416-417.
Crombie WM (1958). Fatty acids in chloroplasts and leaves. J
Experim Botany 2: 254-261.
Chrelashivili MN, Mgaloblishvili MP (1974). Reactions of the
carbohydrates in leaves of different ages in evergreen plants
during fall and winter. Turdy Instituta Bot Academiia Nauk
Gruzinskoi SSR 27: 247-259.
Fischer R, Linse E (1930). Microchemical detection of abrutin
and ursone in plants. Arch Pharmazie 268: 185-190.
Fritzsch S (1983). Les baies toxiques. Thèse de Médecine N° 303
Strasbourg, France.
Garnier R. Ressources médicinales de la flore française.
Editeurs Vigot Frères.
Gessner O (1974). Gift und Arzneipflanzen von Mitteleuropa. 3e
Edition, Heidelberg, Carl Winter, Universitätsverlag.
Ishikura N (1971). Paper chromatographic analysis of
anthocyanins in the red epicarp of Ilex aquifolium. Botanical
Magazine, Tokyo 24: 113-117.
Jungfleisch, Leroux (1908). Identity of Ilicic alcohol with
alpha amyrin. Comptes rendus hebdomadaires des séances de
l'Académie des Sciences 147: 862-864.
Knapp R, Liskens HF (1954). Amino acids from leaf straw of
plant species of forests with different soils.
Naturwissenschafte 41: 480-481.
Lechevalier (1947). "Le livre des plantes médicinales et
vénéneuses de France. Encyclopédie Biologique, Paris.
Mitchell J, Rook A (1979). Botanical dermatology. Greengrass,
Vancouver.
Nooyen AM (1920). Urson and its distribution in the plant
world. Pharmaceutisch Weekblad 57: 1128-1142.
Personne MJ (1884). Sur un nouvel alcool retiré de la glu du
houx. Compte rendus hebdomadaires des séances de l'académie des
sciences 98: 1585-1587.
Poisindex
Rodriguez TD, Johnson PN, Jeffrey LP (1984). Holly berry
ingestion : case report. Vet Hum Toxicol 26: 157-158.
Santamour FS (1973). Anthocyanins of holly fruits.
Phytochemistry 12: 611-615.
Schindler H, Herb M (1955). Chemistry of Ilex aquifolium.
Isolation of ursolic acid and rutin from the leaves. Arch
Pharmazie 288: 372-377.
Thomas H, Budzikiewicz H (1980). Ilex lactone, ein
bisnormonoterpen neuartiger strukture aus Ilex aquifolium.
Phytochemistry 19: 1866-1868.
Thomas H, Budzikiewicz H (1980). Inhaltstoffe der Fruchte von
Ilex aquifolium. L Z Pflanzenphysio 99: 271-276.
Valadon LRG, Sellens AM, Mummery RS (1975). Carotenoids of
various berries. Ann Botany 39: 785-790.
Vermont J (1977). Toxicologie des plantes à baies ou à fruits
bacciformes. Thèse Lyon.
Waud RA (1932). A digitalis-like action of extracts made from
holly. J Pharmacol Exp Ther 45: 27.
Waud RA (1932). Further studies on extracts made from holly.
Proc Soc Exp Biol Med 30: 393-398.
Willems M (1988). Quantitative determination in Ilex
aquifolium. Planta Medica 55: 195.
14. AUTHOR(S), REVIEWER(S), DATES, COMPLETE ADDRESSES
Author: Professeur A. Jaeger, Doctor F. Flesch
Centre Anti-Poisons de Strasbourg
Hospices Civils - BP. 426
67091 Strasbourg
France
Tel: 33-88161144
Fax: 33-88161330
Tlx: 770 880 CHU STG
Date: 26 April 1990
Peer review: Strasbourg, France, April 1990