Conium maculatum L.
| 1. Name |
| 1.1 Scientific name |
| 1.2 Family |
| 1.3 Common name(s) |
| 2. Summary |
| 2.1 Main risk 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 (molecular weight), |
| 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 in vitro data |
| 7.3 Carcinogenicity |
| 7.4 Teratogenicity |
| 7.5 Mutagenicity |
| 7.6 Interactions |
| 8. Toxicological/toxinological and biomedical investigations |
| 9. Clinical effects |
| 9.1 Acute poisoning: |
| 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 (acute, chronic, |
| 9.4.1 Cardiovascular |
| 9.4.2 Respiratory |
| 9.4.3 Neurologic |
| 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 Other |
| 9.4.7 Endocrine and reproductive systems |
| 9.4.8 Dermatological |
| 9.4.9 Eye, ear, nose, throat: local effects |
| 9.4.10 Haematological |
| 9.4.11 Immunologic |
| 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 analysis 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, controversies, research |
| 11. Illustrative cases |
| 11.1 Case reports from literature |
| 11.2 Internally extracted data on cases (from writer of monograph) |
| 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), Date(S) (including each update), complete addresses |
1. Name
1.1 Scientific name
Conium maculatum L.
1.2 Family
Umbelliferae (Apiaceae)
1.3 Common name(s)
Bunk (Canada)
Cashes (Canada)
Cige (Canada, France)
Poison hemlock (USA)
Poison parsley (USA)
Poison root (USA)
Snake weed (USA)
Spotted hemlock (USA)
Spotted parsley (USA)
Winter fern (USA)
Cicuta (Spain, Uruguay, Argentina, Portugal)
Perejil lobuno (Spain)
Cicuta negra (Uruguay)
2. Summary
2.1 Main risk and target organs
The central nervous system is the main target organ: initial
stimulation is followed by severe CNS depression associated
with muscle paralysis and respiratory failure.
2.2 Summary of clinical effects
Usually rapid onset of irritation of oral mucosa with
salivation, nausea, emesis and slight abdominal pain.
Diarrhoea is uncommon. Bradycardia, miosis and hypertension may
rapidly change to tachycardia, hypotension and mydriasis.
Seizures followed by ascendant muscle paralysis can be seen in
severe cases leading to respiratory failure.
2.3 Diagnosis
Blood gases and electrolytes
Sample of the plant should be obtained for botanical and
pharmacognostic identification.
2.4 First-aid measures and management principles
Immediate gastric lavage or emesis followed by administration
of activated charcoal with a cathartic. Treatment is
supportive, mainly ensuringadequate respiratory function.
2.5 Poisonous parts
The entire plant contains toxic alkaloids, especially the
root and seeds.
2.6 Main toxins
The main poisonous principle is coniine, a pyridine derivative
similar in structure and function to nicotine; there are also
four other structurally related alkaloids.
3. Characteristics
3.1 Description of the plant
3.1.1 Special identification features
Conium maculatum is a herb growing up to nine feet high
that resembles a carrot plant. The leaves are large (may
reach up to 4 feet) and lacy, with alternate
distribution. The small and white flowers are borne in
flat clusters like an umbrella ("umbelliferae"). The
stem is typically hollow and has purple spots. The
tuberous root is white. The fruit is small, 3 to 4
millimeters long and flattened on its sides. When
crushed, the leaves and flowers produce an offensive
"mousy" odour.
Conium maculatum blossoms in Spring and its fruits are
ripe in Summer (Font-Quer, 1979; Pronczuk, 1988; Lampe,
1985)
3.1.2 Habitat
Conium maculatum often grows abundantly on waste areas or
on land not maintained either by cultivation or cutting,
such as ditch banks, fence rows, low-lying rocky outcrops
and timbered areas. (Keeler, 1978; Pronczuk, 1988)
3.1.3 Distribution
Originally from Europe, conium maculatum has adapted to
America and Asia. Now it has a worldwide distribution,
mostly in temperate areas below 5000 feet of altitude.
3.2 Poisonous parts of the plant
The whole plant is toxic, but especially the root and seeds.
3.3 The toxin(s)
3.3.1 Name(s)
The whole plant contains coniine, N-methyl coniine,
conhydrine, lambda-coniceine and pseudoconhydrine.
3.3.2 Description, Chemical Structure (molecular weight),
Stability
Coniine is a piperidine alkaloid (2-propylpiperidine)
(Keeler, 1978).
No other data available.
3.3.3 Other physico-chemical characteristics
The characteristic odour is at least in part attributable
to coniine, which is a volatile a colourless liquid with
a bitter taste (Schvarstman, 1979; Gosselin, 1976;
Keelers, 1978).
3.4 Other chemical contents of the plant
Other alkaloids related to coniine have been isolated from the
plant. According to Keeler and Balls (1978), over 98% of the
total alkaloid of the fresh vegetative Conium maculatum was
coniceine, and in the dry plant less than 20% was coniceine,
and one third was coniine. Other authors believe that coniine
and coniceine are the main active principles. Other alkaloids
include N-methylconniine, conhydrin and pseudoconhydrine, which
have a toxic action similar to that of coniine. (Keeler, 1978;
Schvarstman, 1979)
4. Uses / circumstances of poisoning
4.1 Uses
Preparations containing the active principle were used as an
analgesic or sedative by herbalists. As the bromhydrate, the
recommended maximal dose is 15 mg per day. Powder from the
dried fruits is also used; the maximal dose recommended is 1 g.
(Font Quer, 1979). The recommended dose of a tea prepared from
dried leaves is 1 g in 100 cc water (Font Quer, 1979).
4.2 High risk circumstances
A large number of the umbelliferae family are used as aromatics
or edible plants. The fruits of Conium maculatum have been
confused with aniseed; the leaves can be confused with parsley,
or wild carrots; and the root with parsnip (Hardin, 1974). In
mid-summer the whole plant exudes a fetid odour reminiscent of
mouse or cat urine (Gosselin, 1976).
4.3 High risk geographical areas
It is found in Asia, Europe, North and South America. The plant
is widely distributed and grows mainly in moist waste areas not
maintained by cultivation or cutting. Consequently, the stands
are dense along ditch banks, fence rows, low-lying rocky
outcrops, and timbered areas.
5. Routes of entry
5.1 Oral
Pieces of the plant, medicinal preparations or teas can be
ingested accidentally, in suicide attempts, or because of
confusion with other plants.
5.2 Inhalation
Toxicity has been reported from prolonged inhalation of the
vapour of coniine (Gosselin, 1976).
5.3 Dermal
Coniine and coniceine can be absorbed through the skin when the
plant is used as an analgesic "plaster" (Font Quer, 1979).
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
Coniine is mainly absorbed orally. It may rarely be absorbed
by inhalation and through the skin.
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
Coniine is normally excreted rapidly after biotransformation
(Geehr, 1984).
6.5 Elimination by route of exposure
7. Toxicology / Toxinology / Pharmacology
7.1 Mode of action
Coniine produces muscular paralysis similar to that from
curare. Nicotine-like ganglionic blockade also occurs
(Dreisbach, 1987).
7.2 Toxicity
7.2.1 Human data
7.2.1.1 Adults
In man, 3 mg of coniine is said to have produced
symptoms, but 150 mg have been tolerated without
discomfort. Perhaps 30-60 mg is dangerous and
death may occur with doses greater than 100 mg. It
has been reported that a lethal dose may be 6 to 8
fresh leaves (Gosselin, 1976; Pronczuk, 1988).
7.2.1.2 Children
No data available.
7.2.2 Animal data
Toxic doses in animals: cows 3.3 mg/kg, horses 15.5 mg/kg
and sheep 44 mg/kg (Keeler, 1980).
7.2.3 Relevant in vitro data
No data available.
7.3 Carcinogenicity
No data available.
7.4 Teratogenicity
Conium maculatum has caused congenital malformations when fed
to cattle, pigs and sheep (Poisindex, 1990).
7.5 Mutagenicity
No data available.
7.6 Interactions
No data available.
8. Toxicological/toxinological and biomedical investigations
9. Clinical effects
9.1 Acute poisoning:
9.1.1 Ingestion
The clinical effects are mainly neurological and when
death occurs it is probably secondary to respiratory
paralysis with hypoxia. The most prominent signs are due
to peripheral paralysis and loss of sensation.
Symptoms include irritation of the mucous membranes,
nausea, vomiting and profuse salivation. Abdominal pain
is usually minimal and diarrhoea is infrequent.
Drowsiness, paresthesiae, ataxia and gradually increasing
muscular weakness followed by ascending paralysis leads
to respiratory failure. Bradycardia, miosis,
hyperventilation may rapidly change to tachycardia,
hypotension, mydriasis and respiratory paralysis.
Seizures may occur terminally (Lampe, 1985; Geehr, 1984;
Gosselin, 1976; Dreisbach, 1987).
9.1.2 Inhalation
Inhalation of vapours may occur rarely and clinical
effects would be predicted to be similar to those seen
following ingestion.
9.1.3 Skin exposure
Skin contact can result in a burning sensation,
numbness, dermatitis and possible systemic absorption
(Poisindex, 1990, Font Quer, 1979).
9.1.4 Eye contact
Because conium can cause dermal irritation conjunctivitis
might occur following eye exposure. However, no such
cases have been reported.
9.1.5 Parenteral exposure
No data available.
9.1.6 Other
No data available.
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
In non-fatal cases, the effects are relatively transient
(Gosselin, 1976).
In severe cases, there is usually a rapid onset of symptoms;
death occurs rapidly (in less than 3 hours) if no treatment is
given. Death is due to respiratory arrest from paralysis of
respiratory muscles, although central depression may play a
role after ingestion of very large doses (Lampe, 1985).
9.4 Systematic description of clinical effects (acute, chronic,
etc.)
9.4.1 Cardiovascular
Tachycardia or bradycardia and vasoconstriction may
occur.
9.4.2 Respiratory
Respiratory failure is due to muscular paralysis.
9.4.3 Neurologic
9.4.3.1 CNS
Drowsiness, ataxia and seizures in severe cases.
9.4.3.2 Peripheral nervous system
Numbness, paresthesiae and ascending paralysis.
9.4.3.3 Autonomic nervous system
Initial symptoms of coniine poisoning resulting
from transitory stimulation of autonomic ganglia.
9.4.3.4 Skeletal and smooth muscle
Progressive muscular paralysis.
9.4.4 Gastrointestinal
Irritation of oral mucosa, nausea, vomiting and slight
abdominal pain.
9.4.5 Hepatic
No data available.
9.4.6 Urinary
9.4.6.1 Renal
9.4.6.2 Other
9.4.7 Endocrine and reproductive systems
No data available.
9.4.8 Dermatological
Dermal absorption can result in a burning sensation,
numbness, dermatitis and possibly systemic absorption
(Poisindex, 1990, Font Quer, 1979).
9.4.9 Eye, ear, nose, throat: local effects
Because conium can cause dermal irritation,
conjunctivitis might occur following eye exposure.
However no such cases have been reported.
9.4.10 Haematological
No data available.
9.4.11 Immunologic
No data available.
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
No data available.
9.4.14 Other clinical effects
No data available.
9.4.15 Special risks: Pregnancy, breast feeding, enzyme
deficiencies
Conium maculatum is a known animal teratogen. No human
data are available.
9.5 Others
No data available.
10. Management
10.1 General principles
Immediate induction of emesis or gastric lavage and
administration of activated charcoal and a cathartic are
indicated. Treatment is otherwise symptomatic. Provision of
adequate respiratory care is the main treatment measure (Lampe,
1985; Geehr, 1984).
10.2 Relevant laboratory analysis and other investigations
10.2.1 Sample collection
Plant specimen should be collected for botanical and
pharmacognostic identification if possible. Plant
portions found in vomitus should be stored in a plastic
bag (see 8.1.1).
10.2.2 Biomedical analysis
Blood gases and ECG provide valuable data.
10.2.3 Toxicological/Toxinological analysis
(In preparation)
10.2.4 Other investigations
As required by patients' clinical condition.
10.3 Life supportive procedures and symptomatic treatment
Immediate induction of emesis gastric lavage and administration
of activated charcoal and cathartic are indicated. Treatment
is otherwise symptomatic. Provision of adequate respiratory
care is the main treatment measure (Lampe, 1985; Geehr, 1984).
10.4 Decontamination
Immediate induction of emesis or gastric lavage and
administration of activated charcoal and cathartic are
indicated.
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, controversies, research
needs
Alternatives and controversies.
11. Illustrative cases
11.1 Case reports from literature
11.2 Internally extracted data on cases (from writer of monograph)
No cases have been registered at CIAT (Uruguay PCC).
11.3 Internal cases (added by the PC using monograph)
To be added by the centre.
12. Additional information
12.1 Availability of antidotes and antisera
Not relevant.
12.2 Specific preventive measures
Not relevant.
12.3 Other
Not relevant.
13. References
13.1 Clinical and toxicological
Dreisbach, RH; Robertson, WO, Handbook of Poisoning. Appleton
Lange, Norwalk, Connecticut. Twelfth edition. Page 4.99, 1987.
Font Quer, P. Plantas medicinales Editorial Labour.
Barcelona. Page 484, 1979.
Geehr, E. Common Toxic Plant Ingestion. Emergency Medicine
Clinics of North America 2 (3): 556, 1984.
Gosselin, RE. et al. Clinical Toxicology of Commercial
Products. Williams-Wilkins, Baltimore. Fourth Edition 1976.
Hardin, JW; Arena, JM. Human poisoning from native and
cultivated plants. Duke University Press. Second Edition.
Kingsport, Tennessee, 1974.
Keeler, RF; Balls, LD. Teratogenic effects in cattle on Conium
maculatum and conium alkaloids and analogs. Clinical
Toxicology 12 (1): 49-64, 1978.
Lampe, KF; McCann, MA. AMA Handbook of poisoning and injurious
plants. American medical Association, Chicago, Illinois, 1985.
Pronczuk, J; Laborde, A. Plantas silvestres y de cultivo:
riesgo de intoxicacion para el hombre. Universidad de la
Republica. Montevideo, 1988.
Schvartsman, S. Plantas venenosas. Sarvier, Sao Pablo, 1979.
Bowman, WC; Sanghvi, IS. Pharmacological actions of hemlock
alkaloids. J Pharm Pharmacol 1963; 15:1-25.
Cromwell, BT. The separation, micro-estimating and
distribution of the alkaloids of hemlock (Conium maculatum L).
Biochem J 1956; 64: 259-266.
de Boer, J. The death of Socrates. A historical and
experimental study on the action of coniine and conium
maculatum. Arch Int Pharmacodyn 1950; 83:473-490.
Fairbairin, JW; Challen, SB. The alkaloids of hemlock (conium
maculatum L). Biochem J 1958; 72:556-561.
Hill, RK. Stereochemistry of the hemlock alkaloids. I.
conhydrine. J Am Chem Soc 1958; 80: 1609-1611.
Keeler, RF. Coniine, a teratogenic principle from conium
maculatum producing congenital malformations in calves. Clin
Toxicol 1974; 7:195-206.
Keeler, RF; Balls, LD. Teratogenic effects in cattle of Conium
maculatum and Conium alkaloids and analogs. Clin Toxicol 1978;
12: 49-64.
Keeler, RF; Balls, LD; Shupe, JL et al. Teratogenicity and
toxicity of coniine in cows, ewes and mares. Cornell Vet 1980;
70:19-26.
Mitchell, J; Rook, A. Botanical Dermatology. Greengrass Ltd,
Vancouver, BC, 1979.
Ober, WB. Did Socrates die of hemlock poisoning? NY State J
Med 1977; Feb: 254-258.
Panter, KE; Bunch, TD; Keeler, RF. Maternal and foetal
toxicity of poison hemlock (Conium maculatum) in sheep. Am J
Vet Res 1988; 49: 281-283.
Panter, KE; Keeler, RF; Buck, WB. Induction of cleft palate in
newborn pigs by maternal ingestion of poison hemlock (conium
maculatum). Am J Vet Res 1985; 46: 1368-1371.
Panter, KE; Keeler, RF; Buck, WB. Congenital skeletal
malformations induced by maternal ingestion of Conium maculatum
(poison hemlock) in newborn pigs. Am J Vet Res 1985a; 46:
2064-2066.
Sollmann, T. A Manual of Pharmacology, 8th ed, Saunders,
Philadelphia, 1957.
13.2 Botanical
14. Author(S), Reviewer(S), Date(S) (including each update), complete
addresses
J. Higa de Landoni
Jefa de Seccion Toxicologia
Hospital de Clinicas "Jose de San Martin"
Facultad de Medicina
Universidad de Buenos Aires
Cordoba 2351
Buenos Aires
Argentina
Tel: 54-1-7989552
Fax: 54-1-3318605
Reviewer: Dr J. Pronczuk
CIAT 7Ø
Hospital de Clinicas
Av Italia s/n
Montevideo
Uruguay
Tel: 598-2-470300
Fax: 598-2-470300
Peer Review: London, UK, March 1990