IPCS INCHEM HomeInocybe, clitocybe, omphalotus and others
INOCYBE, CLITOCYBE, OMPHALOTUS AND OTHERS
International Programme on Chemical Safety
Poisons Information Monograph (Group monograph) G028
Fungi
Please note that further information on Sections 1, 3 and 8 is
pending.
1. NAME
1.1 Scientific name
The muscarine-containing species known to cause the
majority of toxic exposures are:
Inocybe patouillardi
Inocybe fastigiata
Inocybe geophylla
Inocybe fragans
Inocybe cincinnata
Inocybe maculata
Inocybe corydalina
Inocybe godey
Clitocybe dealbata
Clitocybe rivulosa
Clitocybe candicans
Clitocybe cerussata
Clitocybe phyllophila
Omphalotus olearius
Omphalotus illudens
Omphalotus subilludens
Amanita echinocephala
Entoloma rhodopolium
The main toxin is muscarine.
1.2 Family
Inocybe
Inocybe (English and French)
Risspilz (German)
Clitocybe
Clitocybe (English and French)
Trichtering (German)
Omphalotus
"Jack O'lantern" (North America).
1.3 Common name(s) and synomym(s)
2. SUMMARY
2.1 Main risks and target organs
Muscarine containing mushrooms are responsible for
parasympathicomimetic poisoning with a number of symptoms, of
which the most severe signs are: bradycardia, hypotension and
respiratory distress.
2.2 Summary of clinical effects
The symptoms are similar to cholinergic poisoning:
general hyper-secretion (sweating, lacrimation, salivation,
rhinorrhea, bronchorrhea), bradycardia, miosis, blurred
vision and digestive troubles (nausea, vomiting, diarrhoea,
abdominal pain).
2.3 Diagnosis
As the symptoms appear within 30 minutes to a few hours
after ingestion of the mushrooms, the diagnosis is possible
on the basis of the typical clinical syndrome. The
identification of the mushroom and the description of the
meal could be helpful.
2.4 First aid measures and management principles
The management of the patients (it is often collective
poisoning with several patients) should be performed in
hospital in order to provide symptomatic treatments for the
pronounced digestive troubles. For the cases with important
cholinergic symptoms, atropine is injected (2 mg
intravenously for adults, and if necessary, repeated doses as
required, for children, 0.05 mg/kg of atropine). In case of
early admission, gastric emptying and/or Activated Charcoal
are indicated.
2.5 Poisonous parts
The muscarine is present in all the different parts of
the fungi. The toxic species contain between 0.1 and 0.3% of
the dry weight of mucarine. The species containing less are
not responsible for cholinomimetic signs (example: Amanita
muscaria which contains less than 0.002% of the dry weight
of muscarine is only occasionally responsible for muscarine
symptoms).
2.6 Main toxins
The main toxin in muscarine which is a
parasympathomimetic alkaloid. Its pharmacological activity
is close to acetylcholine.
3. CHARACTERISTICS
3.1 Description of the fungus
3.1.1 Special identification features
Must be completed by specialists.
3.1.2 Habitat
Inocybe species are very common in European
forests of deciduous trees like oaks (for
I. patouillardi) or conifers (other toxic Inocybe).
Clitocybe species grow in grasslands or open woods.
In North America, Omphalotus species grow on dead
wood in clusters.
3.1.3 Distribution
In Europe, the small white mushrooms of the
genus Inocybe and Clitocybe are eaten after
misidentification concerning famous edible species
like Tricholoma terreum, Tricholoma georgii
and Marasme oreades (global common name for the
three species in French of "Grisets") (Lambert,
1988).
In North America, "Jack O'lantern" mushrooms (genus
Omphalotus) can be the origin of confusion with
sulfur shelves (Laetiporus sulphureus) (French,
1988).
In Japan, cases with accidental ingestion of Entoloma
rhodopolium have been reported.
3.2 Poisonous parts of the fungus
All the different parts of the mushrooms contain
muscarine, and are toxic.
3.3 The toxin(s)
3.3.1 Names
The main toxin is muscarine which is a
parasympathicomimetic alkaloid.
3.3.2 Description, chemical structure, stability
The formula of the muscarine is 3 hydroxy - 2
methyl - 5 trimethyl ammonium methyl
tetrahydrofurune. Its pharmacological activity is
close to acetylcholine. There is in toxic fungi four
isomers. The most toxic molecule is L-muscarine.
None of these molecules are destroyed by heating
during cooking (Lambert, 2000).
3.3.3 Other physico-chemical characteristics
No data available.
3.4 Other chemical contents of the fungus
Some muscarinic toxic mushrooms may contain in different
proportions other molecules like acethylcholine, choline,
histamine, muscimol, muscazone or ibotenic acid.
4. USES/CIRCUMSTANCES OF POISONING
4.1 Uses
4.1.1 Uses
4.1.2 Description
In most cases, the mushrooms responsible for
muscarine poisonings are eaten because they are
mistaken for the following species: Tricholoma
terreum, Tricholoma georgii and Marasme oreades.
Accidental poisonings also occur with children.
However, in some published case series, more than one
quarter of the poisonings are collected with patients
who ate unidentified mushrooms (de Haro, 1999). Cases
are often observed after ingestion of fresh mushrooms,
but poisonings after ingestion of frozen or dried
mushrooms also occur.
4.2 High risk circumstances
The high risks are eating small mushrooms growing on
grass and in parks during spring and autumn. But poisoning
may occur during the whole year.
4.3 High risk geographical areas
Muscarine mushroom poisonings are common in some
countries where wild mushrooms are frequently eaten, such as
France, Italy or Switzerland (Lambert, 2000). However, in
other countries, muscarine mushroom poisoning may
occur.
5. ROUTES OF EXPOSURE
5.1 Oral
The poisoning is possible after ingestion of a meal made
with fresh, dried or frozen mushrooms. The heating during
cooking does not destroy the toxic molecules.
5.2 Inhalation
Not applicable.
5.3 Dermal
Not applicable.
5.4 Eyes
Not applicable.
5.5 Parenteral
Never reported.
5.6 Others
Never reported.
6. KINETICS
6.1 Absorption by route of exposure
A very low part of ingested Muscarine and derivatives is
absorbed in the digestive tract (Lambert, 2000).
6.2 Distribution by route of exposure
Absorbed muscarine is quickly distributed in throughout
the body and the symptoms may occur within 30 minutes to a
few hours after the meal. In several cases, the patients did
not finish eating their dish when the first symptoms appeared
(de Haro, 1999).
6.3 Biological half life by route of exposure
No data available.
6.4 Metabolism
6.5 Elimination by route of exposure:
No data available.
7. TOXINOLOGY
7.1 Mode of action
Muscarine and related molecules bind to the
acethylcholine receptor of the post-ganglionary nerves,
leading to a permanent depolarisation responsible of smooth
muscle contraction (iris, bronchia, digestive tract,...), of
the exocrine glands. There are muscarinic receptors in the
cardiac atrium.
7.2 Toxicity
7.2.1 Human data
7.2.1.1 Adults
See case reports.
7.2.1.2 Children
See case reports.
7.2.2 Relevant animal data
Case report: after ingestion of Inocybe
phaeocomis and other non toxic mushrooms, a
14-year-old female springer spaniel developed
hyper-salivation, hypothermia and digestive troubles.
The animal was better within 24 hours (Yam,
1993).
7.2.3 Relevant in 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 ANALYSES
8.1 Material sampling plan
8.1.1 Sampling and specimen collection
8.1.1.1 Toxicological analyses
8.1.1.2 Biomedical analyses
8.1.1.3 Arterial blood gas analysis
8.1.1.4 Haematological analyses
8.1.1.5 Other (unspecified) analyses
8.1.2 Storage of laboratory samples and specimens
8.1.2.1 Toxicological analyses
8.1.2.2 Biomedical analyses
8.1.2.3 Arterial blood gas analysis
8.1.2.4 Haematological analyses
8.1.2.5 Other (unspecified) analyses
8.1.3 Transport of laboratory samples and specimens
8.1.3.1 Toxicological analyses
8.1.3.2 Biomedical analyses
8.1.3.3 Arterial blood gas analysis
8.1.3.4 Haematological analyses
8.1.3.5 Other (unspecified) analyses
8.2 Toxicological Analyses and Their Interpretation
8.2.1 Tests on toxic ingredient(s) of material
8.2.1.1 Simple Qualitative Test(s)
8.2.1.2 Advanced Qualitative Confirmation Test(s)
8.2.1.3 Simple Quantitative Method(s)
8.2.1.4 Advanced Quantitative Method(s)
8.2.2 Tests for biological specimens
8.2.2.1 Simple Qualitative Test(s)
8.2.2.2 Advanced Qualitative Confirmation Test(s)
8.2.2.3 Simple Quantitative Method(s)
8.2.2.4 Advanced Quantitative Method(s)
8.2.2.5 Other Dedicated Method(s)
8.2.3 Interpretation of toxicological analyses
8.3 Biomedical investigations and their interpretation
8.3.1 Biochemical analysis
8.3.1.1 Blood, plasma or serum
8.3.1.2 Urine
8.3.1.3 Other fluids
8.3.2 Arterial blood gas analyses
8.3.3 Haematological analyses
8.3.4 Interpretation of biomedical investigations
8.4 Other biomedical (diagnostic) investigations and their
interpretation
8.5 Overall interpretation of all toxicological analyses and
toxicological investigations
8.6 References
9. CLINCAL EFFECTS
9.1 Acute poisoning
9.1.1 Ingestion
The ingestion of muscarine containing mushrooms
leads to symptoms similar to cholinergic poisoning:
general exocrine glands hyper-secretion (sweating,
lacrimation, salivation, rhinorrhea, bronchorrhea),
bradycardia, miosis, blurred vision and digestive
troubles like nausea, vomiting, dairrhoea and
abdominal pain (Young, 1994).
9.1.2 Inhalation
Not applicable.
9.1.3 Skin exposure
Not applicable.
9.1.4 Eye contact
Not applicable.
9.1.5 Parenteral exposure
Never reported.
9.1.6 Other
Never reported.
9.2 Chronic poisoning
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
Onset is within 30 minutes to a few hours (average 2
hours, in one reported case, less than 10 minutes). As soon
as they appear, the symptoms are at maximal level, and begin
to decrease after a few hours. All the signs disappear
before 24 hours (average delay of recovery 13 hours) (de
Haro, 1999). In old literature, fatalities have been
reported. In modern times, no fatalities have been reported
(Lambert, 2000).
9.4 Systematic description of clinical effects
9.4.1 Cardiovascular
Sinus bradycardia is often observed.
Hypotension with or without peripheral vasodilation is
frequent.
9.4.2 Respiratory
Bronchorrhea and bronchoconstriction leading to
hypoxemia may occur.
9.4.3 Neurological
9.4.3.1 Central Nervous system
Headaches and behaviour disturbance
(anxiety, euphoria, fear of death) may
occur.
9.4.3.2 Peripheral Nervous system
Never reported.
9.4.3.3 Autonomic Nervous system
All symptoms are due to autonomic
nervous system stimulation.
9.4.3.4 Skeletal and smooth muscle
Never reported.
9.4.4 Gastrointestinal
Excessive salivation is an important sign of
this intoxication. Nausea, vomiting, increased
peristalsis with diarrhoea and abdominal pain are
frequent. A bitter taste in the mouth and dysphagia
have been reported.
9.4.5 Hepatic
Never reported.
9.4.6 Renal/Urinary
Bladder contraction, painful need for urination
and increased ureter peristalsis may occur (Young,
1995).
9.4.7 Endocrine and reproductive systems
Never reported.
9.4.8 Dermatological
Excessive perspiration is a frequent sign of
this intoxication. The sweating is so important that
the patient's clothes and bed are completely
wet.
9.4.9 Eyes, ears, nose, throat, local effects
Miosis, blurred vision, excessive lacrimation,
nasal congestion and rhinorrhea are often observed.
Diplopia has been reported.
9.4.10 Haematological
Never reported.
9.4.11 Immunological
Never reported.
9.4.12 Metabolic
Never reported.
9.4.13 Allergic reaction
Never reported.
9.4.14 Other clinical effects
Never reported.
9.4.15 Special risks
Severe poisonings have been reported with
patients who have gastrectomy or a history of cardiac
disease (de Haro, 1999).
9.4.16 Local effects
Not applicable.
9.5 Other
Never reported.
9.6 Summary
30 minutes to a few hours after the ingestion of the
mushrooms, symptoms appear at the maximum level, and begin to
decrease after few hours. The symptoms are similar to
cholinergic poisoning: general hyper-secretion (sweating,
lacrimation, salivation, rhinorrhea, bronchorrhea),
bradycardia, hypotension, bronchoconstriction, miosis,
blurred vision and digestive disturbances (nausea, vomiting,
diarrhoea, abdominal pain).
10. MANGEMENT
10.1 General principles
As gastrointestinal symptoms are often present during
muscarine mushroom poisonings, gastric emptying and/or
Activated Charcoal is indicated in the early stage and before
the onset of the symptoms. Atropine should be administered
when cholinergic symptoms are pronounced.
10.2 Life support procedures and symptomatic/specific treatment
Intravenous fluids and electolytes should be
administrated in order to treat dehydration. Spontaneous
vomiting should not be treated. Bradycardia, bronchorrhea
and bronchoconstriction should be treated with atropine.
Diazepam may be used as the patients are often very anxious.
Diazepam should be administered after atropine
treatment.
10.3 Decontamination
Gastric emptying and/or Activated Charcoal are most
effective if initiated within 30 minutes of ingestion. In
published case series in France, gastric lavage has been done
for 6% of the patients.
10.4 Enhanced elimination
Not indicated.
10.5 Antidotes/Antitoxin treatment
10.5.1 Adults
When cholinergic symptoms are pronounced,
atropine should be administered. A first dose of 2
mg/IV is administrated. If the cholinergic symptoms
do not decrease, this dose can be repeated as required
every 30 minutes (maximum dose 8mg).
10.5.2 Children
When cholinergic symptoms are pronounced, the
atropine treatment protocol is the same, but with the
doses of 0.05mg/kg.
10.6 Management discussion
Atropine effectively counteracts the cholinergic
symptoms but does not shorten the duration of the symptoms.
Administration of Activated Charcoal does not further shorten
the duration of the symptoms (de Haro, 1999).
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
A series of 248 incidences of muscarine mushroom
poisonings occurring in southern France between 1973 and 1998
was published (de Haro, 1999). The 248 incidences included
483 patients (41 children between 1 to 14 years old). The
average onset of the symptoms was 2 hours. The most frequent
signs were perspiration (96% of the patients), vomiting
(70%), diarrhoea (62%), hypotension (36%), abdominal pain
(32%), miosis (25%), blurred vision (22%), bradycardia (20%),
rhinorrhea (6%) and lacrimation (6%). 58% of the patients
were treated at hospital, and the treatments were atropine
(24% of the 483 patients), Activated Charcoal (21%), gastric
lavage (6%). The average time to recovery was 13 hours
without modification for patients treated with atropine or
Activated Charcoal.
Two cases of this paper were exceptional because of the
severity of the clinical feature.
* A man, 58 years old, with previous history of gastrectomy
and alcoholic hepatic disease presented with a
cardio-respiratory arrest 1.5 hours after ingestion of
Inocybe patouillardi. During the transportation to the
hospital, bradycardia, bronchorrhea and
bronchoconstriction were observed. The patient was
treated in the intensive care unit (atropine, adrenaline,
broncho-suction, artificial ventilation), and recovered
on the third day.
* A woman, 70 years old, treated with digitalis for
supra-ventricular rhythm, presented 3 hours after
ingestion of Inocybe sp. Severe bradycardia and
hypotension leading to a shock, was treated in the
intensive care unit with atropine, and she recovered
within one day.
12. ADDITIONAL INFORMATION
12.1 Specific preventive measures
In order to avoid all types of mushrooms poisonings,
people have to ingest only clearly identified species.
Muscarine containing species like Inocybe sp. and
Clitocybe sp. are able to grow in edible mushrooms groups
(Lambert, 2000). These small white mushrooms can be eaten by
error with edible mushrooms, but the most common circumstance
is the misidentification with edible Tricholoma
species.
12.2 Other
13. REFERENCES
de Haro L, Prost N, David JM, Arditti J, & Valli M (1999)
Syndrome sudorien ou muscarinien: exp駻ience du Centre Antipoison
de Marseille. Presse M馘 28 (20): 1069-70.
French AL, Garrettson LK (1988) Poisoning with the north american
Jack O'lantern mushroom Omphalotus illudens. J Toxicol Clin
Toxicol 26 (1): 81 - 8.
Lambert H & Larcan A (1988) Intoxications par champignons
Encycl M馘 Chir. Toxicologie - Pathologie professionnelle,
16077A10: 14p.
Lambert H, Zitoli JL, Pierrot M, & Manel J (2000) Intoxications
par les champignons: syndromes mineurs. Encycl M馘 Chir
Toxicologie - Pathologie professionnelle, 16077B10: 10p.
Saviuc P& Moreau PA (1999) Intoxications par les champignons
sup駻ieurs. In: Danel V, Barriot P. Intoxications aigu?s en
r饌nimation. Second Ed. Arnette Ed. Rueil-Malmaison, France:
523 - 48.
Yam P(1993) Mushroom poisoning in a dog. Vet Rec 133: 24.
Young A (1994) Muscarine containing Mushrooms. In: Spoerke D,
Rumack BH Handbook of mushroom poisoning. CRC Press, Boca raton,
Fl.
14. AUTHOR(S), REVIEWER(S) DATA (INCLUDING EACH UPDATING), COMPLETE
ADDRESSES
Author:
Luc de HARO, MD.
Centre Antipoison de Marseille
H?pital Salvator
249 boulevard Sainte Marguerite
3009 Marseille
France
Tel: +33 491 74 50 75
Fax: +33 491 74 41 68
E-mail: deharo.l@jean-roche.univ-mrs.fr
Reviewed by:
* Dr Heinz Faulstich, Dr Luc de Haro, Dr Jonas H?jer, Dr
Christine Karlson-Stiber, Dr Hans Persson and Thomas Zilker
(Meeting on Mushroom Poisoning, 19-21 October 2000,
Stockholm, Sweden).
* Dr B. Groszek and Dr H. Persson (INTOX-12, 6-11 November
2000, Erfurt, Germany).