Senecio Vulgaris 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 in vitro data |
| 7.3 Carcinogenicity |
| 7.4 Teratogenicity |
| 7.5 Mutagenicity |
| 7.6 Interactions |
| 8. TOXICOLOGICAL/TOXINOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS |
| 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. 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 |
| 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 systems |
| 9.4.8 Dermatological |
| 9.4.9 Eye, ears, 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 |
| 9.5 Others |
| 9.6 Summary |
| 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/antitoxin treatment |
| 10.6.1 Adults |
| 10.6.2 Children |
| 10.7 Management discussion |
| 11. ILLUSTRATIVE CASES |
| 11.1 Case reports from literature |
| 11.2 Internally extracted data on cases |
| 11.3 Internal cases |
| 12. ADDITIONAL INFORMATION |
| 12.1 Availability of antidotes/antitoxins |
| 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 UPDATES), COMPLETE ADDRESS(ES) |
POISONOUS PLANTS
1. NAME
1.1 Scientific name
Senecio Vulgaris L.
1.2 Family
Compositae
1.3 Common name(s)
Common Groundsel (USA, UK)
Groundsel (USA, UK)
2. SUMMARY
2.1 Main risks and target organs
The plant is poisonous and has been found to contain
pyrrolizidine alkaloids which produce hepatic necrosis.
The target organs are the liver, kidneys, and lungs.
2.2 Summary of clinical effects
The manifestations of acute and chronic poisoning are well
described in animals: weight loss, icterus, ataxia, and
symptoms of hepatic failure. In acute poisoning, death occurs
within about 7 days due to severe liver damage secondary to
severe veno-occlusive disease. Chronic liver damage may
follow administration of single sublethal dose or repeated
low doses.
Children are particularly vulnerable to the effects of
pyrrolizidine alkaloids. The clinical picture is
characterized by upper abdominal discomfort that progresses to
the swelling of the abdomen, oliguria and swelling of the
feet. Vomiting of blood may appear in the advanced stages of
poisoning. The disease progresses rapidly and mortality is
high.
2.3 Diagnosis
Symptoms include upper abdominal discomfort that progresses to
the swelling of the abdomen, oliguria and swelling of the
feet. Vomiting of blood may occur in the advanced stages of
poisoning.
The interval between ingestion of pyrrolizidine-containing
material and the development of the veno-occlusive liver
disease makes sample collection difficult. However, samples
of plant material must be obtained and kept in airtight
containers for further identification and analyses.
Methods of isolation and identification of pyrrolizidine
alkaloids have been described. Mass spectrophotometry,
reverse phase exchange, gas liquid, paper and thin layer
chromatography methods have been used on samples including
human serum, plasma and urine.
Liver biopsy shows characteristic changes of centrilobular
haemorrhagic necrosis with occlusion of hepatic venules.
Hepatic sinusoids and central veins are congested but the
hepatic architecture remains intact. Extensive portal and
sinusoidal fibrosis may appear, leading to cirrhosis.
Coagulopathies, hypoglycaemia, leucocytosis,
hyperbilirubinaemia and grossly elevated hepatic
aminotransferase levels are found.
2.4 First-aid measures and management principles
Remove any parts (leaves, flowers, fruits) still in the mouth
and wash thoroughly with water or a saline solution. Induce
vomiting (e.g. by giving syrup of ipecac).
Do not induce vomiting if the patient's consciousness is
impaired or if he is having fits. The remnants of the plant
and the vomitus should be collected in a clean bottle.
The treatment of acute poisoning is symptomatic and
supportive.
Ensure patient's airway and ventilation. Supportive measures
include oxygen, artificial respiration, intravenous fluids.
All cases of ingestion should be closely observed in a
hospital.
Emesis and gastric lavage are indicated in recent ingestion.
Activated charcoal should be administered in a slurry (1 g/kg)
and should be repeated every four hours for 48 hours.
Correction of dehydration and hypovolaemia are indicated.
Since massive hepatic necrosis represents the greatest threat
to life, some authors even recommend the same treatment as for
Amanita phalloides poisoning (charcoal haemoperfusion, forced
diuresis and presumed antidotes such as penicillin G, thioctic
acid, silibinin and, in extreme cases, liver transplantation).
2.5 Poisonous parts
All parts of the plants are toxic. The alkaloid content of
the different parts of the plant is variable and depends on
changes of climate, soil conditions, and time of harvesting.
2.6 Main toxins
142 species of Senecio are known to contain pyrrolyzidine
alkaloids of proved hepatotoxicity, or with a molecular
structure that would make them very probably hepatotoxic. In
Senecio Vulgaris the following pyrrolizidine alkaloids are
found: senecionine, seneciphylline, retrorsine, riddelline,
intergerrimine, spartioidine, and usaramine.
3. CHARACTERISTICS
3.1 Description of the plant
3.1.1 Special identification features
Perennial or annual, glabrous, more or less woody plant;
branched succulent stem of 20-60 cm in height; small
cylindrical heads of yellow tubular flowers with whorl
of bract below; the light ribbed dark-grey fruits bear a
soft, feathery tuft of hair (pappus) (Encyclopaedia
Britannica, 1963).
3.1.2 Habitat
Senecio grows wild in fields, as a weed in gardens, and
along roadsides in temperate and subtropical climates.
3.1.3 Distribution
Widely distributed throughout the world.
3.2 Poisonous parts of the plant
All parts of the plant contain the poisonous pyrrolizidine
alkaloids.
3.3 The toxin(s)
3.3.1 Name(s)
The Toxins are:
senecionsine, seneciphylline; retrorsine; riddelline;
intergerrimine; spartioidine; usarsmine.
3.3.2 Description, chemical structure, stability
The hepatotoxic alkaloids have a 1,2-double bond in the
pyrrolizidine ring and branched chain acids, esterifying
a 9-hydroxyl and possibly also the 7-hydroxyl
substituent. The alkaloids occur as free bases and N-
oxides. The latter are reduced to free bases in the
gastrointestinal tract of animals and have a similar
toxicity when ingested orally.
Senecionine: 12-Hydroxysenecionan-11, 16 dione.
Formula = C18H25NO5
Molecular weight = 335.39
Melting point = 236
Practically insoluble in water; freely soluble
in chloroform; slightly soluble in alcohol,
either.
Intergerrimine: C15-trans Isomer of senecionine.
Melting point = 172 - 172.5
Seneciphylline: 13,19-Didehydro-12 Hydroxysenecionan-11,
16-dione: jacodine; alpha-longilobine; trans-15-Ethylidene-
12-ß-hydroxy-12-ý-methyl-13-methylenesenec-1-enine.
CAS 480-81-9
Cancer Chemotherapy National Service Centre
Number: NSC30622 (USA)
Formula C18H23NO5
Melting point = 217-218
Colorless prisms, easily soluble in chloroform,
ethylene chloride; less soluble in alcohol,
acetone. Relatively insoluble in ether, ligroin.
Volatility: low.
Stability: stable at room temperature in
closed containers; best stored under nitrogen at
15°C,
Reactivity: readily hydrolysed with alkali;
reacts readily with oxidizing agents (slowly with
atmospheric oxygen) to form dihydropyrrolizine
and other derivatives (IARC 1976).
Retrorsine: 12,18-Dihydroxysenecionan-11, 16-dione;
ß-longilobine. 3-Etherylidene-3,4,5,6,9,11,13,14,14 ý,
14 ß decahydro-6-hydroxy-6-hydroxymethyl-5-methyl (1,6)
dioxycyclododeca [2,3,3-gh] pyrrolizidine-2,7-dione;
trans-15-ethylidene-12-ß-hydroxy-12-ý-hydroxymethyl-13-ß-
mehylsene-1-enine (IARC, 1976).
CAS: 480-54-6
Formula: C18H25NO6
Molecular weight = 351.4
Melting Point = 212°C
Colourless prisms readily soluble in alcohol,
chloroform. Slightly soluble in water,
acetone, ethyl acetate. Practically insoluble
in ether. (Merck Index, 1983)
Volatility: Low
Stability: stable at room temperature in
closed container; best stored under nitrogen
at 15°C.
Reactivity : readily hydrolysed with alkali:
reacts with oxidizing agents to form
dihydropyrrolizine and other derivatives
(IARC, 1976).
Riddelline: 13, 19-Didehydro-12, 18-dhydroxysenecionan-11,
16-dione; trans-15-Ethylidene-12-ß-hydroxy-12-ý-
hydroxymethyl-13-metehylenesenec-1-enine; stereoisomer of
3-ethylidene-3,4,5,6,9,11,13,14,14-ý,
14-ß-decahydro-6-hydroxy-6-(Hydroxymethyl)-5-methylene
(1,6)doxacyclododecino [2,3,4-gh]-pyrrolizidine-
2,7-dione; riddelline (IARC,1976).
CAS : 23246-96-0
Formula: C18H23NO6
Melting point: 198°C
Colourless soluble in chloroform; slightly
soluble in acetone, ethanol and water;
soluble in water as the hydrochloride.
Volatility: low.
Stability: stable at room temperature in
closed containers: best stored under nitrogen
-15°C.
Reactivity: readily hydrolysed in aqueous
alkali; reacts readily with oxidizing agents
to form dihydropyrrolizidine and other
derivatives (IARC, 1976).
3.3.3 Other physico-chemical characteristics
3.4 Other chemical contents of the plant
No data available.
4. USES/CIRCUMSTANCES OF POISONING
4.1 Uses
The plants grow wild in fields, in gardens and along
roadsides. Senecio Vulgaris was used in Europe for
treatment of dysmenorrhoea and amenorrhea, and in the
United States as a diaphoretic, diuretic, tonic and
emmenagogue (IARC, 1976).
Senecio vulgaris now has no known uses; there is no
consumption for medicinal or dietary purposes. A
pyrrolizidine alkaloid derivative, indicine-N-oxide, was
tested in man as an antitumour agent (WHO, 1988a).
4.2 High risk circumstances
Incidents of poisoning are reported predominantly in grazing
animals. Under normal conditions, the plant is unpalatable and
is avoided by grazing animals but it may be eaten during
drought conditions.
Animals may also ingest the plant material in hay or silage
(The Merck Veterinary Manual, 1979). Consumption of
contaminated grain or the use of pyrrolizidine alkaloid-
containing plants as herbal medicines, beverages, or food by
man, or grazing on contaminated pastures by animals may cause
acute or chronic disease (WHO, 1988b).
Children appear to be more susceptible than adults (Ellenhorn,
1988).
4.3 High risk geographical areas
All temperate and subtropical regions. Instances of human
toxicity caused by pyrrolizidine alkaloid-containing plants
were described in the USA, United Kingdom, USSR, Afghanistan,
Hong Kong, India, South Africa, West Indies, and Ecuador (WHO,
1988).
5. ROUTES OF ENTRY
5.1 Oral
Oral consumption of the plant, contaminated grain or in
preparations as food, herbal medicines or beverages.
5.2 Inhalation
No data available.
5.3 Dermal
May be absorbed through the skin.
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
The absorption of pyrrolizidine alkaloids in man has been
inferred from studies in animals. The alkaloids are absorbed
in the ileum and jejunum, but not the stomach. After dermal
application the excreted metabolites in urine amounted to 0.1-
0.4% of the dose (WHO, 1988a).
6.2 Distribution by route of exposure
In animal studies highest concentrations were found in the
liver, lungs, kidneys and spleen.
6.3 Biological half-life by route of exposure
Within a few hours, only a relatively small proportion of the
administered dose remains in the body. Much of this is in the
form of metabolites bound to tissue contents. A pyrrolizidine
N-oxide, as indicine-N-oxide, disappeared from the serum after
IV administration in animals, with initial half-lives of 3 -
20 minutes (WHO, 1988a).
6.4 Metabolism
In animals, the major metabolic routes of pyrrolizidine
alkaloids are: (a) hydrolysis of the ester groups; (b) N-
oxidation; and (c) dehydrogenation of the pyrrolizidine
nucleus to pyrrolic derivatives.
Routes (a) and (b) are believed to be detoxification
mechanisms. Route (c) leads to toxic metabolites. Route (a)
occurs in liver and blood; routes (b) and (c) are brought
about in the liver by the microsomal mixed function oxidase
system (WHO 1988a).
6.5 Elimination by route of exposure
In animals, the urinary excretion of metabolites and unchanged
alkaloids is rapid and almost complete within the first 24
hours (WHO, 1988a).
7. TOXICOLOGY/TOXINOLOGY/PHARMACOLOGY
7.1 Mode of action
The activation of the alkaloids by mixed-function oxidases
leads to pyrrolic dehydro-alkaloids which are reactive
alkylating agents. The liver necrosis results from binding of
the metabolites with the liver cell. Some metabolites are
released into the circulation and are believed to pass beyond
the liver to the lung causing vascular lesions. The pyrrolic
metabolites are cytotoxic and act on the hepatocytes and on
the endothelium of blood vessels of the liver and lung. From
evidence in experimental animals and circumstantial evidence
in one human case report, the possibility of toxic pulmonary
disease in man cannot be ruled out (WHO, 1988a).
In man, poisoning is manifested as acute veno-occlusive
disease, leading to hepatomegaly, ascites, massive pleural
effusion, and in many cases progressing to cirrhosis.
7.2 Toxicity
7.2.1 Human data
7.2.1.1 Adults
Data are not available for Senecio vulgaris.
7.2.1.2 Children
There have been two cases of poisoning from
riddeline and retrorsine contained in S.
longilobus. The estimated daily intakes were 0.8-
0.17 mg/kg and 3 mg/kg body weight respectively,
and the total doses were 12-25 mg/kg and 12
mg/kg. These levels led to the rapid
development of veno-occlusive disease in infants,
and in one case to death (WHO, 1988a).
7.2.2 Animal data
Considerable differences in LD50 values have been
reported for the same alkaloids in different species.
LD50 for male rats after a single intraperitoneal dose
(i.p.) is:
Retrorsine = 34 mg/kg (time range = 4 or 7 days)
One to 7 days IV LD50's in mice and rats are about 90
and 80 mg/kg body weight, respectively. In rats, 3-day
i.p. LD50 doses for males and females are 77 and 83
mg/kg, respectively (IARC, 1976).
Seneciphyline = 77 mg/kg (time range = 3 days) (WHO,
1988a)
The LD50 varies from 34 mg/kg for male rats to 279 mg/kg
for quail and over 800 mg/kg body weight for guinea
pigs. There are also differences between sexes in the
same species: males are more susceptible to the acute
toxicity of retrorsine than females (WHO, 1988a).
Riddelline LD50 IV in mice is 105 mg/kg body weight
(IARC, 1976).
7.2.3 Relevant in vitro data
Human embryo liver slices (not lung slices) converted
some pyrrolizidine alkaloids, including retrorsine, to
pyrrolic metabolites in vitro (WHO, 1988a).
7.3 Carcinogenicity
Most studies have examined the effects in the liver; the
tumours produced are mostly of epithelial origin, but a
significant number are also vascular. Possible types of tumour
include: hepatomas; hepatocellular carcinoma with metastases;
mammary tumours; lung carcinoma; renal carcinomas; colonic
carcinoma; splenic haemangioendothelioma; osteosarcoma bone;
leukaemia; "spindle cell" tumour (neck); uterine carcinoma;
retroperitoneal sarcoma; and squamous cell carcinoma (of the
jaw) were described for retrorsine. Epidemiological studies
to assess the carcinogenic role of pyrrolizidine alkaloids for
man are not available (WHO, 1988a).
7.4 Teratogenicity
The teratogenic potential of heliotrine and its pyrrole
metabolite was demonstrated (WHO 1988a).
7.5 Mutagenicity
Senecionine, seneciphylline, retrorsine, and intergerrimine
have been shown to be powerful dose-dependent mutagens (WHO,
1998a).
7.6 Interactions
No data available.
8. TOXICOLOGICAL/TOXINOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
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
Serum electrolytes, glucose, bilirubin, serum
transaminase, and prothrombin.
8.3.1.2 Urine
Urinalysis
8.3.1.3 Other fluids
8.3.2 Arterial blood gas analyses
Requested according to patient's condition.
8.3.3 Haematological analyses
Full blood count.
8.3.4 Interpretation of biomedical investigations
There is an increase in leucocyte numbers in blood and
red blood cells in urine.
There is an increase of blood bilirubin, transaminases,
and urea. Hypoglycaemia is present.
Bilirubin is detected in the urine.
Progressive hyperpnoea and encephalopathy may cause
disturbances in acid-base balance.
Liver biopsy shows characteristic changes of
centrilobular haemorrhagic necrosis with extensive
portal and sinusoidal fibrosis leading to cirrhosis
(Ellenhorn, 1988).
8.4 Other biomedical (diagnostic) investigations and their
interpretation
8.5 Overall Interpretation of all toxicological analyses and
toxicological investigations
8.6 References
9. CLINICAL EFFECTS
9.1 Acute poisoning
9.1.1 Ingestion
In humans, symptoms are generally acute in onset and are
characterized by upper abdominal discomfort that
develops rapidly and progresses to swelling of abdomen
resulting in so-called veno-occlusive disease. The
disease progresses rapidly and the mortality is high
(WHO, 1988b).
The acute form of the disease is rare in animals. It is
characterized by sudden death due to acute haemorrhagic
liver necrosis and visceral haemorrhage. In acute
poisoning, death occurs within about 7 days due to
severe liver damage.
9.1.2 Inhalation
No data available.
9.1.3 Skin exposure
No clinical 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
9.2.1 Ingestion
In man, there is generally recovery after an acute
episode, but the disease may continue for a long time
leading to liver cirrhosis. Some patients may have only
vague symptoms. The only sign of the disease may be
persistent hepatomegaly (WHO, 1988a).
In animals chronic liver damage may follow
administration if a single sublethal dose or of repeated
doses.
9.2.2 Inhalation
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
Children appear to be more susceptible than adults. A dose of
70 to 140 mg of Senecio alkaloids resulted in liver cirrhosis
in a 6 month-old girl (Ellenhorn, 1988). In the acute phase
of the disease the dominant symptom is rapidly-filling
ascites. The disease often progresses rapidly and the
mortality is high. There may be haematemesis in the advanced
stages. Causes of death are haemorrhagic states (such as
oesophageal haemorrhage), liver failure and necrosis,
progressive hyperpnoea and encephalopathy (WHO, 1988a;
Ellenhorn, 1988).
9.4 Systematic description of clinical effects
9.4.1 Cardiovascular
Cardiac failure.
9.4.2 Respiratory
Progressive hyperpnoea.
9.4.3 Neurological
9.4.3.1 CNS
Lethargy, encephalopathy.
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
Anorexia, nausea, vomiting, diarrhoea, abdominal cramps.
Vomiting of blood in advanced stages.
9.4.5 Hepatic
Hepatotoxicity is a well-recognized complication.
Jaundice, ascites and hepatomegaly are described.
Chronic cirrhosis. The potential risk of cancer in man
should be seriously considered.
9.4.6 Urinary
9.4.6.1 Renal
Not specific; renal effects are a consequence of
the veno-occlusive disease.
9.4.6.2 Others
No data available.
9.4.7 Endocrine and reproductive systems
No data available.
9.4.8 Dermatological
No data available.
9.4.9 Eye, ears, nose, throat: local effects
Not described.
9.4.10 Haematological
Leucocytosis
9.4.11 Immunological
No data available.
9.4.12 Metabolic
9.4.12.1 Acid base disturbances
Acid base disturbances may occur.
9.4.12.2 Fluid and electrolyte disturbances
Vomiting and diarrhoea may result in loss of
fluids and electrolytes.
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
No data available.
9.5 Others
No data available.
9.6 Summary
10. MANAGEMENT
10.1 General principles
Maintain a clear airway and respiration; administer oxygen.
Remove any parts of the plant present in the mouth and wash
with water or saline solutions. Remove ingested parts of
the plant by gastric lavage or emesis. Administer activated
charcoal. Correct hydration. Watch for signs of
gastrointestinal haemorrhage such as haematemesis. Follow-
up is recommended.
10.2 Relevant laboratory analyses and other investigations
10.2.1 Sample collection
Plant material should be placed between sheets of
paper in a plastic bag and kept for botanical
identification. Vomitus or gastric aspirate should
be stored in a plastic bag.
10.2.2 Biomedical analysis
Request full blood count, serum electrolytes, glucose,
bilirubin, and transaminases. Urinalysis to detect
red blood cells. Arterial 02 and CO2 concentration
and acid-base balance.
10.2.3 Toxicological/toxinological analysis
There is no quantitative analytical method available
to measure pyrrolizidine alkaloids in body fluids
(Ridker & McDermott, 1989), thus diagnosis of
pyrrolizidine alkaloid poisoning must be made by
exclusion of other causes of veno-occlusive disease
in all patients with hepatic failure; by recognition
of the pathognomic histological changes in hepatic
biopsy specimens; and by analytical detection of
pyrrolizidine alkaloids in preparations the patient
has been exposed to (Huxtable, 1979b).
10.2.4 Other investigations
10.3 Life supportive procedures and symptomatic treatment
Monitor pulse, respiration, and blood pressure. Maintain
fluid balance. Haemorrhage, hypoglycemia and massive
hepatic necrosis represent the greatest threat to life
(Ellenhorn 1988).
Maintain respiration: assess ventilation and establish an
adequate airway. Correct anoxia by mechanical ventilation
and oxygen. Endotracheal intubation and assisted
ventilation may be necessary.
In case of hypotension or shock: volume expansion with
normal saline or Ringer's lactate solution; monitor central
venous pressure administer dopamine 200 mg in 250 or 500 ml
of saline or 5% dextrose in water and titrate dose to a rate
of 2-50 g/kg/minute up to the desired response. Fresh-
frozen plasma or blood as needed (Noji & Kelen, 1989).
Administer intravenous glucose immediately in case of
hypoglycemia.
10.4 Decontamination
Remove any parts of the plant present in the mouth and wash
thoroughly with water or a saline solution. If convulsions
are not imminent, induce vomiting or perform gastric lavage
Gastric lavage may be performed if emesis fails. Attention
to the hazard of imminent convulsion.
Administer a slurry of activated charcoal.
10.5 Elimination
No data available.
10.6 Antidote/antitoxin treatment
10.6.1 Adults
No data available.
10.6.2 Children
No data available.
10.7 Management discussion
alternatives and controversies, research needs
Management is mainly symptomatic. Ellenhorn (1988) states:
"Since massive hepatic necrosis represents the greatest
threat life, the usual measures listed under amanita
poisoning for hepatic dysfunction should be administered".
These measures include antidotes such as thioctic acid,
silibinin, penicillin G, although their efficacy is
uncertain, and also hemoperfusion and liver transplantation.
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
Ellenhorn (1988) refers to a case of ingestion of a dose of
80 to 147 mg of Senecio alkaloids which resulted in liver
cirrhosis of a 6 month-old-girl. Death resulted from acute
pulmonary oedema and cardiovascular collapse, 2.5 hours
after ingestion.
WHO's Environmental Health Criteria on pyrrolizidine
alkaloids (1988a) states: "The disease has an acute onset,
characterized by rapidly developing and progressing symptoms
of upper abdominal discomfort, dragging pain in right
hypochondrium, ascites, and sometimes oliguria and oedema of
the feet. Nausea and vomiting may be present. Jaundice and
fever are rare. There is generally gross, tender, smooth
hepatomegaly, often accompanied by massive pleural effusion
and sometimes slight splenomegaly and minimal ankle oedema.
The acute disease is associated with high mortality, and a
subacute or chronic onset may lead to cirrhosis. Death
often occurs after oesophageal haemorrhage"
11.2 Internally extracted data on cases
No data available.
11.3 Internal cases
12. ADDITIONAL INFORMATION
12.1 Availability of antidotes/antitoxins
There are no antidotes or antisera.
12.2 Specific preventive measures
Teach children never to put leaves, stems, bark, seeds, nuts
or berries from any plant into their mouths.
Keep poisonous house plants out of the reach all children.
12.3 Other
No data available.
13. REFERENCES
13.1 Clinical and toxicological
Ellenhorn MJ & Barceloux DG (1988). Medical Toxicology;
diagnosis and treatment of human poisoning. New York:
Elsevier, 1512
IARC. Pyrrolizidine alkaloids. In: Some naturally occurring
substances. Lyon: International Agency for Research on
Cancer 10: 265-342.
Reynolds JEF. Martindale, The Extra Pharmacopoeia, 29th ed.
London: Pharmaceutical Press, 1989, 1876
Merck Index; and encyclopedia of chemical, drugs, and
biogicals, 10th ed. Rahway: Merck, 1983 10000 .
Merck Veterinary Manual. 5th ed. Siegmund OH, ed. Rahway:
Merck, 1979.
Noji EK & Kelen GD (1989). Manual of Toxicological
Emergencies, Chicago, London, Boca Raton: Year Book Medical
Publishers, 850
WHO (1988a). Pyrrolixidine Alkaloids, Environmental Health
Criteria 80. Geneva: World Health Organization, 345
WHO (1988b). Pyrrolizidine Alkaloids, Health and Safety
Guide 26. Geneva: World Health Organization, 20
13.2 Botanical
Encyclopedia Britannica (1963). Chicago, London, Toronto,
Geneva: William Benton Publisher, 20: 322.
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE
ADDRESS(ES)
Author: Dr A. Furtado Rahde
Rua Riachuelo 677 ap 201
90010 Porto Alegre
Brazil
Date: September 1989
Peer review: London, United Kingdom, March 1990