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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--hydroxy-12--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 
                  15C,
                  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;  
             -longilobine. 3-Etherylidene-3,4,5,6,9,11,13,14,14 ,
             14  decahydro-6-hydroxy-6-hydroxymethyl-5-methyl (1,6) 
             dioxycyclododeca [2,3,3-gh] pyrrolizidine-2,7-dione; 
             trans-15-ethylidene-12--hydroxy-12--hydroxymethyl-13--
             mehylsene-1-enine (IARC, 1976).
                 CAS:  480-54-6
                 Formula: C18H25NO6
                 Molecular weight = 351.4

                 Melting Point = 212C
                 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 15C.
                 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--hydroxy-12--
                 hydroxymethyl-13-metehylenesenec-1-enine; stereoisomer of 
                 3-ethylidene-3,4,5,6,9,11,13,14,14-,
                 14--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: 198C
                      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
                      -15C.
                      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



    See Also:
       Toxicological Abbreviations