Colchicum Autumnale L

Colchicum autumnale L.

1. NAME

1.1 Scientific name

1.2 Family

1.3 Common name(s) and synonyms

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

4.1.1 Uses

4.1.2 Description

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http://www.inchem.org/documents/pims/plant/pim142.htm#PartTitle:4.%20%20USES/CIRCUMSTANCES%20OF%20POISONING

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:3.4%20%20Other%20chemical%20contents%20of%20the%20plant

http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:3.3.3%20%20Other%20physico-chemical%20characteristics

http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:3.3.2%20%20Description,%20chemical%20structure,%20stability

http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:3.3.1%20%20Name(s)

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:3.3%20%20The%20toxin(s)

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:3.2%20%20Poisonous%20parts%20of%20the%20plant

http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:3.1.3%20%20Distribution

http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:3.1.2%20%20Habitat

http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:3.1.1%20%20Special%20identification%20features

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:3.1%20%20Description%20of%20the%20plant

http://www.inchem.org/documents/pims/plant/pim142.htm#PartTitle:3.%20%20CHARACTERISTICS

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:2.6%20%20Main%20toxins

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:2.5%20%20Poisonous%20parts

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:2.4%20%20First-aid%20measures%20and%20management%20principles

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:2.3%20%20Diagnosis

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:2.2%20%20Summary%20of%20clinical%20effects

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:2.1%20%20Main%20risks%20and%20target%20organs

http://www.inchem.org/documents/pims/plant/pim142.htm#PartTitle:2.%20%20SUMMARY

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:1.3%20%20Common%20name(s)%20and%20synonyms

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:1.2%20%20Family

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:1.1%20%20Scientific%20name

http://www.inchem.org/

4.2 High risk circumstances

4.3 High risk geographical areas

5. ROUTES OF EXPOSURE

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 and excretion

7. TOXINOLOGY

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 Relevant 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

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http://www.inchem.org/documents/pims/plant/pim142.htm#PartTitle:8.%20%20TOXICOLOGICAL/TOXINOLOGICAL%20ANALYSES%20AND%20BIOMEDICAL%20INVESTIGATIONS

http://www.inchem.org/documents/pims/plant/pim142.htm#PartTitle:8.%20%20TOXICOLOGICAL/TOXINOLOGICAL%20ANALYSES%20AND%20BIOMEDICAL%20INVESTIGATIONS

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:7.6%20%20Interactions

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:7.5%20%20Mutagenicity

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:7.4%20%20Teratogenicity

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:7.3%20%20Carcinogenicity

http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:7.2.3%20%20Relevant%20in%20vitro%20data

http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:7.2.2%20%20Relevant%20animal%20data

http://www.inchem.org/documents/pims/plant/pim142.htm#DivisionTitle:7.2.1.2%20%20Children

http://www.inchem.org/documents/pims/plant/pim142.htm#DivisionTitle:7.2.1.1%20%20Adults

http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:7.2.1%20%20Human%20data

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:7.2%20%20Toxicity

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:7.1%20%20Mode%20of%20action

http://www.inchem.org/documents/pims/plant/pim142.htm#PartTitle:7.%20%20TOXINOLOGY

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:6.5%20%20Elimination%20and%20excretion

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:6.4%20%20Metabolism

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:6.3%20%20Biological%20half-life%20by%20route%20of%20exposure

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:6.2%20%20Distribution%20by%20route%20of%20exposure

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:6.1%20%20Absorption%20by%20route%20of%20exposure

http://www.inchem.org/documents/pims/plant/pim142.htm#PartTitle:6.%20%20KINETICS

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:5.6%20%20Others

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:5.5%20%20Parenteral

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:5.4%20%20Eye

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:5.3%20%20Dermal

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:5.2%20%20Inhalation

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:5.1.%20Oral

http://www.inchem.org/documents/pims/plant/pim142.htm#PartTitle:5.%20%20ROUTES%20OF%20EXPOSURE

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:4.3%20%20High%20risk%20geographical%20areas

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:4.2%20%20High%20risk%20circumstances

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






8.1.3 Transport of laboratory samples and specimens






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





8.2.2.5 Other Dedicated Method(s)

8.2.3 Interpretation of toxicological analyses

8.3 Biomedical investigations and their interpretation

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http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:8.2.3%20%20Interpretation%20of%20toxicological%20analyses

http://www.inchem.org/documents/pims/plant/pim142.htm#DivisionTitle:8.2.2.5%20%20Other%20Dedicated%20Method(s)

http://www.inchem.org/documents/pims/plant/pim142.htm#DivisionTitle:8.2.2.4%20%20Advanced%20Quantitative%20Method(s)

http://www.inchem.org/documents/pims/plant/pim142.htm#DivisionTitle:8.2.2.3%20%20Simple%20Quantitative%20Method(s)

http://www.inchem.org/documents/pims/plant/pim142.htm#DivisionTitle:8.2.2.2%20%20Advanced%20Qualitative%20Confirmation%20Test(s)

http://www.inchem.org/documents/pims/plant/pim142.htm#DivisionTitle:8.2.2.1%20%20Simple%20Qualitative%20Test(s)

http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:8.2.2%20%20Tests%20for%20biological%20specimens

http://www.inchem.org/documents/pims/plant/pim142.htm#DivisionTitle:8.2.1.4%20%20Advanced%20Quantitative%20Method(s)

http://www.inchem.org/documents/pims/plant/pim142.htm#DivisionTitle:8.2.1.3%20%20Simple%20Quantitative%20Method(s)

http://www.inchem.org/documents/pims/plant/pim142.htm#DivisionTitle:8.2.1.2%20%20Advanced%20Qualitative%20Confirmation%20Test(s)

http://www.inchem.org/documents/pims/plant/pim142.htm#DivisionTitle:8.2.1.1%20%20Simple%20Qualitative%20Test(s)

http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:8.2.1%20%20Tests%20on%20toxic%20ingredient(s)%20of%20material

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:8.2%20%20Toxicological%20Analyses%20and%20Their%20Interpretation

http://www.inchem.org/documents/pims/plant/pim142.htm#DivisionTitle:8.1.3.5%20%20Other%20(unspecified)%20analyses

http://www.inchem.org/documents/pims/plant/pim142.htm#DivisionTitle:8.1.3.4%20%20Haematological%20analyses

http://www.inchem.org/documents/pims/plant/pim142.htm#DivisionTitle:8.1.3.3%20%20Arterial%20blood%20gas%20analysis

http://www.inchem.org/documents/pims/plant/pim142.htm#DivisionTitle:8.1.3.2%20%20Biomedical%20analyses

http://www.inchem.org/documents/pims/plant/pim142.htm#DivisionTitle:8.1.3.1%20%20Toxicological%20analyses

http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:8.1.3%20%20Transport%20of%20laboratory%20samples%20and%20specimens






http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:8.1.2%20%20Storage%20of%20laboratory%20samples%20and%20specimens






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


9.2.6 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

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http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:9.4.2%20%20Respiratory

http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:9.4.1%20%20Cardiovascular

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:9.4%20%20Systematic%20description%20of%20clinical%20effects

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:9.3%20%20Course,%20prognosis,%20cause%20of%20death

http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:9.2.6%20%20Other

http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:9.2.5%20%20Parenteral%20exposure

http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:9.2.4%20%20Eye%20contact

http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:9.2.3%20%20Skin%20exposure

http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:9.2.2%20%20Inhalation

http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:9.2.1%20%20Ingestion

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:9.2%20%20Chronic%20poisoning

http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:9.1.6%20%20Other

http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:9.1.5%20%20Parenteral%20exposure

http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:9.1.4%20%20Eye%20contact

http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:9.1.3%20%20Skin%20exposure

http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:9.1.2%20%20Inhalation

http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:9.1.1%20%20Ingestion

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:9.1%20%20Acute%20poisoning

http://www.inchem.org/documents/pims/plant/pim142.htm#PartTitle:9.%20%20CLINICAL%20EFFECTS

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:8.6%20%20References

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:8.5%20%20Overall%20interpretation%20of%20all%20toxicological%20analyses%20and%20toxicological%20investigations

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:8.5%20%20Overall%20interpretation%20of%20all%20toxicological%20analyses%20and%20toxicological%20investigations

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:8.4%20%20Other%20biomedical%20(diagnostic)%20investigations%20and%20their%20interpretation

http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:8.3.4%20%20Interpretation%20of%20biomedical%20investigations

http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:8.3.3%20%20Haematological%20analyses

http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:8.3.2%20%20Arterial%20blood%20gas%20analyses

http://www.inchem.org/documents/pims/plant/pim142.htm#DivisionTitle:8.3.1.3%20%20Other%20fluids

http://www.inchem.org/documents/pims/plant/pim142.htm#DivisionTitle:8.3.1.2%20%20Urine

http://www.inchem.org/documents/pims/plant/pim142.htm#DivisionTitle:8.3.1.1%20%20Blood,%20plasma%20or%20serum

http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:8.3.1%20%20Biochemical%20analysis

9.4.3.1 Central nervous system (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 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 Life supportive procedures and symptomatic/specific treatment

10.3 Decontamination

10.4 Enhanced elimination

10.5 Antidote/antitoxin treatment

10.5.1 Adults

10.5.2 Children

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http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:10.5.1%20Adults

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:10.5%20Antidote/antitoxin%20treatment

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:10.4%20Enhanced%20elimination

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:10.3%20Decontamination

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:10.2%20Life%20supportive%20procedures%20and%20symptomatic/specific%20treatment

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:10.1%20General%20principles

http://www.inchem.org/documents/pims/plant/pim142.htm#PartTitle:10.%20MANAGEMENT

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:9.6%20%20Summary

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:9.5%20%20Others

http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:9.4.15%20Special%20risks

http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:9.4.14%20Other%20clinical%20effects.

http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:9.4.13%20Allergic%20reactions

http://www.inchem.org/documents/pims/plant/pim142.htm#DivisionTitle:9.4.12.3%20Others

http://www.inchem.org/documents/pims/plant/pim142.htm#DivisionTitle:9.4.12.2%20Fluid%20and%20electrolyte%20disturbances

http://www.inchem.org/documents/pims/plant/pim142.htm#DivisionTitle:9.4.12.1%20Acid-base%20disturbances

http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:9.4.12%20Metabolic

http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:9.4.11%20Immunological

http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:9.4.10%20Haematological

http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:9.4.9%20%20Eye,%20ear,%20nose,%20throat:%20local%20effects

http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:9.4.8%20%20Dermatological

http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:9.4.7%20%20Endocrine%20and%20reproductive%20systems

http://www.inchem.org/documents/pims/plant/pim142.htm#DivisionTitle:9.4.6.2%20%20Other

http://www.inchem.org/documents/pims/plant/pim142.htm#DivisionTitle:9.4.6.1%20%20Renal

http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:9.4.6%20%20Urinary

http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:9.4.5%20%20Hepatic

http://www.inchem.org/documents/pims/plant/pim142.htm#SubSectionTitle:9.4.4%20%20Gastrointestinal

http://www.inchem.org/documents/pims/plant/pim142.htm#DivisionTitle:9.4.3.4%20%20Skeletal%20and%20smooth%20muscle

http://www.inchem.org/documents/pims/plant/pim142.htm#DivisionTitle:9.4.3.3%20%20Autonomic%20nervous%20system

http://www.inchem.org/documents/pims/plant/pim142.htm#DivisionTitle:9.4.3.2%20%20Peripheral%20nervous%20system

http://www.inchem.org/documents/pims/plant/pim142.htm#DivisionTitle:9.4.3.1%20%20Central%20nervous%20system%20(CNS)

10.6 Management discussion

11. ILLUSTRATIVE CASES

11.1 Case reports from literature

12. ADDITIONAL INFORMATION

12.1 Specific preventative measures

12.2 Other

13. REFERENCES

14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESS(ES):

COLCHICUM AUTUMNALE

International Programme on Chemical Safety Poisons Information Monograph 142 Plant

1. NAME

1.1 Scientific name

Colchicum autumnale L.

1.2 Family

Colchicaceae

1.3 Common name(s) and synonyms

Common names:

Autumn crocus (UK); azafran silvestre; colchico (Italy); colchico autumnale (Italy); colchico comun colchicum; colchique (France); dame nue; fall crocus (USA); Herbstblume (Germany); Herbstzeitlose (Germany); meadow crocus; meadow saffron (UK); Michelwurz (Germany); mysteria; Nackte Jungfer (Germany); naked boys; naked ladies (UK); purple crocus; safran des prés; tue-chien; veilleuse; Wiesensafran (Germany); Winterhauch (Germany); wonder bulb; zafferano bastorda (Italy);

http://www.inchem.org/documents/pims/plant/pim142.htm#PartTitle:14.%20AUTHOR(S),%20REVIEWER(S),%20DATE(S)%20(INCLUDING%20UPDATES),%20COMPLETE%20ADDRESS(ES):

http://www.inchem.org/documents/pims/plant/pim142.htm#PartTitle:14.%20AUTHOR(S),%20REVIEWER(S),%20DATE(S)%20(INCLUDING%20UPDATES),%20COMPLETE%20ADDRESS(ES):

http://www.inchem.org/documents/pims/plant/pim142.htm#PartTitle:13.%20REFERENCES

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:12.2%20Other

http://www.inchem.org/documents/pims/plant/pim142.htm#SectionTitle:12.1%20Specific%20preventative%20measures

http://www.inchem.org/documents/pims/plant/pim142.htm#PartTitle:12.%20ADDITIONAL%20INFORMATION

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zafferano salvatico (Italy); Zeitlose (Germany).

Latin synonyms:

C. autumnale subspecies pannonicum (Griseb. & Schenk) Nyman; C. autumnale var. bulgaricum (Velen.) Domin; C. borisii Stef.; C. bugaricum Velen.; C. commune Neck.; C. drenowskii Degen & Rech.f.; C. haynaldii Heuff.; C. pannonicum Griseb. & Schenk; C. polyanthon Ker Gawl.; C. praecox Spenn.; C. rhodopaeum Kov.; C. transsilvanicum Schur; C. vernale Hoffm.; C. vernum Kunth; (Strid & Tan, 1991; Tutin et al., 1980).

2. SUMMARY

2.1 Main risks and target organs

Colchicine exerts multi-organ toxicity. The main toxic effects are related to the effects of colchicine on mitosis and account for diarrhoea, bone marrow depression, cardiotoxicity, central nervous system disturbances and alopecia. Other acute effects are hypovolemia, shock and coagulation disturbances, which may lead to death.

2.2 Summary of clinical effects

Toxic manifestations appear after a delay of 2 to 12 hours following ingestion or parenteral administration. Symptomatology progresses in three stages: Stage I (Days 1-3) Gastrointestinal and circulatory phase: -Severe gastrointestinal irritation: nausea, vomiting, abdominal cramps, severe diarrhoea. Central nervous system excitation and/or depression. -Dehydration, hypovolemia, shock. Cardiogenic shock may occur and may result in death within the 72 hours. -Hypoventilation, acute respiratory distress syndrome. Stage II (Days 3-10) Bone marrow aplasia phase: -Bone marrow aplasia with agranulocytosis. -Coagulation disorders with diffuse haemorrhages. -Rhabdomyolysis. -Polyneuritis, myopathy, ascending paralysis. -Acute renal failure.

-Infectious complications. Stage III (After 10 days) Recovery phase: -Alopecia.

2.3 Diagnosis

Colchicine levels are not clinically useful: biological samples must be stored in airtight conditions and protected from light.

Monitor the following: -Electrolytes, particularly potassium, calcium. -Acid-base balance. -Full blood count and platelets. -Coagulation parameters and fibrin/fibrinogen degradation products. -Creatinine phosphokinase and transaminases.

2.4 First-aid measures and management principles

Patients with C. autumnale poisoning should always be admitted as soon as possible in an intensive care unit (and monitored for at least 48 hours). Treatment may include:

-Early gastric emptying. Activated charcoal in repeated doses. -Rehydration, plasma expander infusion, inotropic and vasopressor drugs. -Artificial ventilation. -Correction of electrolyte and acid-base disorders.Early forced diuresis. -Prevention of infectious complications. Monitor vital signs (ECG, blood pressure, respiration, central venous pressure), fluid and electrolyte balance, haematological and coagulation parameters.

2.5 Poisonous parts

The active principles are contained in all parts of the plant, especially in the seeds and bulbs.

2.6 Main toxins

The main toxin is colchicine. Several other less toxic principles have been isolated (Gessner & Orzechowski, 1974).

3. CHARACTERISTICS

3.1 Description of the plant

3.1.1 Special identification features

Colchicum autumnale is a small herbaceous perennial plant 10 to 40 cm high, flowering typically in the autumn after the leaves have disappeared. Leaves: lanceolate, dark green, shiny (15 to 35 cm x 2 to 7 cm). They appear in the spring, then die back before the flowers appear. Flowers: showy pink, purple to white flowers in groups of 1 to 6 are produced from an underground bulb. Each petal is about 3 to 4.5 cm long and is fused below into a pale stalk-like tube 5-20 cm long. Fruit: an oblong to ovoid green then brown capsule containing many seeds (180 to 200). Bulb: thickened, vertical, underground stem, 2.5 to 6 x 2 to 4 cm, covered in a brown tunic. Different aspects of C. autumnale may be seen throughout the year: -in spring: leaves with fruit (April to July) -in autumn: flowers. (August to October) (Huxley, 1992).

3.1.2 Habitat

C. autumnale grows in wet meadows, woodland clearings and shady rocky habitats on non calcareous substrates. It may be found up to an altitude of 2,000 metres.

3.1.3 Distribution

C. autumnale is a native plant of south, west and central Europe, extending to the eastern banks of the Black Sea, in Georgia (Bruneton, 1995; Tutin et al., 1980). The plant is cultivated throughout much of the world, primarily as an outdoor ornamental.

3.2 Poisonous parts of the plant

All parts of the plant contain toxins. The greatest concentration of toxins is found in the seeds and the bulb (corm) (Cooper & Johnson, 1984; Frohne & Pfänder, 1983). Colchicine is present in the flowers (0.1 to 0.8% in fresh flowers; up to 1.8% in dried flowers), in the seeds (0.2 to 0.8%) in the bulb (corm) (0.4 to 0.6%). The leaves contain very low amounts of colchicine (Gessner & Orzechowski, 1972).

3.3 The toxin(s)

3.3.1 Name(s)

C. autumnale contains several active principles. Colchicine, the major toxin, is an alkaloid which was isolated by Pelletier and Caventou in 1820 but at the time was thought to be veratrine which is similar in effect. It was Geiger in 1833 that identified the toxin as colchicine (Neuwinger, 1994). The other toxins present, which are closely related to colchicine, include: desacetylmethylcolchicine, desacetylthiocolchicine, colchicoside, demethyl desacetylcolchicine.

3.3.2 Description, chemical structure, stability

CAS number: colchicine: 64-86-6 desacetylmethylcolchicine: 477-30-5 desacetylthiocolchicine: 2731-16-0 Molecular weight: colchicine: 399.48 desacetylmethylcolchicine: 371.47 desacetylthiocolchicine: 373.50 Chemical structure: colchicine: C22H25NO6

desacetylmethylcolchicine: CHNO5

desacetylthiocolchicine: CH23NO4S The biological activity of colchicine is due to a portion of its tricyclic molecule, a seven-membered aromatic cyclopentatrieolone ring (tropolene) (Neuwinger, 1994).

3.3.3 Other physico-chemical characteristics

Colchicine is freely soluble in alcohol or chloroform and slightly soluble in petroleum ether. Solubility in water is 1/25. On exposure to light, colchicine is transformed to lumicolchicine. Colchicine is not altered by desiccation of the plant and it is thermostable.

3.4 Other chemical contents of the plant

No data available.

4. USES/CIRCUMSTANCES OF POISONING

4.1 Uses

4.1.1 Uses

Miscellaneous pharmaceutical product Other therapeutic preparation

Other drug; veterinary

4.1.2 Description

Medical: Several extracts of C. autumnale have been used in therapeutics: powder of seeds, tincture of seeds or bulb, alcoholic extracts. 2.5 g of seeds and 25 g of tincture contain 10 mg colchicine. Although colchicine has been used for several diseases including neoplastic and allergic diseases, and as a diuretic, it is currently almost exclusively used as a pharmaceutical in the treatment of gout attack and familial Mediterranean Fever. Homeopathic medicine: C. autumnale is used for gout and polyarthritis. Veterinary medicine: C. autumnale is used for arthritis and as a diuretic.

4.2 High risk circumstances

Poisoning by C. autumnale is a rare event. Several circumstances of poisoning have been reported (Gessner & Orzechowski, 1974). Accidental poisoning: -ingestion of seeds by children using the dried seed parts as rattles; -ingestion of leaves as "salad"; -ingestion of bulbs in mistake for onions; -ingestion of powder of seeds; -ingestion in order to induce abortions; -poisoning of nursing animals or of human beings after use of milk from poisoned animals (goats, sheep). (Cooper & Johnson, 1984; Gessner & Orzechowski, 1974; Kingsbury, 1964). Voluntary intoxication: -Ellwood and Robb (1971) reported a case of a 16-year-old girl who had eaten a dozen flowers. Criminal intoxication: -by alcoholic extract has been reported (Gessner & Orzechowski, 1974).

4.3 High risk geographical areas

See section 3.1.3.

5. ROUTES OF EXPOSURE

5.1. Oral

Intoxication is always due to oral absorption of parts of the plant or extracts.

5.2 Inhalation

No data available.

5.3 Dermal

No data available.

5.4 Eye

No data available.

5.5 Parenteral

No data available.

5.6 Others

No data available.

6. KINETICS

6.1 Absorption by route of exposure

Oral: Rapidly absorbed from the gastrointestinal tract. Peak plasma concentration is reached 0.5 to 2 hours after ingestion (Wallace & Ertel, 1973). Half time of absorption is 15 minutes (Galliot, 1979). Absorption may be modified by pH, gastric contents, intestinal motility (Wallace et al., 1990) Colchicine is not totally absorbed. There is an important hepatic first pass effect.

6.2 Distribution by route of exposure

Protein binding is 10 to 20% (Bennett et al., 1980). Colchicine distributes in a space larger than that of the body. The apparent volume of distribution is 2.2 L/kg (Wallace et al., 1970). In severe renal or liver diseases the volume of distribution is smaller (1.8 L/kg). Colchicine accumulates in the kidney, liver, spleen, gastrointestinal wall and leukocytes but not in heart, brain, skeletal muscle.

Colchicine crosses the placenta and has also been found in maternal milk.

6.3 Biological half-life by route of exposure

a) Parenteral: After a single 2 mg intravenous dose the average plasma half- life is 20 minutes (Wallace et al., 1970). Plasma half-life is increased in severe renal disease (40 minutes) and decreased in severe hepatic disease (9 min) (Wallace et al., 1970). b) Oral: After oral administration plasma concentrations reach a peak within 0.5 to 2 hours and afterwards decrease rapidly within 2 hours (Wallace & Ertel, 1973). The plasma half-life is 60 minutes (Galliot, 1979). Colchicine may remain in tissues for as long as 10 days.

6.4 Metabolism

Colchicine undergoes some hepatic metabolism. Colchicine is partially deacetylated in the liver (Naidus et al., 1977). Large amounts of colchicine and of its metabolites undergo enterohepatic circulation. This may explain the occurrence of a second plasma peak concentration observed 5 to 6 hours after ingestion (Galliot, 1979; Walaszek et al., 1960).

6.5 Elimination and excretion

Colchicine is excreted unchanged (10 to 20%) or as metabolites. Kidney: Urinary excretion amount to 16 to 47% of an administered dose (Heaney et al., 1976). 50 to 70% of colchicine is excreted unchanged and 30 to 50% as metabolites. 20% of the dose administered is excreted in urine in the first 24 hours and 27.5% in the first 28 hours. Colchicine is detected in urine up to 7 to 10 days after ingestion. Urinary excretion is increased in patients with impaired hepatic function (Wallace et al., 1970). Bile: 10 to 25% of colchicine is excreted in the bile (Heaney et al., 1976). Faeces: Large amounts of the drug are excreted in the faeces. After intravenous administration 10 to 56% is excreted in the faeces within the first 48 hours (Walaczek et al., 1960). Breast Milk:

Colchicine may be eliminated in breast milk.

7. TOXINOLOGY

7.1 Mode of action

Colchicine binds to tubulin and this prevents its polymerization into microtubules. The binding is reversible and the half-life of the colchicine-tubulin complex is 36 hours. Colchicine impairs the different cellular functions of the microtubule: separation of chromosome pairs during mitosis (because colchicine arrests mitosis in metaphase), amoeboid movements, phagocytosis. Toxicodynamics Mitosis blockade accounts for diarrhoea, bone marrow depression and alopecia. Colchicine may have a direct toxic effect on muscle, including heart muscle, central and peripheral nervous system and liver. Inhibition of cellular function does not, however, account for all the organ failures seen in severe overdose. Pharmacodynamics Gout inflammation is initiated by urate crystals within tissues. The crystals are ingested by neutrophils but this leads to the release of enzymes and the destruction of the cells. Chemotactic factors are released and attract more neutrophils. Colchicine may act by preventing phagocytosis, the release of chemotactic factors and the response of neutrophils. Colchicine, in therapeutic doses, has other properties such as antipyretic effects, respiratory depression, vasoconstriction and hypertension.

7.2 Toxicity

7.2.1 Human data

7.2.1.1 Adults

5 g seeds = 50 g tincture = 20 mg colchicine is a lethal dose.

7.2.1.2 Children

The lethal dose for child is said to be c. 1 to 1.5g (Frohne & Pfänder, 1983). Ellwood & Robb (1971) reported a fatal outcome in a 16-year-old girl who had eaten a dozen flowers of C. autumnale (for details see section 11.1).

7.2.2 Relevant animal data

Livestock loss due to C. autumnale has been reported in Europe. In oxen, ingestion of 8 to 10 g/kg fresh leaves or 2-3 g/kg dried leaves (in hay) was

lethal (Kingsbury, 1964). Poisonings in dogs have also been reported.

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/TOXINOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS

8.1 Material sampling plan

8.1.1 Sampling and specimen collection






8.1.2 Storage of laboratory samples and specimens






8.1.3 Transport of laboratory samples and specimens






8.2 Toxicological Analyses and Their Interpretation

8.2.1 Tests on toxic ingredient(s) of material





8.2.2 Tests for biological specimens





Colchicine may be analysed in biological fluids by different methods: -Fluorometric method: Fluorescence of organometallic (Gallium) complexes (Bourdon & Galliot, 1976).

-Radioimmunoassay: (Ertel et al., 1976; Scherrman et al., 1980) -High performance liquid chromatography: (Jarvie et al., 1979; Caplan et al., 1980; Haizer, 1984; Lhermitte et al., 1985).

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

Plasma -Bourdon and Galliot (1976) reported plasma levels lower than 20 ng/mL at the 6th hour in severe intoxications. -Jarvie et al. (1979) in an overdose with 7.5 mg, noted plasma levels of 21 ng/mL at the 6th hour and below 5 mg/mL at the 24th hour.

-In severe intoxications plasma levels usually range between 20 to 50 ng/mL during the 24 first hours. After the 24th hour only small amounts of colchicine (< 20 ng/mL) are detected in plasma (Bismuth et al., 1977; Lambert et al., 1981; Jaeger et al., 1985). -Haizer (1984) reported post-mortem serum blood levels of 170 and 240 ng/mL (at the 4th and 8th hour) in 2 heroin addicts following intravenous injection. -Lhermitte et al. (1985) noted the following plasma levels in an overdose with 31 mg orally: 720, 212, 132, and 120 ng/mL at the 20, 125, 305, 605 minutes respectively. Blood Colchicine levels in blood are higher than those in plasma.

-In an overdose with 20 mg colchicine orally Caplan et al. (1980) noted a blood level of 250 ng/mL at the 2nd hour. No colchicine could be detected at the 40th hour.

8.3.1.2 Urine

Colchicine levels in urine range between 200 and 2500 ng/mL over the first 24 hours (Bismuth et al., 1977; Jaeger et al., 1985; Lambert et al., 1981). Jaeger et al. (1985) studied urinary excretion in 5 cases. Concentrations in urine are 2 to 80 fold higher than those in plasma. 4 to 25 of the dose ingested was excreted in urine over 3 to 10 days. Excretion was specially high during the first 24 hours following ingestion. Colchicine is eliminated in urine up to the 10th day.

8.3.1.3 Other fluids

Gastric lavage fluid: In 4 cases, gastric lavage performed 3 to 6 hours post ingestion removed 7 to 25% of the dose ingested (Jaeger et al., 1985). Diarrhoea: In an overdose with 25 mg colchicine orally, 1.4 mg were eliminated in diarrhoea on the 2nd day (Jaeger et al., 1985).

8.3.2 Arterial blood gas analyses

8.3.3 Haematological analyses

"Basic analyses" "Dedicated analyses" "Optional 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

Colchicine may be measured in biological fluids but levels are not useful or necessary for the management of colchicine poisoning. Sample collection Blood samples for colchicine should be drawn in plastic tubes with heparin. Colchicine may be analysed in whole blood or plasma. Biological samples (blood, plasma, urine...) should be stored in airtight conditions and protected from light. Concentrations in whole blood are markedly higher than those in plasma. Concentrations in urine are 10 to 80 fold higher than those in plasma. Biomedical analysis A biochemical profile with glucose, BUN, electrolytes, creatinine, blood cell count, coagulation parameters, liver and muscle enzymes, and blood gases should be obtained on admission and repeated every 12 hours. Samples for bacteriological analysis should be obtained at the stage of aplasia or when fever occurs. Toxicological analysis Colchicine analysis in biological fluids is not necessary or useful for the management of the poisoning. Other investigations No other specific investigations are required. Bone marrow biopsy may be indicated but it is not performed routinely

8.6 References

9. CLINICAL EFFECTS

9.1 Acute poisoning

9.1.1 Ingestion

Toxic manifestations appear after a delay of 2 to 12 hours following ingestion. The delay may be increased if other drugs decreasing gastrointestinal motility have also been ingested (phenobarbitone, psychotropic drugs, opium derivatives). Symptomatology progresses in 3 stages and may include:

Stage I (Day 1-3) Gastrointestinal and circulatory phase: -Severe gastrointestinal irritation: Nausea, vomiting, abdominal cramps, severe diarrhoea. -Dehydration, hypovolemia, shock, prolongation of prothrombin time, leucocytosis. Cardiogenic shock may occur and may result in death within the first 72 hours. -Hypoventilation, acute respiratory distress syndrome. Central nervous system excitation and/or depression. -Hypoventilation, acute respiratory distress syndrome. Stage II (Day 3-10) Bone marrow aplasia phase: -Bone marrow aplasia with agranulocytosis. -Coagulation disorders with diffuse haemorrhages. -Rhabdomyolysis. -Polyneuritis, myopathy, ascending paralysis. -Acute renal failure. -Infectious complications. Stage III: (After 10 days) Recovery phase: -Alopecia.

9.1.2 Inhalation

Not relevant.

9.1.3 Skin exposure

Not relevant.

9.1.4 Eye contact

Not relevant.


9.1.6 Other

(Ellenhorn et al., 1996; Gaultier & Bismuth, 1978; Stapczynski et al., 1981).

9.2 Chronic poisoning

9.2.1 Ingestion

Chronic administration of colchicine may induce similar toxicity to that seen in acute poisoning: gastrointestinal symptoms (vomiting, diarrhoea), agranulocytosis, aplastic anaemia, myopathy (Goodman & Gilman, 1985).

9.2.2 Inhalation

No data available.

9.2.3 Skin exposure

No data available.

9.2.4 Eye contact

No data available.


9.2.6 Other

No data available.

9.3 Course, prognosis, cause of death

Course: (see section 9.1.1.) Prognosis: Prognosis is related to the dose ingested (see section 7.2.1) and therapeutic measures (especially early intervention). Occurrence of cardiogenic shock indicates a poor prognosis (Sauder et al., 1983). If the patient has recovered from aplasia and has not developed acute respiratory distress syndrome or systemic infectious complications, prognosis is usually good. Cause of death: At the early stage (day 1 to 3), cause of death will be due to cardiovascular shock and/or acute respiratory distress syndrome. Death due to haemorrhagic or infectious complications may occur at the stage of bone marrow aplasia (day 3 to 10).

9.4 Systematic description of clinical effects

9.4.1 Cardiovascular

Shock: Cardiovascular shock is always present in severe intoxications. Most deaths result form shock within

the first 72 hours. Hypotension is usually the result of hypovolemia due to gastrointestinal fluid loss. Hypovolemia with decreased central venous pressure is initially always present but some patients may develop cardiogenic shock (Sauder et al., 1983; Bismuth & Sebag, 1981). Haemodynamic studies showed two different profiles: patients with a hyperkinetic state (increased cardiac index and decreased systemic vascular resistances); patients with cardiogenic shock (decreased cardiac index and increased systemic vascular resistances) (Sauder et al., 1983). Occurrence of cardiogenic shock indicates a poor prognosis. Septic shock may occur during the phase of aplasia.

9.4.2 Respiratory

Acute respiratory failure is usually concomitant with circulatory failure, although Murray et al., 1983, reported a case with ascending paralysis occurring more than 4 hours post-exposure. Acute respiratory distress syndrome due to diffuse interstitial and alveolar oedema has been reported in severe cases (Davies et al., 1988; Hill et al., 1986; Hobson et al., 1986).

9.4.3 Neurological

9.4.3.1 Central nervous system (CNS)

In severe cases, hypotension and/or hypoxemia can lead to confusion, agitation, and mental depression. Coma and seizures are observed. Profound coma may be due to cerebral complications such as haemorrhages.

9.4.3.2 Peripheral nervous system

Peripheral neuritis, neuromyopathy and myopathy have been reported (Bertrand,1979; Bismuth, 1977; Carr, 1965; Favarel-Garrigues et al., 1975; Kontos, 1962; Mouren et al., 1969). Ascending paralysis may be responsible for respiratory failure (Carr, 1965; Murray et al., 1983. Polyneuritis usually recovers within one month (Bertrand, 1979; Bismuth et al., 1977) but may last longer (Mouren et al., 1969).

9.4.3.3 Autonomic nervous system

No data available.

9.4.3.4 Skeletal and smooth muscle

Rhabdomyolysis may occur with an increase in muscle enzymes and myoglobinuria (Kontos et al., 1962; Letellier et al., 1979; Murray et al., 1983).

Letellier et al. (1979) reported a case of rhabdomyolysis in a 58-year-old patient treated with 3 mg colchicine daily over 6 days. The patient developed proximal scapular weakness with muscle oedema and increase in muscle enzymes.

9.4.4 Gastrointestinal

a) Acute: Gastrointestinal symptoms develop after a delay of 2 to 12 hours following ingestion and include nausea, vomiting, abdominal pain and severe diarrhoea. Usually diarrhoea lasts for 48 hours and may induce

hypovolemia and electrolyte disturbances. Gastrointestinal symptoms also occur after colchicine overdose by the intravenous route. Paralytic ileus may develop (Heaney et al., 1976). Gastrointestinal disturbances may be lacking or decreased if drugs decreasing gastrointestinal motility (atropine, phenobarbitone, opium tincture) have also been ingested. b) Chronic: Gastrointestinal symptoms are a common feature during colchicine treatment. Paralytic ileus has been reported after intravenous colchicine treatment.

9.4.5 Hepatic

Colchicine may exert direct hepatic toxicity. Hepatomegaly has been reported. Hepatic damage may occur in severe poisoning and include cytolysis and hepatocellular insufficiency, increase in glutamic pyruvic transaminase (SGOT) (alanine amino transferase, ALT) and glutamic oxaloacetic transaminase (SGOT) (aspartate amino transferase, AST) and in alkaline phosphatase, a decrease in coagulation factors. Histologic examination has shown necrosis and steatosis of hepatocytes.

9.4.6 Urinary

9.4.6.1 Renal

No direct nephrotoxic effect has been reported. Functional renal insufficiency is usually observed and is secondary to fluid and electrolyte losses or hypovolemia.

Acute renal failure may occur following cardiovascular or septic shock. Proteinuria and haematuria have been reported.

9.4.6.2 Other

No data available.

9.4.7 Endocrine and reproductive systems

a) Endocrine Transient diabetes mellitus has been reported by Hillemand et al. (1977) in a 58 year old woman after an overdose with 25 mg. Inappropriate antidiuretic syndrome has been reported by Gauthier et al. (1975). b) Reproductive Acute Lambert et al. (1981) reported a case of colchicine poisoning (40 mg) in a 18-year-old pregnant woman. The patient developed severe poisoning with coagulopathy, acute respiratory distress syndrome (ARDS) and abortion on day 7 following ingestion. The patient recovered. Chronic A reversible complete azoospermia has been reported in a 36-year- old man treated with colchicine for gout (Merlin, 1972). Two cases of Down's syndrome babies have been reported. Ehrenfeld et al. (1987) reported the obstetric histories of 36 women with familial Mediterranean fever on long-term colchicine treatment between 3 and 12 years. Seven of 28 pregnancies ended in miscarriage. 13 women had periods of infertility. All 116 infants born to mothers who had taken colchicine during pregnancy were healthy. The authors do not advise discontinuation of colchicine before planned pregnancy but recommend amniocentesis for karyotyping and reassurance.

9.4.8 Dermatological

Acute Alopecia begins at about the 12th day and is complete by 3 weeks after ingestion. Hair regrowth begins after the first month. Sometimes the colour of the hair may change. Cutaneous and subcutaneous haemorrhages are frequent in severe poisoning. They are due to coagulation disturbances.

9.4.9 Eye, ear, nose, throat: local effects

Eyes: Subconjunctival haemorrhage may occur. Ear: Definitive unilateral deafness due to an inner ear haemorrhage has been observed (personal experience). Nose: Nasal haemorrhages may occur especially after local trauma due to insertion of tracheal or gastric tubes. Throat: Stomatitis may also occur (Lambert et al., 1981; Wallace, 1974).

9.4.10 Haematological

At toxic doses, colchicine induces marked bone marrow depression. Leukocytes: At the initial stage, a peripheral leukocytosis occurs frequently. However, the leucocytes seem at this stage to be functionally deficient. A leucopenia with agranulocytosis begins at the third day and reaches a maximum at day 5 to 7. White blood cells (WBC) return to normal values at about the 10th to 12th day. Erythrocytes Anaemia is frequent in severe cases and may be due to different factors: -Hypoplastic anaemia due to bone marrow suppression may be observed but is rarely important. -Haemolytic anaemia with Heinz body has been rarely reported (Heaney et al., 1976). -Acute intravascular haemolysis with haemoglobinemia and haemoglobinuria has been observed in 6 severe cases (Lambert et al., 1981). -Severe anaemia is mostly secondary to multiple diffuse haemorrhages. Bleeding diatheses and coagulopathy: -A tendency towards bleeding is always present in severe cases. It appears 2 to 3 days following ingestion and may last for 8 to 10 days.

-Usually the earliest clinical sign of coagulopathy is persistent bleeding from venous or arterial puncture sites and subcutaneous haemorrhages. -Other types of bleeding include epistaxis, gingival, conjunctival and gastrointestinal haemorrhages. Bleeding may be due to thrombocytopenia or a intravascular coagulopathy.

-A consumptive coagulopathy with prolongation of coagulation time, hypoprothrombinaemia, a decrease in fibrinogen, elevated fibrin degradation products and thrombocytopenia is observed in severe intoxication (Bismuth et al., 1977; Crabie et al., 1970; Lambert et al., 1981).

9.4.11 Immunological

No data available.

9.4.12 Metabolic

9.4.12.1 Acid-base disturbances

Metabolic acidosis due to dehydration and/or shock may be seen.

9.4.12.2 Fluid and electrolyte disturbances

The gastrointestinal syndrome often results in marked dehydration and hypovolaemia with haemoconcentration and functional renal failure. Hypokalaemia due to gastrointestinal losses is also frequent at the initial stage. Hypocalcaemia may be seen and can persist for several days. Frayha et al. (1984) reported, in a 20-year-old girl who had ingested 20 mg, convulsions and paralytic ileus which were related to a hypocalcaemia (1.25 mmol/L). Hypocalcaemia may be due to a direct toxic effect of colchicine (Heath et al., 1972).

9.4.12.3 Others

Hyperglycaemia: Hillemand et al. (1977) reported a 58-year-old woman who ingested 25 mg and developed transient diabetes mellitus.

Hyperlipaemia: A transient hyperlipaemia has been reported (Hillemand et al., 1977). Hyperuricaemia: A transient hyperuricaemia as also been noted (Hillemand et al., 1977). Hyperthermia-fever: occurrence of fever may be related to an infectious complication, especially during the stage of aplasia.

9.4.13 Allergic reactions

No data available.

9.4.14 Other clinical effects.

No data available.

9.4.15 Special risks

Pregnancy Two cases of Down's syndrome babies have been reported. Ehrenfeld et al. (1987) reported the obstetric histories of 36 women with familial Mediterranean fever on long-term colchicine treatment between 3 to 12 years. Seven of 28 pregnancies ended in miscarriage. 13 women had periods of infertility. All 16 infants born to mothers who had taken colchicine during pregnancy were healthy. The authors do not advise discontinuation of colchicine before planned pregnancy but recommend amniocentesis for karyotyping and reassurance. Breast-feeding As colchicine is eliminated in the breast milk breast- feeding should be avoided.

9.5 Others

No data available.

9.6 Summary

10. MANAGEMENT

10.1 General principles

Patients with C. autumnale poisoning should always be admitted to an intensive care unit. Treatment depends on the dose ingested, the symptomatology and the delay following ingestion. It includes gastric emptying, activated charcoal, early forced diuresis, and supportive treatment with correction of the shock, artificial ventilation, treatment and prevention of haemorrhagic coagulation and infectious complications. Vital signs (ECG, blood pressure, central venous pressure, respiration) should be monitored. Be careful about venous and arterial punctures if there is a severe coagulopathy.

10.2 Life supportive procedures and symptomatic/specific treatment

a) Observation and monitoring: Monitor systematically vital signs, ECG, blood pressure and central venous pressure. Repeated monitoring of central venous pressure is essential to avoid circulatory overload during plasma expander infusion. If shock is present, insertion of a pulmonary artery catheter for monitoring of haemodynamic parameters may be useful for guiding the treatment in the initial phase.

The patient remains at risk until at least 48 hours after exposure. b) Diarrhoea: Diarrhoea should not be treated because some colchicine is eliminated in faeces. c)Dehydration - Electrolyte disturbances - Acidosis: Give intravenous fluids and electrolytes according to clinical and biological status. If metabolic acidosis is present give intravenous bicarbonate. Monitor potassium levels and blood gases. Maintain adequate urinary output (&gt100 mL/hour). d)Hypotension, shock: Hypotension should be anticipated and treated with adequate fluid replacement and vasoactive drugs. Monitor blood pressure. Early institution of haemodynamic monitoring is very helpful for adequate treatment of shock.

Hypotension and shock are due primarily to hypovolaemia. Cardiogenic shock may occur. -Plasma expanders:

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Colchicum Autumnale L