Brucine
| 1. NAME |
| 1.1 Substance |
| 1.2 Group |
| 1.3 Synonyms |
| 1.4 Identification numbers |
| 1.4.1 CAS number |
| 1.4.2 Other numbers |
| 1.5 Brand names, Trade names |
| 1.6 Manufacturers, Importers |
| 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 |
| 3. PHYSICO-CHEMICAL PROPERTIES |
| 3.1 Origin of the substance |
| 3.2 Chemical structure |
| 3.3 Physical properties |
| 3.4 Other characteristics |
| 4. USES/CIRCUMSTANCES OF POISONING |
| 4.1 Uses |
| 4.2 High risk circumstance of poisoning |
| 4.3 Occupationally exposed populations |
| 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 |
| 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 |
| 7.2.4 Workplace standards |
| 7.2.5 Acceptable daily intake (ADI) and other guideline levels |
| 7.3 Carcinogenicity |
| 7.4 Teratogenicity |
| 7.5 Mutagenicity |
| 7.6 Interactions |
| 8. TOXICOLOGICAL 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 analysis |
| 10.2.4 Other investigations |
| 10.3 Life supportive procedures and symptomatic treatment |
| 10.4 Decontamination |
| 10.5 Elimination |
| 10.6 Antidote treatment |
| 10.6.1 Adults |
| 10.6.2 Children |
| 10.7 Management discussion |
| 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 |
| 12.2 Specific preventive measures |
| 12.3 Other |
| 13. REFERENCES |
| 14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESSES |
1. NAME
1.1 Substance
Brucine
1.2 Group
Alkaloid
1.3 Synonyms
(-) Brucine
10.11 - Dimethystrychnine
2-3-Dimethoxystrychnine
2.3 - Dimethoxystrychnine-10-one
Brucin (German)
Brucina (Italian, Portuguese)
Brucine Alkaloid
Dimethoxy Strychnine
Strychnidin-10-one
1.4 Identification numbers
1.4.1 CAS number
357-57-3
1.4.2 Other numbers
CEC: 614-006-00-1
RTECS:EH 8925000
1.5 Brand names, Trade names
(Note: In Portugal there are no rodenticides with brucine)
1.6 Manufacturers, Importers
To be done by each centre
(Note: In Portugal there are no pesticides with brucine)
2. SUMMARY
2.1 Main risks and target organs
Brucine is an alkaloid resembling strychnine but it is much
less potent than strychnine. Brucine causes paralysis of the
peripheral nerve endings and produces violent convulsions.
Highly toxic by ingestion and inhalation; irritant.
When heated, brucine emits highly toxic fumes of nitrogen
oxides.
2.2 Summary of clinical effects
Brucine may produce nausea, vomiting restlessness, excitement,
twitching and convulsions in large doses.
Contact irritates eyes.
2.3 Diagnosis
Brucine can be measured in urine, blood, gastric contents, and
vomitus, but concentrations are not relevant for management.
Determine acidosis and serum potassium.
Determine SGOT, LDH and CPK.
2.4 First-aid measures and management principles
Management is symptomatic and supportive.
Avoid any secondary sensory input.
Prevent or control convulsions with diazepam, or phenytoin or
phenobarbital.
Gastric aspiration and lavage may be indicated when seizures
are controlled.
Administer activated charcoal with a cathartic.
3. PHYSICO-CHEMICAL PROPERTIES
3.1 Origin of the substance
Brucine is an alkaloid obtained from strychnos seeds:
(Strychnos nux-vomica L. and s. ignatii Berg, Loganiaceae).
S. nux-vomica L. contains approximatly 1.1% brucine
S. ignatii Berg contains approximately 1 to 1.2% brucine
"Upas tient_" (arrow poison) contains 2.4% of this alkaloid
(Kohn-Abrest, 1955).
The bark of S. nux-vomica contains 2.4% brucine (Fabre and
Truhaut, 1961).
3.2 Chemical structure
Chemical name: 2,3-Dimethoxystrychnidin-10-one
Empirical formula: C23H26N2O4
Molecular weight: 394.51
(Merck Index, 1989).
Structural formula:
3.3 Physical properties
needles from acetone + water
melting point
anhydrous base 178 °C
hydrated form 105 °C (Clark, 1969)
pH (saturated water solution) 9.5
solubility: 1 g dissolves in:
0.8 ml methanol
1.3 ml alcohol
5 ml chloroform
25 ml ethyl acetate
36 ml glycerol
about 100 ml benzene
187 ml ether
1320 ml water
750 ml boiling water (Merck Index, 1989).
3.4 Other characteristics
Normal state at room temperature: solid monoclinic prisms;
forms dihydrate or tetrahydrate (loses water at 100°C).
Colour: small white crystals (Clark, 1969).
Odour: odourless (Derobert, 1954).
Taste: very bitter; bitterness threshold 1:220,000 (Merck
Index, 1989).
Products of combustion: when heated emits toxic fumes of
nitrogen oxides (Sax, 1984).
4. USES/CIRCUMSTANCES OF POISONING
4.1 Uses
Industry - Brucine and its salts are used as a
denaturant in oils and alcohols (Cook & Martin, 1953;
Merck Index, 1989), and particularly in cosmetic
preparations (Arena, 1986). Brucine is used in
analytical chemistry for separating racemic mixtures
(Merck Index, 1989). It has been patented as additive
for lubricants (Merck Index, 1984). Brucine may be a
constituent of suntan preparations (Arena, 1986).
Agriculture - Brucine and the other alkaloids obtained
from the seeds of Strychnos have been used for
destroying birds, rodents, moles and predatory animals
(Vallet, 1964).
Medicine - Extracts of nux vomica have been used in some
preparations. Nux vomica (dried ripe seeds of Strychnos
nux) contains strychnine and brucine and is used in the
preparation of homeopathic medicine. Ignatia (the
extract of S. ignatii) is also used in homeopathic
medicine, where it is known as Ignatia amara (Martindale,
1989).
4.2 High risk circumstance of poisoning
Brucine is rarely used and poisoning is uncommon. The
concentration of brucine when used as a denaturant is very
low. Consequently, such preparations do not present any great
hazard, unless an unusually large quantity is ingested (Arena,
1986).
Ingestion of the whole plant, particularly the seeds of S. nux-
vomica and S. ignatii can cause poisoning. These plants
contain the alkaloids strychnine and brucine, but lethality of
nux vomica is believed to parallel its content of strychnine.
The bark of Strychnos, may be used mistakenly for the bark of
Galipea officinalis because of its similar appearance and
cause accidental poisoning (Francone, 1963; Fabre & Truhaut,
1961).
Brucine when heated emits toxic fumes of nitrogen oxides.
4.3 Occupationally exposed populations
Workers who come into contact with the brucine powder in
industry.
5. ROUTES OF ENTRY
5.1 Oral
Ingestion of preparations with brucine or plants of species of
Strychnos (Loganiaceae).
5.2 Inhalation
Inhalation of brucine powder.
Inhalation of fumes of nitrogen oxides resulting from heated
brucine.
5.3 Dermal
No data available.
5.4 Eye
No data available.
5.5 Parenteral
No data available.
5.6 Others
Unknown.
6. KINETICS
6.1 Absorption by route of exposure
VIDE Strychnine.
6.2 Distribution by route of exposure
VIDE Strychnine.
6.3 Biological half-life by route of exposure
Unknown.
6.4 Metabolism
VIDE Strychnine.
6.5 Elimination by route of exposure
VIDE Strychnine.
7. TOXICOLOGY
7.1 Mode of Action
Brucine is a highly toxic alkaloid resembling strychnine, but
it is much less potent.It causes paralysis of the peripheral
nerve endings and, in large doses, produces neuronal
excitability (see Strychnine).
7.2 Toxicity
7.2.1 Human data
7.2.1.1 Adults
The probable fatal dose in adult is estimated at
1 g (Gosselin, 1984).
7.2.1.2 Children
7.2.2 Relevant animal data
oral-rat LD50: 1 mg/kg
ipr -rat LD50: 91 mg/kg
ivn -dog LDLo: 8 mg/kg
oral-rbt LD50: 4 mg/kg
ivn -rbt LDLo: 30 mg/kg
ivn -gpg LDLo: 120 mg/kg
scu -pgn LDLo: 58 mg/kg
(Sax, 1984)
7.2.3 Relevant in vitro data
No data available.
7.2.4 Workplace standards
No data available.
7.2.5 Acceptable daily intake (ADI) and other guideline levels
Aquatic toxicity rating: TLm 96:10-1 ppm (NIOSH, 1979)
7.3 Carcinogenicity
No data available.
7.4 Teratogenicity
No data available.
7.5 Mutagenicity
No data available.
7.6 Interactions
No data available.
8. TOXICOLOGICAL ANALYSES 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
Leukocytosis may occur.
8.3.1.2 Urine
Myoglobin should be detected in cases with
rhabdomyolysis.
8.3.1.3 Other fluids
8.3.2 Arterial blood gas analyses
Arterial pH should be determined.
8.3.3 Haematological analyses
Elevation SGOT, LDH and CPK may occur in cases with
rhabdomyolysis.
Serum potassium concentrations should be determined.
8.3.4 Interpretation of biomedical investigations
No data available.
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
Brucine causes nausea, vomiting, restlessness,
excitement, twitching, paralysis of the peripheral nerve
endings and, in large doses, violent convulsions.
9.1.2 Inhalation
The clinical findings are the same as symptoms described
after ingestion.
9.1.3 Skin exposure
No 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
No data available.
9.2.2 Inhalation
No data available.
9.2.3 Skin exposure
No data available.
9.2.4 Eye contact
No data available.
9.2.5 Parenteral exposure
No data available.
9.2.6 Other
No data available.
9.3 Course, prognosis, cause of death
See strychnine.
9.4 Systematic description of clinical effects
9.4.1 Cardiovascular
See strychnine.
9.4.2 Respiratory
See strychnine.
9.4.3 Neurological
9.4.3.1 CNS
See strychnine.
9.4.3.2 Peripheral nervous system
Brucine may act as a local anesthetic agent and
perhaps as a paralytic substance (Gosselin et
al., 1984).
9.4.3.3 Autonomic nervous system
No data available.
9.4.3.4 Skeletal and smooth muscle
There is no direct effect on skeletal muscle.
Increased muscle tone is due to the central
action of the drug (Goodman et al., 1985).
Rhabdomyolysis associated with myoglobinuria may
occur after intense muscular contractions.
9.4.4 Gastrointestinal
Nausea and vomiting.
Small quantities of brucine may have an extremely bitter
taste in the mouth and cause reflex gastric secretion.
9.4.5 Hepatic
No data available.
9.4.6 Urinary
9.4.6.1 Renal
Rhabdomyolysis and myoglobinuria may produce
renal damage from precipitation of myoglobin in
the renal tubules.
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
9.4.10 Haematological
No data available.
9.4.11 Immunological
No data available.
9.4.12 Metabolic
9.4.12.1 Acid-base disturbances
Seizures and muscular spasms may lead to
lactic acidosis.
9.4.12.2 Fluid and electrolyte disturbances
Hyperkalaemia and dehydration have been
described after repeated convulsions (Gosselin,
1984).
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
See strychnine.
10.2 Relevant laboratory analyses and other investigations
10.2.1 Sample collection
10.2.2 Biomedical analysis
10.2.3 Toxicological analysis
10.2.4 Other investigations
10.3 Life supportive procedures and symptomatic treatment
See strychnine.
10.4 Decontamination
See strychnine.
10.5 Elimination
See strychnine.
10.6 Antidote treatment
10.6.1 Adults
10.6.2 Children
10.7 Management discussion
There are no significant controversies or alternatives for
patient management.
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
No data available.
11.2 Internally extracted data on cases
(Note: we do not know of any case of brucine poisoning).
11.3 Internal cases
No data available.
12. ADDITIONAL INFORMATION
12.1 Availability of antidotes
There is no specific antidote.
12.2 Specific preventive measures
There is no justification for use of brucine as rodenticide.
Follow carefully the instructions for safe use of the
brucine powder and industrial preparations with brucine.
Handle dry powder in a fume hood only (Merck Index, 1989).
Wear butyl rubber gloves, full protective clothing,
respirator mask and protective shoes (ITI, 1979).
According to Council of Europe and Directive EEC for
Dangerous Substances, the packages that contain brucine must
have the following phrases relative to the special risks
attaching to dangerous substances:
R26 Very toxic by inhalation
R28 Very toxic if swallowed
and the following phrases about safety advice concerning
dangerous substances:
S1 Keep locked up
S13 Keep away from food, drink and animal stuffs
S45 In case of accident or if you feel unwell, seek medical
advice immediately (show the label where possible).
12.3 Other
No data available.
13. REFERENCES
Arena JM & Drew RH (1986). Poisoning, toxicology symptoms,
treatments, Springfield, Illinois, USA, CC Thomas, 273, 701 (1128
pp).
Clark EGC (1969). Isolation and identification of drugs, Volume
1, London, The Pharmaceutical Press, 225-226 (870 pp).
Cook EF and Martin EW (1953). Farmacia Practica de Remington,
Mexico, Union Tipografica Editorial Hispano Americana, 972 (1786
pp) (in Spanish).
Derobert L (1954). Poisoning and occupational diseases, Paris
Editions M_dicales Flammarion, 1239 (1515 pp) (in French).
Fabre R and Truhaut R (1961). Pr_cis de Toxicologie, Paris,
Soci_t_ d'Edition d'enseignement sup_rieur, 469-472 (721 pp) (in
French).
Francone MP (1963). Toxicologia, Buenos Aires, Editorial Medica
Panamericana, 243 (336 pp) (in Spanish).
Goodman LS, Gilman AG & Gilman A (1985). The pharmacological
basis of therapeutics, New York, Macmillan Publishing Co. Inc.,
582.
Gosselin RE, Smith RP & Hodge HC (1984). Clinical toxicologyof
commercial product, Baltimore/London, Williams & Wilkins, 5th ed.,
II-249, III-375-379.
ITI (1979). Toxic and hazardous industrial chemicals safety
manual, Tokyo, The International Technical Information Institute,
81-82 (591 pp).
Kohn-Abrest E (1955). Pr_cis de Toxicologie. Paris, G. Doin &
Cie., 394-398 (506 pp) (in French).
Martindale (1989). The extra pharmacopoeia. 29th ed. London, The
Pharmaceutical Press, 1146 (1896 pp).
Merck Index (1989). Rahway, 11th edition, New Jersey, USA, Merck
& Co., Inc., 201.
NIOSH Registry of Toxic Effects of Chemical Substances (1979).
Maryland, Tracor Jitco Incorporated, 324 (1598 pp).
NIOSH Registry of Toxic Effects of Chemical Substances (1983-84
supplement). 524-525 (2049 pp).
Sax NI (1984). Dangerous properties of industrial material. 6th
ed., New York, van Nostrand Reinhold Company, 542-3 (3124 pp).
Substances chimiques and dang_reuses et propositions concernant
leur _tiquettage. Conseil de l'Europe (1978), 4th ed.,
Maisonneuve, 894-4 (951 pp).
Vallet G (1964). Les intoxications en milieu rural. Institut
national de M_dicine agricole, 411-414 (632 pp) (in French).
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES),
COMPLETE ADDRESSES
Author: Arlina Borges
Centro de Informa_ao Antivenenos
Instituto Nacional de Emerg_ncia M_dica
Rua Infante D. Pedro, 8
1700 LISBON
Portugal
Tel: 7930503
Tlx: 13304 SNALP/P
Fax: 7590141
Date: April 1990.
Peer Review: Strasbourg, France, April 1990