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TETRAMETHYLENE DISULFOTETRAMINE

1. NAME

1.1 Name

1.2 Group

1.3 Synonyms

1.4 Identification numbers

1.4.1 CAS number

1.4.2 Other numbers

1.5 Main brand names, main trade names

1.6 Main manufacturers, main 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

3.3.1 Colour

3.3.2 State/Form

3.3.3 Description

3.4 Hazardous characteristics

4. USES

4.1 Uses

4.1.1 Uses

4.1.2 Description

4.2 High risk circumstance of poisoning

4.3 Occupationally exposed populations

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

7.2.4 Workplace standards

7.2.5 Acceptable daily intake (ADI)

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 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 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 Other

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 treatment

10.5.1 Adults

10.5.2 Children

10.6 Management discussion

11. ILLUSTRATIVE CASES

12. ADDITIONAL INFORMATION

12.1 Specific preventive measures

12.2 Other

13. REFERENCES

14. AUTHOR(S), REVIEWER(S) DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESSES

 

International Programme on Chemical Safety

Poisons Information Monograph 982

Chemical

1. NAME

TETRAMETHYLENE DISULFOTETRAMINE

1.1 Substance

2,6-Dithia-1,3,5,7-tetraazadamantane,2,2,6,6-tetraoxide

1.2 Group

Sulfur-nitrogen heterocycle heteroadamantane

1.3 Synonyms

Dushuqiang

Four-Two-Four

NSC 172824

Meishuming

Shanbudao

Tetramine

1.4 Identification numbers

1.4.1 CAS number

80-12-6

1.4.2 Other numbers

RTECS number JO6300000

1.5 Main brand names, main trade names

1.6 Main manufacturers, main importers

2. SUMMARY

2.1 Main risks and target organs

Tetramine acts in the CNS as a potent GABA antagonist, leading to excitation of the central nervous system.

2.2 Summary of clinical effects

The time interval between ingestion and symptom onset ranges from several minutes to half an hour (maximum 13 hours). Mild symptoms include headache, dizziness, fatigue, anorexia, nausea, vomiting, numbness of lips, listlessness. Severe symptoms include loss of consciousness, seizures (grand mal epilepsy type, or may last 1-6 minutes and occur repetitively after several minutes), foaming at the mouth, urinary incontinence, coma (with ECG/EEG abnormalities) and death from respiratory failure.

2.3 Diagnosis

Symptoms of nausea, vomiting, abdominal pain, disturbances of consciousness and convulsions soon after ingestion are consistent with tetramine poisoning. The laboratory diagnosis requires confirmation of the presence of tetramine in blood vomitus or urine of persons with suspected exposure (GC and GC-MS techniques have been developed)

2.4 First aid measures and management principles

There are no specific antidotes, symptomatic and supportive treatment is indicated. Elimination of tetramine by gastric lavage, activated charcoal and charcoal haemoperfusion or haemodialysis are also recommended. The use of vitamin B6 and DMPS with animals poisoned with tetramine has been found to inhibit convulsions and reduce mortality, but the clinical efficacy in patients with acute tetramine poisoning is not conclusive.

3. PHYSICOCHEMICAL PROPERTIES

3.1 Origin of the substance

Synthetic

3.2 Chemical structure

Molecular formula

C4H8N4O4S2

Molecular weight

240.26

Structural name(s)

2,6-Dithia-1,3,5,7-tetraazatricyclo[3.3.1.13,7]decane, 2,2,6,6-tetraoxide (9CI)

2,6-Dithia-1,3,5,7-tetraazaadamantane, 2,2,6,6-tetraoxide (6CI, 7CI, 8CI);

2,6-Dithia-1,3,5,7-tetrazatricyclo[3.3.1.13,7]decane 2,2,6,6-tetroxide (Budavari 1996)

3.3 Physical properties

3.3.1 Colour

White

3.3.2 State/Form

Solid-powder

Cubic crystals from acetone

3.3.3 Description

Slightly soluble in water (0.25 mg/ml) and DMSO, slightly soluble in acetone, insoluble in methanol and ethanol

Stable in mild acid or alkali in solutions up to 0.1N

Melting point > 270 C (Budavari 1996)

3.4 Hazardous characteristics

4. USES

4.1 Uses

4.1.1 Uses

Pesticide for use against vertebrate animals: rodenticide

4.1.2 Description

Rodenticide. Has also been used in acetone solution for the treatment of pine seed by direct seeding to reduce loss by rodents (thought to be trans-located from treated seed to germinating seedling in which the residues are distasteful to deer and mice). The high toxicity of this substance has resulted in deregistration in most countries but there is still some illegal trading in the Asian region.

4.2 High risk circumstance of poisoning

Accidental ingestion particularly by children, suicide and homicide. More poisoning exposures occur where the substance is applied in rural areas for the control of rodents (Chi et al, 2000).

Retention of tetramine in the tissue of poisoned poultry and animals also poses the risk of secondary acute intoxication in humans post-ingestion.

4.3 Occupationally exposed populations

Twelve cases of occupational tetramine poisoning in exposed manufacturers and formulators have been reported (Cao,1991, Fan, 2001; Hao, 1992; Xu et al, 1998).

5. ROUTES OF EXPOSURE

5.1 Oral

Commonly reported route of exposure, including suicide, ingestion of contaminated food and homicide (Chi et al, 2000; Fan, 2001; Huang et al, 1997; Li C. et al, 1999; Ning et al, 1997; Sun, 2001; Sun, Li & Zhao, 2000; Sun et al, 2000; Xu et al, 1998; Yan et al, 2000; Zhang, 1999; Zhao, 1999; Zhu et al, 2001).

5.2 Inhalation

Occupational poisoning via the respiratory tract has been reported (Cao,1991; Hao, 1992; Xu et al, 1998).

5.3 Dermal

Two cases of acute tetramine poisoning due to dermal exposure were reported (Fan, 2001).

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

Rapidly absorbed via the gastrointestinal tract. Drinking of tetramine contaminated water or milk could induce acute poisoning within 1-5 minutes (Zhao 1999).

6.2 Distribution by route of exposure

No data available

6.3 Biological halflife by route of exposure

No data available

6.4 Metabolism

No data available

6.5 Elimination and excretion

Tetramine is slowly eliminated. In a report on 52 cases of acute tetramine poisoning, urinary tetramine was detectable in 9 out of 15 cases at 10 days post-ingestion and the amount of tetramine in urine was about 1/15 of that detected at 48 hours (Ning P et al 1997).

In a patient with acute tetramine poisoning and a blood concentration 70 g/L, the urinary clearance of tetramine was 60 g/24 hours. A total of 80 g of tetramine was excreted via urine within 48 hours (Ge X et al 2002).

7. TOXICOLOGY

7.1 Mode of action

Tetramine is a GABA-gated, chloride-channel blocker, a non-competitive GABA antagonist (Esser et al, 1991).

Tetramine blocks GABA receptors, thus has the potential to lead to excitation of the central nervous system and to induce convulsions (Zhang et al 2001).

7.2 Toxicity

7.2.1 Human data

7.2.1.1 Adults

An oral dosage of 6-12 mg is sufficient to cause death (Yang and Fan, 2002).

7.2.1.2 Children

The toxicity of tetramine in children is expected to be similar to adults.

7.2.2 Relevant animal data

Lowest published lethal dose orally in mice 200 m g/kg (Hagen 1950)

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)

No data available

7.3 Carcinogenicity

No data available

7.4 Teratogenicity

No data available

7.5 Mutagenicity

No data available

7.6 Interactions

No data available

8. TOXICOLOGICAL ANALYSES AND
BIOMEDICAL INVESTIGATIONS

8.1 Material sampling plan

8.1.1 Sampling and specimen collection

8.1.1.1 Toxicological analyses

Plasma, vomitus, urine, and post-column blood after charcoal haemoperfusion should be sampled for the measurement of tetramine concentration (Ning et al, 1997; Wang & Zhao, 2001).

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)

Simple Quantitative Method(s)

A review of the developments in determining tetramine in poisoning cases over a ten-year period has been published. This review outlines four methods of extraction, qualitative and quantitative analysis and their level of detection and application (Wang and Zhao 2001).

8.2.1.4 Advanced Quantitative Method(s)

Advanced Quantitative Method(s)

A simple and fast gas chromatography method for the determination of tetramine has been described. Samples were extracted with acetone. A megabore capillary coated with FFAP and a nitrogen-phosphorus detector were used to obtain satisfactory selectivity and sensitivity. A detection limit of 1 ng and average recovery of 89.8% was achieved for tetramine (Wu et al 2002). A GC NPD method for the detection of tetramine in food and tissues has also been reported. This method used an OV-101 capillary column and gave a limit of detection of 0.02 ng (Cao et al 2000).

Methods for solid phase microextraction of tetramine coupled with GC NPD have also been described (Shen and Xiang 2000; Luan et al 2000).

The analysis of tetramine in biological samples by GC-MS has been described (Cao and Wei 2001; Liang and Wu 2001). Tetramine from blood and tissue was extracted with dichloromethane and analysed by GC-MS. The mass spectra showed peaks at 240, 212, 185, 132, 121, 92, 76 and 42 m/z. (Cao and Wei 2001).

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 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

Increased concentrations of AST, ALT, bilirubin, LDH and CK in blood have been reported in patients with severe acute tetramine poisoning. These values have been found to be correlated to the severity of poisoning (Huang, 1999; Li et al, 1999; Ning et al, 1997; Sun et al, 2000, Wang and Zhang, 1999; Yan et al, 2000; Zhang Y ,1999; Zhu, 2001). CK increase is most likely to have resulted from muscular contraction during convulsions (Wang and Zhang, 1999).

8.3.1.2 Urine

Proteinuria and hematuria have been reported (Zhang, 1999).

8.3.1.3 Other fluids

The cerebrospinal fluid examined in 29 cases of acute tetramine poisoning was normal (Yan et al. 2000; Zhu et al, 2001).

8.3.2 Arterial blood gas analyses

8.3.3 Haematological analyses

The white cells are increased in the majority of acute tetramine poisoning patients (Ning et al, 1997; Zhu et al, 2001).

8.3.4 Interpretation of biomedical investigations

8.4 Other biomedical (diagnostic) investigations and their interpretation

ECG: Tachycardia, bradycardia (even lower than 30 per minute), sinus arrhythmia, premature beat and changes indicating toxic myocarditis have been reported including elevation or depression of ST segment, and flatness or inversion of T wave (Li et al, 1999; Liu et al, 1999; Sun, 2001; Yi et al, 2001; Zhu et al, 2001). The ECG changes were reversible except in one case who developed Adam-Stoke syndrome during acute poisoning and continued to have T wave changes after being followed up for 3 years (Ning et al, 1997).

EEG: Diffuse theta waves and paroxysmal sharp waves and delta waves were found; the majority returned to normal after 2 weeks. The longest recovery was observed to be 3 months (Fan, 2001; Li et al, 1999; Zhu et al, 2001).

Brain CT: The results were normal in 15 detected cases (Zhu et al, 2001).

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

The time interval between ingestion and symptom onset ranges from several minutes to half an hour (maximum 13 hours). Mild symptoms include headache, dizziness, fatigue, anorexia, nausea, vomiting, abdominal pain, numbness of lips and listlessness. Severe clinical features include reduction of consciousness, seizures (grand mal epilepsy type, or may last 1-6 minutes and occur repetitively after several minutes), foaming at the mouth, urinary incontinence, coma (with ECG/EEG abnormalities) and death from respiratory failure (Chi et al, 2000; Fan, 2001; Huang et al, 1997; Li C. et al, 1999; Ning et al, 1997; Sun, 2001; Sun, Li & Zhao, 2000; Sun et al, 2000; Xu et al, 1998; Yan et al, 2000; Zhang, 1999; Zhao, 1999 ; Zhu et al, 2001).

9.1.2 Inhalation

Twelve cases of occupational acute poisoning due to inhalation of tetramine during manufacture have been reported (Cao,1991; Hao, 1992; Xu et al, 1998).

9.1.3 Skin exposure

Two cases of acute tetramine poisoning due to dermal exposure were reported (Fan, 2001).

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

The time interval between ingestion and symptom onset ranges from several minutes to half an hour (maximum 13 hours). In a patient with blood tetramine concentration of 0.64 g/mL, convulsions and coma developed at 10 minutes after ingestion of contaminated food, while another patient in the same incident with a blood tetramine concentration of 0.15 g/mL developed dizziness, nausea, fatigue and convulsions at 45 minutes post- ingestion (Liu et al, 1993).

Mild symptoms include headache, dizziness, fatigue, anorexia, nausea, vomiting, abdominal pain, numbness of lips and listlessness which can recover in a week (Li et al, 1999).

Severe cases with reduction of consciousness, seizures (grand mal epilepsy type which may last 1-6 minutes and occur repetitively after several minutes), foaming at the mouth, urinary incontinence and coma (with ECG/EEG abnormalities) need immediate anticonvulsant treatment and charcoal haemoperfusion (Huang et al, 1997). The convulsions usually stop within 24 hours after these treatments, however, they can persist for 72 hours in a few severely poisoned patients (Zhu et al, 2001). The severe cases recover after 10 to 20 days of treatment. A case with blood tetramine concentration as high as 0.82 g/ML recovered after charcoal haemoperfusion and anticonvulsant treatment (Li, 1999; Guan, 1993). The EEG abnormalities also disappear within 2 weeks, the longest recovery being within 3 months (Zhu, 2001). In a few severe cases, the remaining sequelae such as deterioration of memory, dysphasia, deterioration of vision or blindness and secondary epilepsy eventually recovered several months later (Pan et al, 2001; Sun, 2000; Yan et al, 2000).

Patients with status epilepticus often develop cerebral oedema and can die from respiratory failure or multi-organ failure (Sun, 2000; Zhu et al, 2001 ). The reported fatality rate ranges between 1.7 % to 10% (Li, 1999; Fan, 2001).

Death generally occurs within 3 hours post ingestion (Zhou et al 1998).

9.4 Systematic description of clinical effects

9.4.1 Cardiovascular

Cardiovascular signs include irregular heartbeat (sinus arrhythmia, premature beat), tachycardia or bradycardia. ECG may be abnormal indicating myocardial damage or ischaemia. ECG changes indicating toxic myocarditis have been reported including elevation or depression of the ST segment, and flatness or inversion of the T wave (Li et al, 1999; Liu et al, 1999; Sun, 2001; Yi et al, 2001; Zhu et al, 2001). The ECG changes were reversible, except in one case who developed Adam-Stoke syndrome during acute poisoning; the T wave changes remained for 3 years (Ning et al, 1997).

Myocardial necrosis, petechial haemorrhage in heart muscle and pericardium have been described in post mortem studies (Gong et al, 2001; Li et al, 1999; Zhou et al 1998).

9.4.2 Respiratory

Pulmonary oedema and respiratory insufficiency in severe and fatal cases have been reported (Fan, 2001; Li et al, 1999; Sun et al, 2000; Zhou 2001).

Congestion, petechial haemorrhage and oedema in the lungs have been reported following post-mortem studies (Gong et al, 2001; Li et al, 1999; Zhou et al 1998).

9.4.3 Neurological

9.4.3.1 Central nervous system (CNS)

Headache, dizziness, fatigue and listlessness, or agitation, convulsions and coma are related to the amount of poison ingested and age of the subject. Severe cases usually develop reduction of consciousness and abrupt clonic-tonic convulsions. The seizures are of grand mal epilepsy type, may last 1-6 minutes and occur repetitively after several minutes, with foaming at the mouth, urinary incontinence and coma. Patients with status epilepticus often develop cerebral oedema and can die from respiratory failure or multi-organ failure (Fan, 2001; Li, 1999; Sun, 2000; Zhu et al, 2001).

Diffuse theta waves and paroxysmal sharp waves and delta waves in EEG have been found in the majority of patients with severe poisoning. These can recover after 2 weeks but the latest recovery of EEG changes was observed after 3 months (Fan, 2001; Li et al 1999; Zhu et al, 2001).

The results of brain CT in 15 detected cases were normal (Zhu et al, 2001). The cerebrospinal fluid in 29 cases of acute tetramine poisoning was normal (Yan et al 2000; Zhu et al, 2001). Post mortem findings of deaths with tetramine poisoning revealed cerebral congestion, oedema and petechial haemorrhage (Gong et al, 2001; Li et al, 1999; Zhou et al 1998).

9.4.3.2 Peripheral nervous system

Data not available.

9.4.3.3 Autonomic nervous system

Data not available

9.4.3.4 Skeletal and smooth muscle

Data not available

9.4.4 Gastrointestinal

Nausea, vomiting and abdominal pain occur in the majority of patients. Epigastric burning sensation and diarrhoea have been present in some patients. Haematemesis and melaena in severe cases have been reported (Chi et al, 2000; Fan, 2001; Huang et al, 1997; Li C. et al, 1999; Ning et al, 1997; Sun, 2001; Sun, Li & Zhao, 2000; Sun et al, 2000; Xu et al, 1998; Yan et al, 2000; Zhang, 1999; Zhao, 1999; Zhou et al 1998; Zhu et al, 2001).

Haemorrhagic necrosis of the pancreas has been confirmed by post-mortem study in a case of acute tetramine poisoning (Gong et al, 2001).

9.4.5 Hepatic

Liver enlargement and liver dysfunction (elevation of AST, ALT and bilirubin) occurred in severely poisoned patients (Huang, 1999; Liu et al, 1999; Ning et al, 1997; Sun et al, 2000; Wang and Zhang, 1999;Yan et al, 2000; Zhang Y, 1999; Zhu, 2001).

9.4.6 Urinary

9.4.6.1 Renal

Proteinuria and haematuria have been described (Zhang, 1999).

9.4.6.2 Other

No data available

9.4.7 Endocrine and reproductive systems

No data available

9.4.8 Dermatological

No data available

9.4.9 Eye, ear, nose, throat: local effects

No data available

9.4.10 Haematological

Nose bleeding, haematuria and subcutaneous haemorrhage have been reported in three patients with blood concentrations of greater than 0.15m g/ml, however in another case of a patient ingesting a large amount of tetramine, no bleeding symptoms were reported (Li et al, 1999; Liu et al 1993).

9.4.11 Immunological

No data available

9.4.12 Metabolic

9.4.12.1 Acid-base disturbances

No data available

9.4.12.2 Fluid and electrolyte disturbances

No data available

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 Other

No data available

9.6 Summary

10. MANAGEMENT

10.1 General principles

Treatment is symptomatic and supportive.

10.2 Life supportive procedures and symptomatic/specific treatment

Make a proper assessment of airway, breathing, circulation and neurological status of the patient.

Maintain a clear airway.

Control convulsions with appropriate anticonvulsants (sodium phenobarbital, sodium valproate, valium).

Monitor vital signs.

10.3 Decontamination

Perform gastric lavage.

If the patient is obtunded, convulsing or comatose, insert an oro- or a naso-gastric tube and lavage after endotracheal intubation. Administer activated charcoal. If an oro- or a naso-gastric tube is in place, administer activated charcoal after lavage through the tube.

Emesis is contraindicated.

10.4 Enhanced elimination

Charcoal haemoperfusion and haemodialysis are effective in removing tetramine. In severely poisoned patients, seizures usually stop within 24 hours, however they persisted for 72 hours in a few cases after treatment (Zhu et al, 2001). A severely poisoned patient with a blood tetramine concentration as high as 0.82 g/mL also recovered after charcoal haemoperfusion treatment (Li, 1999; Guan, 1993).

Ge et al 2002 report the measurement of blood tetramine concentrations by gas chromatography in three severe cases of acute tetramine poisoning (having convulsions) before and after haemoperfusion. The average tetramine level in the venous blood collected at the inlet before haemoperfusion was 100 g/L. After haemoperfusion for 2 hours (200-300 mL/min), the tetramine concentration in the venous blood collected at the outlet decreased within 30 minutes and then increased to reach about the same level of pre-perfusion at 72 hours. The amount of tetramine absorbed by the instrument after 2-hr haemoperfusion was 1.03-1.55 mg.

The convulsions decreased significantly after haemoperfusion. This indicates that tetramine was mobilized from nervous tissues to the blood by haemoperfusion leading to the improvement of clinical symptoms and signs. However, the haemoperfusion should not exceed 2 hours, but could be repeated if convulsions have not been well controlled.

The same authors also found that in a patient with acute tetramine poisoning, with a blood tetramine concentration of 70 g/L, the urinary clearance of tetramine was 60 g/24 hours. A total of 80 g of tetramine was excreted via urine within 48 hours.

10.5 Antidote treatment

10.5.1 Adults

There is no specific antidote but the use of vitamin B6 together with dimercaptopropane sulfonate (DMPS) has been successful in treating rodents poisoned with tetramine (Guan et al 1993; Zhang et al 2001). However, the clinical efficacy in human patients is not conclusive.

10.5.2 Children

There is no specific antidote but the use of vitamin B6 together with dimercaptopropane sulfonate (DMPS) has been successful in treating rodents poisoned with tetramine (Guan et al 1993; Zhang et al 2001). However, the clinical efficacy in human patients is not conclusive.

10.6 Management discussion

The administration of DMPS to tetramine poisoned rodents was reported as being effective in inhibiting convulsions and reducing mortality (Zhang et al 2001). The use of vitamin B6 with DMPS in mice in the early stage of poisoning with tetramine demonstrated inhibition of convulsions and decreased mortality (Qui et al 2002). However, the clinical efficacy in human patients is not conclusive.

Charcoal haemoperfusion and haemodialysis are effective in removing tetramine. In severely poisoned patients, seizures usually stop within 24 hours, however, they persisted for 72 hours in a few cases after treatment (Zhu et al, 2001). A severely poisoned patient with a blood tetramine concentration as high as 0.82 g/mL also recovered after charcoal haemoperfusion treatment (Li, 1999; Guan, 1993).

11. ILLUSTRATIVE CASES

Case reports from literature

The pathological findings of 5 fatal cases of poisoning with tetramine have been reported. The results showed obvious signs of asphyxia, and congestion and oedema of the brain. The main clinical symptom of intoxication was frequent clonic-tonic convulsions, which was similar to grand-mal epilepsy (Zhou et al 1998).

On May 22, 1991, seven people were poisoned after eating soup that had accidentally been contaminated with tetramine. Two mildly poisoned patients experience symptoms of light-headedness, dizziness, nausea and vomiting. Two patients suffered convulsions and one had tonic convulsions and became comatose (Liu et al 1993).

In July 1991, 78 people in a factory in Hebei province, China were accidentally poisoned with tetramine. Samples of blood were analysed by GC-MS and used to examine the effectiveness of haemoperfusion in the treatment of the patients. Haemoperfusion was found to be effective at removing tetramine 48 hours post-ingestion (Guan et al 1993).

In September 2002 in Nanjing, there were about 200 cases of poisoning and 4 deaths. The cause of poisoning was homicide. It is estimated that about 6000 cases of tetramine poisoning have occurred in China since 1989 until the end of 2002.

12. ADDITIONAL INFORMATION

12.1 Specific preventive measures

12.2 Other

13. REFERENCES

Budavari S ed. (1996) The Merck Index, An encyclopedia of chemicals, drugs, and biologicals, 12th ed. Whitehouse, NJ, Merck and Co., Inc.

Cao C. (1991) Three cases of acute tetramine poisoning. Chi J Int Med 4(4):46

(in Chinese)

Cao Y, Wei Y (2001) Analysis of tetramine in biological samples by GC-MS. Chemical Analysis and Measurement 10(3): 18-19 ( in Chinese).

Cao Y-L, Zhang R-J, Liu H-L, Li Y-L, Li F-S (2000) Study on the determination alimentary intoxicant by tetramine. Bulletin of Zhengzhou Crops 21(2): 50-52, 72 (in Chinese).

Chi Y, Zhang Li, Yu G, Shi X, Zhang C, Wei L, Cao Y. (2000) An investigation on acute tetramine poisoning. Chi J Ind Hyg Occup Dis 18(3) :157 (in Chinese)

Esser T, Karu A E, Toia R F, Casida J E. (1991) Recognition of tetramethylene disulfotetramine and related sulfamides by the brain GABA-gated chloride channel and a cyclodiene-sensitive monoclonal antibody. Chem Res Toxicol 4(2):162-167

Fan C. (2001) An analysis of misdiagnosis of 23 cases of acute tetramine poisoning. China J Misdiagnosis 1(2):266-267(in Chinese)

Ge X., Li X., Guan L., Ma P., Wang H.(2002) Study on the effect using haemoperfusion to treat tetramine poisoned patients. Chin J Ind Hyg Occup Dis 20(6):403-404.

Guan F, Liu Y, Luo Y, Hu X, Liu F, Li Q, Kang Z (1993) GC/MS identification of tetramine in samples from human alimentary intoxication and evaluation of artificial carbonic kidneys for the treatment of the victims. Journal of analytical Toxicology 17(4): 199-201

Guan F, Liu Y, Luo Y, Liu F, Hu X, Li Q, Kang Z (1993) Identification of tetramine in intoxication samples by gas chromatography coupled with mass spectrometry and evaluation of artificial carbonic kidney for the removal of tetramine from poisoned persons. Analytical Chemistry 21(4): 452-4 ( in Chinese).

Gong Z, Zhao X, Cheng J, Gong Zili, Zhuang W, Xu X. (2001) A case of tetramine poisoning with hemorrhagic necrotic pancreatitis. J Forensic Med 17(1): 50-51(in Chinese)

Hager (1950) Deutsche Medizinische Wochenschrift 75: 183

Hao F. (1992) A case of acute tetramine poisoning. Chi J Ind Hyg Occp Dis 10(1):34-35 (in Chinese)

Huang S, Zhao D, Wu F, et al. (1997) A report of 161 cases of acute tetramine poisoning. J Emerg Med. 6:202 (in Chinese)

Li C, QIN Y, Zhang J, Lin R, Bao J,. (1999) Analysis of 116 cases of acute tetramethylene disulfotetramine poisoning. J Critical Care 5(4):175-176 (in Chinese)

Liang G, Wu F Simultaneous GC/MS determination of several organic poisons (2001) Physical and Chemical Detection, Chemistry Portion 37(4): 176-178, 179 ( in Chinese).

Liu H, Liu B, Sheng L, Sheng Y. (1999) A case of toxic myocarditis induced by acute tetramine poisoning leading to cardiogenic shock . Liaoning Med J 13(3):164 (in Chinese)

Liu J, Fan C, Wu G, Huang M (1993) Determination of the concentration of tetramethylenedisulfotetramine in human blood by GC/FPD. J Forensic Sci 38(2): 236-238.

Luan T, Li G, Zhao M, Zhang Z (2000) Rapid detection of tetramethylene disulfotetramine in human blood by solid-phase microextraction/gas chromatography. Analytica Chimica Acta 404(2): 329-334

Ning P, He Q, Yu F, Feng Z, Deng P, Jia T. (1997) Fifty two cases of acute tetramine poisoning. Chi J Ind Hyg Occp Dis 15 (2):108-109 (in Chinese).

Pan W, Yang G, Ma B. (2001) Treatments for mental disorder in tetramine poisoning. J Qiqihar Med Coll 22(10): 1146 (in Chinese).

Qui Z, Lan H, Zhang S, Xia Y, Huang S (2002) Antidotal effects of vitamin B6 and sodium dimercaptopropane sulfonate on acute poisoning with tetramethylene disulfotetramine in animals. Chi J Int Med 41(3): 186-8 ( in Chinese).

Shen M, Xiang P (2000) Rapid determination of tetramine in urine of rodenticide-poisoned person with SPME and GC/NPD. Chi J Pharmaceut 35(5): 341-343 ( in Chinese).

Sun X. (2001) Emergency treatment of tetramine poisoning. Hebei Med J 23(1): 30 (in Chinese)

Sun Y, Li L, Zhao G. (2000) Diagnosis and treatment of acute tetramine poisoning in children. Ningxia Med J 22(2):115-116 (in Chinese)

Voss E, Haskell A R, Gartenberg L (1961) Reduction of tetramine toxicity by sedatives and anti-convulsants. J Pharm Sci 50: 858-60

Wang W, Zhang W. (1999) Analysis of the changes of LDH, CK in tetramine poisoned children. J Emerg Med 8 (4) :230- 231 (in Chinese)

Wang Y, Zhao J (2001) Survey and development on determination of tetramine poisoning. Pesticides 40(8): 12-14 ( in Chinese)

Wu Q, Zhang M-S, Lan Z-R (2002) Simultaneous determination of fluoroacetamide and tetramine by gas chromatography. Chromatography 20(4): 381-382 ( in Chinese)

Xu L, Mo W, Liu J. et al (1998) Analysis of 71 cases of acute tetramine poisoning. Emerg Med 7:232 (in Chinese)

Yan H, Pang B, Sun X, Wang G, Bu Y. (2000) An analysis of the diagnosis and treatment of 46 cases of acute tetramine poisoning. Chi J Child Health Care 8(2):129 (in Chinese)

Yang J, Fan X. (2002) Analysis of 782 cases of acute tetramine poisoning. Chi J Clin Med and Pharm 3(21): 48-49 (in Chinese)

Yi F, Sun Sh, Cheng W. (2001) Analysis of EKG of 20 cases of acute tetramine poisoning. J Hebei Med 7(11): 716-717 (in Chinese)

Zhao L. (1999) A report of 19 cases of acute tetramine poisoning. J Law & Med

6 (1):34-35 (in Chinese)

Zhang C, Zhu T, Chen X, Hu G, Chen Z.(2001) Actions of sodium dimercaptopropanesulfonate against convulsions induced by tetraethylene disulfotetramine. Chi J Pharmaceutics 36(11): 736-738. ( in Chinese)

Zhang C, Zhu T, Chen X, Hu G, Liu D (2001) Convulsive effects and mechanism of tetramethylenedisulfotetramine. J Health Toxicol 15(1): 5-7 ( in Chinese)

Zhang, C-Y, Zhu T-J, Hu G-X, Chen X-Y, Liu D-X, Chen Z-K (2001) Effect of sodium dimercaptopropanesulfonate on antagonism of tetramethylene disulfotetramnie to GABA receptor. Acta Pharmacologica Sinica 22(5): 435-439. ( in Chinese)

Zhang Y. (1999) Clinical Analysis of 31 cases of acute tetramine poisoning in children. Chi J Cur Pediat 1(1):32-33 (in Chinese)

Zhou Y, Liu L, Tang L (1998) An autopsy analysis on 5 cases of poisoning death with tetramethylene disulphotetramine. J Forensic Med 14(4): 214-7, 217, 252. ( in Chinese)

Zhu S, Fang H, Fang Y. (2001) Retrospective analysis of 79 cases of acute tetramine poisoning in children. J Cur Comb West Trad Med 10(9): 829-830 (in Chinese)

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

Dr Wayne A Temple
National Poisons Centre
Department of Preventive and Social Medicine
Dunedin School of Medicine
University of Otago
Box 913
New Zealand

Dr Nerida A Smith
Department of Pharmacology and Toxicology
Dunedin School of Medical Sciences
University of Otago
Box 913
Dunedin

December 2002

Reviewed and updated in December 2002

Prof. Fengsheng He
National Institute of Occupational Health and Poison Control
Chinese Centre for Disease Control and Prevention
29 Nan Wei Road,
Beijing 100050
P.R. China



    See Also:
       Toxicological Abbreviations