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Triethyltin

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
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 Other characteristics
4. USES/CIRCUMSTANCES OF POISONING
   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 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)
      8.2.3 Interpretation of toxicological analyses
   8.3 Biomedical investigations and their interpretation
      8.3.1 Biochemcial analysis
         8.3.1.1 Blood, plasma or serum
         8.3.1.2 Urine
         8.3.1.3 Other biological specimens
      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 Hematological
      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
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

             Triethyltin

        1.2  Group

             Organotin compounds

        1.3  Synonyms

             Iodotriethylstannane
             Triethyliodostannane
             Triethylstannyl iodide

        1.4  Identification numbers

             1.4.1  CAS number

                    2943-86-4

             1.4.2  Other numbers

                    Not available.

    2.  SUMMARY

        2.1  Main risks and target organs

             Cerebral oedema of the white matter.

        2.2  Summary of clinical effects

             Severe headache, nausea and vomiting, visual and
             psychological disturbances, and sometimes loss of
             consciousness.

        2.3  Diagnosis

             Intolerable severe diffuse headache and signs of
             cerebral oedema 24 to 48 days after exposure to organotin
             compounds is indicative of poisoning.

        2.4  First-aid measures and management principles

             Steroid therapy may diminish the severity of brain
             oedema. Surgical decompression has been considered to be the
             only effective treatment that  offered any benefit in human
             cases.

    3.  PHYSICO-CHEMICAL PROPERTIES

        3.1  Origin of the substance

             No data available.

        3.2  Chemical structure

             (C2H5)3Sn
             
             Molecular weight: 205.88

        3.3  Physical properties

             3.3.1  Colour

                    Colourless.

             3.3.2  State/form

                    Liquid

             3.3.3  Description

                    Melting point:   75°C
                    Boiling point:  161°C 
                    Solubility:
                       insoluble in cold water
                       insoluble in hot water
                       soluble in alcohol and organic solvents
                    (Weast, 1967)

        3.4  Other characteristics

             No data available.

    4.  USES/CIRCUMSTANCES OF POISONING

        4.1  Uses

             4.1.1  Uses

             4.1.2  Description

                    Monosubstituted organotin compounds (RSnX3) are
                    used as stabilisers in polyvinyl chloride films.
                    Disubstituted organotin compounds (R2SnX2) are mainly
                    used in the plastics industry, particularly as
                    stabilisers in polyvinyl chloride. They are also used
                    as catalysts in the production of polyurethane foams
                    and silicones at room-temperature vulcanization.
                    Trisubstituted organotin compounds (R3SnX) have
                    biocidal properties. The most important of these

                    compounds are the tributyl-, triphenyl-,and
                    tricyclohexyltin compounds, which are used as
                    agricultural and general fungicides,bactericides,
                    antihelminthics, miticides, herbicides,molluscides,
                    insecticides, nematocides, ovicides, rodent 
                    repellents, and antifoulants in boat paints. The
                    tetrasubstituted organotin compounds (R4Sn) are mainly
                    used as intermediates in the preparation of other
                    organotin compounds(WHO, 1980).
                    
                    The hazard associated with the use of organotin
                    compounds was unmasked by an incident in 1954
                    involving over 200 cases of poisoning, of which 100
                    were fatal. The cause was the ingestion of an oral
                    preparation containing diethyltin diiodide at 15
                    mg/capsule. It was suggested, however, that ethyl
                    triiodide, triethyltin iodide and tetraethyltin were
                    present as impurities (WHO, 1980).

        4.2  High risk circumstance of poisoning

             Workers involved in the processing of trisubstituted
             compounds may be subject to excessive exposure. Workers
             spraying fields or treating plants with trialkyl compounds
             may also run the risk of exposure to these compounds (WHO,
             1980).

        4.3  Occupationally exposed populations

             No data available.

    5.  ROUTES OF ENTRY

        5.1  Oral

             Main circumstance of poisoning in literature.

        5.2  Inhalation

             Four cases of acute poisoning due to exposure to
             organotin vapours have been reported (Prüll and Rompel,
             1976).

        5.3  Dermal

             Trialkyltin compounds are well absorbed on contact with
             the skin. Application of a 20% fat solution of various
             triethyltin derivates was applied to the skin of rats and
             mice for 10 minutes is fatal for all animals  within 20 to 30
             minutes (Ignatjeva et al., 1968).

        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

             Tin compounds with a short alkyl chain are readily
             absorbed from the intestinal tract.

        6.2  Distribution by route of exposure

             Following intravenous administration of triethyltin, a
             large quantity of triethyltin was found in the liver, with
             smaller quantities in the kidney, brain, and whole blood in
             the rabbit, 2 hours after administration (Cremer 1957,
             1958).

        6.3  Biological half-life by route of exposure

             No data available.

        6.4  Metabolism

             Tri-substituted organotin compounds are dealkylated in
             the liver.

        6.5  Elimination by route of exposure

             Rats fed a diet containing triethyltin accumulated 0.7
             mg triethyltin in their tissues; when a normal diet was then
             substituted no triethyltin could be detected in the tissues
             after 12 days (Cremer 1957). The route of excretion was not
             known.

    7.  TOXICOLOGY

        7.1  Mode of Action

             Triethyltin is a powerful metabolic inhibitor. Three
             interactions with  mitochondrial respiration occur. In
             halide-containing media, the triorganotin compounds mediate
             an exchange of halide for hydroxyl ions across the
             mitochondrial membrane, resulting in a disturbance of the

             existing proton gradient. The triorganotins also bind to a
             component of the ATP-synthetase complex, leading to direct
             inhibition of ATP production. Finally, gross mitochondrial
             swelling occurs after incubation, particularly with the more
             lipophilic triorganotin compounds. As a result  the
             triorganotins are effective inhibitors of mitochondrial ATP
             synthesis (Aldridge and Cremer 1955; Aldridge 1958,1976;
             Aldridge and Street 1964; Selwyn et al., 1970; Selwyn
             1976).
             
             The toxic action of triethyltin on the central nervous system
             of rodents was first described by Stoner et al., (1955). In
             more detailed studies in the rat, Magee et al.,(1979)
             reported that dietary concentrations of 20 mg/triethyltin/kg
             feed induced interstitial oedema of the white matter of the
             brain and spinal cord without obvious neuronal damage. Oedema
             due to a progressive increase in water, sodium, and chloride
             in the central nervous system caused increased cerebral fluid
             pressure (Magee et al., 1957;  Leow et al, 1979).Vascular
             permeability to molecules larger than 3000 D was not altered
             significantly. It was concluded that the basic pathologic
             lesion was limited to myelin. Lesser changes in the
             peripheral nervous system have also been observed (Gerren et
             al., 1976; Graham et al., 1976).
             
             Triethyltin has been shown to reduce concentrations of
             various neurotransmitters, including norepinephrine,
             serotonin, and dopamine in adult rat brain (Moore and Brody
             1961, Bentue-Ferrer et al., 1985). As a consequence of these
             lesions, electrophysiological alterations (Gerren et al.,
             1976; Dyer et al., 1981) and behavioural abnormalities
             (Squibb et al., 1980) have been demonstrated in rodents
             exposed to triethyltin.
             
             In the rat intraperitoneal administered triethyltin is
             associated with a decrease of 30 to 40% in cerebral blood
             flow was observed. After 48 hours an increase of cerebral
             blood flow increased by 13 to 24% above control values. These
             changes were accompanied by macroscopic features of brain
             oedema and changes in the cerebral vascular network. Cerebral
             oxygen consumption was decreased (Pluta and Ostrowska,
             1987).

        7.2  Toxicity

             7.2.1  Human data

                    7.2.1.1  Adults

                             The estimated toxic dose for an
                             adult is reported to be approximately 70 mg
                             of triethyltin over 8 days (Barnes and
                             Stoner, 1959).

                    7.2.1.2  Children

                             Ingestion of 3 capsules of
                             Stalinon(R) was sufficient to cause
                             intoxication in a 9-year-old child (Fontan et
                             al., 1955). Stalinon(R),an oral preparation
                             of 15 mg of diethyltin diiodide and 100 mg
                             vitamin F per capsule, was dispensed as a
                             treatment for staphylococcal skin infections.
                             However it contained also impurities such as
                             monomethyltin triiodide and also triethyltin
                             iodide 1.5 mg in each capsule, what is
                             believed to be the primary agent of
                             intoxication.

             7.2.2  Relevant animal data

                    LD50 intraperitoneal rat triethyltin sulfate:
                    5.7 mg/kg (Stoner, 1966). Triethyltin sulfate was
                    equally toxic to the rat after intravenous,
                    intraperitoneal, and oral administration. The lethal
                    dose was 10 mg/kg, causing death within 4 to 5 days
                    (Stoner et al., 1955). LD50 intraperitoneal rat
                    triethyltin chloride: 5 mg/kg (Robinson,
                    1969).

             7.2.3  Relevant in vitro data

                    Not relevant.

             7.2.4  Workplace standards

                    No data available.

             7.2.5  Acceptable daily intake (ADI) and other guideline
                    levels

                    No data available.

        7.3  Carcinogenicity

             No data available.

        7.4  Teratogenicity

             The physico-chemical characteristics of triethyltin
             indicate that it is likely to cross the placenta, but its
             distribution in the placental-fetal unit is unknown. The
             relative lack of formed myelin in fetal brain may prevent
             cerebral oedema and redistribute the triethyltin to other
             neural elements. No data are available on the possible
             teratogenicity of triethyltin (Reuhl and Cranmer,
             1984).

        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)

             8.2.3  Interpretation of toxicological analyses

        8.3  Biomedical investigations and their interpretation

             8.3.1  Biochemcial analysis

                    8.3.1.1  Blood, plasma or serum

                             Fatal doses of triethyltin in the
                             rat are associated with moderate
                             hyperglycaemia secondary to the release of
                             adrenaline from the adrenal medulla. An
                             increase in  blood non-protein nitrogen  may
                             be secondary to the reduced renal function
                             (Stoner et al, 1955).

                    8.3.1.2  Urine

                             No data available.

                    8.3.1.3  Other biological specimens

                             The cerebrospinal fluid is usually
                             normal.

             8.3.2  Arterial blood gas analyses

                    No data available.

             8.3.3  Haematological analyses

                    No data available.

             8.3.4  Interpretation of biomedical investigations

                    No data available.

        8.4  Other biomedical (diagnostic) investigations and their
             interpretation

             CAUTION: ophthalmoscopy may be completely normal  even
             in case of very severe cerebral oedema (Alajouanine, 1958).
             The cerebrospinal fluid is usually normal but pressure is
             raised. Alajouanine (1958) reported normal lumbar puncture
             even in patients with severe cerebral oedema.
             
             The electroencephalogram may be randomly altered and the
             changes do not suggest any localised lesion (Barnes and
             Stoner 1959).

        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

                    201 case reports, including 98 deaths, have
                    been reviewed by Alajouanine et al., (1958). The
                    predominant symptom, occurring in 98% of  cases, was a
                    diffuse headache, sometimes intolerably severe, which
                    appeared a few days after exposure. Nausea and
                    vomiting occurred in 73%; visual disturbances (mainly
                    photophobia, but also double vision), colour-vision
                    disturbances, and blindness occurred in 33%. Frequent
                    symptoms and signs were urinary incontinence, vertigo,
                    loss of weight, and abdominal pains. Absence of fever
                    and a tendency towards hypothermia were also noted.
                    Psychological disturbances were reported in 70% of the
                    cases. Other findings were meningeal irritation,
                    somnolence, insomnia, convulsions, constipation, and
                    bradycardia.
                    
                    The electrocardiogram was abnormal in some cases but
                    did not suggest any localised lesion. Death was due to
                    respiratory or cardiac changes occurring during
                    convulsive episodes. It is probable that most of the
                    symptoms and signs were attributable to cerebral

                    oedema, the occurrence of which was established at
                    autopsies and at decompressive surgery (Cossa et al,
                    1958; Fontan et al., 1958).
                    
                    It has been reported that only 10 of the 103 subjects
                    who survived recovered completely: in the remainder,
                    symptoms such as headache and asthenia persisted for
                    at least 4 years (Barnes and Stoner 1959).

             9.1.2  Inhalation

                    In four cases of acute poisoning due to
                    exposure to organotin vapours, symptoms included
                    vertigo, headaches, nausea and vomiting and visual
                    disturbances. Clinically, papilloedema was evident and
                    all patients displayed pathological abnormalities on
                    the electroencephalograms. These abnormalities were
                    reversible in 7 to 25 days, and all patients recovered
                    clinically. The organotin compound or compounds
                    involved were not identified (Pruel and Rompel,
                    1976).

             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

                    Muscular weakness, at least partly due to
                    neurological effects and often resulting in partial or
                    total paralysis, has been frequently observed in
                    chronically intoxicated animals (Graham et al, 1976a;
                    Bierkamper and Bassett, 1984). In man, cerebral oedema
                    is the most pronounced finding but muscular weakness
                    and paralysis have also been observed (Alajouanine et
                    al., 1958).

             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

             It has been reported that only 10 of the 103 subjects
             who survived severe poisoning recovered completely; in the
             remainder, symptoms such as headache and asthenia persisted
             for at least 4 years (Barnes and Stoner 1959).

        9.4  Systematic description of clinical effects

             9.4.1  Cardiovascular

                    No data available.

             9.4.2  Respiratory

                    No data available.

             9.4.3  Neurological

                    9.4.3.1  CNS

                             Symptoms and signs attributed to
                             cerebral oedema include (Alajouanine et al.,
                             1958):
                             - diffuse headache, sometimes intolerably
                             severe, and appearing a few days after
                             ingestion of Stalinon(R);
                             - nausea and vomiting;
                             - visual disturbances: mainly photophobia but
                             also double vision, abnormal colour-vision 
                             and blindness;
                             - stupor;

                             - meningeal irritation, somnolence, insomnia,
                             convulsions, constipation, and
                             bradycardia.

                    9.4.3.2  Peripheral nervous system

                             Transitory paralysis lasting 5 to 6
                             hours, and even persisting paresis, were
                             common in patients poisoned by contaminated
                             Stalinon(R) (Alajouanine 1958).

                    9.4.3.3  Autonomic nervous system

                             No data available.

                    9.4.3.4  Skeletal and smooth muscle

                             No data available.

             9.4.4  Gastrointestinal

                    Nausea and vomiting was observed in 146
                    patients and abdominal pain was reported by 19 of the
                    201 persons involved in the Stalinon case.
                    Constipation occurred in 31 patients and diarrhoea in
                    8 (Alajouanine et al., 1958).

             9.4.5  Hepatic

                    No data available.

             9.4.6  Urinary

                    9.4.6.1  Renal

                             Transitory or prolonged urine
                             retention occurred in patients with
                             paraplegia.

                    9.4.6.2  Others

                             No data available.

             9.4.7  Endocrine and reproductive systems

                    No data available.

             9.4.8  Dermatological

                    Various di- and triorganotin compounds are
                    irritant to the skin or eyes in rodents and man, but
                    no data are available on triethyltin.

             9.4.9  Eye, ears, nose, throat: local effects

                    EYE: The commonest effect is photophobia seen
                    in 67 of the 201 patients in the Stalinon poisoning in
                    France. Other visual disturbances include: diplopia
                    due to paralysis of the oculomotor nerve; amblyopia;
                    and transitory or definitive amaurosis within 24 hours
                    of exposure (Alajouanine, 1958).
                    
                    EARS: Hearing may be impaired. Triethyltin and
                    trimethyltin initially disrupt the functional
                    integrity of either inner hair cells or spinal
                    ganglion cells within the cochlea such that
                    depolarisation occurs only following a significant
                    increase in stimulus intensity (Clerici et al,
                    1991).

             9.4.10 Hematological

                     In vitro the most haemolytic organotin
                    compounds are the alkyltin derivatives with alkyl
                    groups of 3 to 6 carbon atoms (Byington et al.,
                    1974).

             9.4.11 Immunological

                    Some of the triorganotin compounds are
                    immunotoxic. Thymus weight reduction, associated with
                    a depletion of cortical lymphocytes, occurs in rats
                    fed with tripropyltin, tributyltin, and triphenyltin
                    compounds at dietary levels as low as 15 to 25 mg/kg
                    (Vos et al., 1984; Krajnc et al., 1984; Snoey et al.,
                    1985). However, these effects may be less apparent
                    than neurotoxicity (Snoey et al., 1985).

             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  Others

             No data available.

    10. MANAGEMENT

        10.1 General principles

             Monitor vital signs and initiate life-supportive measures.

        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

             Studer et al., (1973) reported that steroid therapy
             appeared to diminish the severity of brain oedema and
             mortality in rats.
             
             Surgical decompression has been considered the only effective
             treatment clinically (Alajouanine et al., 1958).

        10.4 Decontamination

             Effective methods are not available.

        10.5 Elimination

             All known methods, even exchange transfusion, have
             proved ineffective.

        10.6 Antidote treatment

             10.6.1 Adults

                    No data available.

             10.6.2 Children

                    Not applicable.

        10.7 Management discussion

             Dimercaprol may be an effective antidote in dialkyl
             poisoning but has no effect in cases of trialkyl
             poisoning.

    11. ILLUSTRATIVE CASES

        11.1 Case reports from literature

             Acute toxicity of an ingested alkyltin compound has
             been observed in man as a result of the Stalinon incident  in
             France in 1954.
             
             Stalinon was an oral preparation containing 15 mg of
             diethyltin diiodide for the treatment of boils and other
             staphylococcal skin infections, osteomyelitis, anthrax and
             acne. The main impurities in Stalinon were monoethyltin
             triiodide and triethyltin iodide. Triethyltin iodide,
             approximately 1.5 mg per capsule, is believed to be the
             primary cause of poisoning.  The striking interstitial oedema
             of the cerebral white matter which occurred in these victims
             was later reproduced by administration of triethyltin to
             laboratory animals.
             
             Over 100 of the 217 known cases of Stalinon poisoning died
             after exposure to an estimated dose of 3 g of triethyltin
             iodide over the course of 6 to 8 weeks. As little as 70 mg of
             triethyltin iodide ingested over an 8-day period appeared to
             be toxic in adults. The signs and symptoms occurred after a
             latent period of about 4 days, with extremely severe,
             persistent headache, often associated with vomiting, vertigo,
             urine retention, photophobia and other signs of visual
             disturbance. Also noted were anorexia, hypothermia, increased
             tendency to sleep and psychiatric disturbances. Severe cases
             were characterised by impaired consciousness followed by
             coma. Death occurred in coma or during convulsions, or from
             respiratory or cardiac failure. Ten of the victims who
             survived appeared to recover completely. The remainder
             experienced attacks of headache and asthenia which persisted
             for more than 4 years. In 4 cases, paraplegia, incontinence
             and loss of sensation appeared to be irreversible (Boyer,
             1989).

        11.2 Internally extracted data on cases

        11.3 Internal cases

    12. ADDITIONAL INFORMATION

        12.1 Availability of antidotes

             Not available.

        12.2 Specific preventive measures

             Not known.

        12.3 Other

             While recent studies suggest that the highly toxic
             alkyltins might be formed by microbial metabolism in the
             environment (Hodge et al., 1979; Hallas et al., 1982) the
             extent to which this occurs naturally and the significance to
             health has not been determined. Detailed studies of
             environmental transformation and bio-accumulation of
             organotins are needed to determine environmental risks (Reuhl
             and Cranmer, 1984).

    13. REFERENCES

        Alajouanine T, Derobert L, Thiefry S (1958) Etude clinique
        d'ensemble de 210 cas d'intoxication par les sels organiques
        d'etain. Rev Neurol 98:85-96.
        
        Aldridge WN (1958) The biochemistry of organotin compounds.
        Trialkyltins and oxidative phosphorylation. Biochem J 69:367-
        376.
        
        Aldrige WN (1976) The influence of organotin compounds on
        mitochondrial functions. Adv Chem Ser 157:186-196.
        
        Aldridge WN, Cremer JE (1955) The biochemistry of organotin
        compounds. Diethyltin dichloride and triethyltin sulphate. Biochem
        J 61:406-418.
        
        Aldridge WN, Street BW (1964) Oxidative phosphorylation.
        Biochemical effects and properties of trialkyltins. Biochem J
        91:287-29
        
        Barnes JM, Stoner HB (1959) The toxicology of tin compounds.
        Pharmacol Rev 11:211
        
        Bentue-Ferrer D, Reymann JM, Van den Driessche J, Allain H, Bagot
        H (1985) Effect of triethyltin chloride on the central aminergic
        neurotransmitters and their metabolites: Relationship with
        pathophysiology of aging. Exp Aging Res 11:137-141.
        

        Bierkamper GG, Bassett DJP (1984) Is trirthyltin-induced muscular
        function a result of mitochondrial compromise? In: Cellular and
        Molecular Neurotoxicology (T.Narahashi, Ed.) pp.109-121.Raven
        Press, New York.
        
        Boyer IJ (1989) Toxicity of dimethyltin and other organotin
        compounds to humans and to experimental animals. Toxicology 55:
        253-298.
        
        Byington KH, Yeh RY, Forte LR (1974) The haemolytic activity of
        some trialkyltin and triphenyltin compounds. Toxicol Appl
        Pharmacol 27:230-240. 
        
        Clerici WJ, Ross B, Fechter LD (1991) Acute Ototoxicity of
        Trialkyltins in the Guinea Pig. Toxicol Appl Pharmacol 109:547-
        556.
        
        Cossa P, Duplay, Fischgold, Arfel-cadevielle, Lafon, Mivielle,
        Radermecker J (1958) Encéphalopathies toxiques au Stalinon.Aspects
        anatomocliniques et electrocéphalographiques. Rev Neurol 98:97-
        108.
        
        Cremer JE (1957) The metabolism in vitro of tissue slices from
        rats given triethyltin compounds. Biochem J 67:87-96.
        
        Cremer JE (1958) The biochemistry of organotin cmpounds:The
        conversion of tetraethyltin into troiethyltin in mammals. Biochem
        J 68:685-692.
        
        Dyer RS, Howell WE, Reiter LW (1981) Neonatal triethyltin exposure
        alters adult electrophysiology in rats. Neurotoxicology 2:609-
        623.
        
        Fontan MM, Verger, Pery, Loiseau, Mulon (1955) Quatre cas dont
        deux mortels d'intoxication par le "Stalinon" chez l'enfant.J Med
        Bordeaux 132:399-405.
        
        Gerren RA, Groswald DE Luttges MW (1976) Triethyltin toxicity as a
        model for degenerative disorders. Pharmacol Biochem Behav 5:299-
        307.
        
        Graham DI, Bonilla E, Gonatis NK, Schotland DL (1976a) Core
        formation in the muscles of rats intoxicated with triethyltin
        sulfate. J Neuropath Exp Neurol 35:1-13.
        
        Graham DI, DeJezus PV, Pleasure DE, Gonatas NK (1976) Triethyltin
        sulfate-induced neuropathy in rats. Arch Neurol 33:40-48.
        
        Hallas LE, Means JC, Cooney JJ (1982) Methylation of tin by
        estuarine microorganisms. Science 215:1505-1507.
        

        Hodge VF, Seidel SL, Goldberg ED (1979) Determination of tin (IV)
        and organotin compounds in natural waters, coastal sediments and
        macroalgae by atomic spectrometry. Analyt Chem :1256-1259. 
        
        Ignatjeva MA, Kuznetsow IG, Mirskow RG, Vlasow VM (1968)
        [Toxicology of acetylene organotin compounds of the
        triethylstannyl range.] Isz sib Otdel Akad Nauk SSSR 1:118-119.(in
        Russian).
        
        Krajnc EI, Wester PW, Loeber JG, Van Leeuwen FXR, Vos JG, Vaessen
        HAMG, Van der Heijden CA (1984) Toxicity of bis(tri-n-
        butyltin)oxide in the rat.I.Short-term effects on general
        parameters and on endocrine and lymphoid systems. Toxicol Appl
        Pharmacol 75:363-386.
        
        Leow ACT, Anderson  McD, Little RA, Leaver DD (1979) A sequential
        study of changes in the brain and cerebrospinal fluid of the rat
        following triethyltin poisoning. Acta Neuropathol 47:117-121.
        
        Magee PN, Stoner HB, Barnes JM (1957) The experimental production
        of oedema in the central nervous system of the rat by triethyltin
        compounds. JPath Bacteriol 73:107-124.
        
        Moore KE, Brody TM (1961) The effect of triethyltin on tissue
        amines. J Pharmacol Exp Ther 132:6-12.
        
        Pluta R, Ostrowsska B (1987) Acute poisoning with trimethyltin in
        the rat. Changes in cerebral blood flow.cerebral oxygen
        consumption,Arterial and cerebral venous blood gasses. Exp Neurol
        98:67-77.
        
        Prüll G, Rompel K (1976) [Neurological and cerebro-electrical
        disturbances in acute poisoning due to organotin compounds]
        Nervenartz 41:516-520.(in German)
        
        Reuhl KR, Cranmer JM (1984) Development Neuropathology of
        organotin compounds. NeuroToxicol 5:187-204.
        
        Robinson IM (1969) Effects of some organotin compounds on tissue
        amine levels in rats. Food Cosmet Toxicol 7:47-52.
        
        Selwyn MJ (1976) Triorganotin compounds as ionophores and
        inhibitors of ion translocating ATPases. Adv Chem Ser 157:204-
        226.
        
        Selwyn MJ, Dawson AP, Stockdale M, Gains N (1970) Chloride-
        hydroxide exchange across mitochondrial,erythrocyte and artificial
        lipid membranes,mediated by trialkyl- and triphenyltin compounds.
        Eur J Biochem 14:120-126. 
        

        Snoey NJ, Van Iersel AAJ, Penninks AH, Seinen W (1985) Toxicity of
        triorganotin compounds:Comparative in vivo studies with a series
        of trialkyltin compounds and triphenyltin chloride in male rats.
        Toxicol Appl Pharmacol 81:274-286.        
        
        Squibb RE, Carmichael NG, Tilson HA (1980) Behavioral and
        neuromorphological effects of triethyltin bromide in adult rats.
        Toxicol Appl Pharmacol 55:188-197.
        
        Stoner HB (1966) Toxicity of triphenyltin. Br.J ind Med 23:222-
        229.
        
        Stoner HB, Barnes JM, Duff JI (1955) Studies on the toxicity of
        alkyltin compounds Brit J Pharmacol. 10:16-25.
        
        Studer RK, Siegel BA, Morgan J, Potchen EJ (1973) Dexamethasone
        therapy of triethyltin induced cerebral edema. Exp Neurol 38:429-
        437.
        
        Vos JG, De Klerk A. Krajnc EI, Kruizinga W, Van Ommen B, Rozing J
        (1984) Toxicity of bis(tri-n-butyltin)oxide in the rat.
        II.Suppression of thymus-           dependint immune responses and
        of parameters of non-specific resistance after short-term
        exposure. Toxicol Appl Pharmacol 75:387-408.
        
        Weast RC (1967) CRC Handbook of Chemistry and Physics 48 ed.   
        The Chemical Rubber Co. Cleveland Ohio.
        
        WHO, World Health Organisation (1980) Environmental Health
        Criteria N0. 15: Tin and Organotin compounds: a preliminary
        review.

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

        Author:              Prof.Dr.A.N.P.van Heijst
                             Baarnse weg 42A
                             3735 MJ Bosch en Duin
                             The Netherlands
                             Telephone -30-287178
                             28-07-1993
        
        Peer Review Group:   Cardiff 14-18 February 1994:
                             N.Besbelli, O.Kasilo, L.Levebvre,
                             J.Szajewski, Temple, A.N.P.van Heijst.
        
        Editor:              M.Ruse
        
        Finalised:           IPCS, April 1997