Triphenyltin acetate
| 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 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/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) |
| 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 |
| 8.1.1.2 Biomedical analyses |
| 8.1.1.3 Arterial blood gas analysis |
| 8.1.1.4 Haematological 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 |
| 8.1.3 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 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 Life supportive procedures and symptomatic treatment |
| 10.3 Decontamination |
| 10.4 Elimination |
| 10.5 Antidote treatment |
| 10.5.1 Adults |
| 10.5.2 Children |
| 10.6 Management discussion |
| 11. ILLUSTRATIVE CASES |
| 11.1 Case reports from literature |
| 12. ADDITIONAL INFORMATION |
| 12.1 Specific preventive measures |
| 12.2 Other |
| 13. REFERENCES |
| 14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESS(ES) |
TRIPHENYLTIN ACETATE
International Programme on Chemical Safety
Poisons Information Monograph 589
Chemical
1. NAME
1.1 Substance
Triphenyltin acetate
1.2 Group
Organotin compound
1.3 Synonyms
(acetyloxy)triphenylstannan;
acetatotriphenylstannane,
acetoxytriphenylstannane,
acetyloxytriphenyltin,
fentin acetate,
phentin acetate,
stannane, (acetyloxy) triphenyl,
tin triphenyl acetate,
TPTA,
triphenylaceto stannane,
1.4 Identification numbers
1.4.1 CAS number
900-95-8
1.4.2 Other numbers
Hazchem code 2Z
NFPA code 2-0-0
NIOSH number WH 6650000
UN number 2786
1.5 Main brand names, main trade names
1.6 Main manufacturers, main importers
2. SUMMARY
2.1 Main risks and target organs
Triphenyltin has a low toxicity.
Liver damage (usually fairly slight) is seen in humans, and
immunotoxicity, fetotoxicity, reproductive toxicity and
respiratory toxicity have been observed in animals. Allergic
reactions are common, especially after dermal exposure.
Respiratory irritation and irritation of the mucosa have been
experienced by workers.
2.2 Summary of clinical effects
Malaise,dizziness, vomiting
Headache
Photophobia
Abdominal pain
Temporary loss of consciousness
Allergic reactions (irritation of
skin/mucosa/conjunctivae)
Liver enlargement
Glycosuria
2.3 Diagnosis
The following clinical symptoms are characteristic of
TPTA poisoning:-
Malaise, dizziness, vomiting
Headache
Abdominal pain
Allergic reactions (irritation of
skin/mucosa/conjunctivae)
Liver enlargement
Laboratory analysis:-
Obtaining urine or blood samples is of prime importance.
Urinary tin levels have been found to peak 5 or 6 days after
poisoning, and provide a specific diagnosis. A decrease in
polymorphonuclear leucocyte activity also indicates TPTA
poisoning, (Colosio et al., 1991).
2.4 First-aid measures and management principles
EYE: Remove any contact lenses, and wash the eye with
flowing water for 10 minutes.
INHALATION: Remove the victim from the area of exposure. If
the victim is conscious make the person lie down quietly and
give oxygen if available.
INGESTION: Do not induce vomiting. If the victim is
conscious give 500ml of water to drink. With usual
precautions and contraindications the use of Ipecac Syrup,
activated charcoal and a cathartic are indicated in the event
of ingestion.
SKIN: Remove any contaminated clothing immediately. Drench
the affected area with running water for at least 10
minutes.
GENERAL: The management of triphenyltin poisoning should be
primarily directed towards decontamination and supportive
care, as there is no specific antidote.
3. PHYSICO-CHEMICAL PROPERTIES
3.1 Origin of the substance
Organotin compounds have been widely used as pesticides
over the last 30 years. Triphenyltin acetate was produced in
1954. It's comparatively low phytotoxicity meant that as the
active principle of Brestanâ it was the first practical
organotin pesticide.
Triphenyltin acetate is produced by the following pathway,
(Bock, 1981).
SnCl4 + 4(C6H5)MgCl -> (C6H5)4Sn + 4MgCl2
(C6H5)4Sn + HCl -> (C6H5)3SnCl + C6H6
(C6H5)3SnCl + MOH -> (C6H5)3SnOH + MCL
Heat the triphenyltin hydroxide with glacial acetic
acid.
3.2 Chemical structure
(C6H5)3SnOOCCH3
3.3 Physical properties
3.3.1 Colour
Normal state at room temperature is white
odourless crystals.
3.3.2 State/form
3.3.3 Description
MW = 409.6
Solubility @ 20°C: 2.8 mg/100ml in water, (Hayes and
Laws, 1991); 0.2% in ethanol, (Bock, 1981); 3.7% in
ether, (Bock, 1981).
Melting point: 122-124°C
Vapour pressure: 60 torr @ 230°C (Bock, 1981); 1.33 ×
10-6 torr @ 30°C, (Hayes and Laws, 1991).
3.4 Hazardous characteristics
Stability:
Slow decomposition (loss of phenol groups as benzene) of the
aqueous solution at room temperature and neutral pH. t1/2 @
30 mins, (Bock, 1981). Lasts indefinitely with dry storage
and normal temperate. Completely decomposes in sunlight after
8 hours. Half life on sugar beet leaves is about 3 days,
(Bock,1981). The half life of TPTA in soil is around 140 days,
(Duncan, 1980).
Combustion:
TPTA produces an acrid smoke and fumes of CO, CO2, tin and
tin oxides when heated to decomposition.
Care should be taken to ensure there is no adverse
phytotoxicity or animal toxicity, especially in aquatic
environments as aquatic organisms are very susceptible
(Solomon et al., 1989). In some aquatic environments it
seems that TPTA persists for long periods of time, (Duncan,
1980).
TPT has been detected in sediments and bivalves of lake
Geneva, although tributyltin and dibutyltin were found at
higher levels, (Becker et al., 1992).
Contaminants of technical grade TPTA (containing 0-95% TPTA)
are approximately 7% tetraphenyltin, 2% diphenyltin and 1%
volatiles (Bock, 1981).
The pesticide Brestan 60, in addition to 60% TPTA contains
15% manganese dithiocarbamate (Maneb), which could confuse
clinical findings in cases of TPTA poisoning, (NIOSH, 1976).
4. USES/CIRCUMSTANCES OF POISONING
4.1 Uses
4.1.1 Uses
4.1.2 Description
Fungicide, yeasticide, bacteriacide,
molluscicide. Organotin compounds are used as
stabilizers in PVC and other plastics. Antifoulant in
ship paint. 200-360 g/ha, 3 to 5 applications per
crop is common (Bock, 1981).
Kills freshwater snails.
Anti-feeding and repellent effects on insects such as
caterpillars.
4.2 High risk circumstance of poisoning
People involved with spraying the pesticide and
preparing the aqueous solution are particularly at risk of
TPTA poisoning.
4.3 Occupationally exposed populations
Crop-duster pilots
Pesticide sprayers
Factory and agricultural workers
5. ROUTES OF ENTRY
5.1 Oral
TPTA may be ingested with vegetable intake. Risk of
harmful effects due to normal dietary intake is very low,
since residues seldom rise above 1 ppm in crops tested.
Compulsory waiting periods allow degradation to levels below
legal limits.
5.2 Inhalation
Poisonings have occurred after respiratory exposure
during crop spraying and mixing of the powder into water.
5.3 Dermal
Cases have been reported in which contact with skin has
caused poisoning. Workers handling the powder are
particularly at risk from this type of exposure, (Colosio et
al., 1991).
5.4 Eye
Airborne TPTA dust irritates the mucous membranes of the
eye.
5.5 Parenteral
No data available
5.6 Others
No data available
6. KINETICS
6.1 Absorption by route of exposure
Absorption through intact skin is poor, (Stoner, 1966).
Intraperitoneal absorption is at least 10-fold more efficient
than oral in laboratory animals, (Stoner, 1966). TPTA given
orally is absorbed well in rats and guinea pigs, but not so
well in sheep, (WHO, 1980).
6.2 Distribution by route of exposure
Triphenyltin is rapidly distributed to all tissues,
including the brains of rats.
Oral dosing of sheep produces slight accumulation in liver,
kidney, lung, pancreas, gall bladder and brain, (Herok and
Götte, 1963).
6.3 Biological half-life by route of exposure
Once absorbed, elimination is slow. One study claims a
half-life in the rat brain of 3 days, while another study
indicated a considerably longer half-life in guinea pigs
(World Health Organization, 1980).
6.4 Metabolism
A large proportion of radioactive Sn is found to be
converted to inorganic tin in sheep, (Bock, 1981). Phenyltin
and diphenyltin are produced in small amounts. TPTA is
resistant to biological oxidation by the microsomal
monooxygenase reaction (Bock, 1981).
Subacute doses of TPTA to rabbits does not greatly influence
the level of liver cytochrome P450, but by some unknown
mechanism there appears to be induction of kidney Cyt P450.
This induction (2-fold at75 ppm in the diet over a70 day
period) could have an effect on the metabolism of endogenous
substrates (Dacasto et al., 1991).
The means of metabolism is unknown. Diphenyltin and
monophenyltin levels in the waste products increase while
triphenytin levels drop, (Freitag and Bock, 1974).
Degradation probably occurs as follows: (C6H5)3Sn+ ->
(C6H5)2Sn2+ -> (C6H5)Sn3+ -> Sn4+
6.5 Elimination by route of exposure
Rats dosed with low levels of TPT in their diet excrete
80-90% unchanged in their faeces within7-10 days, (Bock,
1981; Freitag and Bock, 1974).
Sheep given TPTA orally excreted most of it in the faeces
within a few days, (Herok and Götte, 1963).
7. TOXICOLOGY
7.1 Mode of Action
Low concentrations of triphenyltin and other organotins
inhibit the H+ translocation of the membrane-bound portion of
H+ ATPase, (Papa et al., 1982). Some other ATPases and ion
channels such as the Na+-K+ and the Ca2+ translocating
ATPases are also affected, (Powers and Beavis, 1991).
Triphenyltin has been shown to increase the intracellular
Ca2+ concentration of mouse thymocytes, and the cytotoxicity
could be caused by the resultant disruption of homeostasis. A
likely cause for the increase of intracellular Ca2+ is an
inhibition of the sequestering of Ca2+ by Ca2+ translocating
ATPases, (Oyama et al., 1992).
Organotins may react with thiol groups in proteins, (van der
Bend et al., 1985; Byington et al., 1974).
Anti-inflammatory properties may be caused by the prevention
of phosphorylation of lipomodulin and the subsequent release
of arachidonic acid, (Arakawa and Wada, 1984). Triphenyltin
chloride inhibits histamine release from mast cells, (Nishida
et al., 1992).
Triphenyltin chloride inhibits superoxide production by human
neutrophils, (Matsui et al., 1983; Miura and Matsui, 1991;
Matsui et al., 1983).
The hyperglycaemic action of triphenyltin may be due to the
inhibition of insulin release, (Manabe and Wada, 1981).
7.2 Toxicity
7.2.1 Human data
7.2.1.1 Adults
No data available.
7.2.1.2 Children
No data available.
7.2.2 Relevant animal data
The toxicity of organotin compounds increases
with the number of alkyl groups attached. Of the
trialkyltins, triphenyltin is moderately toxic, but
less toxic than trialkyltins with shorter alkyl
chains, such as trimethyltin.
Acute oral toxicities:
LD50 in guinea pigs 10-41 mg/kg, (Bock, 1981).
LD50 in rabbits 30-50 mg/kg, (Bock, 1981).
LD50 in mice ranges from 81-93 mg/kg, (Bock, 1981).
LD50 in rats ranges from 136-491 mg/kg, (Bock, 1981;
Attahiru et al., 1991).
Acute dermal toxicity:
Rat dermal LD50 of TPTA in oil is around 450 mg/kg,
(Bock, 1981).
Dermal LD50 in mice is 350 mg/kg, (Bock, 1981).
Dermal LD50 in rabbits is approximately 125 mg/kg,
(Bock, 1981).
Chronic oral toxicity:
In guinea pigs, the cumulative toxic oral dose appears
to be of the same order as the acute toxic dose,
(Stoner, 1966). The guinea pig dietary NOEL is no more
than 5 ppm, (Verschuuren et al., 1966). Rats fed TPTA
at levels of 300 ppm become ill and die, (Stoner,
1966). NOEL for dogs is less than 5 ppm, (Stoner,
1966).
7.2.3 Relevant in vitro data
Haemolysis is caused by TPT chloride at low
concentrations in animal blood, but not in human
blood, (Byington et al., 1974).
7.2.4 Workplace standards
In 1965 the ACGIH set the TLV TWA for all
organotins at 0.1 mg/m3, (measured as tin). The
paucity of both human and animal toxicity data at low
organotin concentrations has meant that this TLV was
derived by analogy with mercury, selenium and thallium
data. There are no specific standards for individual
organotin compounds, although the toxicity of
different organotin compounds varies greatly, (NIOSH,
1976).
7.2.5 Acceptable daily intake (ADI)
The ADI is 0.0005 mg/kg, (FAO/WHO,
1971).
7.3 Carcinogenicity
Carcinogenicity tests show no carcinogenic effects in
mice, (Innes et al., 1969). Organotin compounds may actually
have antitumour activity, (Saxena and Tandon, 1983).
7.4 Teratogenicity
Triphenyltin has no known teratogenic effects. A study
by Noda et al., (1991) suggests that TPTA given to maternal
rats in their days7-17 phase does not induce foetal
malformations. Embryotoxic effects were, however, seen at
doses above 3.0 mg/kg maternal body weight.
7.5 Mutagenicity
Results of the dominant lethal assay suggest that TPTA
is not a mouse mutagen, (Duncan, 1980).
7.6 Interactions
No data available
8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
8.1 Material sampling plan
8.1.1 Sampling and specimen collection
Toxicological analyses
8.1.1.2 Biomedical analyses
8.1.1.3 Arterial blood gas analysis
8.1.1.4 Haematological analyses
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
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
Sample collection
No data available
Biomedical analysis
Allergological investigations should be made, in order
to try to confirm TPTA as the toxic agent. Liver and
brain should be tested for signs of damage (Colosio et
al., 1991).
Toxicological analysis
High urinary tin excretion is indicative of recent
exposure. The normal value ranges from 10-65 ng Sn/ml
urine, (Manzo and Richelmi, 1981).
Tin levels in blood above the average range,
(10-20ng/ml) are indicative of tin toxicity, (Manzo
and Richelmi, 1981).
Other investigations
No data available
8.6 References
9. CLINICAL EFFECTS
9.1 Acute poisoning
9.1.1 Ingestion
After a lethal dose, death in laboratory
animals occurs over several days. Signs and symptoms
include weakness, anorexia, watery diarrhoea,
staggering, reddish tears, coma and death, (Bock,
1981).
9.1.2 Inhalation
Human cases of TPTA inhalation have resulted in
malaise, headache, dizziness, loss of consciousness,
epigastric pain, dryness of the mouth, photophobia,
and liver damage, (Colosio et al., 1991; Manzo and
Richelmi, 1981; World Health Organization, 1980).
Animals exposed to TPTA dust showed signs of
irritation of mucous membranes, eyes and respiratory
tract. Restlessness, grooming and coughing were also
seen, but the animals did not die. Post mortem showed
respiratory tract irritation, (Bock, 1981).
9.1.3 Skin exposure
Although it has been claimed that TPTA does not
readily penetrate intact skin, (Stoner, 1966)there
have been cases of human intoxication. TPTA
poisonings in man have resulted in allergic reactions,
liver damage, malaise, metabolic and enzymatic
changes, (Colosio et al., 1991), headaches, epigastric
pain, and weakness, (World Health Organization,
1980).
Severe inflammation is produced in rats given TPTA in
oil, (Bock, 1981).
Tests of dermal toxicity of triphenyltin fluoride
(TPTF) have been conducted on humans, (Andersen and
Petri, 1982). In the aromatic solvent it gave rise to
burning sensations, erythema and dermal necrosis after
30 mins. It should however be noted that TPTA seems to
be more acutely dermally toxic than TPTF.
9.1.4 Eye contact
Triphenyltin is irritating to the eyes, (Bock,
1981; World Health Organization, 1980).
9.1.5 Parenteral exposure
No data available
9.1.6 Other
No data available
9.2 Chronic poisoning
9.2.1 Ingestion
Reduced immune responses and weight loss
(mainly related to reduced food intake) have been
observed in rats fed with 15 ppm triphenyltin, (Bock,
1981).
Decreased levels of peripheral lymphocytes have been
observed in rabbits, (Dacasto et al., 1991).
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
Irritation of the eye, respiratory and nasal mucosa are
experienced before airborne TPTA causes signs of
toxicity.
Early symptoms of poisoning are malaise, dizziness, vomiting
and headache, and it can take between a few hours to days for
them to appear. These symptoms can be found in minor
poisoning (dermal or inhalation). Allergic symptoms may
persist for over a week even after slight poisonings.
Moderately poisoned individuals will often experience
abdominal pain, with continued nausea/vomiting for up to
several days.
Severe acute TPTA toxicity has not been well documented in
the literature.
9.4 Systematic description of clinical effects
9.4.1 Cardiovascular
Heart failure is seen in rats given a lethal
oral dose, (Attahiru et al., 1991).
9.4.2 Respiratory
Upper respiratory tract irritation and
shortness of breath have been reported in human
inhalation cases, (World Health Organization,
1980).
Rats orally given a high lethal dose of TPTA were
found to have severe congestion and haemorrhages of
the lungs,(Attahiru et al., 1991).
9.4.3 Neurological
9.4.3.1 CNS
Headache, dizziness, photophobia,
and occasionally loss of consciousness and
epileptic seizures are seen. Cerebral oedema
is seen in rats given lethal oral doses,
(Attahiru et al., 1991).
Triphenyltin has an excitotoxic effect on
neurons at concentrations ranging from 10-5
to 10-7 M, (Oyama and Akaike, 1991; Oyama,
1992).
Triphenyltin has been shown to increase the
severity of maximal electroshock seizures in
mice at greater than7.17 mg/kg, (Doctor and
Fox, 1982).
9.4.3.2 Peripheral nervous system
Spraying with Brestan 60 has been
associated with lower limb parasthesia,
(Manzo and Richelmi, 1981).
9.4.3.3 Autonomic nervous system
Dry mouth and unquenchable thirst
have been reported with poisonings involving
Brestan 60 containing dithiocarbamate,
(National Institute for Occupational Health
and Safety, 1976).
9.4.3.4 Skeletal and smooth muscle
No data available
9.4.4 Gastrointestinal
Nausea and vomiting occur after poisoning,
(Manzo and Richelmi, 1981; Colosio et al., 1991).
Heartburn and dryness of the mouth seem to precede the
more severe symptoms in the case of Brestan 60
poisoning, (National Institute for Occupational Health
and Safety, 1976).
9.4.5 Hepatic
Abdominal pain, liver damage, hepatomegaly, and
elevated serum enzyme levels have been reported in
poisoning cases. A study on hepatotoxicity in rats
showed a decrease in certain hepatic enzyme activities
and biliary excretion, (Di Nucci et al., 1986).
High doses given orally to rats cause liver
congestion, (Attahiru et al., 1991).
9.4.6 Urinary
9.4.6.1 Renal
Lethal doses of TPTA given orally to
rats cause renal congestion, (Attahiru et
al., 1991).
9.4.6.2 Others
Mild to severe glycosuria has been
found in TPTA poisoning cases, (Colosio et
al., 1991).
9.4.7 Endocrine and reproductive systems
In female rats, 80 ppm in food caused a slight
decrease in litter numbers. 250 ppm caused a distinct
reduction of food intake, growth rate and reproductive
capability, (Bock, 1981). Female rats fed 20 mg TPTA
per kg body weight per day had small ovaries and
decreased fertility, (Newton and Hayes, 1968). Male
rats fed at 20 mg TPTA/kg body weight per day
presented with degenerative changes of the testes,
which were shrunken and infertile. It is unknown
whether these are primary or secondary effects ofTPTA,
(Pate and Hayes, 1968).
9.4.8 Dermatological
Dermatitis has been seen. Irritation of hands,
skin and scrotum were seen in workers spraying 20%
TPTA, (WHO,1980).
9.4.9 Eye, ears, nose, throat: local effects
Irritation of mucous membranes of the eye and
respiratory tract have been observed in laboratory
animals treated with airborne TPTA dust, (Bock,
1981).
Identical symptoms were seen in workers spraying 20%
TPTA, (WHO, 1980).
9.4.10 Hematological
Haemolysis is caused by TPT chloride at low
concentrations in animal blood, but not in human
blood, (Byington et al., 1974).
9.4.11 Immunological
Subacute administration of dietary TPTA at
levels as low as 15 ppm have been shown to have an
immunosuppressive effect on rabbits, (Dacasto et al.,
1991).
Triphenyltin is immunotoxic in rats, but it is thought
that the triorganotins with shorter alkyl chain
lengths are more immunotoxic, (Snoeij 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
Kidney cytochrome P450 levels have
become elevated in rabbits treated
subchronically with 15 ppm TPTA.
Transient hyperglycaemia, glycosuria, and an
increase in liver transaminase activity can
persist for weeks after poisoning in humans,
(Colosio et al., 1991).
9.4.13 Allergic reactions
Allergic reactions in the form of dermatitis
and erythematous eruptions have been reported in
humans, (Colosio et al., 1991).
9.4.14 Other clinical effects
No data available
9.4.15 Special risks
Radiolabelled tin in the milk of pregnant
sheep fed at 3.2 ppm was detected at a level of 2 mg/L
during the 25 days of feeding, and gradually subsided
when doses were stopped, (Bock, 1981).
9.5 Others
No data available
10. MANAGEMENT
10.1 General principles
Generally poisonings are not life-threatening, but
vital signs should be watched in severe cases. Treatment must
be symptomatic.
10.2 Life supportive procedures and symptomatic treatment
Symptomatic treatment.
10.3 Decontamination
Remove and discard contaminated clothing.
Remove any contact lenses and irrigate exposed eyes with
copious amounts of water (or saline).
Induce vomiting, only if the poison does not contain
hydrocarbon solvents.
Perform gastric lavage.
Administer a cathartic.
10.4 Elimination
Not applicable
10.5 Antidote treatment
10.5.1 Adults
No data available
10.5.2 Children
No data available
10.6 Management discussion
No data available
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
Case 1. Adult male, dermal occupational exposure. A
case has been reported in which a 36 year old man was exposed
to an unknown amount of 18.95% TPTA, (Brestan formulation).
While handling the powder without gloves he accidentally
spilt some on the exposed cutaneous area of his arms. He
washed immediately afterwards, but 12 hours later experienced
bilateral plantar pain, and after 24 hours severe genital
oedema, followed by an erythematous reaction on his torso.
Two days after exposure he was experiencing general malaise,
dizziness and abdominal pain. Tests showed an impairment of
glucose metabolism, slight glycosuria, liver enlargement, a
brief increase in IgE, however patch tests with Brestan did
not produce any positive results. Steroid treatment did not
prevent urticarial recurrences, but antihistamine was found
to be helpful, (Colosio et al., 1991).
Case 2. Adult male, occupational exposure by inhalation. A75
year old farmer inhaled some Brestan 60 powder (60% TPTA)
while preparing the aqueous solution. A few days later he
suffered from episodes of sudden malaise, dizziness and
temporary loss of consciousness, followed by a severe
headache, vomiting and photophobia. Once admitted to hospital
he received 10 mg metoclopramide IM twice a day and 6.5 mg
diethylperazine twice a day as a suppository. Despite the
treatment, nausea, vomiting and photophobia persisted for 4
days. He underwent a complete recovery in 10 days. All
laboratory tests were within normal limit, (Manzo and
Richelmi, 1981).
Case 3. Adult male epileptic, occupational exposure. A 53
year old farmer, suffering from primary epilepsy was
admitted to hospital 3 hours after spraying Brestan 60 (60%
TPTA). He had experienced general malaise, dizziness,
headache, asthenia and dryness of the mouth, but the symptoms
had mostly disappeared at the time of hospitalization. His
liver was slightly enlarged. Symptoms reappeared the next
day, and he developed an epileptic seizure which was treated
with intravenous diazepam. The following day headache and
dizziness were accompanied by lower limb paresthesia. Nine
days after admission the patient developed diffuse erythema
on the face, which was treated successfully with 25 mg
promethazine orally per day, (Manzo and Richelmi, 1981).
12. ADDITIONAL INFORMATION
12.1 Specific preventive measures
Workers exposed to TPTA either in the aqueous form or
the powdered form should wear adequate protective clothing.
Respirators should be used if there is any chance of
inhalation of the powder or the aerosol. Exposed workers
would be advised to regularly have their urinary tin levels
checked.
12.2 Other
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14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE
ADDRESS(ES)
Author: William R. Norris
National Toxicology Group
P.O Box 13
Dunedin
New Zealand.
Date: 6 April 1994