WORLD HEALTH ORGANIZATION FOOD AND AGRICULTURE ORGANIZATION
ORGANISATION MONDIALE DE LA SANTE ORGANISATION POUR L'ALIMENTATION
ET L'AGRICULTURE
VBC/PDS/DS/85.65
ORIGINAL: ENGLISH
DATA SHEET ON PESTICIDES No. 65
BIS(TRIBUTYLTIN)OXIDE
CLASSIFICATION
Primary use: Fungicide
Secondary use: Molluscicide, Algicide, Bactericide
It must be noted that the issue of a Data Sheet for a
particular pesticide does not imply endorsement of the pesticide by
WHO or FAO for any particular use, or exclude its use for other
purposes not stated. While the information provided is believed to
be accurate according to data available at the time when the sheet
was compiled, neither WHO nor FAO are responsible for any errors or
omissions, or any consequences therefrom.
The issue of this document does Ce document ne constitue pas une
not constitute formal publication. Il ne doit faire
publication. It should not be l'objet d'aucun compte rendu ou
reviewed, abstracted or quoted résumé ni d'aucune citation sans
without the agreement of the l'autorisation de l'Organisation
Food and Agriculture des Nations Unies pour
Organization of the United l'Alimentation et l'Agriculture
Nations or of the World Health ou de l'Organisation Mondiale de
Organization. la Santé.
1. GENERAL INFORMATION
1.1 COMMON NAME: No officially recognized common name
1.1.1 Identity:
IUPAC: Bis(tributyltin)oxide
CAS No. 1: Distannoxane, hexabutyl-
CAS Reg. No.: 56-35-9
Molecular formula: C24H54OSn2
Molecular weight: 596.1
Structural formula:
1.1.2 Synonyms: Biamet TBTOR; BTOR; ButinoxR; C-Sn-9R; ENT 24,979;
hexabutylditin; LS 3394; tributyltin oxide; TBTO;
Bis(tributyloxide) of tin; Bis(tributylstannyl)oxide;
Oxybis-(tributyltin)
1.2 SYNOPSIS: Bis(tributyltin)oxide is a broad spectrum, non-systemic
and cumulative organometal pesticide; a metabolic inhibitor with
good contact and limited stomach action; and, a very persistent
poison. It is a primary irritant and highly toxic to mammals,
other non-target animals and to plants. It is used primarily as an
antifouling agent and preservative.
1.3 SELECTED PROPERTIES
1.3.1 Physical characteristics - Bis(tributyltin)oxide is a colourless
to light yellow liquid. It boils at 180°C at 2 mmHg; freezing
point -45°C. Its viscosity at 25°C is 4.8 x 10-6 m2/s; density
(d204), 1.14; refractive index n20D, 1.4870. It is
non-corrosive to most metals.
1.3.2 Solubility - In water, 100 mg/l at 25°C; in sea water, 60 mg/l;
miscible with most organic solvents.
1.3.3 Stability - It is stable in storage in dark, closed containers,
usually forms tributyltin carbonate on exposure to air.
1.3.4 Vapour pressure - Negligible at 20°C.
1.4 AGRICULTURE, HORTICULTURE, FORESTRY AND INDUSTRY
1.4.1 Common formulation - Bis(tributyltin)oxide is readily emulsified
with many anionic, cationic and non-polar surfactants at various
concentrations.
1.4.2 Pests controlled - The compound is used against moulds, yeasts
and algae.
1.4.3 Use pattern - It is primarily used as an antifouling agent in
paints, industrial water systems and on inner surfaces of
cardboard and cellophane containers for tomatoes, and as a wood
preservative.
1.4.4 Unintended effects - It is phytotoxic and unsuitable for use on
or near growing crops or cultivated soil.
1.5 PUBLIC HEALTH USE - Bis(tributyltin)oxide has been effectively
used in hospitals and other public buildings, and in industrial
plants to control mould and bacterial growth in damp areas not
associated with food preparation or storage; to prevent odours in
garbage pails and equipment; and to control athletes foot in
shower areas and locker rooms. It has also been used in
manufacturing processes (e.g., leather goods, textiles, wood, and
plastics) and to mothproof stored garments.
1.6 HOUSEHOLD USE - No recommended uses.
2. TOXICOLOGY AND RISKS
2.1 TOXICOLOGY - MAMMALS
2.1.1 Absorption route - Bis(tributyltin)oxide (TBTO) is absorbed
through the intact skin; only to a limited extent from the
digestive tract and through inhalation of spray mist.
2.1.2 Mode of action - The exact mode of action of TBTO is not well
understood. It is a metabolic inhibitor, as are most trialkyl-
tin compounds, inhibiting oxidative phosphorylation and causing
mitochondrial swelling. Death is usually caused by respiratory
or cardiac failure, or coma.
2.1.3 Excretion products - The absorption and metabolism of TBTO has
not been well studied. It appears that only a small fraction of
the ingested compound is absorbed. Metabolism of trialkyl-tin
compounds to mono- or dialkyl compounds is a rare occurrence, and
breakdown to inorganic tin has not been demonstrated in mammalian
systems. Mice fed 14-C labelled TBTO in drinking-water excreted
most of the radioactivity in the faeces and very little in urine.
Evidence suggests that the faecal radioactivity represented a
large component of unabsorbed TBTO and bile circulated TBTO.
Initially elimination was rapid, the half-life being from one to
two days; after two weeks time the elimination became much slower
and the half-life increased to three to four weeks.
2.1.4 Toxicity, single dose
Oral LD50:
Rat 194 mg/kg bw; technical material in aqueous suspension
Rat 87 mg/kg bw; technical material in aqueous suspension
Mouse 55 mg/kg bw; technical material in aqueous suspension
Rabbit 50 mg/kg bw; technical material in aqueous suspension
Dermal LD50:
Rat 11 700 mg/kg bw; technical material in aqueous suspension
Rabbit 900 mg/kg bw; technical material in aqueous suspension
Intravenous LD50:
Mouse 6 mg/kg bw; technical material in aqueous suspension
Intraperitoneal LD50:
Mouse 16 mg/kg bw; technical material in aqueous suspension
Rat (F) 7.2 mg/kg bw; technical material in aqueous suspension
2.1.5 Toxicity, repeated doses
Oral: See Cumulation of compound.
Inhalation: No information available.
Dermal: Five daily applications of paper disks containing 8 ppm
of TBTO to the shaved backs of rabbits produced no evidence of
toxicity or dermal irritation.
Primary irritation: In rabbits, 0.46, 0.61, 4.6 or 6.1 mg/kg bw
of TBTO was administered to the eye in a 0.3 ml volume. A dose-
related response was produced with several mortalities occurring
at the highest dose. Within one to three minutes conjunctival
inflammation, severe lacrimation, miosis and belpharospasms were
seen in all animals. The severity of the signs increased with
time, including extensive tissue necrosis. Within two to five
days, in the highest dosage group, irreversible eye deterioration
occurred (ulcerations of the eyelid and cornea, and complete
suppression of the pupil reflex). Autopsies of the dead animals
revealed brain and abdominal organ hyperaemia, necrotic corneas,
oedematous sclera and hyperplasia of the reticuloendothelial
cells of the spleen.
Cumulation of compound: Mice given TBTO in their drinking-water
at concentration levels of 0.51, 3.75 or 18.5 ppm for periods of
up to 30 days showed evidence of concentration dependent tissue
accumulation of the compound. Rapid body clearance occurred upon
cessation of treatment; no mortalities and no signs of toxicity.
Adipose tissue demonstrated the highest cumulative activity.
2.1.6 Dietary studies
Short-term: Groups of 10 rats, male and female, were fed TBTO in
their diets at concentration levels of 0, 32, 100 or 320 ppm for
30 days. At 100 ppm growth was suppressed though food
consumption was normal. At 320 ppm both bodyweights and food
consumption were reduced. Approximately 60% of the animals on
the highest diet died. There were no gross pathological changes
observed in the dead animals except depletion of fat depots.
Prior to death the animals displayed typical signs of acute
poisoning including progressive respiratory failure.
Long-term: No information available.
2.1.7 Supplementary studies of toxicity
Carcinogenicity: Tributyltin fluoride (TBTF) did not exhibit
carcinogenic activity in a six-month dermal application test.
Four groups of 50 Swiss white mice were tested; a vehicle
control, a positive control and two treatment groups initially
receiving 10% and 30% TBTF preparations in propylene glycol three
days a week. The highest dosed group developed severe skin
lesions after only three weeks of treatment; the dosage was
reduced to 5% for the remainder of the test period. There were
no signs of abnormal behaviour nor systemic poisoning in either
group. There were no neoplastic lesions nor gross pathological
changes related to TBTF treatment.
Mutagenicity: TBTO demonstrated mutagenic potential in several
pre-screening tests including a Drosophila melanogaster test and
mammalian cell culture tests.
Teratogenicity: No information available.
Neurotoxicity: No information available.
Reproduction: No information available.
2.1.8 Modification of toxicity - No information available.
2.2 TOXICOLOGY - MAN
2.2.1 Absorption - TBTO may be absorbed percutaneously, by ingestion
and by inhalation, of spray mist or dust.
2.2.2 Dangerous doses
Single: No information available.
Repeated: No information available.
2.2.3 Observations on occupationally exposed workers - Women using a
latex spray paint containing a TBTO additive experienced
immediate toxic effects: profuse lacrimation, eye inflammation,
eye and nasal mucosa irritation. After 14 days of spray painting
the signs and symptoms became more severe but subsided on
weekends and disappeared completely when the additive was
discontinued.
Seventy per cent. of the workers in a rubber factory using TBTO
in the vulcanizing process experienced upper respiratory tract
and eye irritations. Approximately 20% also experienced lower
chest symptoms (irritation, tightness, and pain) though none of
those tested showed any adverse changes in pulmonary function
test parameters (FVC and FEV-1). Approximately 20% complained of
skin irritation and loss of appetite. In another rubber device
manufacturing unit, the rubber dust from polishing activity found
to be a significant source of TBTO, caused mild symptoms of
poisoning.
2.2.4 Observations on exposure of the general public - No information
available. If recommended use practices are followed the general
population are not likely to be exposed to hazardous amounts of
TBTO.
2.2.5 Observations on volunteers - Dermal applications of undiluted
TBTO to the back of the hands of five volunteers produced
follicular inflammation and pustulations. Healing was usually
complete in seven days.
2.2.6 Reported mishaps - No information available.
2.3 TOXICITY TO NON-MAMMALIAN SPECIES
TBTO is toxic to all animal types: vertebrates and
non-vertebrates.
3. FOR REGULATORY AUTHORITIES - RECOMMENDATIONS ON REGULATION OF
COMPOUND
3.1 RECOMMENDED RESTRICTIONS OF AVAILABILITY
(For definition of categories, see the Introduction to Data Sheets)
Liquid formulations over 10%, Category 3.
Other liquid formulations, Category 4.
3.2 TRANSPORTATION AND STORAGE
Formulations in categories 3 and 4 - Should be transported or
stored in clearly labelled rigid and leakproof containers and away
from containers of food and drink. Storage should be under lock
and key and secure from access by children and other unauthorized
persons.
3.3 HANDLING
Formulations in categories 3 and 4 - Full protective clothing (see
part 4) should be provided for all handling of the compound.
Adequate washing facilities should be available at all times
during handling and should be close to the site of handling.
Eating, drinking and smoking should be prohibited during handling
and before washing after handling.
3.4 DISPOSAL AND/OR DECONTAMINATION OF CONTAINERS
Containers must either be burned or crushed and buried below
topsoil. Care must be taken to avoid subsequent contamination of
watersources. Decontamination of containers in order to use them
for other purposes should not be permitted.
3.5 SELECTION AND TRAINING AND MEDICAL SUPERVISION OF WORKERS
Pre-employment and periodic medical examinations are necessary and
should include the skin, blood, eyes and central nervous system,
and pulmonary, liver and kidney function tests. Comprehensive
medical and work records should be maintained. Workers with
active hepatic or renal diseases should be excluded from contact.
Special account should be taken of worker's ability to comprehend
and follow instructions. Training in techniques to avoid contact
is essential.
3.6 ADDITIONAL REGULATIONS RECOMMENDED IF DISTRIBUTED BY AIRCRAFT
Not applicable: It is phytotoxic and unsuitable for use on growing
crops, forest lands or on cultivated soil.
3.7 LABELLING
All formulations - "DANGER - POISON" (skull and cross-bones
insignia). Bis(tributyltin)oxide is a metabolic poison of very
high toxicity. Contact with the skin, swallowing or inhalation of
spray may be fatal. Wear protective gloves, clean protective
clothing, and a respirator of the organic-vapour type when
handling concentrated material. Bathe immediately after work.
Ensure that containers are stored under lock and key. Empty
containers must be disposed of in such a way as to prevent all
possibility of accidental contact with them. Keep the material
out of reach of children and well away from foodstuffs, animal
feed and their containers.
In case of contact, immediately remove contaminated clothing and
wash the skin thoroughly with soap and water; flush with water for
15 minutes. If poisoning occurs, call a physician.
3.8 RESIDUES IN FOOD
Maximum residue levels - The Joint FAO/WHO Meeting on Pesticide
Residues has recommended maximum residue levels.
4. PREVENTION OF POISONING IN MAN AND EMERGENCY AID
4.1 PRECAUTIONS IN USE
4.1.1 General - Bis(tributyltin)oxide is a metabolic poison of very
high toxicity. It penetrates the intact skin and is also
absorbed from the gastrointestinal tract and by inhalation to a
limited extent. Concentrated material should be handled only by
trained personnel wearing protective clothing.
4.1.2 Manufacture and formulation - TLV - (A.C.G.I.H.) 0.1 mg/m3.
Formulation should not be attempted without advice from the
manufacturer. Although volatality is low, vapour and dusts
should be controlled preferably by mechanical means. Wear safety
glasses, polyvinyl gloves and a direct connection gas mask.
4.1.3 Mixers and applicators - When opening the container and when
mixing, protective impermeable boots, clean overalls, safety
glasses, gloves and respirator should be worn. Mixing, if not
mechanical, should always be carried out with a paddle of
appropriate length. The applicator should avoid working in spray
mist and avoid contact with the mouth. Particular care is needed
when equipment is being washed after use. All protective
clothing should be washed immediately after use, including the
inside of the gloves. Splashes must be washed immeditely from
the skin or eyes with large quantities of water. Before eating,
drinking or smoking, hands and other exposed skin should be
washed.
4.1.4 Other associated workers (including flagmen in aerial operations)
- Persons exposed to the compound and associated with its
applications should wear protective clothing and observe the
precautions described above in 4.1.3 under "Mixers and
applicators".
4.1.5 Other populations likely to be affected - With good application
practice subject to 4.2 below, other populations should not be
exposed to hazardous amounts of bis(tributyltin)oxide.
4.2 ENTRY OF PERSONS INTO TREATED AREAS - Unprotected persons should
be kept out of treated areas until the compound is dry.
4.3 SAFE DISPOSAL OF CONTAINERS AND SPILLAGE - Residues in containers
should be emptied in a diluted form into a deep pit taking care to
avoid contamination of ground waters. The empty container may be
decontaminated by rinsing two or three times with water and
scrubbing the sides. An additional rinse should be carried out
with 5% sodim hydroxide solution which should remain in a
container overnight. Impermeable gauntlets should be worn during
this work and a soakage pit should be provided for the rinsings.
Decontamination of containers in order to use them for other
purposes should not be permitted. Spillage of
bis(tributyltin)oxide and its formulations should be removed by
washing with 5% sodium hydroxide solution and then rinsing with
large quantities of water.
4.4 EMERGENCY AID
4.4.1 Early symptoms of poisoning - Early symptoms of poisoning may
include tears; irritation and inflammation of the skin, eyes, and
mucous membranes, headaches, dizziness, vision disturbances; sore
throat and coughing; nausea, vomiting, abdominal pains and
diarrhoea. Tributyl compounds may cause acute and non-painful
burns to the skin upon contact.
4.4.2 Treatment before a person is seen by a physician, if these
syptoms appear following exposure - The person should stop work
immediately, remove contaminated clothing and wash the affected
skin with water and soap, if available, flush the area with large
quantities of water, and call a physician immediately. If
swallowed, call a physician and transport to nearest hospital
immediately. Often the milder symptoms will rapidly cease upon
removal from the source of contamination.
5. FOR MEDICAL AND LABORATORY PERSONNEL
5.1 MEDICAL DIAGNOSIS AND TREATMENT IN CASES OF POISONING
5.1.1 General information - Bis(tributyltin)oxide is a metabolic poison
of very high toxicity. It is absorbed from the gastrointestinal
tract, by inhalation and through the intact skin. The mode of
action is probably by inhibition of oxidative phosphorylation.
Trialkyltin compounds show a predilection for the central nervous
system where they may cause interstitial oedema of the white
matter, a potentially fatal condition.
5.1.2 Symptoms and signs - These include profuse lacrimation,
headaches, dizziness, photophobia and progressive weakness;
convulsions and flaccid paralysis in severe cases; irritation and
inflammation of the skin and mucous membranes upon contact; sore
throat and coughing upon inhalation; nausea, vomiting, abdominal
pain and diarrhoea after ingestion. Occasionally EEG changes have
been observed. Weight loss and loss of appetite are common in
chronic poisonings.
5.1.3 Laboratory - The presence of tributyltin may be detected in all
body tissues after exposure, and in urine, faeces and vomit. In
forensic studies, brain levels of tin are specifically diagnostic
of organotin poisoning.
5.1.4 Treatment - If the pesticide has been ingested, unless the
patient is vomiting, rapid gastric lavage should be performed
with water, followed by activated charcoal and a mild laxative.
For skin contact the skin should be washed with soap and water.
If the compound has entered the eyes they should be washed with
isotonic saline or water. There is no specific antidote for
organotin poisoning. In extreme cases, if the patient is
unconscious or is in respiratory distress, oxygen may be
required. Provide patient support as required, including:
suction of secretions, maintenance of airways, intravenous fluids
pro re nata and bladder catheterization. Symptomatology and
autopsy findings indicate that oedema of the white matter of the
brain is usually the cause of fatality. In severe cases of
poisoning intracranial and spinal pressures should be monitored;
surgical decompression of the brain may be the only useful
treatment if these pressures are elevated.
5.1.5 Prognosis - If the acute toxic effect is survived the chances of
complete recovery are very good provided brain damage has not
occurred.
5.1.6 References of previously reported cases - There have been no
published reports of bis(tributyltin)oxide poisoning. Useful
references involving other organotin compounds are:
Alajauamine, T. et al. (1958) Rev. Neurol., 98 85
Lyle, W. H. (1958) Br. J.Ind. Med., 15, 193
Prull, G. & Rompel, K. (1970) Electroencephologr. Clin.
Neurophysiol., 29, 215
5.2 SURVEILLANCE TESTS
Medical surveillance should be provided where occupational
exposure is likely. A comprehensive medical and work record
should be maintained for each worker. A periodic comprehensive
medical examination should include pulmonary efficiency, serum
enzymes (SGOT and SGPT) and other tests of hepatic function, eye
examination (acuity, colour vision, pupillary reaction, glaucoma,
etc.), an ECG, a neurological examination with specific attention
to intracranial and spinal pressures, urinalysis and a medical
history.
5.3 LABORATORY METHODS
5.3.1 Detection and assay of compound
Clark, R. E. D. (1936) Analyst (London), 61, 242
Clark, R. E. D. (1937) Analyst (London), 62, 661
Kumpulainen, J. & Koivistoinen, P. (1977) Residue Rev., 66, 1
Sherman, L. R. & Carlson, T. L. (1980) J. Anal. Toxicol., 4(1),
31
Sherman, L. R. & Hiep Hoang (1981) Anal. Proc. (London), 18(5),
196
5.3.2 Other tests in case of poisoning - No information.