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.