This report contains the collective views of an international group of experts and does not necessarily represent the decisions or the stated policy of the United Nations Environment Programme, the International Labour Organization, or the World Health Organization.

Concise International Chemical Assessment Document 65

First draft prepared by Mr Paul Howe, Centre for Ecology & Hydrology, Monks Wood, United Kingdom; and Mr Peter Watts, Toxicology Advice & Consulting Ltd, Surrey, United Kingdom

Published under the joint sponsorship of the United Nations Environment Programme, the International Labour Organization, and the World Health Organization, and produced within the framework of the Inter-Organization Programme for the Sound Management of Chemicals.

World Health Organization

Geneva, 2005

The International Programme on Chemical Safety (IPCS), established in 1980, is a joint venture of the United Nations Environment Programme (UNEP), the International Labour Organization (ILO), and the World Health Organization (WHO). The overall objectives of the IPCS are to establish the scientific basis for assessment of the risk to human health and the environment from exposure to chemicals, through international peer review processes, as a prerequisite for the promotion of chemical safety, and to provide technical assistance in strengthening national capacities for the sound management of chemicals.

The Inter-Organization Programme for the Sound Management of Chemicals (IOMC) was established in 1995 by UNEP, ILO, the Food and Agriculture Organization of the United Nations, WHO, the United Nations Industrial Development Organization, the United Nations Institute for Training and Research, and the Organisation for Economic Co-operation and Development (Participating Organizations), following recommendations made by the 1992 UN Conference on Environment and Development to strengthen cooperation and increase coordination in the field of chemical safety. The purpose of the IOMC is to promote coordination of the policies and activities pursued by the Participating Organizations, jointly or separately, to achieve the sound management of chemicals in relation to human health and the environment.

WHO Library Cataloguing-in-Publication Data

Tin and inorganic tin compounds.

(Concise international chemical assessment document ; 65)

1.Tin - adverse effects 2.Tin compounds - adverse effects

3.Risk assessment 4.Environmental exposure I.International

Programme on Chemical Safety II.Series.

ISBN 92 4 153065 0 (LC/NLM Classification: QV 618)

ISSN 1020-6167

©World Health Organization 2005

All rights reserved. Publications of the World Health Organization can be obtained from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel: +41 22 791 2476; fax: +41 22 791 4857; email: bookorders@who.int). Requests for permission to reproduce or translate WHO publications — whether for sale or for noncommercial distribution — should be addressed to WHO Press, at the above address (fax: +41 22 791 4806; email: permissions@who.int).

The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement.

The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters.

All reasonable precautions have been taken by WHO to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either express or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall the World Health Organization be liable for damages arising from its use.

Risk assessment activities of the International Programme on Chemical Safety, including the production of Concise International Chemical Assessment Documents, are supported financially by the Department of Health and Department for Environment, Food & Rural Affairs, UK, Environmental Protection Agency, Food and Drug Administration, and National Institute of Environmental Health Sciences, USA, European Commission, German Federal Ministry of Environment, Nature Conservation and Nuclear Safety, Health Canada, Japanese Ministry of Health, Labour and Welfare, and Swiss Agency for Environment, Forests and Landscape.

Technically and linguistically edited by Marla Sheffer, Ottawa, Canada, and printed by Wissenchaftliche Verlagsgesellschaft mbH, Stuttgart, Germany

FOREWORD

Concise International Chemical Assessment Documents (CICADs) are the latest in a family of publications from the International Programme on Chemical Safety (IPCS) — a cooperative programme of the World Health Organization (WHO), the International Labour Organization (ILO), and the United Nations Environment Programme (UNEP). CICADs join the Environmental Health Criteria documents (EHCs) as authoritative documents on the risk assessment of chemicals.

International Chemical Safety Cards on the relevant chemical(s) are attached at the end of the CICAD, to provide the reader with concise information on the protection of human health and on emergency action. They are produced in a separate peer-reviewed procedure at IPCS. They may be complemented by information from IPCS Poison Information Monographs (PIM), similarly produced separately from the CICAD process.

CICADs are concise documents that provide summaries of the relevant scientific information concerning the potential effects of chemicals upon human health and/or the environment. They are usually based on selected national or regional evaluation documents or on existing EHCs. Before acceptance for publication as CICADs by IPCS, these documents undergo extensive peer review by internationally selected experts to ensure their completeness, accuracy in the way in which the original data are represented, and the validity of the conclusions drawn.

The primary objective of CICADs is characterization of hazard and dose–response from exposure to a chemical. CICADs are not a summary of all available data on a particular chemical; rather, they include only that information considered critical for characterization of the risk posed by the chemical. The critical studies are, however, presented in sufficient detail to support the conclusions drawn. For additional information, the reader should consult the identified source documents upon which the CICAD has been based.

Risks to human health and the environment will vary considerably depending upon the type and extent of exposure. Responsible authorities are strongly encouraged to characterize risk on the basis of locally measured or predicted exposure scenarios. To assist the reader, examples of exposure estimation and risk characterization are provided in CICADs, whenever possible. These examples cannot be considered as representing all possible exposure situations, but are provided as guidance only. The reader is referred to EHC 170.¹

While every effort is made to ensure that CICADs represent the current status of knowledge, new information is being developed constantly. Unless otherwise stated, CICADs are based on a search of the scientific literature to the date shown in the executive summary. In the event that a reader becomes aware of new information that would change the conclusions drawn in a CICAD, the reader is requested to contact IPCS to inform it of the new information.

Procedures

The flow chart shows the procedures followed to produce a CICAD. These procedures are designed to take advantage of the expertise that exists around the world — expertise that is required to produce the high-quality evaluations of toxicological, exposure, and other data that are necessary for assessing risks to human health and/or the environment. The IPCS Risk Assessment Steering Group advises the Coordinator, IPCS, on the selection of chemicals for an IPCS risk assessment based on the following criteria:

• there is the probability of exposure; and/or
• there is significant toxicity/ecotoxicity.

Thus, it is typical of a priority chemical that

• it is of transboundary concern;
• it is of concern to a range of countries (developed, developing, and those with economies in transition) for possible risk management;
• there is significant international trade;
• it has high production volume;
• it has dispersive use.

The Steering Group will also advise IPCS on the appropriate form of the document (i.e., a standard CICAD or a de novo CICAD) and which institution bears the responsibility of the document production, as well as on the type and extent of the international peer review.

The first draft is usually based on an existing national, regional, or international review. When no appropriate source document is available, a CICAD may be produced de novo. Authors of the first draft are usually, but not necessarily, from the institution that developed the original review. A standard outline has been developed to encourage consistency in form. The first draft undergoes primary review by IPCS to ensure that it meets the specified criteria for CICADs.

The second stage involves international peer review by scientists known for their particular expertise and by scientists selected from an international roster compiled by IPCS through recommendations from IPCS national Contact Points and from IPCS Participating Institutions. Adequate time is allowed for the selected experts to undertake a thorough review. Authors are required to take reviewers’ comments into account and revise their draft, if necessary. The resulting second draft is submitted to a Final Review Board together with the reviewers’ comments. At any stage in the international review process, a consultative group may be necessary to address specific areas of the science. When a CICAD is prepared de novo, a consultative group is normally convened.

The CICAD Final Review Board has several important functions:

• to ensure that each CICAD has been subjected to an appropriate and thorough peer review;
• to verify that the peer reviewers’ comments have been addressed appropriately;
• to provide guidance to those responsible for the preparation of CICADs on how to resolve any remaining issues if, in the opinion of the Board, the author has not adequately addressed all comments of the reviewers; and
• to approve CICADs as international assessments.

Board members serve in their personal capacity, not as representatives of any organization, government, or industry. They are selected because of their expertise in human and environmental toxicology or because of their experience in the regulation of chemicals. Boards are chosen according to the range of expertise required for a meeting and the need for balanced geographic representation.

Board members, authors, reviewers, consultants, and advisers who participate in the preparation of a CICAD are required to declare any real or potential conflict of interest in relation to the subjects under discussion at any stage of the process. Representatives of nongovernmental organizations may be invited to observe the proceedings of the Final Review Board. Observers may participate in Board discussions only at the invitation of the Chairperson, and they may not participate in the final decision-making process.

This CICAD² on tin and inorganic tin compounds was prepared jointly by Toxicology Advice & Consulting Ltd and the Centre for Ecology & Hydrology. The CICAD was based on three source documents. The first of these source documents was prepared by the Nordic Expert Group for Criteria Documentation of Health Risks from Chemicals and the Dutch Expert Committee on Occupational Standards and considered the literature identified as of March 2002 (Westrum & Thomassen, 2002). The second source document was the monograph prepared by the 55th meeting of the Joint FAO/WHO Expert Committee on Food Additives, published in 2001 (JECFA, 2001). The third source document was the 2003 draft updated Toxicological profile for tin and compounds, produced by the US Agency for Toxic Substances and Disease Registry (ATSDR, 2003). In December 2003, Toxicology Advice & Consulting Ltd and the Centre for Ecology & Hydrology carried out comprehensive literature searches of online databases to identify any very recent references. Information on the nature of the peer review and the availability of the source documents is presented in Appendix 2. Information on the peer review of this CICAD is presented in Appendix 3. This CICAD was approved as an international assessment at a meeting of the Final Review Board, held in Hanoi, Viet Nam, on 28 September – 1 October 2004. Participants at the Final Review Board meeting are listed in Appendix 4. The International Chemical Safety Cards for tin(II) chloride, tin(II) chloride dihydrate, tin(II) fluoride, tin(II) oxide, tin(IV) chloride, and tin(IV) oxide, produced by the International Programme on Chemical Safety (IPCS, 2004a–f), have also been reproduced in this document.

Tin is a grey-white metal. The most important inorganic tin compounds include the tin(II) and tin(IV) chlorides, tin(II) oxide, tin(II) fluoride, and the potassium and sodium stannates. The 2+ and 4+ oxidation states of tin, also known as tin(II) and tin(IV), are both fairly stable.

The annual world production of tin has been growing slowly in recent years and reached about 268 000 tonnes in 2003. About 10–15% of this figure is recovered metal. The major tin-producing countries are China, Indonesia, Peru, Bolivia, Brazil, and Australia, and significant quantities are also produced in Malaysia and Thailand. The main use of tin, accounting for about 34% of annual global production, is for solder alloys for electrical/electronic and general industrial applications. Tin also finds extensive use (about 25–30% of production) as a protective coating for other metals, especially for food containers. Tin(II) chloride is commercially the most important inorganic compound and is used mainly as a reducing agent in organic and inorganic syntheses and in the manufacture of metallized glazing, glass, and pigments. Tin(IV) chloride is used in organic synthesis, in plastics, as an intermediate in organotin compound manufacture, and in the production of tin(IV) oxide films on glass. Tin(II) fluoride is broadly used in preventive dentistry.

Tin may be released to the atmosphere from both natural and anthropogenic sources. Tin is a component of many soils and may be released in dusts from wind storms, roads, and agricultural activities. Other less significant natural sources include forest fires and volcanic emissions. Gases, dusts, and fumes containing tin may be released from smelting and refining processes, industrial uses of tin, waste incineration, and burning of fossil fuels. The vapour pressure of elemental tin is negligible; tin and inorganic tin compounds are non-volatile under environmental conditions. Tin(II) chloride is soluble in water, whereas other tin compounds tend to be only slightly soluble. Tin compounds are likely to partition to soils and sediments. Inorganic tin may undergo oxidation–reduction, ligand exchange, and precipitation reactions in the environment. The biomethylation of inorganic tin has been demonstrated in pure bacterial cultures, sediments, and decaying plant material. Inorganic tin compounds may be bioconcentrated by organisms, but data are limited.

Average tin concentrations in air are generally below 0.1 µg/m³ (ranging up to 0.8 µg/m³), with higher concentrations near some industrial facilities. In general, tin occurs in trace amounts in natural waters. Higher inorganic tin concentrations are associated with industrial discharges and tributyltin use. In a survey of lakes and rivers, nearly 80% of samples were found to contain inorganic tin at concentrations below 1 µg/litre; higher levels of up to 37 µg/litre were reported near pollution sources. Inorganic tin concentrations ranging from 0.001 to 0.01 µg/litre have been reported for coastal waters, with levels of up to 8 µg/litre near pollution sources. Inorganic tin concentrations in sediment ranged up to 8 mg/kg dry weight in coastal areas and up to 15.5 mg/kg in rivers and lakes. Tin concentrations in the Earth’s crust are approximately 2–3 mg/kg. Total tin concentrations in soil can range from <1 to 200 mg/kg, but levels of 1000 mg/kg may occur in areas of high tin deposits. Certain ore deposits may contain up to 50 000 mg/kg as tin.

For the general population, the diet is the main source of exposure to inorganic tin. JECFA recently concluded that mean tin intakes in seven countries ranged from <1 up to 15 mg/day per person, but maximum daily intakes could reach 50–60 mg for certain individuals who routinely consume canned fruits, vegetables, and juices from unlacquered cans. Drinking-water is not a significant source of inorganic tin and might contribute approximately 0.012–0.02 mg/day. Similarly, the low levels of inorganic tin in air mean that the amount of inhaled tin is very low, probably below approximately 0.01–0.02 mg/day.

In humans and laboratory mammals, absorption of inorganic tin from the gastrointestinal tract is low (generally less than 5%), but is influenced by dose, anion (compound solubility), and the presence of other substances. Unabsorbed ingested tin is mostly (95–99%) excreted in the faeces within 48 h. Absorbed tin distributes mainly to the bone, but also to the lungs, liver, and kidneys. Limited evidence suggests that inorganic tin does not readily cross the blood–brain barrier. Absorbed tin is mainly excreted in the urine, with some additional biliary excretion occurring. In mice, the biological half-life of absorbed inorganic tin was approximately 30 days.

Transient eye and nasal irritation occurred in guinea-pigs exposed to tin(IV) chloride by inhalation. Metallic tin is unlikely to have skin irritation potential, whereas tin(II) and tin(IV) chloride are skin irritants. In some studies, the inclusion of tin(II) chloride in the diet for 4–13 weeks produced gastrointestinal tissue changes indicative of local irritation. The early literature contains reports of gastrointestinal effects (nausea, abdominal cramps, vomiting, and diarrhoea) in humans following consumption of fruit or juice from unlacquered tin cans. The effects appear to result from local gastric irritation due to dissolved tin. This aspect is addressed further below. A small number of individuals have given skin reactions indicative of a local allergic response when patch-tested with tin or tin(II) chloride, but, given its widespread use, tin would not appear to be an important skin allergen.

In the early literature, there are a number of cases where occupational exposure to dust and fumes containing insoluble tin(IV) oxide led to a benign pneumoconiosis (stannosis). This condition is characterized by mottled shadows on the lungs, apparently caused by tin(IV) oxide deposits. Stannosis is not associated with fibrosis or loss of lung function.

In laboratory animals, the repeated ingestion of tin(II) chloride had adverse effects on the body status of copper, iron, zinc, and calcium. Tin salt-induced decreases in the calcium content of bone have led to reduced bone strength. Reductions in haemoglobin and effects on red blood cells, leading to anaemia, have been observed. Certain studies involving repeated administration of tin(II) chloride by the oral route have reported tissue effects in the liver, kidneys, testes, pancreas, and brain. In the most comprehensive of the available lifetime oral studies, there were no microscopic changes in a wide range of tissues of rats or mice given tin at up to about 60 mg/kg body weight per day (rats) or 180–270 mg/kg body weight per day (mice) as tin(II) chloride in the diet. In this study, the NOAELs were 30 mg/kg body weight per day in rats and 130 mg/kg body weight per day in mice, with reduced survival seen at the higher doses.

Tin(II) chloride gave no clear evidence of carcinogenic activity when given in the diet to rats and mice for 2 years. More limited bioassays carried out on tin metal, tin(II) chloride, and a small number of other tin compounds also failed to detect carcinogenic activity. In short-term screening assays for genotoxicity potential, tin(II) chloride did not induce mutations in Ames bacterial tests, mutations or gene conversions in yeast, DNA damage in rat liver cells in culture, mutations in mouse lymphoma cells in vitro, or chromosome damage (micronuclei) in vivo in the bone marrow of mice treated by intraperitoneal injection. In bacterial rec assays (in which activity is an indirect indication of DNA damage), tin(II) chloride was active in Escherichia coli but (along with other tin salts) inactive in Bacillus subtilis. In culture, tin(II) chloride induced chromosome damage and SCEs in hamster ovary cells and DNA damage in human lymphocytes, hamster ovary cells, and plasmid DNA. Tin(IV) chloride tested in vitro did not damage DNA in hamster ovary cells but induced chromosome aberrations, micronuclei, and SCEs in human lymphocytes. Tin(II) fluoride caused DNA damage in cultures of human lymphocytes, but did not induce micronuclei formation in the bone marrow following injection into the peritoneum of mice; Ames tests on this compound gave no convincing evidence of activity. Limited evidence is consistent with the suggestion that tin-induced DNA damage might result from the production of reactive oxygen species. The mechanism underlying tin-induced chromosome damage in cultured mammalian cells is unclear, although it is known that certain inorganic compounds can yield positive results in such assays as a result of pH or ionic changes in the test medium.

Only limited data were identified on the potential of inorganic tin compounds to cause reproductive and developmental toxicity. No adverse effects were found in rats when tin (an uncharacterized form, produced by mixing aqueous tin(II) chloride with casein prior to dietary inclusion) was given in the diet for three generations or when tin(II) fluoride, sodium pentachlorostannite, or sodium pentafluorostannite were given in the diet throughout pregnancy. Similarly, repeated gavage treatment of pregnant rats, mice, and hamsters with tin(II) chloride was without adverse effect on the fetuses.

Limited data are available on the ability of ingested tin to adversely affect zinc absorption in humans. In one volunteer study, plasma appearance of zinc 1–4 h following a zinc dose was unaffected by concomitant ingestion of up to 100 mg tin (as tin(II) chloride). Another study reported that a single dose of 36 mg tin (again, as tin(II) chloride), taken with zinc, resulted in a lower zinc retention. Moderate disturbances in zinc excretion rates were reported in a third study in which the normal diet was supplemented with tin at 50 mg/day (as tin(II) chloride in fruit juice). Although a no-effect level for inhibition of zinc absorption has not been clearly established, the lowest dose reported to have this effect (36 mg) is about 2.5 to >36 times higher than the estimated mean population intakes as summarized by JECFA. However, those who routinely consume canned fruits, vegetables, and juices from unlacquered cans could have tin intakes (50–60 mg) that are similar to the acute (36 mg) or repeated (50 mg) dose levels reported in some studies to affect zinc absorption or balance. Whether this would have any clinical effect is likely to be critically dependent upon an adequate dietary supply of zinc.

The tin doses involved in the early reports of gastrointestinal effects following consumption of canned fruit or juice have been estimated (at 30–200 mg), but confidence in the accuracy of these figures is low. Two recent volunteer studies provide a better insight into effective doses and, perhaps more importantly, concentrations. The first study involved ingestion of tomato juice to which tin(II) chloride had been added to give tin concentrations of 161, 264, or 529 mg/kg (tin doses of about 40, 66, and 132 mg, respectively). At 161 mg/kg, one volunteer (of 18) reported mild gastrointestinal symptoms; typical acute symptoms were seen at 264 and 529 mg/kg. Serum levels of tin did not increase 0.5–4 h post-dosing at any dose, supporting the view that acute effects of tin ingestion are dependent upon concentration (resulting in local gastric irritation) rather than due to systemically absorbed tin. A second study involved ingestion of tomato soup containing tin that had migrated from unlacquered cans. The tin concentrations studied were <0.5, 201, and 267 mg/kg, providing acute tin doses of up to about 67 mg. No evidence of any acute effects was seen in this study. The low-effect or no-effect dose of approximately 67 mg tin in these studies is about 4.5 to >67 times higher than the JECFA estimates of mean population daily intakes and is similar to the estimated daily intake (50–60 mg) of individuals who routinely consume fruits, vegetables, and juices contained in unlacquered cans.

Under environmental speciation conditions, inorganic tin compounds have low toxicity in both aquatic and terrestrial organisms, largely due to their low solubility, poor absorption, low accumulation in tissues, and rapid excretion. Most laboratory testing with aquatic organisms has been carried out with the soluble tin(II) chloride. The most sensitive microalgae are the marine diatoms Skeletonema costatum and Thalassiosira guillardii, with 72-h EC₅₀s of tin(II) cations, based on growth inhibition, of around 0.2 mg/litre. Acute LC/EC₅₀s of tin(II) for aquatic invertebrates range from 3.6 to 140 mg/litre, with a 21-day EC₅₀, based on reproductive success in daphnids, of 1.5 mg of tin(II) per litre. Fish toxicity tests clearly show that tin(IV) chloride is less toxic than the more soluble tin(II) chloride. Ninety-six-hour LC₅₀s for fish range from 35 mg of tin(II) per litre to >1000 mg of tin(IV) per litre. Embryo-larval test results (i.e. 7- to 28-day LC₅₀s) for fish and amphibians range from 0.1 to 2.1 mg/litre for tin(II).

Concentrations showing toxicity to organisms are generally several orders of magnitude higher than those found in the environment. The most sensitive test results were 72-h exposures of diatoms and embryo-larval amphibian studies, with toxic effects seen at 0.1–0.2 mg of tin(II) per litre. Even at these concentrations, toxic effects caused by inorganic tin are unlikely, even near sources of local pollution. It should be noted that where concentrations are expressed as total tin, a percentage is likely to be in the form of organotins (e.g. tributyltin), which are more bioavailable and toxic. For more information on the environmental fate and toxicity of tributyltin, please refer to IPCS (1990, 1999).

Tin (CAS No. 7440-31-5) has the atomic symbol Sn, the atomic number 50, and an atomic mass of 118.71. Tin occurs naturally as the stable isotopes ¹¹²Sn (0.97%), ¹¹⁴Sn (0.65%), ¹¹⁵Sn (0.36%), ¹¹⁶Sn (14.5%), ¹¹⁷Sn (7.7%), ¹¹⁸Sn (24.2%), ¹¹⁹Sn (8.6%), ¹²⁰Sn (32.6%), ¹²²Sn (4.6%), and ¹²⁴Sn (5.8%) (de Bièvre & Barnes, 1985). The most commercially significant inorganic tin compounds include tin(II) chloride, tin(IV) chloride, tin(IV) oxide, potassium and sodium stannates, tin(II) fluoride, tin(II) difluoroborate, and tin(II) pyrophosphate. Chemical formulae, synonyms, relative molecular masses, and CAS registry numbers of the important inorganic tin compounds covered in this CICAD are listed in Table 1. Table 2 contains other inorganic tin compounds that also feature in this CICAD.

Table 1: Chemical identification of tin and inorganic tin compounds reviewed in this CICAD.

^a CAS number given in Westrum & Thomassen (2002).

Table 2: Chemical identification of some further^a inorganic tin compounds featured briefly in this CICAD.

Pure tin exists in two allotropic crystalline modifications: grey tin (alpha form) and white tin (beta form). At low temperatures (at about 18 °C and below), the grey tin changes to white tin. Physical and chemical properties of tin and some inorganic tin compounds are listed in Table 3.

Table 3: Physical and chemical properties of tin and some inorganic tin compounds.^a

^a From Lide (1998–1999).

The 2+ (stannous) and 4+ (stannic) oxidation states are both reasonably stable and interconverted by moderately active reagents. The Sn²⁺/Sn⁴⁺ potential is −0.15 V, and tin(II) can act as a mild reducing agent. Due to its amphoteric nature, tin reacts with strong acids and strong bases but remains relatively resistant to neutral solutions. A thin protective oxide film forms on tin exposed to oxygen or dry air at ordinary temperatures; heat accelerates this reaction. Tin is readily attacked by hydrogen iodide and hydrogen bromide and less readily by hydrogen chloride. Hot concentrated sulfuric acid reacts with tin to form tin(II) sulfate, whereas the diluted acid reacts only slowly with tin at room temperature. Reaction of tin with dilute nitric acid yields soluble tin nitrates; in concentrated nitric acid, tin is oxidized to insoluble hydrated tin dioxide. Organic acids such as lactic, citric, tartaric, and oxalic acid attack tin slowly in the presence of air and oxidizing substances (Gaver, 1997). Molten tin reacts with phosphorus, forming a phosphide. Stannates are produced by the action of strong potassium hydroxide or sodium hydroxide on tin (Mark, 1983). Tin(IV) chloride reacts with water to generate colloidal tin oxides (Wiberg et al., 2001).

Tin is readily measured in multielement analyses of air, water, and solid waste samples by ICP-AES. For samples that are free of particulate matter, such as drinking-water, direct aspiration AAS, such as EPA Method 7870, may be used. Other samples, such as groundwater, industrial wastes, soils, sediments, sludges, and other solid wastes, require digestion prior to analysis to determine total and acid-leachable metal (US EPA, 1992). EPA Method 3050B, which describes acid digestion of sediments, sludges, and soils, does not list tin as an analyte; however, it states that other elements and matrices may be analysed by this method if performance is demonstrated for that analyte in that matrix at the concentrations of interest (US EPA, 1996).

The standard methods using either flame atomic absorption (Standard Method 3111B) or electrothermal atomic absorption (Standard Method 3113B) may be used for analysis of tin in water, depending on the sensitivity desired (APHA et al., 1998b,c). Although tin is not specifically listed as an analyte for the ICP-MS method (Standard Method 3125), this method may also be used in most cases and has lower detection limits (APHA et al., 1998a).

The method recommended by NIOSH for measuring airborne inorganic tin and its compounds, except oxides, is filter collection followed by acid digestion and AAS or ICP-AES (NIOSH, 1994a). If the aerosol phase is believed to contain tin(IV) oxide, the acid solution is centrifuged and the tin compounds in the supernatant are determined as above. The precipitate is then treated with alkali, rendering tin(IV) oxide to a soluble stannate, and the determination is made as above (Beliles, 1994). Other acid digestion procedures (aqua regia plus hydrogen fluoride) are available for simultaneous measurements of total tin and other elements by, for example, ICP-AES (Butler & Howe, 1999) or ICP-MS (Schramel et al., 1997). Radiochemical neutron activation analysis has been used for the measurement of tin in human biological materials at background levels (Versieck & Vanballenberghe, 1991). A field portable X-ray fluorescence spectrometer has been developed as a rapid, non-destructive, on-site alternative for analysis of membrane filters used in NIOSH Method No. 7300 (NIOSH, 1994a) for metals (Bernick & Campagna, 1995). An ICP-AES method with a limit of quantification of 30 µg/litre (which equated to 0.8 mg/kg product) has been used successfully to measure total tin in various foods (Perring & Basic-Dvorzak, 2002).

Although not specifically listed, tin can be quantified in water using ICP-MS, according to ISO 17294-2 (ISO, 2003a). ISO guidelines also exist to measure tin in canned milk (e.g. ISO, 2003b) and in fruit (ISO, 1998, 2004).

When selecting samplers for aerosol collection, their sampling characteristics should comply with internationally accepted sampling criteria, such as those outlined by the ISO (2000). NIOSH (1994b) also offers internationally accepted sampling criteria.

Savolainen & Valkonen (1986) reported analysis of tin in tissue (brain and blood) samples down to a detection limit of 5 nmol/kg wet weight. Tissue samples were digested in a mixture of nitric, sulfuric, and perchloric acids (3:1:1 by volume), with a gradual increase in temperature to 275 °C. Tin was then converted to stannane using sodium borohydride and sodium hydroxide and, after argon purging, was analysed by AAS.

Analytical methods for total inorganic tin in water, sediment, and biological material are summarized in Table 4.

Table 4: Analytical methods.

^a Tin not listed specifically as an analyte, but can be determined by ICP-AES.

Tin occurs naturally in the Earth’s crust, with an average concentration of approximately 2–3 mg/kg (Budavari, 2001). Tin compounds are found in various environmental media in both inorganic and organic forms. Tin may be released to the environment from natural and anthropogenic sources. Tin is a component of many soils, and inorganic tin compounds may be released in dusts from wind storms, roads, and agricultural activities. Other less significant natural sources include forest fires and volcanic emissions. Releases of tin to environmental media may occur from the production, use, disposal, and recovery of tin and tin compounds. Gases, dusts, and fumes containing tin may be released from smelting and refining processes, industrial uses of tin, waste incineration, and burning of fossil fuels (Lantzy & Mackenzie, 1979; IPCS, 1980; Byrd & Andreae, 1986; Senesi et al., 1999). Tin may be released to soil from landfilling of tin-containing wastes, including used cans (IPCS, 1980). The application of pretreated municipal sludge and urban refuse as soil amendments may also introduce tin to soils. Inorganic tin can be formed as a breakdown product of organotin degradation (Blunden & Chapman, 1982; Maguire et al., 1983; Maguire & Tkacz, 1985; Kawai et al., 1998).

Other point sources that might introduce tin to the soil include application of manure, corrosion of metal objects, and dispersion of metallic ores during transport (Senesi et al., 1999).

Total global emissions to the atmosphere from anthropogenic sources (industrial emissions and burning of fossil fuels) were estimated at 43 000 tonnes (~90% of total emissions) in the 1970s. Emissions from natural sources include continental dusts (~10% of total emissions), forest fires (<2% of total emissions), and volcanoes (<1% of total emissions) (Lantzy & Mackenzie, 1979). Worldwide emissions of tin to the atmosphere from coal and oil combustion, refuse incineration, and copper/nickel production facilities were estimated at 1470–10 810 tonnes in 1983 (Nriagu & Pacyna, 1988). No more recent data were identified.

Tin is mined chiefly as cassiterite (SnO₂). The other ores are complex sulfides such as stannite (Cu₂FeSnS₄), teallite (PbSnS₂), canfieldite (Ag₈SnS₆), and cylinderite (PbSn₄FeSb₂S₁₄) (Beliles, 1994). Annual world production of tin was quite stable at approximately 210 000–230 000 tonnes for decades (Westrum & Thomassen, 2002) but is growing slowly and reached 268 000 tonnes in 2003 (K. Nimmo & S. Blunden, personal communication, 2004). Of this, about 10–15% is secondary metal recovered mainly from scrap waste and, to a much lesser degree, detinning (Westrum & Thomassen, 2002; K. Nimmo & S. Blunden, personal communication, 2004). More than 22 countries produce tin, but the 6 largest producers in 2001 were China (36%), Indonesia (23%), Peru (17%), Brazil (6%), Bolivia (6%), and Australia (4%) (ATSDR, 2003). Significant quantities are also produced from smelters in Malaysia and Thailand (Westrum & Thomassen, 2002; K. Nimmo & S. Blunden, personal communication, 2004). In Europe and North America (e.g. Belgium, Russian Federation, USA), the tin produced is mainly secondary; the USA (which is not a primary producer) is believed to be the world’s largest producer of secondary tin. In 2002, about 13 000 tonnes of tin from old and new scrap were recycled (ATSDR, 2003; Carlin, 2003a). Tin mining depends on the character of the deposit. About 20% of the primary deposits are embedded in underground granitic rock, and recovery methods are complex; the more important veins or lodes are secondary deposits (about 80%) in the form of an alluvial mud in the stream beds and placers, and the recovery is simpler (Gaver, 1997). The processing of tin ore following recovery involves smelting. The ore is mixed with salt and roasted at about 600 °C, washed in water, and then mixed with anthracite as a reducing agent and smelted at about 1500 °C. After refining, the tin is cast into bars (Robertson, 1960, 1964). Smelted ore may be further refined by heat treatment or electrolytic processes (Gaver, 1997). Certain ore deposits may contain tin at up to 50 000 mg/kg (K. Nimmo & S. Blunden, personal communication, 2004).

Currently, the major use for tin is for solder alloys for electrical/electronic and general industrial applications; this use accounts for about 34% of the tin produced and is growing with the introduction of lead-free soldering technology. A further 25–30% of tin is used as a protective coating for other metals, especially for food containers (K. Nimmo & S. Blunden, personal communication, 2004). Altogether, about 25 000 million cans are produced and filled in Europe annually, about 20% of these having plain internal (unlacquered) tin-coated bodies. Globally, the total for food packaging is approximately 80 000 million cans (JECFA, 1989; Blunden & Wallace, 2003). Tin is also used in transportation applications (ATSDR, 2003; Carlin, 2003b).

An important property of tin is its ability to form alloys with other metals. Tin alloys cover a wide range of compositions and many applications. Common solder, an alloy of 63% tin and lead, is mainly used in the electrical industry; lead-free tin solders containing up to 5% silver or antimony are used at higher temperatures. A large number of tin alloys are widely employed, including those containing lead, antimony, silver, zinc, or indium; babbit (containing mainly copper, antimony, tin, and lead; Wood’s metal (50% bismuth, 25% lead, 12.5% tin, and 12.5% cadmium); brasses and bronzes (essentially tin–copper alloys); pewter (0–95% tin plus 1–8% bismuth and 0.5–3% copper); and dental amalgams (silver–tin–mercury alloys) (Bulten & Meinema, 1991). Tin alloys are important in the production of coatings by electroplating and hot tinning (the most important of these are tin–zinc, tin–nickel, tin–cobalt, and tin–copper) (Gaver, 1997; ATSDR, 2003). Among the newer alloys are niobium–tin and indium–tin alloys used in superconducting cables and magnets (Stewart & Lassiter, 2001) and indium–tin oxide for metallic photonic crystals (Giessen, 2004). Dental amalgam alloys have been used for centuries. Principally, three-compound (ternary) alloys of silver, tin, and copper with smaller amounts of other elements have been widely used in dentistry. Today’s dental alloys are composed of silver (40–70%), tin (12–30%), copper (12–30%), indium (0–4%), palladium (0.5%), and zinc (0.1%) (Berry et al., 1994). Tin coatings can be applied to most metal surfaces by electrodeposition, while in hot-dipping, molten tin wets and adheres readily to clean iron, steel, copper, and copper-base alloys. This tin coating provides protection against oxidation of the base metal/alloy and aids in subsequent fabrication, because it is ductile and solderable (Mark, 1983).

Tin(II) chloride is obtained by dissolving metallic tin in hydrochloric acid or by reducing a solution of tin(IV) chloride with metallic tin. The anhydrous salt is produced by the direct reaction of chlorine and molten tin or by heating tin with hydrogen chloride gas. It is an important industrial reducing agent, used in the preparation of glass and plastic for metallizing, metallized glazing, and electronic components on a plastic base, as a soldering flux, as a mordant in dyeing, and in the manufacture of tin chemicals, colour pigments, and sensitized paper (Graf, 1987; Gaver, 1997; ILO, 1998a; K. Nimmo & S. Blunden, personal communication, 2004). Tin(II) chloride is added to lyophilized kits to prepare ^99mTc-labelled tracers (which account for about 80% of radiopharmaceuticals). It is important in nuclear medicine as an essential component in diagnostic agents used to visualize blood, heart, lung, kidney, and bone (Francis et al., 1981; Popescu et al., 1984; Rao et al., 1986). Tin(II) chloride is also used in certain countries as a food additive (as a preservative and colour retention agent) (ATSDR, 2003). Tin(IV) chloride is produced commercially by the direct chlorination of tin at 110–115 °C and is used as a dehydrating agent in organic synthesis, in the production of organotin compounds, in the production of tin(IV) oxide films on glass, as a mordant in the dyeing of silks, in the manufacture of blueprint and other sensitized paper, and as an antistatic agent in synthetic fibre (Graf, 1987; Gaver, 1997; K. Nimmo & S. Blunden, personal communication, 2004).

Tin(II) oxide is prepared from the precipitation of tin(II) chloride with alkali. It is used as a reducing agent, in the preparation of stannous salts, and in the preparation of gold–tin and copper–tin ruby glass (Graf, 1987; Gaver, 1997). Tin(IV) oxide is produced by the combustion of powdered tin or sprayed molten tin in a hot stream of air. It is used in the polishing of glass and enamels, in the manufacture of milk-coloured ruby and alabaster glass and enamels, as a mordant in printing and dyeing of fabrics, and in fingernail polish (Graf, 1987).

Tin(II) fluoride is produced commercially by the reaction of tin(II) oxide and aqueous hydrofluoric acid or by dissolving tin in anhydrous or aqueous hydrofluoric acid and is used primarily as an ingredient of caries-preventing toothpaste (Gaver, 1997). Sn²⁺ ions have a profound and long-lasting inhibiting effect on the oral microflora in vivo (Attramadal & Svatun, 1984). Topical application of tin(II) fluoride appears to provide dentine with a layer of tin and fluoride, which might provide mechanical and chemical protection and be of clinical significance in restorative dentistry. Sn²⁺ ions possess antibacterial activity, whereas Sn⁴⁺ ions do not (Svatun et al., 1977; Ferretti et al., 1982; Rolla et al., 1983; Ellingsen & Rolla, 1987; Rykke et al., 1991). Tin(II) pyrophosphate is prepared from pyrophosphoric acid and tin(II) chloride and is used as an ingredient in caries-preventing toothpaste (Budavari, 2001).

5.1.1 Air

The vapour pressure of elemental tin is negligible (Cooper & Stranks, 1966), and the high boiling points of elemental tin and many inorganic tin compounds indicate that they are non-volatile under environmental conditions. However, the wind may carry airborne particles for long distances before deposition, depending on the type of emitting source, physical form and properties (e.g. size, density), physical or chemical changes that may occur during transport, adsorption processes, and meteorological conditions (Senesi et al., 1999).

5.1.2 Water

In the environment, tin compounds are generally only sparingly soluble in water and are likely to partition to soils and sediments. In water, inorganic tin may exist as either divalent (Sn²⁺) or tetravalent (Sn⁴⁺) cations under environmental conditions. Cations such as Sn²⁺ and Sn⁴⁺ will generally be adsorbed by soils to some extent, which reduces their mobility. Tin(II) dominates in reduced (oxygen-poor) water and will readily precipitate as tin(II) sulfide or as tin(II) hydroxide in alkaline water. Tin(IV) readily hydrolyses and can precipitate as tin(IV) hydroxide. The solubility product of tin(IV) hydroxide has been measured at approximately 10–56 g/litre at 25 °C. In general, tin(IV) would be expected to be the only stable ionic species in the weathering cycle (Wedepohl et al., 1978). Tin(II) can be hydrolysed into SnOH⁺, Sn(OH)₂⁰, and Sn(OH)₃⁻ at low concentrations, whereas the Sn₂(OH)₂²⁺ and Sn(OH)₄²⁺ polynuclear species predominate at higher concentrations (Seby et al., 2001). On release to estuaries, inorganic tin is principally converted to the insoluble hydroxide and is rapidly scavenged by particles, which are the largest sink for the metal. Subsequent release of inorganic tin from benthic sediments is unlikely, except at highly anoxic sites (Byrd & Andreae, 1982; Andreae, 1983). Inorganic tin, as cassiterite, is usually the predominant form in sediments of estuaries associated with metal mining in south-west England (Bryan & Langston, 1992). In seawater, inorganic tin is most commonly present as SnO(OH₃)⁻ (Bruland, 1983).

Tin is generally regarded as being relatively immobile in the environment (IPCS, 1980; Gerritse et al., 1982). However, tin may be transported in water if it partitions to suspended sediments (Cooney, 1988), but the significance of this mechanism has not been studied in detail. Analysis of inorganic tin from an enclosed harbour revealed that a large percentage (up to 93%) was present in particulate form (Langston et al., 1987).

5.1.3 Soils and sediments

From the information available, it appears likely that inorganic tin will partition to soils and sediments and will not volatilize from water (IPCS, 1980; Cooney, 1988). Transfer coefficients for tin in a soil–plant system were reported to be 0.01–0.1 (Kloke et al., 1984).

5.1.4 Biota

Marine plants are also important in the cycling of inorganic tin. Both live macroalgae and decaying plant material accumulate inorganic tin compounds and ultimately remove tin from water and release it to the atmosphere by the formation and release of tetramethyltins (Donard et al., 1987).

Inorganic tin may undergo oxidation–reduction, ligand exchange, and precipitation reactions in the environment (HSDB, 2003). The biomethylation of inorganic tin has been demonstrated in pure bacterial cultures, sediments, and decaying plant material, with a variety of products being detected, including mono-, di-, tri-, and tetramethyltins (Hallas et al., 1982; Tugrul et al., 1983; Gilmour et al., 1987; Falke & Weber, 1994). The net methylation rate was found to be independent of the inorganic tin content of the sediments (Tugrul et al., 1983). Methylation of tin in sediments was found to be positively correlated with increasing organic content in sediment and to follow predominately a biotic pathway (Hadjispyrou et al., 1998). Inorganic tin may also be converted to stannane in extremely anaerobic (oxygen-poor) conditions by decaying algal material (Donard & Weber, 1988). Conversely, methyltin compounds can also be demethylated sequentially to inorganic tin by photolysis (Blunden, 1983).

Inorganic tin compounds may be bioconcentrated, but data are limited. It was estimated that the bioconcentration factors of inorganic tin were 100, 1000, and 3000 for marine and freshwater plants, invertebrates, and fish, respectively (Thompson et al., 1972). Marine macroalgae can bioconcentrate the Sn⁴⁺ ion by a factor of 1900 (Seidel et al., 1980). Donard et al. (1987) reported inorganic tin concentrations of up to 4.4 mg/kg dry weight in macroalgae. Tin-resistant bacteria contained tin at 3.7–7.7 g/kg dry weight (Maguire et al., 1984).

There is no information available on the potential transfer of inorganic tin compounds from lower trophic levels to higher levels.

Ambient levels of tin in the environment are generally quite low, except in the vicinity of local pollution sources. Analytical results based on inorganic tin have been included where possible. However, many studies have analysed for total tin only; in these cases, the data are provided for information, while bearing in mind that the concentrations may include some organic tin compounds. The proportion of inorganic tin in total tin concentrations will vary depending on sampling time and site.

6.1.1 Air

Tin is detected in air infrequently and at low concentrations, except in the vicinity of industrial sources. Air concentrations of tin in US cities from several studies were as high as 0.8 µg/m³. Average concentrations are generally below 0.1 µg/m³, with higher concentrations near some industrial facilities (IPCS, 1980; US EPA, 1982). Average concentrations have been estimated to be 0.002–0.03 µg/m³ (Biégo et al., 1999), 0.001 µg/m³ in northern hemisphere air (Byrd & Andreae, 1982), and less than 0.3 µg/m³ (JECFA, 1989). Davison et al. (1974) reported that the total tin content of airborne fly ash from coal-burning power plants ranged from 7 mg/kg (particle diameter >1.7 µm) to 19 mg/kg (particle diameter 3.3–4.7 µm).

Atmospheric tin is associated with particulate matter, and peak concentrations were found on smaller respirable particles (1–3 µm) (IPCS, 1980). Samples of airborne inhalable particulate matter were collected in two urban/industrial areas in Illinois, USA (south-east Chicago and East St. Louis) and a rural area in Bondville, also in Illinois, over a 2-year period. Average total tin concentrations in the coarse (2.5–10 µm) and fine (<2.5 µm) particulate fractions were <7 ng/m³ and 12 ng/m³, respectively, for East St. Louis; and <7 ng/m³ for both the fine and coarse fractions in samples from south-east Chicago as well as the rural site in Bondville (Sweet et al., 1993). The average total tin concentration in highway tunnel exhaust aerosol in the Elbtunnel in Hamburg, Germany, between August 1988 and January 1989 was 10.9 ng/m³ (Dannecker et al., 1990). Tin has been identified in air collected at 6 of the 214 current or former US EPA National Priorities List hazardous waste sites where it was detected in some environmental media (HazDat, 2003).

6.1.2 Water

Tin occurs in trace amounts in natural waters; however, it is seldom measured (NAS, 1977; IPCS, 1980). Higher inorganic tin concentrations are associated with industrial discharges and tributyltin use (IPCS, 1980; Maguire & Tkacz, 1985; Maguire et al., 1986). Inorganic tin concentrations of up to 0.003 µg/litre were reported for rainwater in the USA during 1981 (Tugrul et al., 1983). Tin has been identified in groundwater and surface water at 78 and 36 sites, respectively, of the 214 US EPA National Priorities List hazardous waste sites where it was detected in some environmental media (HazDat, 2003). In surface waters, tin was detected in only 3 of 59 samples from 15 US and Canadian rivers at concentrations ranging from 1.3 to 2.1 µg/litre, and it was not detected in 119 samples from 28 US rivers. A mean tin concentration of 0.038 µg/litre was reported for surface water in Maine, USA (NAS, 1977; IPCS, 1980). In a survey of Canadian waters, nearly 80% of samples were found to contain inorganic tin at concentrations below 1 µg/litre; higher levels of up to 37 µg/litre were reported near pollution sources (Maguire et al., 1986). Mean tin(IV) concentrations in Lake Michigan during 1978 ranged from 0.08 to 0.5 µg/litre (Hodge et al., 1979). Similarly, mean inorganic tin concentrations of 0.004 µg/litre were detected in the Lamas River, Turkey, between 1981 and 1983. Industrial pollution was found to increase inorganic tin levels in the river estuary to up to 0.7 µg/litre (Yemenicioglu et al., 1987).

Total tin is present in seawater at about 0.2–3 µg/litre (NAS, 1977; IPCS, 1980). Inorganic tin concentrations ranging from 0.001 to 0.01 µg/litre have been reported for coastal waters, with levels of up to 8 µg/litre near pollution sources (Tugrul et al., 1983; Valkirs et al., 1986). Tin(IV) concentrations ranging from 0.003 µg/litre for open seawater to 0.04 µg/litre in San Diego Bay, California, USA, have been reported (Hodge et al., 1979). Langston et al. (1987) found that concentrations of dissolved inorganic tin displayed extreme variability both temporally and spatially within an enclosed harbour and were largely influenced by localized inputs. Concentrations generally ranged from <0.005 to 0.2 µg/litre; however, levels of up to 48.7 µg/litre were found near local pollution sources.

Tin concentrations in drinking-water, including the United Kingdom supply, have been reported to be below 10 µg/litre (Sherlock & Smart, 1984; JECFA, 2001). Tin concentrations in public water supplies ranged from 1.1 to 2.2 µg/litre in 42 US cities and from 0.8 to 30 µg/litre in 32 of 175 water supplies in Arizona, USA (NAS, 1977; IPCS, 1980). An average concentration of 6 µg/litre has been reported in US municipal drinking-water (Hadjimarkos, 1967).

Tin concentrations in fresh snow from the French Alps collected in 1998 at different altitudes ranged from 0.16 to 0.44 µg/litre (Veysseyre et al., 2001).

6.1.3 Sediment

Mean total tin concentrations in Antarctic sediment were 2.1 and 5.1 mg/kg dry weight for the <2 mm and <63 µm fractions, respectively (Giordano et al., 1999). Inorganic tin was detected in 100 of 235 sediment samples collected from Canadian waterways. Concentrations ranged up to 8 mg/kg dry weight in coastal areas and up to 15.5 mg/kg in rivers and lakes (Maguire et al., 1986). Sediment concentrations of inorganic tin in Toronto Harbour, Canada, during 1983 were found to be highest (up to 13.8 mg/kg) near areas of tributyltin contamination (Maguire & Tkacz, 1985). Sediment cores collected in January 1996 from Central Park Lake in New York City, New York, USA, contained average tin concentrations ranging from 4.0 mg/kg at a depth of 44–47 cm to 67 mg/kg at a depth of 22–24 cm. The average tin concentration in surface sediments (0- to 2-cm depth) in Central Park Lake was 32 mg/kg. The similarities between the history of municipal solid waste incineration in New York City and the accumulation of trace metals in the Central Park Lake sediments appear to be consistent with incineration being the major source of emissions of several metals to the New York City atmosphere (Chillrud et al., 1999). Total tin concentrations in sediments from the Wah Chang Ditch and the north-east corner of Swan Lake, an area that received runoff from a tin smelter in Texas, USA, during the 1940s and 1950s, were found to be as high as 8000 mg/kg (Park & Presley, 1997). Total tin concentrations up to 1000 mg/kg dry weight have been reported for metal-rich sediments in estuaries associated with metal mining in south-west England (Bryan & Langston, 1992).

6.1.4 Soil

Tin concentrations in soil are generally low, except in areas where tin-containing minerals are present (Bulten & Meinema, 1991). Tin concentrations in the Earth’s crust are approximately 2–3 mg/kg (Budavari, 2001). Crockett (1998) reported total tin concentrations in Antarctic soils ranging from 2.5 to 3.1 mg/kg. Total tin concentrations in soil can range from <1 to 200 mg/kg; however, in areas of high tin deposits, such as south-west England, levels of 1000 mg/kg may occur (IPCS, 1980; Schafer & Femfert, 1984). The mean background soil concentration in the USA is 0.89 mg/kg (Eckel & Langley, 1988).

Tin concentrations in topsoil (0–7.6 cm) from the western end of East St. Louis, Illinois, USA, ranged from <13 to 1130 mg/kg. The raised concentrations are thought to be the result of current or recent industrial facilities, including smelters of ferrous and non-ferrous metals, a coal-fired power plant, chemical producing companies, and petroleum refineries (Kaminski & Landsberger, 2000). Tin has been identified in soil at 120 sites and in sediment at 50 sites collected from 214 US EPA National Priorities List hazardous waste sites where it was detected in some environmental media (HazDat, 2003).

Concentrations of total tin in sewage sludges from countries in Europe and North America ranged from 40 to 700 mg/kg dry weight. Manure and poultry wastes contained tin at concentrations of 3.7–7.4 and 2.0–4.1 mg/kg dry weight, respectively (Senesi et al., 1999)

6.1.5 Biota

Total tin concentrations in marine macroalgae varied between 0.5 and 101 mg/kg dry weight and clearly demonstrated that most species of aquatic flora bioconcentrate tin from seawater (Eisler, 1989). Local and imported edible seaweeds obtained in British Columbia, Canada, were found to contain total tin concentrations ranging from <0.01 to 0.46 mg/kg dry weight (van Netten et al., 2000).

Total tin concentrations in muscle and liver samples of juvenile Japanese common squid (Todarodes pacificus) collected from three locations in and near Japanese coasts were 0.04–0.05 mg/kg wet weight and 0.08–0.13 mg/kg wet weight, respectively (Ichihashi et al., 2001). Inorganic tin concentrations in fish collected from the Great Lakes in North America (1982–1984) ranged up to 0.9 mg/kg wet weight (Maguire et al., 1986).

Mean total tin concentrations in the feathers of seabirds from the North Pacific and water birds from the coast of Namibia ranged from 0.2 to 15.2 mg/kg dry weight (Burger & Gochfeld, 2000, 2001; Burger et al., 2001).

Total tin concentrations in the kidneys of mink (Mustela vison) collected from the Kootenay River and lower Fraser River in British Columbia, Canada, were 6.25 and 5.5 µg/g dry weight, respectively. Tin concentrations in the livers of mink from the upper and lower Fraser River were 5.5 and 5.2 µg/g dry weight, respectively. Tin concentrations were <4 µg/g dry weight in the livers of otters (Lontra canadensis) collected from the Kootenay, lower and upper Columbia, and upper Fraser rivers and 2.7 µg/g in livers of otters from the lower Fraser River (Harding et al., 1998). Mean total tin concentrations in striped dolphins (Stenella coeruleoalba) from the Mediterranean Sea ranged from 0.4 mg/kg wet weight in lung tissue to 1.3 mg/kg in liver (Cardellicchio et al., 2002). Total tin concentrations in the livers of Antarctic fur seals (Arctocephalus gazella) were less than 0.4 mg/kg dry weight (<0.1 mg/kg wet weight) (Malcolm et al., 1994).

6.1.6 Food

Data presented in ATSDR (2003) indicate that organic tin accounts for only a small fraction of total tin in most foods. On that basis, in this section, tin figures are total tin, but essentially represent inorganic tin.

In most unprocessed foods, inorganic (and total) tin levels are generally less than 1 mg/kg. Higher concentrations can arise as tin(II) in canned foods due to dissolution of the tin coating or tin plate. Tin levels are usually below 25 mg/kg in lacquered food cans, but may exceed 100 mg/kg in unlacquered cans. Tin concentrations in canned foods increase with storage time and temperature. Once opened, the tin content in foods stored in metal cans increases more quickly over time, since tin can rapidly dissolve in the presence of oxygen. Acidic foods are more aggressive to the tin coating in metal cans, and canned acidic foods have higher tin contents. Oxidizing agents (nitrates, iron salts, copper salts, sulfur) accelerate detinning, whereas tin salts, sugars, and gelatin reduce the dissolution rate. Can size and the nature of the base steel might also affect the detinning rate (JECFA, 1989; Blunden & Wallace, 2003).

Tin concentrations of vegetables, fruits and fruit juices, nuts, dairy products, meat, fish, poultry, eggs, beverages, and other foods not packaged in metal cans are generally below 2 mg/kg. Tin concentrations in pastas and breads have been reported to range from <0.003 to 0.03 mg/kg. Mean tin concentrations ranging from <1 to 1000 mg/kg have been found in foods packaged in unlacquered or partially lacquered cans, whereas the average tin concentration in foods in lacquered cans has been reported to be up to 6.9 mg/kg (Biégo et al., 1999; Ysart et al., 1999; JECFA, 2001). Data from the Can Manufacturers Institute indicate that more than 90% of tin-lined cans used for food today are lacquered (CMI, 1988). Only light-coloured fruit and fruit juices are packed in unlacquered cans, since tin helps maintain the colour of the fruit (JECFA, 2001).

Local and imported edible seaweeds obtained in British Columbia were found to contain tin in concentrations ranging from 0.01 to 0.46 mg/kg dry weight (van Netten et al., 2000). A study in Lithuania in 1990–1992 found an average of 0.22 mg/kg in raw milk (Ramonaityte, 2001). In a dietary tin intake study for adults in France, a range of fresh foods contained tin at concentrations of <0.003–0.2 mg/kg (average 0.03 mg/kg) (Biégo et al., 1999). Foods in lacquered cans contained tin at concentrations generally below 10 mg/kg and ranging from 0.5 mg/kg (in cherries) up to 13.4 mg/kg (in mushrooms) (Biégo et al., 1999). Tin concentrations ranged from 24 to 156 mg/kg in food from unlacquered cans, the highest concentration being detected in tomatoes (Biégo et al., 1999). Canned vegetables and fruit products were found to have mean tin concentrations of 44 and 17 mg/kg fresh weight, respectively, in a 1994 total diet study in the United Kingdom (Ysart et al., 1999). A study of metal concentrations in canned milk products in Lithuania in 1990–1992 found mean tin concentrations in evaporated sterilized milk, concentrated sterilized milk, and sweetened condensed milk of 85, 89, and 40 mg/kg, respectively. Tin concentrations in canned milk were shown to increase during storage (Ramonaityte, 2001).

Studies in the United Kingdom showed mean concentrations of tin in the diet of 1–2 mg/kg. The primary sources of tin were said to be canned goods (Evans & Sherlock, 1987). Tin density figures for selected diets in France, New Zealand, and the United Kingdom ranged from 1.2 to 4.4 mg/kg (JECFA, 2001).

6.1.7 Indoor dust

Analysis (using energy-dispersive X-ray fluorescence) of dust in eight US homes found tin at <10 mg/kg (the detection limit) in five cases and at 12, 14, and 73 mg/kg in the other three cases. These houses were selected because they were near the homes of men employed as electric cable splicers. Dust in the homes of these workers contained higher tin concentrations (45–242 mg/kg), and levels were higher in the laundry area (geometric mean 117 mg/kg) than in the rest of the house (66 mg/kg), suggesting that the tin source was occupational contamination of the clothing (Rinehart & Yanagisawa, 1993).

The major source of tin for the general population is food. Intake from the diet is highly dependent on the type and amount of canned food consumed (JECFA, 1989). For those consuming no canned food, intake might be approximately 3 mg/day (Sherlock & Smart, 1984). Individuals who routinely consume canned fruit, vegetables, and juices from unlacquered cans could ingest 50–60 mg tin daily, assuming about four servings per day (Johnson & Greger, 1982; Sherlock & Smart, 1984). An adult consuming 1 litre of juice with a tin content of 100 mg/litre (from unlacquered cans) daily would ingest 100 mg of tin per day from this source alone (JECFA, 1989). People with low incomes or living in institutions such as nursing homes, boarding schools, or prisons may routinely select or be served canned food and juices because of economic factors and ease of storage, and those who consume about four daily servings of food from open, unlacquered cans could consume about 200 mg of tin per day (Greger & Baier, 1981; Greger, 1988; JECFA, 2001).

JECFA has summarized data on estimates of mean dietary tin intakes for Australia, France, Japan, the Netherlands, New Zealand, the United Kingdom, and the USA. In Australia, results of a total diet study produced estimated mean tin intakes (for six sex–age groups) ranging from 0.4 to 5.2 mg/day, with the highest 95th percentile being 7.4 mg/day (Marro, 1996). Using the DIAMOND method of modelling nutrition data, the Australia New Zealand Food Authority estimated a mean intake of 1.9–2.4 mg/day for consumers aged 2–70 years, with a 95th percentile value of 10 mg/day (Baines, 2000). Australian surveys produced intake figures of 2.2–2.7 mg/day, with a 95th percentile of 12 mg/day (Baines, 2000). For French adults, it was estimated that the mean dietary intake of tin would be 0.05 mg/day from a fresh food diet, 0.34 mg/day from a diet with usual canned foods in lacquered cans, and 7.4 mg/day from a diet with usual canned foods in unlacquered cans (Biégo et al., 1999). In Japan, the average tin intake of 456 women in 22 cities and villages during the winters of 1990–1995 was estimated to be 0.64 mg/day (based on duplicate food samples and food composition databases), although this was probably an underestimate, because not all food types were included (Shimbo et al., 1996). Dutch total diet studies, based on the consumption by 18-year-old men of 221 food items within 23 food commodity groups, produced average tin intakes of 1.7 mg/day during 1976–1978 and 0.65 mg/day (maximum 1.8 mg/day) in 1984–1986 (van Dokkum et al., 1989). Based on analysis of selected foods in the 1997–1998 New Zealand total diet study, the estimated mean dietary intakes of tin ranged from 2.9 mg/day (for children aged 1–3 years) to 7.5 mg/day for adult female vegetarians. Canned spaghetti, baked beans, apricots, tomatoes, and peaches contributed 77% of the dietary exposure of men aged 19–24 years and of children aged 1–3 years (Vannoort et al., 2000). In the 1974–1975 New Zealand total diet study, it was estimated that young New Zealand men eating 3.5 kg of food per day might ingest a mean of 15 mg of tin per day (Dick et al., 1978). In the United Kingdom, results from total diet studies suggest that tin intake has been falling (mean daily intakes were 4.4, 2.4, and 1.8 mg in 1976, 1994, and 1997, respectively), possibly due to use of an increasing proportion of lacquered cans (Ysart et al., 1999; UK MAFF, 2000; JECFA, 2001). However, a study in 35 female vegetarians in the United Kingdom (using a duplicate-diet sampling method) found a mean intake of 3.8 mg/day (range 0.03–16 mg/day), about twice as high as reported for the general population (UK MAFF, 2000). JECFA did not identify any reliable estimates for the US diet, noting that tin was not measured in the USA’s total diet study, but small studies provided mean estimates of 1 mg/day from a diet without canned food (Schroeder et al., 1964) and 1.5–3.5 mg/day for (undefined) adults (Schroeder et al., 1964; Tipton et al., 1969). JECFA noted that a small, early study focusing on metabolism had claimed that a diet containing "substantial amounts of canned vegetables, fruit juices, and fish could supply as much as 38 mg/day" (Schroeder et al., 1964).

Drinking-water is not considered a significant source of tin. If it is assumed that concentrations of tin in drinking-water are 6–10 µg/litre (see section 6.1.2) and that adults consume 2 litres/day, these figures suggest an intake of 12–20 µg/day from this source (JECFA, 1989, 2001).

Inhaled air represents very low tin exposure. Based on tin levels in air of <0.3 µg/m³ (JECFA, 1989), an adult inhaling 20 m³ of air per day would in general inhale less than 6 µg/day. Air concentrations of tin in US cities ranging from below the detection limit to 0.8 µg/m³ (US EPA, 1982) imply an inhaled dose of up to about 16 µg/day. Based on estimated average tin concentrations of 0.002–0.03 µg/m³ (Biégo et al., 1999), an adult is unlikely to inhale more than 0.6 µg of tin per day. Exposures are presumably higher near emission sources such as waste incineration and non-ferrous metal production (Byrd & Andreae, 1982) (see section 6.1.1).

Most of the operations associated with the extraction of tin ore are wet processes, but tin and tin(IV) oxide dust and fumes may escape during bagging of concentrate, in ore rooms, and during smelting operations (mixing plant and furnace tapping), as well as during the periodic cleaning of bag filters used to remove particulate matter from smelter furnace flue gas (ILO, 1998a). Tin reclamation from tin-plated steel trimmings, rejects from companies manufacturing tin cans, rejected plating coils from the steel industry, tin drosses and sludges, solder drosses and sludges, used bronze and bronze rejects, and metal-type scrap also involve possible exposure to tin dusts and fumes (ILO, 1998b). Gases, dusts, and fumes containing tin may be released from smelting and refining processes, industrial uses of tin, waste incineration, and burning of fossil fuels (IPCS, 1980; Senesi et al., 1999; ATSDR, 2003).

No systematic data on occupational exposure levels in tin production or processing were found by the authors of the Nordic/Dutch source document (Westrum & Thomassen, 2002). The Norwegian occupational exposure database EXPO contains data from all samples analysed at the National Institute of Occupational Health in Oslo since 1984. Most of these samples have been collected due to the desire of different enterprises to control their exposures and are likely to represent "worst-case measurements" (Rajan et al., 1997). Of the 3407 air filter samples (8-h personal monitoring) analysed for tin, 420 contained amounts above the detection limit (0.002 mg/m³). In Table 5, the branches and job functions with tin exposures above 0.05 mg/m³ are listed, together with the mean and range of concentrations.

Table 5: Branches and job functions in EXPO where tin concentrations of >0.05 mg/m³ air were detected.

Limited information on past occupational exposure to tin was found in the older literature. Analysis of dust samples collected in the vicinity of a worker grinding tin ore in a tin smelting works in Liverpool, United Kingdom, showed that the dust fraction with particle size <5 µm contained more than 33% metallic tin and no detectable silica. The tin ore handlers were said to be "exposed to considerable quantities of dust" (Robertson, 1960). In this smelting works, concentrations of total tin or tin(II) oxide were not measured, but particles <5 µm in diameter were collected using a Hexlet in "places where dust concentration was likely to be especially high." Preliminary figures for concentrations (in mg/m³) of tin as particles <5 µm in diameter in the workroom air were as follows: check sampling shed, 2.22; and dracco room (an area containing filters for furnace gases), 1.50. In addition, air samples were taken near workers: smelting furnace man, 1.55; refining furnace man, 0.82; orehouse skipman, 0.34; plumber, 0.12; electrician, 0.05; and engineer, 0.02. The methods of sampling and analysis were not described (Robertson, 1964). An environmental survey to determine the type of exposure in a Chilean tin foundry showed air concentrations of metal tin between 8.6 and 14.9 mg/m³ (Oyanguren et al., 1958).

In a review, Alessio et al. (1994) reported that tin concentrations in ambient air in three copper alloy industries ranged from 1 to 4 µg/m³. Atmospheric concentrations of tin of 16 and 0.2 µg/m³ were reported for manual metal arc mild steel welding and arc stainless steel high nickel welding, respectively. A tin concentration of 1 µg/m³ was found for silver brazing.

Tin concentrations in the particulate matter in the ambient air at art glass manufacturing plants measured by personal samples from oven charger and batch mixer workers ranged from 0.1 to 3.5 µg/m³ from three plants that use arsenic as a fining agent (an agent that is added to disperse air bubbles in glass). Tin was not detected in the particulate matter in the air at three other plants that used antimony compounds instead of arsenic (Apostoli et al., 1998).

Tin production may also involve exposure to silica, lead, and arsenic in the mining of the sulfide ores of tin, as well as to bismuth and antimony in the roasting and smelting process. Exposure to these toxic metals might also occur during the preparation and use of tin alloys and solders. Tin mining might involve exposure to radon, thorium, and uranium (Fox et al., 1981; Qiao et al., 1989, 1997; Taylor et al., 1989; Hodgson & Jones, 1990; Oresegun & Babalola, 1990; Forman et al., 1992; Beliles, 1994).

Generally, absorption of tin from the gastrointestinal tract is low in humans and laboratory animals, including rats, mice, rabbits, cats, and dogs (JECFA, 2001; Stewart & Lassiter, 2001), but it may be influenced by aqueous solubility, dose, anion, and the presence of other substances. In vitro studies using rat small intestine suggested that absorption of tin occurs by passive diffusion (Kojima et al., 1978).

In a balance study in which eight healthy volunteers were given a control diet providing 0.11 mg of tin per day for 20 days, mean faecal excretion was 55% of the daily dose, suggesting a mean net absorption of 45% at this low dose (although the range was wide, varying from −4 to 71%). When the diet was supplemented (with tin(II) chloride) to provide an additional 50 mg of tin per day for 20 days, mean faecal excretion was 97% of the daily dose, suggesting a net absorption of 3% (range −7 to 9%) at this higher dose (Johnson & Greger, 1982).

Four human volunteers with tin blood levels of <2 ng/ml (<17 nmol/litre) each consumed 60 mg of tin in the form of fruit juice from an unlacquered can, and blood samples were taken after 2, 5, and 24 h. The two females had detectable tin blood levels (3 ng/ml) only in the 5-h samples. The two males had peak blood tin concentrations of 4.7 ng/ml after 2 h and 3.9 ng/ml after 24 h (Byrne & Kosta, 1979).

Anodic stripping voltammetry was used to study tin concentrations in the urine of 89 men and 85 women (aged 20 years or more) in the Japanese prefecture of Aichi over a 3-year period from 1986 to 1988. For 79 subjects, data were available for each year. Expressed as µg/g creatinine, the mean tin concentration was significantly higher in women (5.9 ± 3.0; range 1.9–16.0) than in men (3.7 ± 2.2; range 0.8–13.4; P < 0.001). Distributions of concentrations were lognormal in both sexes. Mean concentrations tended to increase with age in both men (3.3 ± 2.5 at 20–29 years, 4.7 ± 2.2 at >60 years) and women (5.1 ± 3.6 at 20–29 years, 7.3 ± 2.7 at >60 years). In men, mean concentrations increased significantly, in a dose-related manner, with frequency of fish consumption (2.9 ± 1.8, 3.5 ± 2.0, and 4.7 ± 2.9 for consumption on 1–2, 3–4, and 5–7 days per week, respectively). A similar dose-related increase was seen in females (5.3 ± 1.9, 5.8 ± 3.1, and 6.3 ± 3.2 for consumption on 1–2, 3–4, and 5–7 days per week, respectively), although the differences between groups were not statistically significant. Organotin contamination of fish was the suggested explanation for these findings. Urinary tin concentrations showed no relationship with the level of consumption of canned food (Hayashi et al., 1991).

Following single gavage administration of ¹¹³Sn(II) or ¹¹³Sn(IV) as the citrate or fluoride to rats, absorption was estimated to be 2.85% and 0.64% of the 20 mg/kg body weight dose for the 2+ and 4+ oxidation states, respectively, based on 48-h recovery of radioactivity in the urine and tissues. Absorption was lower when tin was given as the pyrophosphate, presumably due to this anion’s greater tendency to form insoluble tin complexes (Hiles, 1974). These figures are in line with reports that absorption of tin(II) chloride is generally below 5% (Kutzner & Brod, 1971; Furchner & Drake, 1976; Fritsch et al., 1977; Sullivan et al., 1984). In one case, rats reportedly absorbed 7.65% of a single oral dose of tin(IV) chloride (Kojima et al., 1978). The recovery of 99% of administered tin in the faeces and the lack of detectable urinary tin in the 24 h following ingestion of tin (7–20 mg/kg body weight) in orange juice by rats and cats indicate a very low gastrointestinal absorption of tin (Benoy et al., 1971). The presence of certain organic acids can increase tin absorption from the gastrointestinal tract (Kojima et al., 1978).

No increase in blood levels of tin was seen when male Wistar rats were given tin(II) chloride in the drinking-water at up to 250 mg/litre for 1–18 weeks (tin dose probably between 8 and 21 mg/kg body weight per day). At a tin(II) chloride concentration of 500 mg/litre, tin concentrations in blood rose in the first week and remained at 2–7 µg/litre (equivalent to 2–5 times control values) for the rest of the study. The data suggest that mucosal barriers are effective in preventing tin absorption at low doses but are overcome at higher doses (Savolainen & Valkonen, 1986).

Rabbits fed tin at 2 mg/kg body weight per day for 5 days (as tin(II) chloride) had blood tin concentrations of 2.3 µg/litre after 24 h and 0.7 µg/litre after 120 h. Tin was not detected (detection limit not stated in the source document) in the controls (Zareba & Chmielnicka, 1992).

Adequate data on uptake following inhalation or dermal exposure appear to be lacking (Westrum & Thomassen, 2002).

Inorganic tin distributes mainly to bone, but also to the lungs, liver, kidneys, spleen, lymph nodes, tongue, and skin. Certain data indicate that tin may have a higher affinity for the thymus than for other organs. Laboratory animal data suggest that inorganic tin does not readily cross the blood–brain barrier (Hiles, 1974; Furchner & Drake, 1976; Hasset et al., 1984; Savolainen & Valkonen, 1986; JECFA, 2001).

Tin was seldom present in the lung tissue of newborn babies in the USA. In adults, the tin content in human lung tissue was higher in the USA than in Africa (Schroeder et al., 1964). These data suggest that tin levels in the human lung increase with age, and the likely source might be polluted air.

In an analysis of the tin content in tissue samples from adults who had died in accidents, the highest concentrations were found in the bone ash (4.1 mg/kg), followed by the lymph nodes, lungs, liver, and kidneys (1.5, 0.8, 0.4, and 0.2 mg/kg wet weight, respectively), whereas levels in muscle (0.07 mg/kg wet weight) and brain (0.06 mg/kg wet weight) were lower (Hamilton et al., 1973). Autopsy samples from 78 deceased Spaniards contained mean tin concentrations of 0.47, 0.27, 0.25, 0.24, and 0.16 mg/kg in the bone, brain, kidneys, lungs, and liver, respectively (Garcia et al., 2001). Analysis of tissue samples from 20 deceased Spanish subjects (without known occupational tin exposure) found highest and lowest tin levels in bone (mean 6.2 mg/kg) and brain (mean 1 mg/kg), respectively (Llobet et al., 1998). Median tin concentrations (in mg/kg wet weight) in samples from adult US citizens were as follows: adrenal, 5.1; lung, 3.4; liver, 1.8; kidney, 1.5; spleen, 0.8; muscle, <0.4; and brain, 0.3 (Tipton & Cook, 1963). In healthy Japanese males, tin concentrations of 9.8 mg/kg dry weight in hilar lymph nodes and 1.5 mg/kg dry weight in lung tissue were reported (Teraoka, 1981). Analysis (using AAS) of several human organs from 11–13 adult males found mean concentrations (mg/kg dry weight) as follows: liver, 1.05; kidney cortex, 0.83; heart, 0.75; lung, 0.45; rib bone, 0.61; and testis, 2.08 (Chiba et al., 1991). The tin concentration in liver specimens from 11 US citizens ranged from 0.14 to 0.17 mg/kg wet weight (determined by neutron activation analysis), and the tin concentration in Japanese human liver specimens (n = 23) ranged from 0.08 to 1.12 mg/kg wet weight (determined by AAS) (Chiba et al., 1994). An average tin concentration of 12.8 mg/kg wet weight was reported in the thymus of two children (Sherman et al., 1985). Tin was detected at 4.6–15 mg/kg in adipose tissue samples from nine US subjects in a 1982 survey (Stanley, 1986).

In humans with no occupational exposure to tin compounds, blood tin concentrations of 2–9 µg/litre are reported (detection limit 2 µg/litre) (Hamilton et al., 1973; Kazantzis, 1994). Others reported normal tin concentrations of 11.6 ± 4.4 nmol/litre (mean ± SD) in plasma and 21.7 ± 6.7 nmol/litre in red blood cells in 12 humans (8 women, 4 men, mean age 77.8 years) (Corrigan et al., 1992). Background tin concentrations of <1 µg/litre in serum and urine have been reported (Versieck & Vanballenberghe, 1991; Schramel et al., 1997), and a 95th upper percentile of 20 µg/litre in urine was calculated for a group of 496 US residents (Paschal et al., 1998).

Autopsy analysis of the internal organs of 7 Japanese metal industry workers and 12 Japanese males without occupational exposure found elevated concentrations of tin in the lungs, spleen, liver, and kidneys of chromate plating and chromate refining workers. In one chromate refining worker, marked concentrations of tin were found in the hilar lymph nodes (100 mg/kg dry weight) and lungs (100 mg/kg dry weight) (Teraoka, 1981).

Following a single gavage dose of 20 mg/kg body weight of radiolabelled ¹¹³Sn(II) or ¹¹³Sn(IV) as the fluoride or citrate, the tissue distribution of tin in rats after 48 h as a percentage of the administered tin(II) or tin(IV), respectively, was as follows: skeleton, 1.0% and 0.24%; liver, 0.08% and 0.02%; and kidneys, 0.09% and 0.02%. When oral tin doses of 20 mg/kg body weight were given on 6 days/week for 4 weeks, only the bone contained higher tin concentrations after day 28 than after day 1. The half-time of tin in the femur was estimated to be 34–40 days. The investigator concluded that, of the soft tissues, only liver and kidneys are likely to accumulate significant amounts of tin as a result of the oral ingestion of tin salts. No ¹¹³Sn was found in the brain of rats 48 h following administration of ¹¹³Sn(II) or ¹¹³Sn(IV) as citrate or fluoride as a single oral dose (4 mg), as oral doses of 20 mg/kg body weight on 6 days/week for 4 weeks, or as a single intravenous dose (0.4 mg) (Hiles, 1974).

Studies on the retention of the radionuclide ¹¹³Sn administered as tin(II) chloride intraperitoneally in rats showed that most of the tin retained in the body was deposited in the bone, followed by muscle, pelt, liver, and kidneys. In contrast to all other organs, the relative amount of tin in bone increased during the study (Furchner & Drake, 1976).

A study of the pharmacodynamics of several tin compounds in rabbits, using ¹¹³Sn(II) chelates also labelled with ^99mTc (meta-stable technetium-99), showed that free Sn²⁺ ions localize mainly in bone. The distribution of ¹¹³Sn in bone was similar to that of calcium and other bone-seeking metal ions (Dewanjee & Wahner, 1979).

Tin concentrations of 0.1–0.29 mg/kg wet weight and 0.69 mg/kg dry weight have been reported in the bone tissue of unexposed mice (Chiba et al., 1991).

The concentrations of tin in the tibias of rats fed diets supplemented with tin(II) chloride (100–2000 mg of tin per kg of diet) were more than 5 times greater than the tin concentrations in the kidneys and nearly 20 times greater than the concentrations in the liver. No other organs were analysed. Tin accumulated in the tibia and kidneys in a dose-dependent manner (Johnson & Greger, 1985).

After lifelong administration of about 0.37 mg of tin per kg body weight per day as tin(II) chloride in the drinking-water of rats, mean tin concentrations were increased approximately 2- to 3-fold in the liver, heart, lungs, and spleen, but the differences were not statistically significant. Bone was not examined (Schroeder et al., 1968). In mice, a similar study (reported intake of about 0.37 mg/kg body weight per day) found tin levels of 1.2–4.5 mg/kg wet tissue in kidneys, liver, heart, lungs, spleen, and thyroid, compared with less than 0.5 mg/kg in tissues in the control group (Schroeder & Balassa, 1967).

A 2-year carcinogenesis study of tin(II) chloride administered at 1000 or 2000 mg/kg in the diet to F344 rats and B6C3F1 mice showed a dose-dependent difference in the concentration of tin in examined organs (i.e. bone, liver, and kidneys). For the low and high doses, tin levels in bone were, respectively, 9 and 38 mg/kg in male rats and 23 and 41 mg/kg in female mice. Tin concentrations in the kidneys were, respectively, 17 and 30 mg/kg in male rats and 0.7 and 0.9 mg/kg in female mice. In the liver, tin concentrations were, respectively, 0.2 and 0.4 mg/kg in male rats and 0.4 and 0.5 mg/kg in female mice. In both species, tissue levels tended to be higher in the females. Untreated rats and mice had tin concentrations that were below the detectable limits, which ranged from 0.01 to 0.1 mg/litre of "digested tissue" (NTP, 1982).

Some data indicate that the tin content is higher in the thymus than in other representative organs. In four young adult dogs, the tin concentration in thymus was about twice the concentrations in the spleen or muscle (Sherman & Cardarelli, 1988). Analysis of unexposed adult Lewis rats, adult COBS mice, and adult A/KI mice showed thymus tin concentrations of 20, 5.5, and 4.3 mg/kg, respectively. Tin concentrated in the thymus gland as the gland atrophied with age (Sherman et al., 1986).

The tin content of the brain (7–19 nmol/kg wet weight) of Wistar rats given tin(II) chloride dihydrate at 100 mg/litre in the drinking-water for 18 weeks was not significantly different from that in control rats (5–10 nmol/kg). At 250 mg/litre, brain tin was increased after 15 weeks (19 ± 8 nmol/kg) and 18 weeks (38 ± 8 nmol/kg). At 500 mg/litre, the tin content of the brain rose steadily throughout the 18 weeks to about 80 nmol/kg (Savolainen & Valkonen, 1986).

In pregnant rats fed tin at 20 mg/kg body weight per day as radioactive tin(II) or tin(IV) fluoride, no tin was found in fetal or placental tissues on day 10 of pregnancy. On day 21, fetuses of dams administered tin(II) fluoride apparently contained approximately 0.2% of the cumulative dose (Hiles, 1974). Fetal tin values were slightly elevated (0.8–1.3 mg/kg body weight) in Sprague-Dawley rats on day 20 of gestation when the maternal diets contained tin salts (tin(II) fluoride, sodium pentachlorostannite, or sodium pentafluorostannite) at 125–625 mg/kg in the feed (about 10–50 mg of tin per kg body weight per day). The increases were generally dose-related. Untreated rats had fetuses containing 0.64 mg of tin per kg body weight (Theuer et al., 1971). Others have reported briefly that "considerable" tin concentrations were noted in embryos of rats exposed to tin(II) chloride (Chmielnicka et al., 1981). Data are very limited but suggest the possibility of a low level of transfer across the placenta (ATSDR, 2003).

Few data on biotransformation are available. The difference in the relative affinity of the kidneys and liver for tin(II) and tin(IV) indicates a valence stability of the administered tin (Hiles, 1974). The difference observed between tin(II) and tin(IV) chloride in their effects on the immune response in C57BL/6J mice (see section 8.7) also suggests that these two oxidation states are not readily interconverted in vivo (Dimitrov et al., 1981). Together, these data suggest that tin cations are not rapidly oxidized or reduced during absorption and systemic transportation in mammals.

Ingested tin is largely unabsorbed and excreted mainly in the faeces, with additional slow elimination of the absorbed fraction in the urine (JECFA, 2001).

In a mineral balance study, eight adult human males ate food providing 0.11 mg or 50 mg of tin per day (as tin(II) chloride) for 20-day periods. Their urinary excretion was 29 ± 13 µg/day (mean ± SD) and 122 ± 52 µg/day, respectively, representing 36% and 2.4% of the dose, respectively. Mean faecal excretion accounted for 55% and 97% at the low and high daily dose, respectively (Johnson & Greger, 1982). A review stated that, in humans, 20% of absorbed tin was cleared with a half-time of 4 days, a further 20% with a half-time of 25 days, and the remaining 60% with a longer half-time of 400 days. No further details were given (Magos, 1986). When nine healthy adults were given diets consisting of fresh foods (10 mg of tin per day), cold-stored cann