A Preliminary Review

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

    Published under the joint sponsorship of the United Nations
    Environment Programme and the World Health Organization

    World Health Organization
    Geneva, 1980

    ISBN 92 4 154075 3

    (c) World Health Organization 1980

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         1.1. Chemistry and uses of tin compounds
               1.1.1. Inorganic tin
               1.1.2. Organotin compounds
         1.2. Analytical methods
         1.3. Environmental concentrations and exposures
               1.3.1. Environmental exposures
               1.3.2. Occupational exposure
         1.4. Metabolism
               1.4.1. Inorganic tin
               1.4.2. Organotin compounds
         1.5. Effects on experimental animals
               1.5.1. Inorganic tin
                Local effects
                Systemic effects
               1.5.2. Organotin compounds
                 Local effects
                 Systemic effects
         1.6. Effects in man
               1.6.1. Inorganic tin
               1.6.2. Organotin compounds
                Local effects
                Systemic effects
         1.7. Recommendations for further studies
               1.7.1. Analytical methods
               1.7.2. Environmental data
               1.7.3. Metabolism
               1.7.4. Effects

         2.1. Elemental tin
         2.2. Tin(II) compounds
         2.3. Tin(IV) compounds
         2.4. Organometallic compounds of tin
         2.5. Analytical methods
               2.5.1. Determination of inorganic tin
                Atomic absorption spectrocopy
                Emission spectroscopy
                Neutron activation analysis
                X-ray fluorescence
                Miscellaneous analytical methods
               2.5.2. Determination of organotin compounds
                Diorganotin compounds
                Triorganotin compounds

         3.1. Natural occurrence
         3.2. Industrial production
         3.3. Tin consumption
         3.4. Uses of tin
               3.4.1. Tin and inorganic tin compounds
               3.4.2. Organotin compounds
         3.5. Tin-containing waste

         4.1. Transport and bioconcentration
         4.2. Environmental chemistry of tin
         4.3. Degradation of organometallic tin compounds

         5.1. Ambient air
         5.2. Soils and plants
         5.3. Water and marine organisms
         5.4. Food
         5.5. Organotin residues
         5.6. Working environment
         5.7. Estimate of effective exposure of man through environmental

         6.1. Inorganic tin
               6.1.1. Absorption
               6.1.2. Distribution
                Distribution in human tissues and
                                 biological fluids
               6.1.3. Excretion
               6.1.4. Biological half-time
         6.2. Organotin compounds
               6.2.1. Absorption
               6.2.2. Distribution
               6.2.3. Excretion
               6.2.4. Biotransformation

         7.1. Inorganic tin compounds
               7.1.1. Effects on the skin
               7.1.2. Respiratory system effects
               7.1.3. Effects on the gastrointestinal system
               7.1.4. Effects on the liver
               7.1.5. Effects on the kidney
               7.1.6. Effects on the blood-forming organs
               7.1.7. Central nervous system effects
               7.1.8. Effects on the reproductive system and the fetus
               7.1.9. Carcinogenicity and mutagenicity

               7.1.10. Other effects
               7.1.11. Effective doses and dose rates
               Lethal doses
               Minimum effective and no-observed effects
         7.2. Organotin compounds
               7.2.1. Effects on the skin and eyes
               7.2.2. Respiratory system effects
               7.2.3. Effects on the gastrointestinal system
               7.2.4. Effects on the liver and bile duct
               7.2.5. Effects on the kidney
               7.2.6. Effects on lymphatic tissue and immunological
               7.2.7. Haematological effects
               7.2.8. Central nervous system effects
               7.2.9. Effects on reproduction and the fetus
               7.2.10. Carcinogenicity
               7.2.11. Effects on chromosomes
               7.2.12. Other effects
               7.2.13. Mechanisms of action
               7.2.14. Effective doses and dose rates
               Lethal doses
               Minimum effective and no-observed-effect

         8.1. Inorganic tin compounds
               8.1.1. Acute poisoning
               8.1.2. Prolonged exposure
                Effects of inhalation
                Effects of ingestion
         8.2. Organotin compounds
               8.2.1. Local effects
               8.2.2. Systemic effects
                Effects of dermal exposure
                Effects of inhalation
                Effects of ingestion
         8.3. Treatment of poisoning




        While every effort has been made to present information in the
    criteria documents as accurately as possible without unduly delaying
    their publication, mistakes might have occurred and are likely to
    occur in the future. In the interest of all users of the environmental
    health criteria documents, readers are kindly requested to communicate
    any errors found to the Division of Environmental Health, World Health
    Organization, Geneva, Switzerland, in order that they may be included
    in corrigenda which will appear in subsequent volumes.

        In addition, experts in any particular field dealt with in the
    criteria documents are kindly requested to make available to the WHO
    Secretariat any important published information that may have
    inadvertently been omitted and which may change the evaluation of
    health risks from exposure to the environmental agent under
    examination, so that the information may be considered in the event of
    updating and re-evaluation of the conclusions contained in the
    criteria documents.



    Professor R. Lauwerys, Unité de Toxicologie industrielle et médicale,
        Université catholique de Louvain, Bruxelles, Belgium

    Dr J. G. Noltes, Department of Organic and Organo-Element Chemistry,
        Institute for Organic Chemistry, Organization for Applied
        Scientific Research (TNO), Utrecht, Netherlands

    Professor M. Piscator, Department of Environmental Hygiene, The
        Karolinska Institute, Stockholm, Sweden

    Professor A.B. Roscin, Department of Occupational Hygiene, Central
        Institute for Advanced Medical Training, Moscow, USSR

    Dr M. Sharratt, Division of Environmental Health & Chemical Hazards,
        Department of Health & Social Security, London, England

    Professor M. Timar, State Institute of Occupational Health, Budapest,
        Hungary  (Vice-Chairman)

    Dr L. Cemisanska, Department of Occupational Toxicology, Centre of
        Hygiene, Sofia, Bulgaria


    Dr L. Fishbein, National Centre for Toxicological Research, US Food &
        Drug Administration, Jefferson, AR, USA  (Temporary Adviser)

    Dr Y. Hasegawa, Control of Environmental Pollution and Hazards,
        Division of Environmental Health, WHO, Geneva, Switzerland

    Dr J. E. Korneev, Control of Environmental Pollution and Hazards,
        Division of Environmental Health, WHO, Geneva, Switzerland

    Dr A. Stiles, Division of Vector Biology and Control, WHO, Geneva,

    Dr V. B. Vouk, Control of Environmental Pollution and Hazards,
        Division of Environmental Health, WHO, Geneva, Switzerland

        The following list of organotin compounds includes the trivial name of the compound used throughout the document, the Chemical Abstracts
    Service (CAS) name and number, the molecular formula, and alternative names,

                                                      ORGANOTIN COMPOUNDS

    Name used in text              CAS Index name                            CAS number    Molecular             Synonyms

     Monosubstituted compounds

    ethyltin trichloride           stannane, trichloroethyl-(9Cl) (8Cl)      1066-57-5     C2H5Cl3Sn        trichloroethylstannane;
    ethyltin triiodide             stannane, ethyltriiodo- (9Cl) (8Cl)       3646-94-46    C2H5I3Sn         triiodoethyltin
    butyltin trichloride           stannane, butyltrichloro- (9Cl) (8Cl)     1118-46-3     C4H9Cl3Sn        monobutyltin trichloride;
                                                                                                            stannane, trichlorobutyl-
    butylstannoic acid             stannane, butylhydroxyoxo- (9Cl) (8Cl)    2273-43-0     C4H10O2Sn        1-butanestannoic acid;
                                                                                                            butyltin hydroxide
                                                                                                            oxide; butylstannoic acid (VAN)
    butylthiostannoic acid         stannane, butylmercaptooxo- (8Cl)         26410-42-4    C4H10O S Sn
    butyltin-S,S',S"-tris          acetic acid, 2,2',2"-                     25852-70-4    C34H66O6S3Sn     butyltin tris(isooctyl

                                                      ORGANOTIN COMPOUNDS

    Name used in text              CAS Index name                            CAS number    Molecular             Synonyms

    Monosubstituted compounds cont'd.

    (isooctylmercaptoacetate)      ((butylstannylidyne)) tris (thio)                                        stannane, butyltris
                                   tris-, triisooctyl ester                                                 ((carboxymethyl) thio)-,
                                   (9Cl);                                                                   triisooctyl ester; butyltin
                                   acetic acid, ((butylstannylidyne)                                        tris(isooctyl thioglycollate);
                                   trithio) tri,-triisooctylester (8Cl)                                     monobutyltin tris 
                                                                                                            monobutyltin tris(isooctyltin
                                                                                                            thioglycolate); butyltin tris
                                                                                                            (isooctyl mercaptoacetate);
                                                                                                            trithio) triacetate;
                                                                                                            butylstannane tris(isooctyl
    butyltin-S,S',S"-tris          8 oxa-3,5-dithia-4-                       26864-37-9    C34H66O6S3Sn     monobutyltin tris(2-ethylhexyl
    (2-ethyl                       stannatetradecanoic acid,                                                thioacetate), monobutyltin
    hexylmercaptoacetate)          4 butyl-10-ethyl-4-((2-((2-                                              tris(2-ethylhexyl thioglycolate)
                                   thio)-7-oxo-, 2-ethylhexyl
                                   ester (9Cl); acetic acid,
                                   ester (8Cl)
    butyltin sulfide               distannathiane,                           15666-29-2    C8H18S3Sn2       butyl thiostannoic arthydride;
                                   dibutyldithioxo-(9Cl);                                                   monobutyltin sulfide
                                   distannthiane, 1,3-dibutyl-
                                   1,3-dithioxo- (8Cl)

                                                      ORGANOTIN COMPOUNDS

    Name used in text              CAS Index name                            CAS number    Molecular             Synonyms

    Monosubstituted compounds cont'd.

    octyltin trichloride           stannanne,                                3091-25-6     C8H17Cl3Sn       trichlorooctylstannane;
                                   trichlorooctyl-(9Cl) (8Cl)                                               octyltrichlorostannane;
                                                                                                            n-octyltin trichloride;
                                                                                                            mono-n-octyltin tri-chloride;

    octyltin tris(2-ethyl          8-oxa-3,5-dithia-4-                       27107-89-7    C38H74O6S3Sn
    hexylmercaptoacetate)          stannatetradecanoic acid,
                                   -2-oxoethyl) thio)-4-octyl-7-oxo-,
                                   2-ethylhexylester (9Cl);
                                   acetic acid, ((octylstannylidyne)
                                   trithio)tri-, tris(2-ethylhexyl)
                                   ester (8Cl)

    cyclohexylstannoic acid        stannano, cyclohexylhydroxyoxo-           22771-18-2    C6H12O2Sn        cyclohexanestannoic acid
                                   (9Cl) (8Cl)

    Disubstituted compounds
    dimethyltin dichloride         stannane, dichlorodimethyl-               753-73-1      C2H6Cl2Sn        dichlorodimethylstannane;
                                   (9Cl) (8Cl)                                                              dichlorodimethyltin;

                                                      ORGANOTIN COMPOUNDS

    Name used in text              CAS Index name                            CAS number    Molecular             Synonyms

    Disubstituted compounds cont'd.

    dimethyltin S,S'-bis           acetic acid, 2,2'-((dimethyl-             26636-01-1    C22H44O4S2Sn     TM 181; diisooctyl
    (isooctyl mercaptoacetate)     stannylene) bis (thio))bis-,                                             ((dimethylstannylene)
                                   diisooctyl ester (9Cl)                                                   dithio)diacetate;
                                                                                                            dimethylfin bis
                                                                                                            dimethylfin; T 40 (ester);
                                                                                                            TM 181S; Advastab TM 181S;
                                                                                                            Advastab TM 181 S
    diethyltin dichloride          stannane, dichlorodiethyl-                866-55-7      C4H10Cl2Sn       tin, dichlorodiethyl-;

    diethyltin diiodide            stannanne, diethyldiiodo-                 2767-55-7     C4H10I2Sn        tin, diethyldiiodo-;
    diethyltin dioctanoate         stannane, diethylbis((1-oxo               2641-56-7     C20H40O4Sn       diethyldiiodostannane
                                   octyl)oxy) (9Cl);                                                        diethyltin dicaprylate
                                   stannane, diethylbis
                                   (octanoyloxy) (8Cl)
    dipropyltin dichloride         stannane, dichlorodipropyl-               867-36-7      C6H14Cl2Sn       dipropyltin chloride;
                                   (9Cl) (8Cl)                                                              dichlorodipropylstannane;
                                                                                                            di-n-propyltin dichloride
    diisopropryltin dichloride     stannane, dichlorobis                     38802-82-3    C6H14Cl2Sn
                                   (1-methylethyl)- (9Cl)

                                                      ORGANOTIN COMPOUNDS

    Name used in text              CAS Index name                            CAS number    Molecular             Synonyms

    Disubstituted compounds cont'd.

    dibutyltin dichloride          stannane, dibutyldichloro- (9Cl) (8Cl)    683-18-1      C8H18Cl2Sn       dichlorodibutyltin; dibutyltin 
                                                                                                            di-n-butyltin dichlorlde;
    dibutyltin oxide               stannane, dibutyloxo- (9Cl) (8Cl)         818-08-6      C8H18OSn         di-n-butyltin oxide; tin,
                                                                                                            dibutylstannane oxide;
    dibutyltin diacetate           stannane, bis(acetyloxy)dibutyl- (9Cl)    1067-33-0     C12H24OSn        diacetoxydibutyltin;
                                                                                                            T 1[catalyst]; T 1 (VAN);
                                                                                                            Ba 2726
    dibutyltin dilaurate           stannane, dibutylbis                      77-58-7       C32H64O4Sn       Butynorate; DBTL; dibutylbis
                                   ((1-oxododecyl)oxy)-                                                     (lauroyloxy)-tin; Stabilizer
                                                                                                            D-22; tin dibutyl dilaurate;
                                                                                                            Stanclere DBTL; Davainex;
                                                                                                            TVS Tin Lau;
                                                                                                            dibutyltin didodecanoate;
                                                                                                            Mark 1038; Tinostat; dibutyl-
                                                                                                            tin n-dodecanoate; Stavinor
                                                                                                            1200 SN; T 12 (catalyst);
                                                                                                            dibutylstannylene dilaurate;
                                                                                                            T 12 (VAN)

                                                      ORGANOTIN COMPOUNDS

    Name used in text              CAS Index name                            CAS number    Molecular             Synonyms

    Disubstituted compounds cont'd.

    dibutyltin maleate             1,3,2-dioxastannepin-4,7-dione,           78-04-6       C12H20O4Sn       dibutyl(maleoyldioxy)tin;
                                                                                                            Advastab DBTM;
                                   2,2'-dibutyl-(9Cl) (8Cl)                                                 Advastab T 290; Stavinor
                                                                                                            1300 SN; dibutyl-stannylene
                                                                                                            maleate; Advastab T 340;
                                                                                                            Nuodex V 1525; Irgastab T 290
    dibutyltin sulfide             stannane, dibutylthioxo-                  4253-22-9     C12H20O4Sn       tin dibutyl mercaptide
                                   (9Cl) (8Cl)
    dibutyltin di                  stannane, dibutylbis                      2781-10-4     C24H48O4Sn       dibutyltin bis
    (2-ethylhexoate)               ((2-ethyl-1-oxohexyl)oxy)- (9Cl)                                         (2-ethylhexanoate); dibutyltin

    dibutyltin dioctanoate         stannane, dibutyl-                        4731-77-5     C24H48O4Sn       dibutyltin dioctoate;
                                   bis((1-oxooctyl)oxy)- (9Cl);                                             dibutyltin dicaprylate;
                                   stannane, dibutyl                                                        dibutyltin octanoate
                                   bis(octanoyloxy)- (8Cl)
    dibutyltin di                  5,7,12-trioxa-6-stannahexa                15546-16-4    C24H40O8Sn       dibutyltin bis(monobutyl
    (butyl maleate)                deca-2,9-dienoic acid,6,6-dibutyl-                                       maleate); maleic acid
                                   4,8,11-trioxo, butyl ester,                                              dibutyltin salt (2:1)
                                   (Z,Z)- (9Cl) stannane, dibutylbis                                        diisobutyl ester; B5
                                   (3-carboxyacryloyl)oxy-,                                                 [stabilizer]; dibutyltin
                                   dibutyl ester,(Z,Z)-(8Cl)                                                bis(butyl maleate)
    dibutyltin di                  stannane, dibutylbis                      10584-97-1    C34H60O8Sn
    (nonylmaleate)                 ((3-carboxyacryloyl)oxy)
                                   -dinonyl ester, (z,z)-(8Cl)

                                                      ORGANOTIN COMPOUNDS

    Name used in text              CAS Index name                            CAS number    Molecular             Synonyms

    Disubstituted compounds cont'd.

    dibutyltin ß-mercapto          6H-1,3,2-oxathiastannin-6-one,            78-06-8       C11H22O2S Sn     Thermolite 35; Advastab T-306;
    propanoate                     2,2-dibutyldihydro-                                                      Mark 488; dibutyltin
                                                                                                            dibutyltin ß-mercaptopropionate
    dibutyltin bis(lauryl          stannane, dibutylbis                      1185-81-5     C32H68S2Sn       dibutylbis(dodecylthio)tin;
    mercaptide)                    (dodecylthio)-(9Cl) (8Cl)                                                Mellite 39; dibutyltin
                                                                                                            dibutyltin; dibutylbis 
                                                                                                            Advastab TM 98; Mellite 139;
                                                                                                            Thermolite 20; dibutyltin
    dibutyltin "laurate-           2-butenoic acid, 4,4'-                    73246-84-1    C32H64O4Sn       solution of dibutyltin dilaurate
    maleate"                       [(dibutylstannylene)bis(oxy)]                           C16H24O8Sn       and dibutyltin maleate;
                                   bis [4-oxo-, (Z,Z)- mixed with dibutyl                                   Thermolite 17
                                   bis [(1-oxododecyl)oxy] stannane (1-1)
    dibutyltin S,S'-bis            acetic acid, 2,2' (dibutyl                25168-24-5    C28H56O4S2Sn     dibutyltin bis(isooctyl
    (isooctylthioglycolate)        stannylene)bis(thio)bis-,                                                mercaptoacetate); dibutyltin
                                   diisooctyl ester (9Cl);                                                  S,S'-bis(isooctyl
                                   acetic acid, ((dibutylstannylene)                                        mercapto-acetate);
                                   dithio)di, diisooctyl ester (8Cl)                                        diisooctyl((dibutylstannylene)-
                                                                                                            Thermolite 31; bis(iso-

                                                      ORGANOTIN COMPOUNDS

    Name used in text              CAS Index name                            CAS number    Molecular             Synonyms

    Disubstituted compounds cont'd.

    dibutyltin S,S'-bis                                                                                     octyioxycarbonylmethylthiolato)
    (isooctylthioglycolate)                                                                                 dibutyibis((((isooctyloxy)
    cont'd.                                                                                                 carbonyl)methyl)-thio)tin;
                                                                                                            BTS 70; T 101 (accelerator);
                                                                                                            Irgastab 17M; T 101
    dibutyltin S,S'-bis(2-         8-oxa-3,5-dithia-4-stannatetra            10584-98-2    C28H56O4S2Sn     dibutyltin bis(2-ethyihexyl
    ethylhexylmercaptoacetate)     decanoic acid 4,4-dibutyl-10-                                            thioglycolate); dibutyltin
                                   ethyl-7-oxo-2-ethylhexyl ester (9Cl);                                    S,S'-bis(2-ethylhexyl
                                   acetic acid, ((dibutylstannylene)                                        thio-glycolate)
                                   dithio)di-, bis(2-ethylhexyl)
                                   ester (9Cl)
    dipentyitin dichloride         stannane, dichlorodipentyl- (9Cl)         1118-42-9     C10H22Cl2Sn      dichlorodipentyltin
    dioctyltin dichloride          stannane, dichlorodioctyl- (9Cl) (8Cl)    3542-36-7     C16H34Cl2Sn      dichlorodioctyltin;

    dioctyltin oxide               stannane, dioctyloxo- (9Cl) (8Cl)         870-08-6      C16H34O Sn       tin, dioctyloxo-; di-n-octyltin
                                                                                                            oxide; dioctyloxostannane

    dioctyltin acetate             stannane, bis(acetyloxy)dioctyl- (9Cl)    17586-94-6    C20H40O4Sn       dioctyldiacetoxytin

    dioctyltin dilnurate           stannane, dioctylbis                      3648-18-8     C40H30O4Sn       lauric acid, dioctyltin deriv;
                                   ((1-oxododecyl)oxy)-(9Cl);                                               dioctyl-dilauroyloxytin;
                                   stannane, bis(lauroyloxy)                                                dioctyltin didodecanoate
    dioctyltin maleate             1,3,2-dioxastannepin-4,7-dione,           16091-18-2    C20H36O4Sn       di-n-octyltin maleate;
                                   2,2-dioctyl- (9Cl);                                                      Thermolite 813; Estabex U 18;
                                                                                                            dioctylstannylene maleate;
                                                                                                            Mellite 825

                                                      ORGANOTIN COMPOUNDS

    Name used in text              CAS Index name                            CAS number    Molecular             Synonyms

    Disubstituted compounds cont'd.

    dioctyltin dibutylmaleate      5,7,12-trioxa-6-stannahexadeca-           29575-02-8    C32H36O8Sn       dioctyltinbis(butylmaleate)
                                   2,9-dienoic acid, 6,6-dioctyl-
                                   4,8,11-trioxo-, butyl ester,
                                   stannane, bis(3-carboxyacryloyl)
                                   oxy)dioctyl-, dibutyl ester (Z,Z)-
    dioctyltin-S,S'-(ethylene      1,3-dioxa-6,9-d ithia-2-stanna            56875-68-4    C22H42O4S2Sn     ethylenebisthioglycolate
    glycol-bis-mercaptoacetate)    cycloundecane-4,11-dione,2,2-                                            dioctyltin
    dioctyltin-S,S'-bis            acetic acid, 2,2'-                        26401-97-8    C36H72O4S2Sn     diisooctyl((dioctylstannylene)
    (isooctyl-mercaptoacetate)     ((dioctylstannylene)bis(thio)                                            dithio)-diacetate; dioctyltin
                                   bis-,diisooctyl ester (9Cl);                                             bis(isooctylmercapto-acetate);
                                   acetic acid, ((dioctylstannylene)                                        Thermalite 831; dioctyltin
                                   dithio)di-, diisooctyl ester (8Cl)                                       di(iso- octylthyoglycolate);
                                                                                                            di-n-octyltin bis(iso-
                                                                                                            octylmercaptoacetate), bis
                                                                                                            methyl)thio)dioctyltin; Mellite
                                                                                                            831C; Irsastab 17 MOK;
                                                                                                            dioctyltin bis
                                                                                                            dioctyltin bis 

    dioctyltin mercaptoacetate     1,3,2-oxathiastannolan-5-one,             15535-79-2    C18H36O2S Sn     dioctyltin S,O-mercaptoacetate
                                   2,2-dioctyl-(9Cl) (8Cl)

                                                      ORGANOTIN COMPOUNDS

    Name used in text              CAS Index name                            CAS number    Molecular             Synonyms

    Disubstituted compounds cont'd.

    dioctyltin ß-mercapto          6H-1,3,2-oxathiastannin-6-one,            3033-29-2     C19H38O2S Sn     dioctyltin
    propanoate                     dihydro-2,2-dioctyl- (9Cl) (8Cl)                                         S,O-3-mercaptopropionate;
                                                                                                            dioctyltin mercaptopropionate
    dioctyltin-S,S'-bis            8-oxa-3,5-dithia-4-stanna                 27107-88-6    C28H56O4S2Sn
    (butyl mercaptoacetate)        dodecanoic acid, 4,4-dioctyi-7-oxo-,
                                   butyl ester (9Cl)
                                   acetic acid, (((dioctylstannylene)
                                   dithio)di-, butyl ester (8Cl)
    dioctyltin-S,S'-bis(2-         8-oxa-3,5-dithia-4-stannatetra            15571-58-1    C36H72O4S2Sn     bis(2-ethylhexyl)
    ethylhexylmercaptoacetate)     decanoic acid, 10-ethyl-4,4-                                             (dioctylstannylene)
                                   dioctyl-7-oxo-, 2-ethylhexyl                                             dithio)diacetate; dioctyltin
                                   ester (9Cl);                                                             bis(2-ethyl-hexyl thioglycolate);
                                                                                                            dioctyltin; Advastab 17 MOK
                                   acetic acid, ((dioctylstannylene)
                                   dithio)di-, bis(2-ethylhexyl)
                                   ester (8Cl)
    dioctyltin-S,S'-bis            8-oxa-3,5-dithia-4-stannaeicosanoic       73246-85-2    C44H88O4S2Sn     dioctyltin bis
    (laurylmercaptoacetate)        acid, 4,4-dioctyl-7-oxo, dodecyl ester                                   (laurylthioglycolate)
    dioctyltin bis(2-              5,7,12-trioxa-6-stannaoctadeca-2,9-       10039-33-5    C40H72O8Sn       di-n-octyltin bis
    ethylhexylmaleate)             dienoic acid, 14-ethyl-6,6-                                              (2-ethylhexylmaleate)
                                   dioctyl-4,8,11-trioxo, 2-ethylhexyl
                                   ester, (Z,Z) (9Cl)

    dioctyltin bis(dodecyl         stannane, bis(dodecylthio)                22205-30-7    C40H84S2Sn       bis(dodecylthio)dioctyltin;
    mercaptide)                    dioctyl-(9Cl) (8Cl)                                                      dioctyltin bis(lauryl
                                                                                                            mercaptide); dioctyltin,
                                                                                                            dilauryl mercaptan salt

                                                      ORGANOTIN COMPOUNDS

    Name used in text              CAS Index name                            CAS number    Molecular             Synonyms

    Disubstituted compounds cont'd.

    dioctyltin-S,S'-(1,4-          1,9-dioxa-4,6-dithia-5-                   69226-46-6    C24H46O4S2Sn
    butanediol-bis-mercapto        stannacyclotridecane-2,8-
    acetate)                       dione, 5,5-dioctyl- (9Cl)
    dioctyltin di(1,2-             1,3,8,11-tetraoxa-2-                      69226-45-5    C27H44O8Sn
    propyleneglycolmaleate)        stannacyclo-pentadeca-5,13-diene
                                   4,7,12,15-tetrone, 9-methyl-2,2-
                                   dioctyl-, (Z,Z)-(9Cl)
    dioctyltin bis(isobutyl        stannane, bis[(3-carboxy-                 15571-59-2    C32H56O8Sn       dioctyltin bis(isobutylmaleato)
    maleate)                       acryloyl)oxy]dioctyl-, diisobutyl                                        tin; 5,7,12-triox-6-stannapenta-
                                   ester, (Z,Z)- (9Cl)                                                      2,9-dienoic acid, 6,6-dioctyl-
                                                                                                            1-methyl-propyl ester
    diphenyltin dichloride         stannane, dichlorodiphenyl- (9Cl) (8Cl)   1135-99-5     C12H10Cl2Sn      dichlorodiphenyltin;
                                                                                                            diphenylstannyl dichloride;
                                                                                                            diphenyl-tin chloride;
    dicyclohexyltin oxide          stannane, dicyclohexyloxo-                22771-17-1    C12H22O Sn
                                   (9Cl) (8Cl)
    didodecyltin dibromide         stannane, dibromodidodecyl-               65264-08-6    C24H50Br2Sn      di-n-dodecyltin dibromide
    dioctadecyltin dibromide       stannane, dibromodioctadecyl-             65264-09-7    C36H74Br2Sn      di-n-octadecyltin dibromide

                                                      ORGANOTIN COMPOUNDS

    Name used in text              CAS Index name                            CAS number    Molecular             Synonyms

    triethyltin bromide            stannane, bromotriethyl- (9Cl) (8Cl)      2767-54-6     C6H15Br Sn
    triethyltin chloride           stannane, chlorotriehyl- (9Cl) (8Cl)      994-31-0      C6H15Cl Sn       chlorotriethyistannane;
                                                                                                            triethylstannyl chloride;
    triethyltin iodide             stannane, triethyliodo-                   2943-86-4     C6H15I Sn        triethyliodostannane;
                                   (9Cl) (8Cl)                                                              triethylstannyl iodide;
    triethyltin suifate            4,6-dioxa-5-thia-3,7-distannanonane,      57-52-3       C12H30O4S Sn2    triethylhydroxytin sulfate;
                                   3,3,7,7-tetraethyl- 5,5-dioxide (9Cl)                                    bis(triethyltin)
                                   stannane, triethylhydroxy-                                               sulfate
                                   sulfate (2:1) (8Cl)
    triethyltin acetate            stannane, (acetyloxy)                     1907-13-7     C8H18O2Sn        acetoxytriethylstannane
                                   stannane, acetoxytriethyl-
    triethyltin hydroxide          stannane, triethylhydroxy-                994-32-1      C6H16O Sn        triethylstannanol;
                                   (9Cl) (8Cl)                                                              triethylstannol;
    trlethylstannylmethyl          stannane, triethyl(3-methoxy              17869-84-0    C11H22O2Sn
    (1-propynyl) formal            methoxy)-l-propynyl-
    triethylstannylphenyl          stannane, trlethyl(phenylethynyl)-        1015-27-6     C14H20Sn
    acetylene                      (9Cl) (8Cl)
    1-triethylstannyl-3-           silane, trimethyl((3-triethylstannyl)-    4628-88-0     C12H26O SiSn
    trimethylsiloxi-1-propyne      2-propynyl)oxy)-

                                                      ORGANOTIN COMPOUNDS

    Name used in text              CAS Index name                            CAS number    Molecular             Synonyms


    2-trichloro-1-(butine-         stannane, (1-(3-butinyloxy)               17869-91-9    C12H21C13O2Sn
    1'-oxide)-1-(triethyl          -2,2,2-trichloroethoxy)triethyl-

    trivinyltin chloride           stannane, chlorotriethenyl-               10008-90-9    C6H9Cl Sn        chlorotrivinyltin;
                                   (9Cl);                                                                   chlorotrivinylstannane
                                   stannane, chlorotrivinyl-
    tributyltin chloride           stannane, tributylchloro-                 1461-22-9     C12H27Cl Sn      tributylchlorotin;
                                   (9Cl) (8Cl)                                                              chlorotributylstannane;
                                                                                                            tributylstannyl chloride
    tributyltin fluoride           stannane, tributylfluoro-                 1983-10-4     C12H27F Sn       tributylfluorostannane;
                                   (9Cl) (8Cl)                                                              fluorotributyltin;
                                                                                                            tri-n-butylstannyl fluoride
    bis(tributyltin) oxide         hexabutyldistannoxane                     56-35-9       C24H54O2 Sn2     C-Sn-9; BioMeT TBTO; Bultinox;
                                   distannoxane, hexabutyl- (9Cl) (8Cl)                                     hexabutyl-distannoxane;
                                                                                                            oxybis(tributyitin); TBTO;
                                                                                                            Lastanox T; Vikol AF-25;
                                                                                                            Vikol LO-25; BioMeT 66;
                                                                                                            BioMeT SRM; Lastanox T20;
                                                                                                            Lastanox Q; Lastanox
                                                                                                            F; Stannicide A; tributyltin
                                                                                                            oxide; Myko-lastanox F

                                                      ORGANOTIN COMPOUNDS

    Name used in text              CAS Index name                            CAS number    Molecular             Synonyms


    tributyltin acetate            stannane, (acetyloxy)tributyl- (9Cl);     56-36-0       C14H30O2Sn       acetoxytributyltin;
                                   stannane, acetoxytributyl- (8Cl)                                         tributylacetoxystannane;
                                                                                                            tri-n-butyltin acetate;
    tributyltin linoleate          stannane, tributyl((1-oxo-9,12-           24124-25-2    C30H58O2Sn       stannane; tributylstannylacetate
                                   octadecad ienyl)oxy)-(Z,Z)-(9Cl);
                                   stannane, tributyl(linoleoyloxy)-
    tributyltin benzoate           stannane, (benzoyloxy)tributyl-           4342-36-3     C19H32O2Sn       tri-n-butyltin benzoate; tin,
                                   (9Cl) (8Cl)                                                              (benzoyloxy) tributyl-
    tributyltin salicylate         phenol, 2-[[(tributylstannyl)oxy]         4342-30-7     C19H32O3Sn       tin, tributyl(salicyloyloxy)-
                                   carbonyl]- (9Cl)
                                   stannane, tributyl(salicyloyloxy)-
    tributyltin methacrylate       stannane, tributyl((2-methyl-1-           2155-70-6     C16H32O2Sn       tributylstannyl methacrylate;
                                   oxo-2-propenyl)oxy)-(9Cl);                                               tributyl- (methacryloxy)stannane;
                                   stannane, tributyl(methacryloyloxy-                                      tin, tributyl-
                                   (8Cl)                                                                    methacrylate; (methacryloyloxy) 
    tributyltin laurate            stannane, tributyl                        3090-36-6     C24H50O2Sn       tin, tributyl(lauroyloxy)-;
                                   ((1-oxo-dodecyl)oxy)-(9Cl)                                               tributyltin laurate;
                                   stannane, tributyl(lauroyloxy)- (8Cl)                                    tributyltin dodecanoate
    tributyltin oleate             stannane, tributyl((1-oxo-9-octa          3090-35-5     C30H60O2Sn       tin, tributyl(oleoyloxy)-;
                                   decenyl)oxy)-, (Z)-(9Cl);                                                N 5117 (Stauffer); N 5117
                                   stannane, tributyl(oleoyloxy)- (8Cl)
    trihexyltin acetate            stannane, (acetyloxy)trihexyl-            2897-46-3     C20H42O2Sn       tin, acetoxytrihexyl-;
                                   (9Cl);                                                                   acetoxytrihexyltin
                                   stannane, acetoxytrihexyl- (8Cl)

                                                      ORGANOTIN COMPOUNDS

    Name used in text              CAS Index name                            CAS number    Molecular             Synonyms


    tricyclohexyltin hydroxide     stannane, tricyclohexylhydroxy-           13121-70-5    C18H34O Sn       Plictran;
                                   (9Cl) (8Cl)                                                              tricyclohexylhydroxystannane;
                                                                                                            Plyctran; M 3180; Cyhexatin;
                                                                                                            Dowco 213; tricyclohexylstannanol

    trioctyltin chloride           stannane, chlotrioctyl- (9Cl) (8Cl)       2587-76-0     C24H51ClSn       tin, chlorotrioctyl-;
                                                                                                            chlorotrioctyltin; tri-n-
                                                                                                            octyltin chloride;
    triphenyltin chloride          stannane, chlorotriphenyl-                639-58-7      C18H15ClSn       LS 4442; GC 8993; General
                                   (9Cl) (8Cl)                                                              Chemicals 8993; TPTC; HOE 2872;
                                                                                                            Brestanoi; Fentin chloride;
    triphenyltin hydroxide         stannane, hydroxytriphenyl-               76-87-9       C18H16OSn        hydroxytriphenyttin; 
                                   (9Cl) (8Cl)                                                              hydroxytriphenyl-stannane;
                                                                                                            TPTH; triphenylstannanol; K 19
                                                                                                            (VAN); Tenhide; Fenolovo; Du-Ter
                                                                                                            Extra; Erithane; Vancide KS;
                                                                                                            Dowco 186; ENT 28009; Du-Ter;
                                                                                                            Fentin hydroxide

                                                      ORGANOTIN COMPOUNDS

    Name used in text              CAS Index name                            CAS number    Molecular             Synonyms


    triphenyltin acetate           stannane, (acetyloxy)triphenyl-           900-95-8      C20H18O2Sn       Brestan;
                                   (9Cl);                                                                   acetoxytriphenylstannane;
                                   stannane, acetyloxytriphenyl- (8Cl)                                      Batasan; Phentin acetate;
                                                                                                            Suzu; acetato-triphenylstannane;
                                                                                                            GC 6936; ENT 25208; Fentin
                                                                                                            acetate; Lirostanol; tin
                                                                                                            triphenyl acetate; TPTA;
                                                                                                            VP 19-40; Brestan 60; Liromatin
    p-bromophenoxy triethyltin     stannane, (p-bromophenoxy)                20961-09-5    C12H19BrOSn
                                   triethyl- (8Cl)

    tetrarnethyltin                stannane, tetramethyl- (9Cl) (8Cl)        594-27-4      C4H12Sn          tetramethylstannane
    tetraethyltin                  stannane, tetraethyl- (9Cl) (8Cl)         597-64-8      C8H20Sn          tetraethylstannane
    tetrabutyltin                  stannane, tetrabutyl- (9Cl) (8Cl)         1461-25-2     C16H36Sn         tetra-n-butyltin;
    tetraisobutyltin               stannane, tetrakis(2-methylpropyl)-       3531-43-9     C16H36Sn         tetraisobutylstannane
                                   stannane, tetraisobutyl- (8Cl)
    tetraphenyltin                 stannane, tetraphenyl- (9Cl) (8Cl)        595-90-4      C24H20Sn         tetraphenylstannane
    tetraoctyltin                  stannane, tetraoctyl- (9Cl) (8Cl)         3590-84-9     C32H68Sn         tetra-n-octyltin;
    stannous octanoate             octanoic acid, tin(2+) salt               1912-83-0     C8H16O2 1/2Sn    tin octanoate; stannous
                                   (9Cl) (8Cl)                                                              dioctanoate; tin(II)octanoate;
                                                                                                            stannous caprylate;
                                                                                                            stannous octcate
    tin (II) cyclopentadienyl      stannocene (9Cl)                          1294-75-3     C10H10Sn         tin, di-pi-cyclopentadienyl-


        This is the first volume in the UNEP/WHO Environmental Health
    Criteria series containing a preliminary review of environmental
    health aspects of a group of chemicals. Such reports are prepared in
    accordance with the second objective of the WHO Environmental Health
    Criteria Programme "to identify new or potential pollutants by
    preparing preliminary reviews on health effects of agents likely to be
    used in industry, agriculture, in the house, and elsewhere" (WHO,
    1976). Organometallic tin compounds are being used in increasing
    amounts for a variety of applications and the annual world production
    has risen from less than 50 tonnes in 1950 to about 25 000 tonnes in
    1975. One of the main applications is the use of dialkyland, to a much
    lesser extent, monoalkytin compounds in the stabilization of
    poly(vinyl chloride). Other applications include the use of
    tributyltin compounds as industrial biocides and surface disinfectants
    and the use of triphenyltin and tricylohexyltin compounds as
    agricultural fungicides and agricultural acaricides.

        Preliminary reviews differ from the criteria documents in that
    they do not contain a separate section on health risk evaluation and
    that the procedure for their preparation is simpler. Draft preliminary
    reviews are not submitted for comments to the national focal points
    for the WHO Environmental Health Criteria Programme. The first draft
    is reviewed by a Task Group of experts, and on the basis of their
    comments, a final draft is prepared and scientifically edited by the
    WHO Secretariat. However, individual members of the Task Group and
    other experts may be consulted during the scientific editing of the

        The first draft of the present document was prepared by Dr L.
    Fishbein, National Center for Toxicological Research, Jefferson, AR,
    USA. Dr A. E. Martin, formerly Principal Medical Officer, Department
    of Health and Social Security, London, England, assisted the
    Secretariat in the preparation of a revised first draft, which was
    circulated to the members of the Task Group prior to the meeting. The
    Task Group on Environmental Health Aspects of Tin and Organotin
    Compounds met in Geneva from 10-14 March 1975 to review and revise
    this draft, and, on the basis of their comments, a final draft was
    prepared by the Secretariat. The Secretariat wishes to acknowledge the
    most valuable assistance in the final phases of preparation of the
    document of Dr Renate Kimbrough, Center for Disease Control, Atlanta,
    GA, USA, Professor Magnus Piscator, Department of Environmental
    Hygiene, Karolinska Institute, Stockholm, Sweden, Dr Robert J. Horton,

    US Environmental Protection Agency, Research Triangle Park, NC, and Dr
    Warren T. Piver, National Institute of Environmental Health Sciences,
    Research Triangle Park, NC, USA. The help is also gratefully
    acknowledged of Dr H. Nordman, Institute of Occupational Health,
    Helsinki, Finland, who assisted both in the preparation of the final
    draft and in the final scientific editing of the document and of
    Professor C. Schlatter and Dr R. Utzinger, Institué de Toxicologie,
    Ecole Fédérale Polytechnique et Université de ZÜrich, Dr. D. S. Valley
    Dr D. F. Walker, National Library of Medicine, Department of Health,
    Education and Welfare, USA, and Dr A. Stiles, Consultant, Department
    of Environmental Health, WHO, Geneva, who helped in compiling the list
    of organotin compounds.

        This document is based primarily on original publications listed
    in the reference section. However, several publications reviewing the
    health effects of inorganic and organotin compounds have also been
    used. These include reviews by Barnes & Stoner (1959), Browning
    (1969), FAO/WHO (1971), International Labour Office (1972), Kimbrough
    (1976), MacIntosh (1969), National Institute of Occupational Safety
    and Health (1976), and Piver (1973).

        Details of the WHO Environmental Health Criteria Programme,
    including definitions of some of the terms used in the documents, may
    be found in the general introduction to the Environmental Health
    Criteria Programme, published together with the environmental health
    criteria document on mercury (Environmental Health Criteria I M
    Mercury, Geneva, World Health Organization, 1976) and now available as
    a reprint.


    1.1  Chemistry and Uses of Tin Compounds

    1.1.1  Inorganic tin

        The annual world production of tin is around 225 000 tonnes, about
    70% of which is obtained from ores, the remaining 30% being recovered
    from scrap metal. Tin is mainly used in tinplated containers, but it
    is also extensively used in solders, in alloys such as bronzes,
    babbit, pewter, and type metal, and in more specialized alloys such as
    dental amalgams and the titanium alloys used in aircraft engineering.

        Inorganic tin compounds, in which the element may be present in
    the oxidation states of +2 or +4 are used in a variety of industrial
    processes for the strengthening of glass, as a base for colours, as
    catalysts, as stabilizers in perfumes and soaps, and as dental
    anticariogenic agents.

    1.1.2  Organotin compounds

        Organotin compounds are classified as R4Sn, R3SnX, R2SnX2, and
    RSnX3. In compounds of industrial importance, R is usually a butyl,
    octyl, or phenyl group and X, a chloride, fluoride, oxide, hydroxide,
    carboxylate, or thiloate. So far, monosubstituted organotin compounds
    (RSnX3) have had a very limited application, but they are used as
    stabilizers in poly(vinyl chloride) films. Disubstituted organotin
    compounds R2SnX2) are mainly used in the plastics industry,
    particularly as stabilizers in poly(vinyl chloride). They are also
    used as catalysts in the production of polyurethane foams and in the
    room-temperature vulcanization of silicones. Trisubstituted organotin
    compounds (R3SnX) have biocidal properties that are strongly
    influenced by the R-groups. The most important of these compounds are
    the tributyl-, triphenyl-, and tricyclohexyltin compounds, which are
    used as agricultural and general fungicides, bactericides,
    antihelminthics, miticides, herbicides, molluscicides, insecticides,
    nematocides, ovicides, rodent repellents, and antifoulants in boat
    paints. The tetrasubstituted organotin compounds (R4Sn) are mainly
    used as intermediates in the preparation of other organotin compounds.

    1.2  Analytical Methods

        A wide variety of analytical methods is available for the
    determination of tin at low concentrations.a However, these methods
    have rarely been compared with regard to their suitability for
    application to a particular problem and, on the basis of available
    information, it is not possible to recommend a specific analytical
    technique for a particular application.

        Inorganic tin in food and biological materials is usually
    determined by atomic absorption. Other spectroscopic methods have also
    been used with satisfactory accuracy and precision, including emission
    spectroscopy for air, water, and food samples and neutron activation
    analysis for geological samples.

        Many analytical methods have been used for the determination of
    organotin compounds. Atomic absorption and other spectroscopic methods
    combined with chromatography have been used for the estimation of
    diorganotin compounds. Pesticide residues have been determined by
    spectroscopic methods and gas-liquid or thin-layer chromatography.
    However, reliable methods have still to be developed for the
    quantitative extraction, separation, and determination of many
    individual tin species in mixtures containing both inorganic tin and
    organotin compounds that may occur in various media.

    1.3  Environmental Concentrations and Exposures

    1.3.1  Environmental exposures

        On the whole, contamination of the environment by tin is only
    slight. The levels of pollution arising from gases and fumes, waste
    slag, and liquid wastes from tin processing are low because of the
    high degree of recovery and reprocessing used in this industry.

        Concentrations of tin in air are often below the detection limits
    and, when detected, the levels are generally below 0.2-0.3 µg/m3,
    except in the vicinity of industrial sources of emission, where
    concentrations up to 5 µg/m3 may occur.


    a  Throughout the document the word concentration indicates mass
       concentration unless otherwise stated.

        Tin has not always been found in soils and plants; however, it is
    possible that in some cases, concentrations have been below the
    detection limits. Tin concentrations in soils are generally below
    200 mg/kg but in regions of tin-containing minerals, the levels may
    exceed 1000 mg/kg. The small amount of evidence available concerning
    the uptake of tin by crops suggests that soil concentrations do not
    markedly influence its uptake by plants.

        Tin has been detected only occasionally in river and municipal
    waters. Values exceeding 1 µg/litre are exceptional, although values
    as high as 30 µg/litre have been found in drinking water. Sea water
    concentrations are of the order of 3 µg/litre. Organotin compounds may
    enter water, for example, from antifouling paints on the bottoms of
    ships or from molluscicides, which, to be effective, should be present
    at concentrations of about 1 mg/litre.

        Food is the main source of tin for man. A diet composed
    principally of fresh meat, cereals, and vegetables, is likely to
    contain a mean tin concentration of about 1 mg/kg. Larger amounts of
    tin exceeding 100 mg/kg may be found in foods stored in plain cans
    and, occasionally, in foods stored in lacquered cans. Some foods such
    as asparagus, tomatoes, fruits, and their juices tend to contain high
    concentrations of tin if stored in unlaquered cans. Organotin
    compounds may be introduced into foods through the use of such
    compounds as pesticides and, to some extent, through migration of tin
    from poly(vinyl chloride) materials. However, the levels of organotin
    compounds in food are generally below 2 mg/kg.

        Experimental studies have provided evidence of the
    biotransformation of some triphenyl-, and tricyclohexyltin compounds.
    There are also limited data suggesting methylation of tin by organisms
    present in the environment. From the available information, it appears
    that bioconcentration of tin and organotin compounds of a magnitude
    that might endanger life or the environment is unlikely to occur.

        The estimated mean total daily intake of tin by man ranges from
    200 µg to 17 mg. A diet consisting of fresh foods probably provides
    about 1-4 mg/day. The likely daily intake from water is estimated to
    be less than 30 µg/day, and the daily amount entering the body from
    air, less than 1 µg.

    1.3.2  Occupational exposure

        Several technological operations associated with the processing of
    tin are known to cause excessive occupational inhalation exposure to
    tin oxide which may result in a benign pneumoconiosis termed
    stannosis, many cases of which have been reported in the past.

        Workers involved in the processing of di- and trisubstituted
    organotin compounds may be subject to excessive exposure from time to
    time. Workers spraying fields or treating plants with trialkyl- or
    triaryltin compounds may also run the risk of exposure to these

    1.4  Metabolism

    1.4.1  Inorganic tin

        The extent of absorption through the respiratory route has still
    to be assessed. The absorption of ingested inorganic tin is likely to
    be less than 5% although figures as high as 20% have been suggested.
    Gastrointestinal absorption is influenced by the oxidation state,
    tin(II) compounds being more readily absorbed than tin(IV) compounds.
    The anion complement may also influence the rate of absorption.

        Absorbed tin leaves the vascular system rapidly. Bone is the main
    site of deposition and the highest concentrations of tin are found in
    the lung, kidney, liver, and bone. Penetration of the blood-brain and
    placental barriers appears to be very slight. With the exception of
    the lungs, inorganic tin does not accumulate in organs with increasing

        Absorbed inorganic tin is mainly excreted in the urine. The
    fraction excreted with the bile varies with the type of compound and
    is probably below 15%.

    1.4.2  Organotin compounds

        In general, organotin compounds are more readily absorbed from the
    gut than inorganic tin compounds; allowance must be made, however, for
    the great variations found between different compounds and different
    species. As a rule, tin compounds with a short alkyl chain are more
    readily absorbed from the intestinal tract. The trialkyltin compounds
    are usually well absorbed through the skin. As far as distribution is
    concerned, the highest concentrations in rats, guineapigs, rabbits,
    and hamsters have mostly been detected in the liver. Trisubstituted
    organotin compounds have been found in the brain of various species
    but the form of tin present in the brain has not been satisfactorily

        Many organotin compounds are transformed, to some extent, in the
    tissues. The dealkylation and dearylation of tetra-, tri-, and
    disubstituted organotin compounds seem to occur in the liver, but the
    dealkylation of diethyltin compounds appears to take place both in the
    gut and in tissues of other organs. The mode of excretion of organotin
    compounds largely depends on the type of the compound. For example,

    ethyltin trichloride seems to be mainly excreted with the urine, but
    diethyltin is eliminated with the faeces, urine, and the bile.
    Triethyltin is not only excreted with the urine, but, at least in
    lactating sheep, also with the milk. The route of excretion for many
    compounds is not known. The biological half-time of different
    organotin compounds varies and many compounds are slow to disappear
    from the organs. Usually the biological half-time seems to be longer
    in the brain than in other organs.

    1.5  Effects on Experimental Animals

        Although there is evidence that tin is essential for the normal
    growth of rats, no evidence exists that it is essential for other
    species including man.

    1.5.1  Inorganic tin  Local effects

        Many of the reported effects of inorganic tin are localized
    because of its irritant properties. Vomiting and diarrhoea are typical
    signs that follow oral intake of foods with a high tin content. In
    cats, tin concentrations of 540 mg/litre or 1370 mg/litre in orange
    juice caused vomiting in 1/11 animals and 3/10 animals, respectively.
    However, these levels did not produce any effects in dogs. The only
    adverse effect produced in guineapigs by both short-term and prolonged
    exposure to 3 mg of tin tetrachloride per m3 of air was transient
    irritation of the nose and eyes, but these findings have not been
    corroborated. Application of 1% tin(II) chloride or 0.25% tin(II)
    fluoride to the abraded skin of rabbits caused intradermal pustule
    formation and epidermal destruction, but did not have any effect on
    intact skin.  Systemic effects

        The major systemic effects of inorganic tin salts in animals
    include ataxia, twitching of the limbs, and fore-and hindleg weakness
    progressing to paralysis. In rats, growth retardation and decreased
    haemoglobin levels may follow administration of tin(II) chloride,
    orthophosphate, sulfate, oxalate, and tartrate at a dietary level of
    3 g/kg. However, administration of iron prevents the development of
    anaemia. Higher dietary levels of tin (10 g/kg) over several weeks may
    induce testicular degeneration, pancreatic atrophy, and a spongy state
    of the white matter of the brain. Doses of pentafluorostannite of
    100 mg/kg body weight may also affect growth, and a dose-related
    decrease in haemoglobin levels may be seen with doses exceeding
    100 mg/kg; no effect on growth was found at a dose of 20 mg/kg
    administered orally to rats. A single intravenous injection of
    pentafluorostannite at a concentration of 35 mg/kg body weight or
    tin(II) chloride dihydrate (SnCl2-2H20) at 44.4 mg/kg in rats

    produced extensive necrosis, mainly in the proximal tubules of the
    kidney. A subcutaneous dose of tin(II) chloride at a concentration of
    5.6 mg/kg body weight caused a 20-30 fold increase in the haem
    oxidation activity in the kidney; this effect was dose-related.
    Administration of tin(II) chloride at a concentration of 5 mg/litre,
    from weaning to natural death, did not affect longevity in mice or in
    male rats, but caused a decrease in longevity in female rats combined
    with an increased incidence of fatty degeneration of the liver. There
    is no conclusive evidence concerning the carcinogenicity or
    teratogenicity of inorganic tin.

    1.5.2  Organotin compounds  Local effects

        Some butyltin compounds are known to produce gastrointestinal
    irritation; submucosal, subserosal, and intraluminar haemorrhages were
    seen in mice after a single oral dose of 4000 mg/kg body weight.
    Dibutyltin dichloride administered at a dose of 50 mg/kg body weight
    per day, for one week, produced gastroenteritis in rats.
    Gastroenteritis was also produced in rats by administration of
    tricyclhexyltin hydroxide (25 mg/kg body weight per day, for 19 days).

        Dermal application of dibutyltin dichloride (10 mg/kg body weight
    per day, for 12 days) caused severe local damage. Local irritation was
    produced in rats by applications to the shaved skin of
    bis(tributyltin) oxide in doses of 0.36-0.95 mg/kg; necrosis was
    produced at doses of 1.4-185 mg/kg. Triphenyltin acetate also
    irritated the skin of the rat, whereas triphenyltin hydroxide was
    reported not to irritate the skin of the rabbit but to be extremely
    irritating to the eyes.  Systemic effects

        The systemic effects of monosubstituted, disubstituted, and
    tri-substituted organotin compounds differ. In general, mono- and
    di-organotin compounds are less toxic than triorganotin compounds. The
    toxicity of trialkyltin compounds decreases as the number of carbon
    atoms in the alkyl chain increases.

        Dibutyltin compounds can produce inflammatory changes in the bile
    duct. Single oral doses of dibutyltin dichloride at 50 mg/kg body
    weight produced this effect in rats, and higher doses produced more
    severe injury; necrotic changes were also produced in the liver of
    mice and rats. Bile duct injury in rats and rabbits was seen following
    dermal application of dibutyltin dichloride (10 mg/kg body weight).
    Dioctyltin compounds produced slight changes in the germinal centres
    of the spleen and steatosis of hepatocytes in mice at a single oral
    dose of 4000 mg/kg body weight. Pulmonary oedema may be seen in rats
    following intravenous administration of diethyl-, dipropyl-,

    diisopropyl-, and dipentyltin compounds. Dibutyltin compounds can slow
    down growth in rats. The no-observed-effect dietary level was reported
    to be 40 mg/kg for a 3 month feeding period and 20 mg/kg for 6 months.
    Recent studies showed that dioctyltin dichloride and dibutyltin
    dichloride administered at dietary levels of 50 and 150 mg/kg,
    respectively for 6 weeks, caused a dose-dependent atrophy of the
    thymus and thymus-dependent organs and suppression of the
    immunological response in rats, but not in mice and guineapigs.

        Some trialkyltin compounds produce a characteristic lesion in the
    central nervous system consisting of oedema throughout the white
    matter. Orally administered trimethyl- and triethyltin compounds are
    more potent in inducing this lesion than the higher homologues. The
    first changes in the rat brain were visible after 3 days of
    administration of triethyltin hydroxide at a dietary level of
    20 mg/kg. Maximum changes were found after 2 weeks. Typical signs of
    such intoxication included prostration and weakness of the progressing
    to flaccid paralysis. The effects disappeared when exposure ceased.

        Administration of triphenyltin compounds produced a reduction in
    weight and in food intake in many species. Lethargy was a typical
    symptom and histological changes in the liver and spleen were also
    seen. A decreased immunological response with a reduction in the
    number of leukocytes and of plasma cells in the lymph nodes of
    guineapigs has been reported. A 2-year study indicated a
    no-observed-effect level for triphenyltin acetate of 0.1 mg/kg body
    weight per day.

        A single intrarumenal dose of tricyclohexyltin hydroxide at
    50 mg/kg body weight produced central nervous depression and diarrhoea
    in sheep, whereas a dose of 15 mg/kg did not result in any adverse
    effects. At higher doses, pulmonary congestion, tracheal haemorrhage,
    enteritis, and eleotrocardiographic changes were seen.
    No-observed-effect doses for long-term intake in the rat and dog were
    given as 3 mg/kg body weight per day and 0.75 (mg/kg) per day,

        Tetraalkyltin compounds may produce muscular weakness, paralysis,
    respiratory failure, tremors, and hyperexcitability as acute effects
    in mice and dogs, while late effects are similar to those seen with
    triorganotin poisoning.

        There is no evidence that organotin compounds are carcinogenic or
    teratogenic. Reported effects of triphenyltin hydroxide on the testes
    and ovaries of rats require further confirmation.

        Information concerning the mechanism of the toxic action of
    organotin compounds is inadequate. Several dimethyl- and dioctyltin
    compounds inhibit the oxidation of keto-acids and block mitochondrial
    respiration. Trialkyltin compounds inhibit oxidative phosphorylation.

    1.6  Effects in Man

    1.6.1  Inorganic tin

        Inhalation of elemental tin does not produce any effects in man,
    whereas extended exposure to tin(IV) oxide dust and fumes can produce
    a benign pneumoconiosis termed stannosis. This condition develops
    after at least 3-5 years of exposure and is characterized by small
    dense shadows in the pulmonary X-ray picture without impairment of
    pulmonary function. Fibrosis is not seen. The generally-accepted
    maximum allowable concentration of tin(IV) oxide in the air of work
    rooms of 2 mg/m3 appears to give protection against this disorder.

        Symptoms that have been reported following ingestion of food with
    a high tin content include nausea, vomiting, diarrhoea, stomach
    cramps, fatigue, and headache. The lowest concentration of tin
    reported in association with such outbreaks was about 250 mg/litre in
    canned orange and apple juice. Five human volunteers did not
    experience any symptoms from the ingestion of fruit juices containing
    concentrations of 500-730 mg/litre but all had gastrointestinal
    disturbances at a level of 1370 mg/litre (corresponding to
    4.4-6.7 mg/kg body weight). Ingestion of 50 mg of tin through eating
    canned peaches that contained tin concentrations of about
    300-600 mg/kg caused acute symptoms in 2 out of 7 persons. The
    relative importance of, on one hand, the total amount of tin ingested
    and, on the other hand, the concentration of tin in relation to the
    development of symptoms has not been satisfactorily assessed.

    1.6.2  Organotin compounds  Local effects

        Dibutyl- and tributyltin compounds produced skin irritation in
    workers 1-8 h after contact. Experimental application to the skin of
    volunteers showed that some compounds (e.g., dibutyltin dichloride and
    tributyltin chloride) produced this effect, whereas others such as
    dibutyltin maleate and tetrabutyltin did not. Di- and tributyltin
    compounds caused eye irritation after brief contact. A 20% solution of
    triphenyltin acetate produced irritation of the skin and the mucous
    membranes of the upper respiratory tract while tricyclohexyltin
    hydroxide was reported not to cause skin irritation at a concentration
    of 0.01 mg/kg body weight.  Systemic effects

        The majority of accidental poisonings involving systemic effects
    have been due to occupational exposure to triphenyltin acetate.
    Systemic effects reported to have followed both dermal and inhalation
    exposure include general malaise, nausea, gastric pain, dryness of the
    mouth, vision disturbance, and shortness of breath. Hepatomegaly and
    elevated levels of liver transaminase activity have been found in some
    cases. Recovery has generally been complete but liver damage has been
    known to persist for up to 2 years.

        The hazard associated with the use of organotin compounds was
    unmasked by an episode of intoxication in 1954 involving over 200
    cases, 100 of which were fatal. The cause was the ingestion of an oral
    preparation containing diethyltin diiodide at 15 mg/capsule. It was
    suggested, however, that ethyltin triiodide, triethyltin iodide, and
    tetraethyltin were present as impurities. Predominant symptoms and
    signs included severe headache, nausea and vomiting, visual and
    psychological disturbances, and sometimes loss of consciousness. At
    autopsies and decompressive surgery, cerebral oedema of the white
    matter was found. In many cases, symptoms lasted for at least 4 years;
    follow-up information on the subjects involved is not available.

    1.7  Recommendations for Further Studies

    1.7.1  Analytical methods

        More information is needed on the specificity, precision, and
    accuracy of methods for the determination of inorganic tin compounds.
    Data concerning interlaboratory comparisons of the methods used are
    also lacking. In view of the variable results obtained in studies on
    the tin contents of various materials and tissues, the use of
    reference laboratories is recommended. Better methods are needed for
    the quantitative extraction and separation of the various organotin
    compounds present in environmental and biological samples. As
    organotin compounds used as pesticides or stabilizers occur in foods
    in minute amounts only, mare sensitive methods for their measurement
    are needed.

    1.7.2  Environmental data

        More information regarding bioconcentration is needed. The fate of
    organotin compounds entering water is largely unknown. The possibility
    of the methylation of tin by organisms present in the environment is
    of particular interest.

        A wide variety of results concerning the daily intake of tin has
    been reported. Although a certain range is to be expected, further
    investigations of the concentrations of tin in food and water, and of
    dietary intake are needed.

    1.7.3  Metabolism

        Information on the rate of absorption of tin from the
    gastrointestinal tract is insufficient and little is known about the
    absorption of various compounds through the respiratory tract which
    may be of importance in occupational exposure. Furthermore, there is a
    gap in information concerning the rate of absorption of organotin
    compounds through the skin.

        Many of the studies conducted on the distribution of tin in human
    tissues may be unreliable because of the analytical methods available
    at that time: thus, data on tissue contents should be obtained using
    as sensitive methods as possible with emphasis on the precision,
    specificity, and accuracy of the assays employed. Information on tin
    concentrations in newborn infants compared with adults is lacking, and
    data concerning tin concentrations in the tissues of occupationally-
    exposed persons compared with unexposed populations are not available.
    The increasing development and use of new organotin compounds will
    necessitate further studies on the metabolism of such compounds.

        At present, there is an obvious lack of information on the
    bio-transformation of several organotin compounds. Data concerning the
    accumulation and retention times of various compounds in animal
    tissues are also desirable. Finally, the route or routes of excretion
    of many organotin compounds are completely unknown.

    1.7.4 Effects

        Probably the most conspicuous lack of information concerns the
    mechanism of action of various organotin compounds. More information
    should be obtained on the carcinogenicity, teratogenicity, and
    mutagenicity of these compounds. Compounds used industrially should be
    studied with reference to possible allergenic properties. Recently
    reported results suggest that the effects of various organotin
    derivatives on the immune system should be studied in more detail.
    Moreover, properly conducted studies on the effects on the sex glands
    of different species using multigeneration studies seem urgent. The
    importance of longitudinal epidemiological studies on
    occupationally-exposed populations and the usefulness of information
    that may be obtained through follow-up studies of accidental
    intoxication should be emphasized.


        Tin can form a variety of both inorganic and organometallic
    compounds. These two classes of compounds have different chemical and
    physical properties which make them suitable for different
    applications in industry, agriculture and elsewhere. They also have
    different toxicities and require separate assessments of health risk.
    The inorganic chemistry of tin has been described in standard texts on
    inorganic chemistry such as those by Cotton & Wilkinson (1972, 1976)
    and Heslop & Jones (1976). Sources of information on new developments
    in the organometallic chemistry of tin include a review by van der
    Verk (1972) and a collection of papers presented at a symposium of the
    American Chemical Society (Zuckerman, 1976).

    2.1  Elemental Tin

        Tin (atomic number 50; relative atomic mass 118.70) is an element
    of group IVb of the periodic system, together with carbon, silicon,
    germanium, and lead. It exits in three allotropic modifications. At
    room temperature, the stable form is a metallic form called ß- or
    white tin. White tin is a silver-white, lustrous and soft metal with
    considerable ductility, and can be rolled into very thin "tin foil".
    Its density is 7.27, melting point 231.9°C, and boiling point 2507°C.
    At ordinary temperatures, it is stable in both air and water. Below
    13.3°C, the stable form of tin is the non-metallic grey tin
    (alpha-tin). Above 161°C, the stable modification is the so-called
    brittle tin, another metallic modification.

        Metallic tin is normally covered with a thin protective film of
    tin dioxide. Because tin is resistant to cold acids, a cohesive tin
    layer will protect iron from corrosion (tin plate). However, if the
    layer is damaged, the iron will rapidly corrode. Tin-plate used in the
    food industry should not contain lead, not only because lead is toxic,
    but also because its presence aids the corrosion of tin by dilute
    organic acids.

        Neutral aqueous salt solutions react slowly with metallic tin in
    the presence of oxygen but solutions containing nitrates, iron(II)
    chloride or sulfate, aluminium chloride or tin(IV) chloride dissolve
    elemental tin.

        Tin can form inorganic compounds in the oxidation state +2 (SnII,
    tin(II) compounds, or stannous compounds), and in the oxidation state
    +4 (SnIV, tin(IV) compounds, or stannic compounds). Because of their
    different physieochemical properties, it is useful to discuss the 2
    groups of compounds separately.

    2.2  Tin(II) Compounds

        Tin(II) compounds are generally more ionic than tin(IV) compounds.
    They are unstable in dilute aqueous solutions, are easily oxidized,
    and normally contain some SnIV; after some time, hydrolysis occurs
    with the formation of the hydrated tin(II) oxide ion [Sn3(OH)4]2+.

        Tin(II) chloride is readily soluble in small amounts of water. It
    is a fairly good reducing agent, and has many uses in industry,
    particularly as a mordant in dye printing. Aqueous solutions of
    tin(II) chloride become turbid on dilution because a basic salt is
    precipitated. The fluoride (SnF2) is slightly soluble in water. It is
    used in fluoride-containing toothpastes. In aqueous solutions,
    SnF3- is the major ion but other ions such as SnF+ and Sn3F5-
    are also present. Tin(II) sulfate is a good source of SnII. Its
    solubility decreases with temperature.

        Tin(II) oxide (SnO) is a stable, blue-black crystalline solid. It
    reacts with both mineral and organic acids, and dissolves in sodium
    hydroxide solutions forming stannites, which probably contain the
    SnO22- ion.

        Other tin(II) compounds that have practical applications are
    tin(II) acetate, tin(II) arsenate, tin(II) fluoroborate, tin(II)
    pyrophosphate, and several tin(II) salts or organic acids, such as
    tin(II) oxalate and tin(II)-2-ethylhexoate (tin(II)"octoate").

    2.3  Tin(IV) Compounds

        Tin in the oxidation state + 4 forms a large number of inorganic
    compounds as well as organometallic compounds, which are discussed in
    section 2.4. Some tin(IV) compounds, such as tin(IV) oxide (SnO2),
    have long been used in industry; Others, e.g., tin(IV) chloride
    (SnCl4), have found technological applications more recently. Also of
    practical importance are the stannates, compounds in which the tin
    atom is part of an anion. The structure of stannates can be
    represented by MnSn(OH)6, where M is a metal ion.

        The physical properties of tin tetrahalides, except those of
    SnF4, correspond to the properties of covalent halides of carbon and
    silicon. Tin(IV) chloride is a colourless liquid that fumes in moist
    air and becomes turbid because of hydrolysis when complex ions such as
    [SnCl3(OH)3]2- are formed. The addition of a limited amount, of
    water to tin(IV) chloride results in the formation of a crystalline
    hydrate, SnCl4.5H2O, the ionic character of which is probably due to
    the presence of a complex ion [Sn(H2O4]4+.

        Tin(IV) oxide occurs naturally as the mineral cassiterite. It has
    a very high melting point (1127°C) and has wide application in
    industry. The fusion of tin(IV) oxide with sodium or potassium
    hydroxide yields stannates.

        Other tin(IV) compounds that have found practical applications
    include tin(IV) sulfide, tin(IV) vanadate, and tin(IV) molybdate.

    2.4  Organometallic Compounds of Tin

        Organometallic tin compounds or organotin compounds have one or
    more carbon-tin covalent bonds that are responsible for the specific
    properties of such molecules. Essentially all organometallic tin
    compounds are of the SnIV type. The only well established compound
    with tin in the oxidation state + 2 is the tin(II)cyclopentadienyl,
    C10H10Sn. There are four series of organotin compounds depending on
    the number of carbon-tin bonds. These series are designated as mono-,
    di-, tri-, and tetraorganotin compounds with the general structure:

                        RnSn X4-n

    where   R   = an alkyl or aryl group
            Sn  = the central tin atom in the oxidation state +4
            X   = a singly charged anion or an anionic organic group.

        In the organotin compounds of practical importance, R is usually a
    butyl, octyl, or phenyl group and X is commonly chloride, fluoride,
    oxide, hydroxide, carboxylate, or thiolate.

        Monoorganotin compounds, RSnX3, are known but so far have found
    only limited application, for example, butyltin sulfide is used as a
    stabilizer in poly(vinyl chloride) (PVC) film.

        Diorganotin compounds, R2SnX2, are chemically reactive and most
    of their applications are based on this property. They are used. as
    stabilizers of PVC, as catalysts in the production of polyurethane
    foams, and in the cold-curing of silicon elastomers.

        Triorganotin compounds, R3SnX, are the most important class of
    organotin chemicals. They are biologically very active and are widely
    used as biocides. The chemical nature of the R group has a strong
    influence on the biological properties of these compounds. The
    X-group, on the other hand, influences their solubility and
    volatility. The two most important groups of triorganotin compounds
    are tributyltin and triphenyltin derivatives.

        Tetraalkyl- and tetraaryltin compounds are primarily used as
    intermediates in the preparation of other organotin compounds.
    Tetraalkyltin compounds are colourless and the compounds of lower
    molecular weight are liquids at room temperature. The tetraaryltin
    compounds are solids. Tetraorganotin compounds possess typical
    covalent bonds and are stable in the presence of air and water.
    Tetrabutyltin, Sn(C4H9)4 is a colourless oily liquid with a
    distinct odour. Tetraphenyltin, Sn(C6H5)4, is a white crystalline
    powder, soluble in organic solvents and insoluble in water.

        Since 1974, a new class of organotin compounds, called estertins,
    has been developed for use as stabilizers in poly(vinyl chloride).
    Their general structure is (R-O-CO-CH2-CH2)2SnX2 or
    R-O-CO-CH2-CH2SnX3 where X may be, for example,
    isooctylmercaptoacetate. They have a comparatively low volatility and
    ex,tractability (Lanigon & Weinberg, 1976).

        Solubility data for organotin compounds are incomplete. In
    general, their solubility in water at ambient temperatures is of the
    order of 5 to 50 mg/litre, but they are very soluble in many common
    organic solvents, such as alcohol, ethers, and halogenated

        Commercial products are usually pure chemicals since, for
    technological reasons, scrupulous care must be taken to avoid metal
    contamination during manufacture. The impurities are primarily solvent
    residues remaining from the product purification and separation

        The carbon-tin bond is susceptible to nucleophilic and
    electrophilic attack, e.g., hydrolysis, solvolysis, acidic and basic
    attack, and halogenation. Water has little effect on symmetrical
    saturated organotin compounds. Dialkyltin compounds react
    spontaneously with moisture and air to form dialkyl hydrated oxides.
    Photochemical reactions of organotin compounds are mentioned in
    connexion with environmental transport and transformations (section
    4). The physicochemical properties of some organotin compounds have
    been listed by Weast (1976).

    2.5  Analytical Methods

    2.5.1  Determination of inorganic tin  Atomic absorption spectroscopy

        Atomic absorption spectroscopy is the method most widely used for
    the detection of low concentrations of tin. In general, the lowest
    limit of detection is obtained with a fuel-rich, air-hydrogen flame,
    e.g., about 1-1.5 mg/kg compared with 2-2.5, and 4-5 mg/kg for
    air-ethylene and nitrous oxide-ethylene flames, respectively
    (Christian & Feldman, 1970). The detection limits at the 3 absorption
    lines, 2246.1, 2354.8, and 2863.3 nm do not differ much. Using some of
    the procedures mentioned later, the detection limit may be reduced to
    about 0.1-0.5 mg/kg.

        Several atomic absorption techniques, modified to suit specific
    purposes, have been reported. A detection limit of 0.5 µg/litre was
    obtained when a hydride generation technique using sodium borohydride
    and a flame-heated silica atomizing tube was used in the air-acetylene
    atomic absorption determination of tin in solution (Thompson &
    Thomerson, 1974). Capacho-Delgado & Manning (1966), using a high
    intensity hollow cathode lamp as the source, reported a detection
    limit of 0.1 mg/litre for water solutions of metallurgical samples,
    while Schallis & Kann (1968) determined tin in lubricating oils with a
    detection limit of about 0.5 mg/litre. Carbon filament atomic
    absorption spectroscopy was employed by Everett et al. (1974) to
    determine tin(II) chloride in aqueous and xylene solutions and tin
    octoate in oil solution.

        Atomic absorption spectroscopy has been used extensively for the
    determination of tin in foods (Allan, 1962; Amos & Willis, 1966;
    Capacho-Delgado & Manning, 1966; Christian & Feldman, 1970; Gatehouse
    & Willis, 1961) and particularly in canned foods, including fruit
    juice, fruits, and vegetables (Catala et al., 1971; Price & Roos,
    1969; Sato et al., 1973; Shiraishi et al., 1972; Woidich &
    Pfannhäuser, 1973). A detection limit of 0.5 mg/kg has been reported
    for the determination of tin in canned fruit juice using a nitrous
    oxide-acetylene flame (Price & Roos, 1969).

        Engberg (1973) compared atomic absorption with a
    spectrophotometric method using 2-(3,4,-dihydroxyphenyl)-3,5,7-
    trihydroxy-4H-1-benzopyran-4-one (quercetin) for the determination
    of tin in food. The methods gave similar results at concentrations of
    tin generally found in canned food, but at very low concentrations
    (e.g., organotin residues), the quercetin method was more suitable
    because of its lower detection limit (section

        Atomic absorption spectroscopy has also been used for the
    determination of tin in biological samples (Pearlman et al., 1970).  Emission spectroscopy

        Emission spectroscopy is a rapid and specific method that has
    frequently been used for the simultaneous determination of several
    elements. Unfortunately, this method is exacting, demanding highly
    qualified personnel, and the cost of the instrument is high. It has
    been used for the determination of tin in atmospheric samples
    (Hasegawa & Sugimae, 1971; Keenan & Byers, 1952; Laamanen et al.,
    1971, Lee et al., 1972; Schroll & Krachsberger, 1970; Sugimae, 1974;
    Tabor & Warren, 1958), tin in water (Ghafouri, 1970; Konovalov &
    Kolesnikova, 1969; Rittenhouse et al, 1969), and for tin in various
    foods including meats (Krylova & Balabuh, 1970), fruits, and
    vegetables (Chisaka et al., 1973). A sensitivity of 0.04 mg/kg fresh
    weight was reported by Tihonova & Zore (1968) for vegetables and
    berries. Several investigators have used emission spectroscopy for the
    determination of tin in biological samples (Avtandilov, 1967;
    Geldmacher-von Mallinckrodt & Pooth, 1969; Kas'yanenko & Kul'skaya,
    1969; Kehoe et al., 1940; Mulay et al., 1971; Saito & Endo, 1970
    Tipton et al., 1963).  Neutron activation analysis

        Although the limit of detection of tin by neutron activation is
    comparatively high, the technique has been used to determine tin in
    air samples (Bogen, 1973; Tuttle et al., 1970). It is also the most
    commonly used method for the determination of tin in geological
    samples (soils, sediments, rocks, off) (Johansen & Steinnes, 1969;
    Obrusnik, 1969; Schramel et al, 1973). A neutron activation electron
    probe was used by Kurosaki & Fusayama (1973) for the estimation of tin
    in teeth. Disadvantages of neutron activation include the need for a
    nuclear reactor and the possibility of interference from formation of
    other isotopes.  X-ray fluorescence

        X-ray fluorescence, a non-destructive method for the determination
    of tin, has been used in the analysis of air for elements ranging from
    titanium to caesium with a detection limit of 0.5 µg/m3 of air
    (Dittrich & Cothern, 1971) and for river water with a detection limit
    of 20-30 µg/litre for metals in the suspended or particulate form, and
    0.25-0.4 mg/litre for ionic metals (Blasius et al., 1972).  Miscellaneous analytical methods

        Among the spectrophotometric methods reported, Kirk & Pocklington
    (1969) recommended the tin-quercetin method for the estimation of the
    tin contents of foods at concentrations ranging from 10 to over
    500 mg/kg. The smallest absolute amount of tin detectable with the
    quercetin method has been reported to be about 1 µg (Engberg, 1973).

    The pyrocatechol violet method has been used for the direct
    determination of tin(II) and tin(IV) compounds at levels of about
    5-50 mg/kg in fats and oils (Lowry & Tinsley, 1972), for the
    determination of tin in metals, and for the determination of tin
    concentrations ranging from 0.01-1.0 mg/kg in biological samples
    (Corbin, 1973). Other spectrophotometric methods have been developed
    for the determination of tin in food samples using phenylfluorone
    (Bennet & Smith, 1959; Bergner & RÜdt, 1968; Luke, 1956; Nakamura &
    Kamiwada, 1973; Smith, 1970) dithiol (Ljaskovskaja & Krasilnikova,
    1961), salicyl-idenamino-2-thiophenol (Horio & Nakaseko, 1972) and
    stilbazo (Kobayashi & Yada, 1968).

        Infrared internal reflection spectroscopy was used in studies on
    tooth enamel treated with tin(II) fluoride (SnF2) (Krutchkoff et al.,

        A fluorometric method using 3'4'7-trihydroxyflavone with a
    detection limit of 0.007 µg was reported for the determination of tin
    in rock, soil, and biological materials (Filer, 1971). Other
    fluorometric procedures have been reported using fiavonal (Coyle &
    White, 1957), oxine-5-sulfonic acid (Pal & Ryan, 1956), and the
    ammonium salt of 6-nitro-2-naphthylamine-8-sulfonic acid (Anderson &
    Lowy, 1956).

        Electroanalytical methods have also been employed for the
    determination of tin in canned foods. Polarographic analysis was used
    for the analysis of canned meat (Janitz, 1971; Jovanovic et al, 1967),
    fruits (Miki & Fukui, 1971), and juices (Hayashi, 1969), and for the
    estimation of tin in cans (Gruenwedel & Patnaik, 1973). Biston et al.
    (1972) obtained good agreement between polarographic and
    spectrophotometric (dithiol and phenylfluorone) methods for estimating
    tin in vegetables at concentrations of 20-400 mg/kg. Anodic stripping
    voltametry has been used for the determination of tin in water
    (Portretnyj et al., 1973).

        Tin estimations were made in biological samples by means of
    spark-source mass spectroscopy (Evans & Morrison, 1968; Hamilton et
    al., 1972/1973) and in canned vegetables and juices by titrimetric
    analysis (Zohm, 1972).

    2.5.2  Determination of organotin compounds

        A number of techniques and procedures for the separation of mono-,
    di-, and trisubstituted organotin compounds with their subsequent
    determination have been described (Brinkman et al., 1977; Freitag &
    Bock, 1974; Getzendaner & Corbin, 1972; Kumpulainen & Koivistoinen
    1977; Meinema et al. 1978; Soderquist & Crosby, 1978; Woggon & Jehle,
    1973, 1975). However, reliable methods have still to be developed for
    the quantitative extraction and determination of many individual tin
    species in mixtures containing inorganic tin (IV) and organotin
    compounds that occur in various media including biological materials,
    industrial effluents, and river sediments.  Diorganotin compounds

        Compounded poly(vinyl chloride) formulations usually contain 1-2%
    of dialkyltin compounds as stabilizers and various techniques have
    been used for the determination of these organotin stabilizers in
    foods. Organotin compounds were separated from inorganic tin
    chromotographically and the inorganic tin was when determined
    spectroscopically as its catechol violet complex. Koch & Figge (1971)
    determined the extent of migration of dioctyltin dichloride and
    di-octyltin bis(2-ethyldexylmercaptoacetate) from PVC bottles into
    beer by the same method. The catechol violet complex was also used, by
    Adamson (1962) and by Ross & White (1961), for the determination of
    dialkyltin compounds in fats and olive oil. Spectroscopic methods
    involving dithizone (Aldridge & Cremer, 1957; Chapman et al., 1959),
    dip henylcarbazone (Skeel & Bricker, 1961) and
    4-(2-pyridylazo)-resorcinol (Sawyer, 1967) have been described.
    Dithizone and diphenylcarbazone were used for the determination of
    diethyl- and dibutyltin compounds respectively, but some difficulties
    may arise using either of these agents because of their inherent
    instability in solution. Concentrations of diethyl- and triethyltin
    compounds ranging up to 30 µg and 20 µg, respectively, could be
    measured using dithizone (Aldridge & Cremer, 1957). The use of atomic
    absorption spectroscopy for the determination of dibutyltin dilaurate
    in animal feeds was described by George et al. (1973).

        Neubert (1964) used thin-layer chromatography for the
    determination of dialkyltin stabilizers obtaining a detection limit of
    1 µg of organotin. Thin-layer chromatographic determination of
    organotin stabilizers using their quercetin chelates yielded a
    detection limit of 1.3/µg (Wieczorek, 1969). Udris (1971) described a
    number of schemes for the analysis of commercial tin stabilizers
    commonly used in poly(vinyl chloride) production. Methods were given
    for the chemical breakdown of a sample and the subsequent separation
    and identification of the degradation products. Schemes for the
    analysis of dialkyltin thio-compounds and dialkyltin carboxylates and
    hemiesters, respectively, were also presented.  Triorganotin compounds

        A number of procedures have been used for the analysis of
    organotin fungicide and miticide residues in food, including
    spectrophotometry (Corbin, 1970; Getzendaner & Corbin, 1972; Trombette
    & Maini, 1970), gas-liquid chromatography (Gauer et al., 1974), and
    thin-layer chromatography (Wieczorek, 1969).

        Corbin (1970) described a dithiol spectrophotometric method for
    the determination of trace amounts of tin residues on fruits
    previously treated with a miticide containing tricyclohexyltin
    hydroxide as the active component. The detection limit with this
    method was at least 0.2 kg tin at a concentration of 3 µg/kg. The
    extraction method was tested for compatibility with 35 elements and
    only arsenic and antimony seemed likely to interfere.

        A sensitive fluorometric technique has recently been developed for
    the determination of triphenyltin residues in potato samples (Vernon.
    1974). Triphenyltin acetate deposits on potato leaves have also been
    determined polarographically by Coussement (1972). The smallest
    quantity of organotin fungicide detected by this method was
    0.32 µg/cm2 leaf.

        Freitag & Bock (1974) reported some methods for the extraction of
    tri-, di-, and phenyltin compounds from mixtures containing these
    compounds as well as inorganic tin(IV). The separated compounds were
    determined by radiometric or photometric methods. Several thin-layer
    chromatographic methods were also described.

        Bönig & Heigener (1972) determined the tin contents of plants
    treated with organotin fungicides by photometric estimation of the
    phenylfluorone complex. In an alternative method, tin was extracted
    with quercetin and the tin-quercetin complex determined
    spectroscopically (Engberg, 1973). Akagi and his collaborators (1972)
    separated some butyl- and phenylorganotin compounds in vinegar and
    tomatoes by thin-layer chromatography.

        A variety of trialkyl and triaryltin biocides have been determined
    by a nonaqueous atomic absorption assay (Freeland & Hoskinson, 1970).
    The limit of detection of this method appeared to be 2-12 mg/litre at
    1% absorption. Studies have been reported by Woggon & Jehle (1973;
    1975) and Woggon et al., (1972) in which anodic stripping was used for
    the determination of a number of alkyl- and aryltin fungicides and
    their degradation and decomposition products. The minimum detectable
    amount was about 3.5 × 10-7 moles per litre for all the compounds

        Polarography (Kockin et al., 1969; Tjurin & Flerov, 1970; Tjurin
    et al., 1969) and oscillopolarography (Geyer & Rotermund, 1969; Shono
    & Matsumura, 1970) have also been used for the determination of a
    variety of organotin compounds.

        Cenci & Cremonini (1969) described the thin-layer chromatographic
    determination of 2 commercial organotin pesticides containing
    triphenyltin acetate and triphenyltin hydroxide, respectively, and
    their degradation products in various soils.

        A gas-liquid chromatographic method was developed by Tonge (1965)
    for the analysis of butyl-, octyl-, and phenyltin halides. A variety
    of gas-liquid chromatographic procedures for the determination of a
    large number of other organotin compounds has been reported (Devjatyh
    et al., 1968; Dressler et al., 1971, 1975; Geissler & Kriegsmann 1964,

        Gauer et al. (1974) reported a gas-liquid chromatographic method
    for separating and determining tricyclohexyltin hydroxide and
    dicyclohexyltin compounds formed by degradation (as the bromide) on
    strawberries, apples, and grapes treated with a miticide. The
    practical minimum limits of detection for tricyclohexyltin hydroxide
    and dicyclohexyltin oxide were 0.1 and 1.0 mg/kg, respectively, in the
    3 crops studied.

        The quantitative determination of mono-, di-, tri- and
    tetra-alkyltin compounds by gas-liquid chromatography after alkylation
    was reported by Neubert & Wirth (1975); the same technique was applied
    for the quantitative detection of tri- and dibutyltin species in
    dilute aqueous solution by Neubert & Andreas (1976). Application of a
    liquid-chromatograph coupled with a flameless atomic absorption
    detector for speciation of trace amounts of triphenyl-and trialkyltin
    compounds in aqueous solution has been reported by Brinkman et al.
    (1977). Recently, Meinema et al. (1978) developed a combined gas
    chromatography/mass spectrometry detection procedure for the
    quantitative determination of trace amounts of tri-, di-, and butyltin
    compounds in aqueous solutions.


    3.1  Natural Occurrence

        Tin is not uniformly distributed over the earth's surface
    (Goldschmidt, 1958; Schroeder et al., 1964) and, hence, it is not
    found consistently in plants and soils (Schroeder et al., 1964). Most
    samples of rock contain tin concentrations of approximately 2-50 mg/kg
    (Johansen & Steinnes, 1969; Mason, 1966; Onishi & Sandell, 1957;
    Vinogradov, 1956), although levels of about 260 and 1200 mg/kg have
    been reported in Czechoslovakian and Norwegian samples of mica
    (Johansen & Steinnes, 1969).

        Of the 9 different tin-bearing minerals found in the earth's
    crust, only cassiterite (tinstone, tin(IV) oxide) is of major
    commercial importance (Heindl, 1970), although small quantities of tin
    are recovered from the complex sulfides, e.g., stannite
    (Cu2.FeS.SnS2); teallite (PbSnS2); cylindrite (PbSn4FeSb2S14)
    and canfieldite (Ag8SnS6). Over 80% of the world's tin ore occurs in
    low-grade deposits averaging about 240g of metallic tin per cubic

    3.2  Industrial Production

        The total world production of tin in 1975 was 236 000 tonnes,
    about 92% of which was produced as primary tin. Six countries together
    produced 72% of the total world production, i.e., China (10%,
    estimated figure), Indonesia (8%), Malaysia (35%), Thailand (7%),
    United Kingdom (6%), and the USSR (6%, estimated figure). The world
    production of secondary tin was about 20 000 tonnes, almost 50% of
    which was produced by France (United Nations, 1977).

        The metallurgy of tin is simple, but its extraction from the ore
    is complicated by the presence of reduced iron that forms "hard head"
    with the tin, and by the high tin content of the slag produced. Thus,
    smelting is carried out in 3 stages: (a) primary smelting in either
    reverberatory or blast furnaces; (b) retreatment of slags, hard head,
    and refinery dross; and (c) refining of the metallic tin to remove the
    last traces of impurities. It should be noted that, because of the
    high cost of tin, dust-collection equipment is necessary for
    successful operation. Low fume production is one of the advantages of
    electric smelting (MacIntosh, 1969).

        During the last 10 years, the amount of tin recovered from
    secondary sources has been practically constant (United Nations,
    1977). The largest sources of scrap are clean tin plate clippings from
    container manufacture; solder in the form of dross or sweepings; dross
    from tinning pots; sludges from tinning lines; bronze rejects and used
    parts; babbitt from discarded bearings; and type metal scrap
    (Macintosh, 1969). Small quantities of tin are recovered at detinning
    plants from used tin containers. (Heindl, 1970).

    3.3  Tin Consumption

        The USA is by far the largest consumer of tin, with Japan, the
    United Kingdom, the Federal Republic of Germany, and France following
    in that order. It has been estimated that, in the future, 30% of the
    total demand for tin will be met by secondary recovery of the metal.
    The total demand for primary tin from 1968 to the year 2000 has been
    estimated to lie between 8.5 and 6.2 million tonnes, with a median
    estimate of 7.5 million tonnes. The world reserve total is
    approximately 6.5 million tonnes and it is considered likely that new
    discoveries and increases in known reserves could result in sufficient
    new tin to meet the median estimate for this period (Heindl, 1970).
    Recently, nearly 40% of the total primary and secondary tin
    consumption in the USA has been used in the production of tin-plate,
    25% in solders, and 20% in bronze and brass, while smaller quantities
    have been used in the production of babbitt and Chemicals
    (approximately 3-4% each).

        It is important to note the large potential for growth in the
    consumption of organotin compounds in the manufacture of plastics.
    This could result in a consumption of approximately 5000 tonnes of tin
    in plastics in the year 2000 (Heindl, 1970).

    3.4  Uses of Tin

    3.4.1  Tin and inorganic tin compounds

        Tin is mainly used by industries producing tin-plate, solder,
    babbit, brasses and bronzes, pewter, printer's alloy (type metal),
    plastics, and tin chemicals. The largest single use of tin is in
    tin-plated steel, either by hot-dipping or by electroplating in a
    continuous process in which thin layers are deposited, and a different
    thickness can be applied on each side of the same sheet steel. In
    addition to its use in food and beverage packaging, tin-plate is used
    extensively in aerosol containers. Tin is also used in the
    transportation, machinery, electrical, plumbing, and heating trades
    and industries as solder, and in bearings and pipes.

        Tin-lead solders contain from 2% tin for container-seaming to 63%
    for electrical connexions. In lead-free solder alloys, tin is alloyed
    with antimony, silver, zinc, or indium to obtain special properties

    such as higher strength or corrosion resistance. The largest
    quantities of solder are used in car radiators, air conditioners, heat
    exchangers, plumbing and sheet metal joining, container seaming,
    generating equipment, electronic equipment, and computers.

        The copper-tin alloys are called bronzes. Phosphor-bronzes (5-10%)
    are the most important of the tin bronzes, the major applications
    being in marine and railway engineering.

        Metals used for casting or lining bearing shells are classed as
    white bearing alloys, but are better known as babbitt. Babbitt alloys
    are used in bearings in marine propulsion, rail and road
    transportation, compressors, motors, generators, and fans.

        Table 1.  Some applications of inorganic tin and its compounds

    Compound                      Application

    tin metal                     manufacture of tin plate, solders, bronzes,
                                  pewter, alloys, amalgams, chemicals
    tin(IV) oxide                 ceramic glaze opacifier, ceramic pigments
    tin(IV) hydride               gas-plate tin on metal, ceramics
    tin(II) acetate               catalyst
    tin(II) chloride              electrotinning of steel strip, tin coating of
                                  sensitized paper antisludge agent for oils,
                                  stabilizer of perfumes in soaps, additive for
                                  drilling muds, electroplating, catalyst in
                                  organic reactions
    tin(II) fluoroborate          tin-plating baths
    tin(II) fluoride              toothpaste and dental preparations
    tin(II) 2-ethylhexoate        catalyst for polyurethane foam production and
                                  incurring silicone oil formulations
    tin(II) oxalate               catalyst for coal hydrogenation, catalyst for
                                  acid-type esterification, transesterification
                                  or polyesterification
    tin(II) oxide                 manufacture of gold-tin and copper-tin ruby glass
    tin(II) sulfate               immersion plating of steel wire, electrotinning
                                  strip, with copper sulfate for lacquer finishes
    tin(II) tartrate              dyeing and printing of textiles
    tin(IV) chloride              mordant in dyeing of silk, preparation of other
                                  inorganic and organic tins, manufacture of
                                  blueprint and other sensitized papers
    sodium stannate               alkaline electroplating tin baths
    sodium pentafluorostannite    dentifrice formulations

        Type metals are lead-based alloys containing 1-25% antimony and
    3-13% tin that are widely used in the printing trade.

        Pewter, which contains 90-95% tin, 1-8% antimony, and 0.5-3%
    copper, is used in the production of a wide variety of household

        Special alloys using tin include dental amalgams, which are mainly
    silver-tin-mercury alloys; alpha-type titanium alloys that are used in
    aircraft, and zirconium alloys used in nuclear reactors.

        Some of the manifold applications of inorganic tin compounds are
    listed in Table 1.

    3.4.2  Organotin compounds

        Worldwide production of organotin compounds, the fourth largest
    synthesis of organometallic compounds, was approximately 27 000 tonnes
    in 1976 (Midwest Research Institute, 1977). This use of tin, however,
    represents only about 0.8% of the total metallic tin consumed

        The annual growth rate is expected to be 10% per year for the next
    10 years, so that, by 1986, worldwide production of organotin
    compounds would be approximately 63 000 tonnes (Midwest Research
    Institute, 1977). This projected market outlet depends on 2 features.
    Since 70% of the total production of organotin compounds is used to
    heat-stabilize poly(vinyl chloride) plastic products, growth in PVC
    production must continue to increase at a projected rate of 10-12% per
    year for the next 10 years. Second, organotin compounds are expensive
    in comparison with other heat stabilizers. Therefore, they must remain
    competitive, at least as far as performance is concerned.

        Of the 4 categories of organotin compounds, dialkyltin derivatives
    are the most important commercially. They are used as heat and light
    stabilizers for PVC plastics to prevent degradation of the polymer
    during the melting and forming of the resin into its final products.
    In addition, dialkyltin derivatives have the unique property of
    protecting the plastic product from degradation during use. Other
    important commercial uses of dialkyltin derivatives are as catalysts
    in the production of polyurethane foam products and as vulcanizing
    agents for silicone rubbers. The trialkyl-tin derivatives, which
    account for approximately 10% of the total production of organotin
    compounds, are used in agriculture as non-systemic fungicides and
    acaricides. The tetraalkyltin derivatives are used as intermediates in
    the manufacture of other organotin compounds. The monalkyltin
    derivatives have a limited commercial use as heat stabilizers for PVC
    plastic films.

        About 0.5-2.0% by weight of dialkyltin derivatives are required in
    the stabilization of rigid and flexible PVC plastics, including
    food-grade PVC for wrapping and containers. In particular, dibutyl-
    and dioctyltin compounds are important heat and light stabilizers for
    PVC. In the USA, the Food and Drug Administration (1971) has set
    specific levels for 2 dioctyltin derivatives that can be present in
    food, packaged in food-grade PVC wrapping and containers. These 2
    chemicals are dioctyltin maleate and dioctyltin
     S,S'-bis(isooctylmercaptoacetate) (Piver, 1973).

        Dialkyltin compounds such as dibutyltin diacetate or-dilaurate are
    used as catalysts in the production of polyurethane foams. Recently,
    dimethyltin compounds have also been found suitable for the
    stabilization of PVC plastics.

        Organotin compounds have many other applications:  (a) as
    antioxidants and anticracking agents to retard rubber deterioration
    and to stabilize chlorinated rubbers in chlorinated paints;  (b) in
    transformers, capacitators, and cables as hydrochloric acid scavengers
    to prevent corrosion when chlorinated diphenyls are present (e.g.,
    tetraphenyltin);  (c) as anti-oxidants for textile oils;  (d) as
    activators, stabilizers, and catalysts for polymers such as polyesters
    and silicone elastomers and as catalysts for the polymerization of
    olefins;  (e) in the treatment of glass to increase crack resistance;
     (f) in the treatment of fibreglass (with alkyl- and aryltin
    compounds) for adhesion go resins; and  (g) as curing catalysts in
    the application of silicone to textiles and paper.

        Organotin compounds have biocidal properties and are used;  (a)
    as agricultural fungicides (triphenyltin acetate, triphenyltin
    hydroxide);  (b) as general biocides (bis(tributyltin) oxide = TBTO)
    in paints; in the preservation of manila and sisal ropes, leather,
    textiles; to make fabrics mildew-resistant; for the protection of jute
    and jute bags; in wood preservatives, slimicides, and in the
    production of paper;  (c) as bactericides and biostasis such as
    disinfectants for use in hospitals and stables (tributyltin benzoate);
     (d) as helminthicides in poultry (dibutyltin dilaurate,
    tetraisobutyltin);  (e) as nematocides ( p-bromophenoxy
    triethyltin);  (f) as herbicides (vinyl-tin compounds, e.g.,
    trivinyltin chloride);  (g) as rodent repellents (tributyltin
    chloride, triphenyltin chloride and acetate);  (h) as molluscicides
    (triphenyl- and tributyltin compounds;  (i) as ovicides (trialkyl-
    and triaryltin chlorides in combination with DDT or pyrethrins);  (j)
    as antifoulants in ship paints and underwater coatings (triphenyl- and
    tributyltin compounds); and (k) as miticides (tricyclohexyltin
    hydroxide). Furthermore, triphenyltin compounds have been suggested as
    insect chemosterilants. More detailed information concerning new uses
    of organotin compounds can be found in the proceedings of a recent
    symposium (Zuckerman, 1976). A schematic presentation of the various
    uses of organotin compounds is given in Fig. 1.

    FIGURE 1

    3.5  Tin-containing Wastes

        Gases and fumes containing tin as well as sulfur dioxide and other
    contaminants, and both soluble and insoluble tin-containing waste
    materials such as water soluble salts, muds, and slags are produced
    during various smelting, refining, and detinning operations. Solid
    domestic and other wastes which may be dumped, incinerated, used for
    land fills or composting, contain much tin, and used cans, aerosol
    containers, and other miscellaneous tin-containing produces in solid
    wastes account for 10-15% of tin-plated steel. The percentage of
    plastics in solid wastes is increasing yearly and includes PVC
    containing organotin compounds.


    4.1  Transport and Bioconcentration

        Tin concentrations in air are usually low except in the
    neighbourhood of some industrial sources (section 5.1). Similarly, it
    has not been consistently detected in all soils, plants, and waters
    (sections 5.2 and 5.3). This seems go support a geochemical
    classification placing tin in a group of elements with a low rate of
    migration in soils and waters (Perel'man, 1972; Bens et al., 1976).
    However, it is widely used and Wood et al. (1975) have included it
    among elements that are relatively accessible in the environment. A
    biological cycle for tin has been recently proposed by Ridley et al.
    (1977) (section 4.2).

        There is a lack of information concerning the environmental
    transport of organometallic tin compounds. It appears, however, that
    the vapour pressures of some organotin compounds are high and that
    environmental mobility is possible although there are no data to
    confirm this deduction. Some organotin compounds seem to be well
    adsorbed in the soil and they have a low solubility in water (Heron &
    Sproul, 1958). A laboratory soil-leaching study (Barnes et al, 1973)
    indicated that triphenyltin is strongly attached to the soil. In
    natural waters, organotin compounds would be primarily adsorbed on the
    suspended particles and sediments (Schramel et al., 1973). More recent
    studies on the determination of tin and organotin compounds in natural
    waters have been reported by Braman & Tompkins (1979) and Hodge et al.

        Little reliable information exists concerning the bioconcentration
    of tin and its derivatives. Schroeder et al. (1964) reported that the
    presence of tin in phosphate fertilizers originating from marine
    phosphate suggested that marine animals in the Pleistocene era
    absorbed tin from the sea. Although tin is present in seawater in
    concentrations of up to about 3 µg/litre (Mason, 1966; Vinogradov,
    1953), there are few reports of its occurrence in marine algae,
    plankton, bacteria, flowering plants, protozoa, sponges,
    coelenterates, echinoderms, crustacea, and most fishes. However, Bowen
    (1966) noted tin levels of 0.2-20 mg/kg in certain marine organisms
    and accumulation of tin by the sponge  Terpios zeteki was also
    reported by Bowen & Sutton (1951).

    4.2  Environmental Chemistry of Tin

        Because of the considerably higher toxicity of some
    organo-metallic tin compounds compared with inorganic forms of tin
    (section 7), the possibility of biomethylation of tin is obviously of
    considerable interest (Wood, 1974). A possible mechanism of such
    bio-methylation has been proposed (Ridley et al., 1977; Wood et al.,
    1978). Recent laboratory studies have indicated that the methylation

    of tin by methylcobalamina (CH3B12) requires a one electron
    oxidation of SnII to a SnIII radical, which can take place in the
    presence of FeIII (SnIV would, of course, require a single electron
    reduction). The stannyl radical (SnIII) can then react with CH3-B12
    (CoIII) to produce (under conditions of high chloride ion
    concentration) CH3-SnCl2 and reduced cobalamin, containing CoII
    (Wood et al., 1978). A demonstration that methylation of tin takes
    place in a strain of  Pseudomonas bacteria found in the Chesapeake
    Bay, USA, is the laboratory work with these bacteria carried out by
    Huey et al. (1974). However, the methylated tin species was not
    identified. Incubation of mercury(II) in the presence of tin(IV)
    resulted in enhanced formation of methylmercury, and the authors
    considered that methylmercury might have been transferred from the
    biologically methylated tin to the mercury(II) ion. Subsequently,
    Brinckman & Iverson (1975) proposed a "mercury-tin cross-over" system,
    which may have some real basis as indicated by Schramel et al. (1973),
    who found that mercury and tin accumulated together in some water
    plants in Bavarian rivers.

    4.3 Degradation of Organometallic Tin Compounds

        Organotin compounds may be degraded both chemically and
    biochemically. Hydrolytic decomposition occurs at rather extreme pH
    values (< 1 or > 13) unless there are other catalytic
    influences. Nevertheless, some authors consider that it could occur
    fairly rapidly in an aquatic environment, although the environmental
    pH is usually between 4 and 10 (Sheldon, 1975, Vizgirda 1972). This
    could be the case, if photochemical decomposition were also involved.
    Indeed, photochemical decomposition of triphenyltin acetate by
    ultraviolet irradiation has been demonstrated under laboratory
    conditions by Chapman & Price (1972) and Barnes et al. (1973). Most
    likely, under environmental conditions, the chemical and
    photo-chemical degradation of organotin compounds is combined with
    biochemical degradation, or degradation may be entirely biological.
    Some available information, mainly on triphenyltin, tricyclohexyltin,
    and tributyl tin compounds, is included in the following summary.


    a  A form of vitamin B12 (cobalamin) in which the methyl carbon
       is directly bonded to the cobalt which is coordinated to the corrin
       ring system in the vitamin B12 structure.

        Bruggemann & Klimmer (1964) and BrÜggemann et al. (1964a,b)
    reported that triphenyltin acetate on sugar beet leaves was rapidly
    broken down during the silage process. Within 5 weeks, triphenyltin
    acetate, originally present at a concentration of 2470 mg/kg of fresh
    leaves, had degraded completely. It was not established whether
    degradation was due to microbial action or resulted from the low pH
    (3.5-4.0) of the silage process. The authors also found that
    triphenyltin acetate was not broken down rapidly by microorganisms
    during its passage through the rumen and intestines of cattle. Similar
    results in feeding experiments with sheep were reported by Herok &
    Götte (1963).

        Using thin-layer chromatography, Cenci & Cremonini (1969) found
    that triphenyltin acetate and hydroxide mixed into soil (80 mg/kg of
    soil) disappeared in 3-10 days, and 3 days, respectively, but the
    degradation products were not identified and the participation of
    microorganisms in the process was not established.

        Akagi & Sakagami (1971) reported that, under their experimental
    conditions, ultraviolet irradiation of a solution of triphenyltin
    chloride yielded a mixture of triphenyl-, diphenyl-, and phenyltin as
    well as inorganic tin compounds, within 6 h. Similarly, irradiation of
    trialkyltin compounds resulted in a mixture of di- and monoalkyltin
    compounds and inorganic tin also within a period of 6 h. Total
    degradation of triphenyltin to inorganic tin required irradiation for
    more than 400 h. Chapman & Price (1972) investigated the degradation
    of an agricultural fungicide containing triphenyltin acetate, which
    had been found to disappear within a few days of spraying on crops,
    probably as a result of weathering and sunlight. They exposed the
    compound in thin layers on glass to ultraviolet light and found that
    the rate of degradation was higher at lower wavelengths and was
    independent of layer thickness (5-10 mµ). This was also true for the
    intermediate diphenyl- and phenyltin compounds and for the parent
    compound. When triphenyltin acetate has irradiated for 60 h
    (wavelength above 235 nm: intensity 120 W/m2: thickness 10 µm), about
    10% of the triphenyltin compound remained unchanged, about 30%
    occurred as diphenyltin, 15% as phenyltin compounds, and approximately
    45% was degraded to inorganic tin in the form of hydroxides or
    hydrated oxides. Similar results were obtained by Barnes et al.
    (1973), who also studied breakdown at concentrations of 5-10 mg/kg
    using triphenyltin acetate in which the phenyl groups had been
    labelled with 14C. Degradation was monitored by measuring the
    evolution of radioactive carbon dioxide; a half-time of about 140 days
    was determined. Since no 14CO2 was evolved when the loam was
    heat-sterilized, it was concluded that the degradation process was due
    to microbial action.

        The decomposition of triphenyltin chloride on sugar beet leaves,
    as reported by Freitag & Bock (1974b) gave the expected series of
    degradation products, the final degradation product being tin oxide.
    After 42 days, about 19% of triphenyltin chloride had undergone

        In studies by Starnes (unpublished data)a and by Smith et al.
    (unpublished data)b quoted by Getzendaner & Corbin (1972),
    tricyclohexyltin hydroxide (the active ingredient of a commercial
    miticide) exposed on thin-layer chromatographic plates to a sun lamp
    yielded dicyclohexyltin oxide and cyclohexylstannoic acid with further
    degradation to inorganic tin. It has also been shown that tin residues
    on apples and pears treated with tricyclohexyltin hydroxide
    (commercial miticide) remained almost constant at a level of
    0.1-0.2 mg/kg (Getzendaner & Corbin, 1972). This concentration was
    relatively independent of the total number of applications and, within
    a month of the final application, independent of the time between the
    last application and harvest.

        Mazaev et al. (1976) reported the degradation of bi(tributyltin)
    oxide (TBTO), dibutyltin bis isooctylmercaptoacetate (BuIOMA),
    tributyltin methacrylate, diethyltin dioctanoate and dioctyltin bis
    (isobutylmaleate), and provided estimates for the half-times of these
    compounds for different aqueous media. In distilled water at 20°C,
    values ranged from 1.14 days (BuIOMA) to 18.2 days (TBTO). From this
    report, it appears that dialkyltin compounds are more rapidly degraded
    than trialkyltin compounds.

        Triorganotin compounds such as TBTO and tributyltin fluoride used
    as antifouling agents in paints for ship bottoms and in underwater
    coatings appear to break down in a multislop process to give tin(IV)
    oxide (Barnes et al., 1973; Sheldon, 1975).

        The mechanism of the biological dealkylation of organotin
    compounds is apparently more complicated than was considered by Blair
    (1975), who thought that the basic process was the oxidative cleavage
    of the carbon-tin bond (section 6.2.4).


    a  Starnes (1966) Unpublished report, The Dow Chemical Co.
       (ALS 66-648).
    b  Smith et al. (1970) Unpublished report, The Dow Chemical Co.
       (OL 30445 Feb. 1. 1970).

        Available information shows that the persistence of organotin
    compounds may vary considerably depending on the conditions and the
    type of compound. Under extreme laboratory conditions, the solvolysis
    may have a half-time ranging from about 1 min to about 100 days
    (Bassindale et al., 1971; Roberts & El Kaissi, 1968). Under
    environmental conditions, it is likely that the half-times for
    triphenyltin compounds are somewhere between a few days and 140 days
    (Freitag & Bock, 1974b). Diorganotin compounds probably have somewhat
    shorter half-times (Mazaev et al., 1976).


    5.1  Ambient Air

        Tin is rarely detected in air, and, when detected, it is generally
    in low concentrations (0.01 µg/m3), except in the proximity of some
    industrial sources. Tin emission concentrations of 10-640 µg/m3 were
    reported from electric furnaces at certain plants in Japan, in 1972.
    At a distance of 700 metres, the atmospheric tin concentrations still
    ranged from 3.8 to 4.4 µg/m3 (Environment Agency, Japan, 1971,
    unpublished data).a

        Concentrations from 0.003 to 0.3 µg/m3 were found in 60.6% of 754
    samples tested from 22 cities in the USA. More than 50% of samples
    from 3 urban and 3 rural sites were below the detectable level. The
    highest concentration of tin (0.8 µg/m3) was found in a sample from a
    Boston, USA, industrial site, which also contained the highest
    concentration of lead together with relatively high concentrations of
    zinc and cadmium (Tabor & Warren, 1958).

        At stations of the US National Air Surveillance Networks during
    1968 and 1969, concentrations ranged from below the minimum detectable
    level to 0.23 µg/m3 in 1968 and 0.12 µg/m3 in 1969. Both these
    concentrations were recorded in East Chicago (US Environmental
    Protection Agency, 1973).

        Concentrations ranging from 0.04 to 0.09 µg/m3, determined by
    emission spectroscopy, were reported for Cincinnati and St Louis in
    1970 by the US National Air Surveillance Cascade Impactor Network (Lee
    et al., 1972). The size distributions of tin-containing particles
    found in this study are given in Table 2.

        Peak concentrations of tin were found in particles ranging from 1
    to 3 µm in diameter. Bogen (1973) found that ambient air levels of tin
    in the Heidelberg area of the Federal Republic of Germany between 30
    April 1971 and 21 May 1971 ranged from 0.096 to 0.167 µg/m3.

        The combustion of coal, oil, and lignite results in the discharge
    of trace amounts of many elements into the atmosphere. Bertine &
    Goldberg (1971) pointed out that the principal sites of fossil fuel
    consumption are in the mid-latitudes of the Northern Hemisphere and
    suggested a need for linking fossil fuel consumption with the
    sedimentary cycles of trace metals from the atmosphere. They reported
    that tin was present in coal and oil at average concentrations of 2
    and 0.01 mg/kg, respectively.


    a  Japanese Background Paper No. 2, prepared for the WHO meeting
       on the Effects on Health of Specific Air Pollutants from Industrial
       Emissions, Geneva, November 4-9, 1974.

        Table 2.  Size distribution of tin-containing particles in urban aira

                                              Cincinnatti    St Louis

                                                             (A)           (B)
                                              4th Quarter    1st Quarter   4th Quarter
                                              1970           1970          1970

    Average concentration (µg/m3)             0.09           0.04          0.05
    Average mass median diameter (µm)         0.93           1.40          1.53
    % particles less than or equal to 1 µm    55             34            28
    % particles less than or equal to 2 µm    86             68            65

    a  Adapted from Lee et al. (1972).

    5.2  Soils and Plants

        Tin has not been consistently found in all soils and plants;
    however, allowance must be made for the possibility that the
    concentrations present may have been below the limits of detection of
    the methods employed. Bowen (1966) reported levels of tin in soil
    ranging from about 2 to 200 mg/kg, the metal being strongly adsorbed
    by the humus.

        Schroeder et al., (1964) observed that concentrations of tin in
    soils were localized and that it had not been detected in many areas.
    In a limited study of tin in vegetation and foods, he found that
    absorption by plants was erratic, even when the soil tin content was
    high. A tin concentration of 157 mg/kg dry weight was recorded in
    forest soil from southern Vermont, USA, but tin concentrations in
    sections of an 100-year-old elm indicated that exposure of this tree
    was not of recent origin.

        Tin concentrations of 30-300 mg/kg have been reported in peat from
    Finland by Gordon (1952), and high concentrations of tin were found by
    Goldschmidt (1958) in forest litter and humus and also in coal. Tin
    was present in all but 7 of 43 samples of foliage from 13 species of
    ornamental plants and trees in New Jersey, USA (Hanna & Grant, 1962).

        Lounamaa (1956), using a spectrographic method that had a limit of
    detection of 10 mg tin/kg of ash, detected tin only sporadically in
    higher plants in Finland. Lichens concentrated tin to exceptionally
    high levels, considering the small amounts present in rocks. For
    example, those growing on silicic rocks had tin concentrations of 72 ±
    4.7 mg/kg ash (range: less than 10-100). Tin was undetected in 6 out

    of 16 mosses while the remainder had concentrations of 10-60 mg/kg of
    ash, concentrations being twice as high in those growing on silicic
    rock as in those growing on calcareous rock. Pasture herbage growing
    in Scotland was reported by Mitchell (1948) to contain tin
    concentrations of only 0.3-0.4 mg/kg dry weight. He also quoted tin
    concentrations in soils from north-east Scotland of up to 200 mg/kg.
    Warren (1964, unpublished data) reported a tin concentration of
    75 mg/kg in soils in unmineralized areas of Devon and Cornwall in
    England, while soils from mineralized areas contained up to more than
    1000 mg/kg.

    5.3  Water and Marine Organisms

        Tin has only been found occasionally in fresh water. It was found
    by Durum & Haffty (1961) in 3 out of 59 samples from 15 major North
    American rivers. No tin was detected by the National Water Quality
    Network (1960) in 119 analyses at 71 locations on 28 major rivers in
    the USA. Kleinkopf (1955, 1960) reported that Maine waters contained a
    mean tin concentration of 0.038 µg/litre with a maximum concentration
    of 2.50 µg/litre.

        Tin has also only been found occasionally in municipal water
    supplies (Durfor & Becker, 1964). Analyses by the US Public Health
    Service showed concentrations of 0.0008-0.03 mg/litre in 32 out of 175
    finished municipal waters (Taylor, 1964, personal communication).a
    Although it is known that acidic or alkaline corrosive waters can
    attack bronze fittings in pumping stations, presumably releasing some
    tin, the relationship between corrosion and the aqueous release of tin
    has not been established (Schroeder et al., 1964).

        It has been reported by Vinogradov (1953) and Mason (1966) that
    tin is present in sea water in amounts of about 0.003 mg/litre; thus,
    its presence in marine organisms is to be expected. Tin levels of
    0.2-20 mg/kg have been reported in marine animals by Bowen (1966) and
    accumulation by the sponge  Terpios zeteki has been noted (Bowen &
    Sutton, 1951). Schroeder et al., (1964) reported that tin had not been
    detected in plankton, bacteria, flowering plants, protozoa,
    coelenterates, echinoderms, crustacea, or most fish. However,
    Vinogradov (1953) reported the presence of small amounts of tin in a
    marine worm, an oyster, and a dogfish.


    a  Taylor, F. B. (1964) Personal communication, cited by Shroeder,
       H. A., Balassa, J. J., & Tipton, I. H. (1964) Abnormal trace metals
       in man; Tin.  J. chron. Dis., 17: 494.

        Organotin compounds may enter water directly from antifouling
    coatings on ship bottoms or they may be used as molluscicides and
    added to vast areas of water for the control of snails, in which case
    the effective concentration has to be about 1 mg/litre (WHO, 1973).
    They may also be present indirectly as a result of industrial,
    agricultural, and other uses of organotin compounds.

        Tin(IV) oxide, suggested to be the final breakdown product of some
    antifouling organotin agents (Shelemon, 1975), will eventually be
    deposited in bottom sediments because of its insolubility. However, no
    information is currently available concerning the rate and mechanism
    of this degradation.

    5.4  Food

        Tin has been reported to occur in trace amounts in most natural
    foods (de Groot et al., 1973). The tin content was determined by
    atomic absorption spectroscopy in 11 known wheats or wheat blends, in
    20 flours prepared commercially from these wheats, and in 25 products
    specially prepared from the flours, as well as in 10 consumer products
    from 10 different cities in the USA. Only one half of the tin in bread
    could have been contributed by the flour. Tin concentrations in common
    hard, common soft, and durum wheat were 5.6 ± 0.6, 7.9 ± 0.9, and 6.8
    ± 0.5 mg/kg respectively, while samples of flour and semolina from the
    above sources of wheat contained tin at 4.1 ± 0.4, 3.7 ± 0.7, and 6.0
    ± 1.2 mg/kg, respectively. The tin concentrations in most products
    exhibited significant regional differences (Zook et al., 1970).

        Schroeder et al. (1964) calculated that a diet composed largely of
    fresh meats, cereals, and vegetables would usually contain a tin
    concentration of less than 1 mg/kg and would supply about 1 mg of tin
    per day. In an area of southern Vermont, USA, where the soil contained
    considerable amounts of tin (about 160 and 33 mg/kg, respectively, in
    2 gardens), 10 out of 18 samples of fresh vegetables contained tin
    levels of less than 1 mg/kg.

        Hadzimicev (1971) measured the content of tin in foods from the
    vegetable belt around Sofia, Bulgaria. Tin concentrations in wheat,
    corn, beans, potatoes, tomatoes, cabbage, carrots, spinach, lettuce,
    onions, apples, and peaches ranged from 0.02 to 1.02 mg/kg.

        Larger amounts of tin may be present in processed foods and
    drinks, because of corrosion and leaching of the metal from plain
    unlacquered cans or from tin foil used for packaging. The corrosion of
    tin-plate in food containers depends upon several factors including
    the type of food product, the time and temperature of storage, the
    acidity of the food and the quantity of air present in the headspace
    of the can (Calloway & McMullen, 1966; Monier-Williams, 1949).
    Oxidizing agents (eg., nitrates, ferric and cupric salts),and
    anthocyanin pigments, methylamine, sulfur dioxide, and other sulfur

    compounds accelerate corrosion, while fin salts in solution, sugars,
    and colloids such as gelatine retard it (Monier & Williams, 1949). The
    introduction of lacquered cans and the crimping of the tops minimizing
    direct contact of food with solder has resulted in a general reduction
    in corrosion and leaching.

        A number of foods are unsuitable for packing in plain cans as they
    promote corrosion. Thus, tin has been found in canned asparagus in
    high concentrations varying from 120 to 550 mg/kg (Adam & Horner,
    1937; Eyrich, 1972; Woidich & Pfannhäuser 1973). Tomato fruit can
    accumulate nitrate when grown under combined conditions of high
    temperature, high nitrogen fertilization levels, and low light
    intensity. Such tomatoes caused excessive detinning of internal plain
    can surfaces (Hoff & Wilcox, 1970). Iwamoto et al. (1968) also showed
    a distinct detinning effect on unlacquered cans of both naturally
    occurring and added nitrate in tomato juices; the authors suggested
    that the concentrations of nitrate-nitrogen in juices should not
    exceed 3 mg/kg. Tin contents exceeding 100 mg/kg have been found in
    other foods in unlacquered cans including fish, orange, grape, and
    mango juices, apricots, bananas, pineapple, and sugar syrup (Catala et
    al., 1971; Eyrich, 1972; Mahadevaiak et al., 1969; Stanculescu et al.,
    1972; Woidich & Pfannhäuser, 1973). In foodstuffs stored in
    all-lacquered cans, the tin content was mainly below 25 mg/kg (Catala,
    et al., 1971; Eyrich, 1972; Woidich & Pfannhäuser, 1973).

        Several investigations have shown that high storage temperatures
    increase the transfer of tin into canned foods (Catala et al., 1971;
    Kimura et al, 1970; Zui, 1970). An increase of 2 mg/kg per month of
    storage was reported by Zui (1970) for an increase of 1°C in

        Nishijama et al. (1971) showed an increase in the tin content from
    50-77 to 260-300 mg/kg in pineapples stored at 8°C in unlacquered cans
    for 72 h after opening the can. The transfer of tin into the fruits
    was also increased by 0.5% aqueous citric or tartaric acid. The
    content of tin in foods in lacquered cans was low and remained low
    after opening. Klein et al. (1970) noted a similar effect of storage
    of fruit juices in opened plain cans. Values exceeding 200 µg/kg were
    found within 48 h of opening the cans.

        A mean concentration of 0.0078 mg/litre was found in bottled
    (glass) cow's milk compared with 16 mg/litre in evaporated milk in
    unlacquered cans (diluted to the equivalent volume of cow's milk). In
    some cases, concentrations of up to 110 mg/litre were found; however,
    only milk from unlacquered cans contained significant amounts of tin,
    while milk in lacquered cans contained less than 5 mg/litre (Hamilton
    et al., 1972). The highest concentration of tin found by Wodsak (1967)
    in canned condensed milk samples, less than 4 weeks old, was
    40 mg/litre. The concentrations did not increase much during a further
    5 months of storage but after 2 years of storage, concentrations up to
    160 mg/litre were detected.

        In addition to contamination by the containers, the presence of
    tin in food may be due to the use of tin as an additive. Tin(II) ions
    are used as additives in asparagus and peas packed in glass containers
    or in lacquered cans, and also in soda water. The stannous ion is
    added to prevent the migration of other heavy metals into the canned
    foods and to inhibit the oxidation of ascorbic acid. Scott & Stewart
    (1944) reported that  Clostridium botulinum would not grow in
    beetroot and carrots in unlacquered cans whereas normal growth
    occurred in lacquered cans. For canned beetroot, the concentration of
    added tin required for the prevention of growth was 150 mg/kg and for
    carrots, 30-60 mg/kg.

        High concentrations of tin have been reported in cheese packed in
    tin foil (Dyer & Taylor, 1931, Elten, 1929).

    5.5  Organotin Residues

        Tin occurring in food and beverages may also result from the use
    of organotin compounds as miticides in agriculture and as stabilizers
    in PVC materials. In several experiments in various parts of the USA,
    apples and pears from trees that had been sprayed 4 times with a
    miticide, tricyclohexyltin hydroxide, had maximum organotin residues
    of less than 2 mg/kg of whole fruit on the day of the final
    application. These concentrations were reduced to about half within
    3-5 weeks and, after 4 weeks, the residues consisted mainly of
    tricyclohexyltin hydroxide with only small amounts of decomposition
    products; inorganic tin concentrations were almost invariably below
    0.2 mg/kg. The mean concentration of inorganic tin on apples and pears
    after 1-5 applications of the miticide was 0.1 mg/kg (equivalent to
    0.3 mg/kg, when calculated as tricyclohexyltin hydroxide); an
    inorganic tin residue of 0.3 mg/kg (equivalent to 1.0 mg/kg of
    tricyclohexyltin hydroxide) was found on pears by Getzendaner & Corbin
    1972). In an appraisal of data on pesticide residues in food, the
    Joint Meeting of the FAO Working Party of Experts and the WHO Expert
    Group on Pesticide Residues (FAO/WHO, 1971) concluded that residues of
    tricyclohexyltin hydroxide on apples and pears decline by 50% in about
    3 weeks due to photodegradation (section 4.3). A 20-50% reduction can
    be achieved by washing and most of the residues can be removed by
    peeling the fruit, after which only 0.1 mg/kg may be expected in the
    fruit flesh. Data on tricyclohexyltin hydroxide on apples and pears
    after 1-4 treatments showed mean values ranging from 0.4 to 2.0 mg/kg.
    Similar concentrations on apples and pears have been reported from the
    Netherlands (WHO, 1975). It has also been reported that the
    concentrations of tricyclohexyltin hydroxide in treated products grown
    under glasshouse conditions including cucumbers, tomatoes, and bell
    peppers are unlikely to exceed 0.5 mg/kg (WHO, 1975).

        The FAO/WHO joint meeting report (FAO/WHO, 1971) included data on
    triphenyltin hydroxide, acetate, and chloride residues in various
    foodstuffs such as potatoes, carrots, and sugar beets. Maximum
    concentrations in potatoes and carrots only rarely exceeded 0.1 mg/kg.
    Residues in food, fruit, and vegetables derived from direct contact
    with the compound could be considerably reduced by washing.

        When cows were fed with sugar beet leaves containing triphenyltin
    acetate at 1 mg/kg a concentration of 0.004 mg/kg was found in the

        In some countries, regulations permit the presence of 2 PVC
    stabilizers in food, viz. dioctyltin  S,S'-bis(isooctyl-
    mercaptoacetate) and dioctyltin maleate polymer, up to a concentration
    of total octyltin of 1 mg/kg (Department of National Health and
    Welfare, Canada 1975; Food and Drug Administration, USA, 1971). The
    migration of tin from PVC bottles into liquid foods contained in them
    was studied by Carr (1969). The increase in the tin content of various
    products during the storage period ranged from 0 to 0.07 mg/kg
    (Table 3).

        Table 3.  Tin concentrations in foodstuffs after storage for 2 months in PVC bottles at 30 °C

                             Tin content    Tin content    Tin extracted  stabilizer
                             at beginning   after ageing   from bottle    extracted from
    Food product             of experiment  in PVC bottle  (mg/kg)        PVC bottle
                             (mg/kg)        (mg/kg)                       (mg/kg)

    mineral water            0.076          0.088          0.01           0.063
    tomato juice             0.03           0.03           0              0
    peanut oil               0.05           0.06           0.01           0.063
    vegetable oil            0.08           0.09           0.01           0.063
    apple juice              0              0.02           0.02           0.126
    cherry soda              0              0.07           0.07           0.443
    beer                     0              0.01           0.01           0.063
    milka                    0.02           0.04           0.02           0.126
    red wine                 0              0              0              0
    blended whisky           0.01           0.02           0.01           0.063

    a  Milk sample in PVC bottle aged for 2 weeks at 65 °C (Carr, 1969).

    5.6  Working Environment

        While most of the operations associated with the extraction and
    treatment of tin ore are wet processes, tin dust or fumes may escape
    during the bagging of concentrate in the ore rooms and during smelting
    operations (mixing plant and furnace tapping), as well as during the
    periodic cleaning of the bag filters used to remove particulate matter
    from smelter furnace flue gas before release into the atmosphere (ILO,
    1972). Exposure to dust and fumes of tin oxide may cause stannosis.

        Additional exposure can occur at the final stage of upgrading the
    cassiterite concentrate and during the roasting of sulfide ore.
    Tin(II) chloride constitutes a hazard, when the rough molten tin is
    separated from the rest of the charge during refining (ILO, 1972).

        Other sources of industrial exposure include tinning of metals
    (Duckering, 1968); the preparation and use of tin alloys and solders;
    the use of tin(II) chloride as a reducing agent in calico printing;
    the use of hydrated stannic acid, sodium metastannate, hydrated
    tin(IV) chloride, and ammonium tin(IV) chloride as mordants in dyeing
    and in the weighting of silk; the use of tin(II) fluoroborate
    [Sn(BF4)2] in plating baths; and the production and use of organotin

    5.7  Estimate of Effective Exposure of Man through Environmental Media

        Food is the main source of exposure to tin for man. Estimates of
    human exposure from all environmental media are difficult to make
    because of the lack of reliable data concerning environmental
    concentrations (mainly in air and water), and because of variations in
    the amounts of different foods and beverages consumed, especially
    canned foods. Earlier estimates of the daily intake of tin by man have
    been difficult to reconcile with more recent estimates. Kehoe et al.
    (1940) reported that the mean daily intake of Gin by a normal adult in
    the USA was 17 mg, while Tipton et al. (1966, 1969), in long-term
    balance studies, reported average daily intakes of between 1.5 and
    8.8 mg in 4 subjects. Schroeder et al. (1964) found 3.6 mg in a day's
    institutional diet and considered that the major portion of the tin
    probably came from canned fruit juices and fruits in the diet.
    However, Schroeder and his colleagues pointed out that human intake
    may vary considerably. They calculated that a 10 MJ (2400 kcal) diet
    composed largely of fresh meats, grain products, and vegetables, which
    usually contain less than 1 mg/kg of tin, would supply 1 mg/day.
    However, a diet including a substantial proportion of canned
    vegetables and fish could supply as much as 38 mg/day. A typical daily
    tin balance for an adult in the USA, as estimated by Schroeder et al.
    (1964), is shown in Table 4.

        Hamilton et al. (1972) reported a daily intake of tin from food
    and beverages by an adult in the United Kingdom of 0.187 ± 0.042 mg
    (Table 5). It seems likely that this diet was composed of fresh foods,
    which would account for the lower values obtained compared with the
    North American data.

    Table 4.  Daily tin balance for an adult in the USAa

             Intake (mg)             Output (mg)

    food              4.0            faeces (estimated)  3.98
             (range,  1-40)                    (range,   1-40)
    water             0.0            urine               0.023
             (range,  0-0.03)                  (range,   0-0.04)
    air               0.003
             (range,  0-0.007)                                    

    total             4.003 (1-40)                       4.003 (1-40)

    a  From: Schroeder et al. (1964).

    Table 5.  The concentration of tin in foods and total daily intake
              for an adult in the United Kingdoma

    Item                   Number of    Concentration of tin (mg/kg)b

    cereals                   3         4.7±1.5 × 10-2
    meat                      4         2.1±0.5 × 10-3
    rats                      4         3.7±0.8 × 10-2
    fruits                    5         0.5±0.1
    root vegetables           3         2.2±1.0 × 10-2
    green vegetables          4         2.3±10-2
    milk (cow's)             17         7.8±1.2 × 10-3 (mg/litre)

    total daily untake                  0.187±0.042

    a  "From Hamilton et al. (1972).
    b  For prepared diet.


        Although a substantial amount of literature exists on the
    absorption, distribution, excretion, and storage of tin, the results
    of much of the early research are questionable in the light of modern
    analytical techniques. For example, some studies depended on tissue
    matrix destruction processes with the risk of loss of tin salts by
    volatilization. In many cases, conditions were not controlled or
    defined making it difficult to know whether pure valence states of
    tin(II) or tin(IV) were being used, and whether the oxidation state of
    the element affected its biological fate. In most cases, the purity of
    the compound used was not indicated.

    6.1  Inorganic Tin

    6.1.1  Absorption

        Evidence obtained from man and several animal species shows that
    ingested inorganic tin is poorly absorbed. Most studies indicate that
    less than 5% is absorbed from the gastrointestinal tract, although
    values as high as 20% have been reported (Furchner & Drake, 1976;
    Hiles, 1974; Kehoe et al., 1940; Kutzner & Brod, 1971,
    Monier-Williams, 1949; Schroeder et al., 1964).

        The influence of oxidation state and anion complement on the rate
    of gastrointestinal absorption was studied by Hiles (1974) by
    administering tin to rats in the form of tin(II) citrate, fluoride, or
    pyrophosphate, and tin(IV) citrate or fluoride as a single oral dose
    at 20 mg/kg body weight. The absorption of tin(II) citrate and
    fluoride was calculated to be 2.8%, whereas only 0.6% of the dose of
    tin(IV) citrate and fluoride was absorbed; the citrate and fluoride
    were equally absorbed. Absorption of tin, when the anion was
    pyrophosphate, was significantly lower than when the anion was citrate
    or fluoride. The author considered that this was because pyrophosphate
    had a greater tendency to form insoluble complexes with tin than
    either fluoride or citrate.

    6.1.2  Distribution

        With both oral and parenteral administration of tin to animals,
    the highest concentrations were found in the kidney, liver, and bone
    (Durbin, 1960; Hiles, 1974; Moskalev, 1964), the principal site of
    deposition being the bone (Furchner & Drake, 1976; Hiles, 1974).

        The amounts of tin remaining in the organs of rats 48 h after
    receiving a single oral dose of 20 mg of tin in the form of a
    radioactive compound are shown in Table 6; the distribution 48 h after
    a single intravenous administration of tin(II) or tin(IV) citrate is
    shown in Table 7 (Hiles, 1974).

        Rats given a daily oral dose of 20 mg of tin per kg of body weight
    as tin(II) or tin(IV) fluoride did not show any detectable
    trans-placental transfer at day 10 after conception, and at day 21,
    the amounts of tin found in rats given the tin(II) compound were so
    close to the limit of detection (= 0.1 µg of tin) that the
    significance of the findings remained doubtful. In rats receiving the
    same compounds at similar daily doses for 28 days, no significant
    amounts of tin could be detected in the brain, heart, testes,
    adrenals, reproductive tract, skeletal muscle, and spleen, while the
    levels in kidney and liver were approximately the same as after a
    single oral dose; however, the levels in bone were about 8 times
    higher than those found after a single oral dose. Tissue
    concentrations were higher following administration of tin(II)
    fluoride than following tin(IV) fluoride administration (Hiles, 1974).

        The results of distribution experiments performed by Hiles (1974)
    suggested that tin is unlikely to be rapidly oxidized or reduced
    during absorption and systemic transportation, although the actual
    oxidation state of the tin in the tissues could not be determined.

        Following intravenous injection of 113Sn(II) and 113Sn(IV)
    citrates in rats, only small quantities of tin could be detected in
    lung tissues (Hiles, 1974). However, tin is found in the human adult
    lung and there is evidence indicating that the concentrations increase
    with age often reaching higher levels than those in other tissues
    (Schroeder et al., 1964). Thus, it seems probable that tin reaches the
    lung primarily through inhalation.

        Levels of 113Sn in the blood of rats, 2 days after oral or
    intravenous administration, were extremely low and were only detected
    in the erythrocytes (Hiles, 1974). Kehoe et al. (1940) found that 80%
    of the tin in the blood of man was in the cells.  Distribution in human tissues and biological fluids

        Tin concentrations found by Hamilton et al. (1972/1973) in some
    tissues of healthy human adults are given in Table 8 together with
    data reported by Kehoe et al. (1940) and Schroeder et al. (1964).
    Comparatively high concentrations were found in lung, kidney, liver,
    bone, and also in lymph nodes. Fairly high levels were reported by
    Storozeva (1963) in the teeth of 24 persons, i.e., a range of
    0.5-1.7 mg/kg of ash.

        Table 6.  113Sn. distribution in rats after a single oral dose of solutions of various 113Sn compoundse

                                                   Percent of dosed radioactivity

                             SnF2                 SnF4            Sn(II) Citrate    Sn(IV) Citrate     Sn2P2O7

    Faeces and
    wash                 100.60±9.9 (10)a     98.40+3.6 (10)       98.00±2.1 (5)    95.40±10.3 (5)     100.0±2.8 (6)
    Urine                1.02±0.58 (10)b,d    0.22±0.13 (10)b     0.90±0.23 (5)c    0.33±0.12 (5)c    0.41±0.19 (6)d
    Kidneys              0.08±0.04 (10)b,d    0.01±0.01 (10)b     0.05±0.02 (5)c    0.01±0.00 (5)c    0.03±0.02 (6)d
    Liver                0.08±0.04 (10)b,d    0.01±0.01 (10)b      0.07±0.02 (5)      < 0.004 (5)     0.02±0.02 (6)d
    Pancreas                < 0.004 (5)        0.02±0.03 (5)        < 0.004 (5)       < 0.004 (5)       < 0.004 (5)
    Recovery              101.74±9.4 (10)     98.66+3.6 (10)       99.02±2.3 (5)    95.74±10.5 (5)    100.46±2.9 (6)

                                                   Percent of dosed 113Sn/g of sample

    Bone (femur)         0.20±0.13 (10)b,d    0.04±0.02 (10)b     0.09±0.04 (5)c    0.03±0.02 (5)c    0.02±0.01 (6)d
    Lymph nodes             < 0.004 (5)        0.08±0.12 (9)        < 0.004 (5)       < 0.004 (5)      0.01±0.01 (5)
    Blood clot            0.01±0.01 (10)          < 0.004          0.01±0.00 (5)      < 0.004 (5)       < 0.004 (6)
    Leg muscle              < 0.004 (5)        0.01±0.01 (5)        < 0.004 (5)       < 0.004 (5)       < 0.004 (6)

    a  % of dosed 113Sn±SD (number of animals) where 1% = 40 µg. Tissues containing < 0.010%, of the dose were not
       normally included in the table.
    b  Significant difference at p < 0.05 between SnF2 and SnF4.
    c  Significant difference at p < 0.05 between Sn(II) citrate and Sn(IV) citrate.
    d  Significant difference at p < 0.05 between SnF2 and Sn2P2O7.
    e  From: Hiles (1974).


        Table 7.  Fate of inorganic tin in rats. Tin distribution after a single intravenous
              dose of 113Sn(11) or 113Sn(IV) citratee

                                        Percent of dosed radioactivity

    Sample                 Sn(II) citrate                         Sn(IV) citrate

                                         Bile-duct                            Bile-duct
                        Intact           cannulated           Intact          cannulated

    Urine               35.3±4.6a        23.3±12.8            39.8±10.8       24.8± 2.5
    Faeces              12.1±1.8b,d      2.2±1.1d             3.1±1.4b        0.5±0.3
    Bile                --               11.5±2.4c            --              0.1±0.1c
    Injection site      3.3±1.8          6.2±4.7              4.1±1.5         3.9±3.3
    Liver               2.0±0.2          5.1±1.6c,d           0.2±0.1d        0.2±0.1c
    Kidney              5.9±0.9          8.3±1.3              5.3±3.4         4.2±2.5
    Lungs               0.12±0.08        0.2±0.1              < 0.04          < 0.06
    Spleen              0.4±0.0          --                   < 0.04          --
    Pancreas            0.2±0.1          --                   < 0.04          --
    Stomach             0.1±0.1a         0.2±0.0d             < 0.04          < 0.06
    Small intestine     0.5±0.1a         0.4±0.4d             < 0.04          < 0.06
    Large intestine     1.0±0.8b,d       0.4±0.3d             0.2±0.3b        < 0.06
    Carcass             33.4±5.3         --                   43.2±5.3        --
    Femur (one)         1.6±0.2          1.9±0.1              3.2±0.6         2.0±0.1

                                           Percent of dosed 113Sn/g

    Bone (femur)        4.5±0.6b,d       8.4±1.0d             8.8±1.8b        7.4±0.9
    Blood clot          0.6±0.2d         0.9±10.3d            < 0.04          < 0.06
    Leg muscle          0.06±0.03        --                   < 0.04          --

    a  % of dosed 113Sn±SD where 1% = 4 µg tin.
    b  Significant difference at p < 0.05 between intact Sn(II) and Sn(IV) animals.
    c  Significant difference at p < 0.05 between bile-duct cannulated Sn(II) and
       Sn(IV) animals.
    d  Significant difference at p < 0.05 between Sn(II) intact and bile-duct cannulated
    e  From: Hiles (1974).

        Schroeder et al. (1964) reported a highly variable distribution of
    tin in human tissues with significant differences related to age and
    geographical location. Variations in the tissue contents of tin among
    several geographical regions throughout the world were quite marked
    but were less noticeable between 8 cities of the USA (Table 9 and 10).
    All kidney, liver, and lung samples from Africa, Asia, and Europe had
    lower mean and median tin contents than samples from the USA (the
    difference being least in lungs). Tin in the tissue of Africans, where
    exposure to tin would be expected to be much lower than in
    industrialized North American and European areas, was, indeed,
    noticeably low. Tin was rarely detected in the tissues of stillborn
    infants, indicating that tin does not readily cross the placental
    barrier. The lungs accumulated tin with advancing age but other organs
    did not. Concentrations of tin in kidney, liver, lungs, and the ileum
    according to decade of life are shown in Table 9. Small amount were
    found in the heart, prostate, uterus, and trachea. Avtandilov (1967)
    studied the trace element contents of normal and atherosclerotic
    aortas. He reported a mean tin concentration of 0.08 mg/kg wet weight
    in 20-39-year-old subjects with no difference between the two
    categories of aorta.

        Table 8.  Tin content of human tissues, concentrations expressed as mg/kg wet weight.

                  Hamilton et al. (1972/73)   Kehoe et al. (1940)   Schroeder et al. (1964)

    Tissue               mean ± S.E.                mean               range (8 cities in

    blood              0.009±0.002
    brain               0.06±0.01                   NDa
    kidney              0.2±0.04                    0.2                      0.23-0.76
    liver               0.4±0.08                                             0.35-1.0
    lung                 0.8±0.2                   0.45                      0.49-1.20
    lymph node           1.5±0.6
    muscle              0.07±0.01                   0.1
    bone                4.1±0.6b                  0.5-0.8

    a  ND = not detected.
    b  mg of element per kg of ash.


        Table 9.  Tin in human tissues by age, mean US values (mg/kg ash)a

    Age group (year)    0         0-1       1-10      11-20     21-30     31-40     41-50     51-60     81-70     71-84

    concentration       0         57b       60b       33        20        34b       28b       22        34        32
    occurrence          0/16      9/10      19/20     10/15     17/21     36/43     22/26     26/27     13/14     8/9
    concentration       0         48b       61b       42        34        33b       25        35        38b       34b
    occurrence          0/21      11/12     22/23     14/14     20/21     39/43     27/28     25/25     13/13     9/9
    concentration       (18)      35        34        45b       27        31b       39b       53b       58        64b
    occurrence          1/10      5/6       5/6       10/13     18/21     34/35     27/27     28/29     13/13     9/9
    concentration       0         101       98        80        174       116       97        53        172       140
    occurrence          0/8       1/2       1/1       9/10      12/13     26/28     16/17     12/12     6/6       3/4
    total occurrence
    (%)                 1.8       86.7      94.0      82.7      88.2      79.8      93.9      97.8      97.7      93.5

    Note:   Concentrations of positive samples.
            Occurrence refers to the number positive/total cases.

    a  From: Schroeder et al. (1964).
    b  Excluding values > 150.


        Table 10.  Geographical distribution of tin in kidney, liver, and lung of man (mg/kg ash)a

                                      No. of        %
                                      samples    present    Mean      Range         Median

       United States of America         161        97        30      < 5-480        20
       Switzerland                        9        33         5      < 5-17         < 5
       Africa                            53        19         5      < 5-30         < 5
       Middle East                       43        42         8      < 5-55         < 5
       Far East                          57        40        11      < 5-110        < 5
       United States of America         163        96        35      < 5-300        24
       Switzerland                        9        78         6      < 5-20         Tc
       Africa                            49        25         4      < 5-20         < 5
       Middle East                       44        55        11      < 5-140        Tc
       Far East                          54        41        10      < 5-74         < 5
       United States of America         159        98        69      < 5-920        39
       Switzerland                        7       100        37       23-62         28
       Africa                            50        60        10      < 5-40         Tc
       Middle East                       45        91        33      < 5-200        17
       Far East                          57        93        65     < 5-1200        29

    Note:   Tc = trace, or barely detectable.
            Mean and median values were obtained by assigning a value of one-half
            the least detectable amount to those cases where tin was not detected.
    a  From: Schroeder et al. (1964).

        Using a spark source mass spectrometric method with a detection
    limit of 0.004 mg/kg wet weight, Hamilton et al. (1972/1973) reported
    a mean concentration of 0.06 mg/kg (± 0.01) in 10 whole brain samples
    from accidentally killed, presumably healthy adults. The concentration
    found in the frontal lobe was 0.03 (± 0.07) and that in the basal
    ganglia was 0.04 (± 0.02) mg/kg, measured in 2 samples. Tin was not
    detected in human brain by Kehoe et al. (1940) and was found in only a
    small percentage of subjects by Tipton (1960) and Schroeder et al.

    6.1.3  Excretion

        The major route of excretion of absorbed inorganic tin is the
    kidney although a small fraction is excreted into the bile (Hiles,
    1974; Moskalev, 1964). The excretion of tin in the urine was studied
    by Perry & Perry (1959) in 24 human adults. A mean of 16.6 µg/litre of
    urine or 23.4 µg/day was reported. Kehoe et al. (1940) reported a mean
    concentration of 18 µg/litre of urine in subjects in the USA. There
    remains some doubt, however, as regards the accuracy of the analytical
    technique used since, in the same paper, the concentration in the
    urine of French males was reported to be zero.

        In an experiment on rats, Hiles (1974) reported that after a
    single oral dose of tin(II) or tin(IV)citrate or fluoride at 20 mg/kg
    body weight (as the metal), about 50% of the absorbed tin was excreted
    within 48 h. Following intravenous administration of 113Sn (2 mg of
    tin per kg body weight), 12% of the 113Sn(II) and only 4% of the
    113Sn(IV) appeared in the faeces of rats indicating that the biliary
    route is probably more important in the elimination of tin(II) than of
    tin(IV) compounds. Most of the biliary excretion (94%) took place
    within 24 h.

    6.1.4  Biological half-time

        A half-time of 3-4 months was reported for 113Sn in the skeleton
    of rats after intramuscular administration (Hamilton, 1948). However,
    Hiles (1974) found a half-time of only 34-40 days for both tin(II) and
    tin(IV) in the bone of rats following oral administration of tin(II)
    fluoride or tin(IV) fluoride for 28 days. The half-time of tin(II) for
    liver and kidney was reported to be 10-20 days. Furchner & Drake
    (1976) using tin(II) chloride administered intraperitoneally and
    intravenously in the mouse, rat, monkey, and dog, described the
    elimination from the body as a 4 component-process that was similar in
    all the species studied. The half-time for the longest component was
    over 3 months.

    6.2  Organotin Compounds

        In this document, consideration will be limited to compounds of
    the general type RSnX3, R3SnX2, R4SnX, and R4Sn where R is a
    simple or complex action. Generally, little information is available
    on the absorption, distribution, and excretion of these substances.

    6.2.1  Absorption

        Absorption from the intestinal tract of tin compounds with short
    alkyl chains varies depending on the compound. There are also
    considerable differences in absorption between species (Barnes &
    Stoner, 1959).

        Ethyltin trichloride administered orally was poorly absorbed by
    rats, 92% of an oral dose of 25 mg/kg being eliminated in the faeces
    within 2 days. It was not excreted in the bile (Bridges et al., 1967).
    Triphenyltin acetate was almost completely eliminated in faeces within
    a few days, when administered orally to sheep (Herok & Götte, 1964)
    and cows (Bruggemann et al., 1964a). However, it was well absorbed,
    when given orally to guineapigs and mice (Stoner, 1966). Results
    obtained with rats were conflicting (Klimmer, 1963, 1964; Stoner,
    1966). Tricyclohexyltin hydroxide was poorly absorbed in rats, only
    about 2% being excreted in the urine after a single 25 mg/kg oral
    dose. The remainder was recovered from the faeces and binary excretion
    did not occur (FAO/WHO, 1971).

        Trialkyltin compounds were well absorbed on contact with the skin,
    since the dermal LD50s of various trimethyltin derivatives in mice
    were of the order of 50-100 mg/kg (Hall & Ludwig, 1972) and that of
    bis(tributyltin) oxide was below 200 mg/kg in rats and mice (Ascher &
    Nissim, 1964; Elsea & Paynter, 1958). When a 20% fat solution of
    various triethyltin derivatives was applied to the skin of rats and
    mice for 10 min, all the animals died within 20-30 min (Ignatjeva et
    al., 1968). In contrast, triphenyltin acetate did not penetrate
    unbroken skin readily (Stoner, 1966).

    6.2.2  Distribution

        Following intravenous administration to mice and rats, the highest
    concentrations of dibutyl- and diethyltin were found in liver and
    kidney tissue; unchanged compounds were excreted in the bile (Barnes &
    Magee, 1958). Rats were fed with 11 mg of triethyltin hydroxide over a
    period of 89 days. At the end of this time, only 0.7 mg of the
    compound could be recovered; 40% of this was in the blood, 28% in the
    liver, and 29% in the skeletal muscle. Smaller amounts of triethyltin
    were found in the kidney, brain, heart, and spleen (Cromer, 1957).

        Species variation in the distribution of triethyltin has been
    reported. When triethyltin (26 µg) was added to rat blood  in vitro,
    most of it (23 pg) was recovered from the erythrocytes and none was
    found in the plasma, whereas in rabbit blood, triethyltin was more
    equally distributed between erythrocytes (9 µg) and plasma (17 µg)
    (Cromer, 1957). This could explain why triethyltin persists in the
    blood of treated rats, whereas it quickly disappears from the blood of
    treated rabbits (Barnes & Stoner, 1959). Triethyltin was found in the
    brain of rats only 1-2 h after intraperitoneal injection of
    triethyltin hydroxide (Cremer, 1957).

        The tissue distribution of triethyltin following intravenous
    administration of tetraethyltin resembled that following
    administration of triethyltin (Cremer, 1957, 1958). Thus, a large
    quantity of triethyltin was found in the liver, with smaller
    quantities in the kidney, brain, and whole blood in a rabbit, 2 h
    after administration.

        After oral or intraperitoneal administration of 113Sn-labelled
    triphenyltin to guineapigs, about 80% of the administered activity was
    excreted in 10 days. The concentration of radioactive tin found in the
    brain of rats and guineapigs after oral and intraperitoneal
    administrations decreased with a half-life of several days. The form
    of tin in the brain was not unequivocally identified, but it was not
    in the form of free stannic ions nor was it necessarily triphenyltin
    (Heath, 1967). Herok & Götte (1964) gave 3 sheep 10 mg of triphenyltin
    acetate orally, every day for 20 days. The compound was labelled with
    113Sn. The animals were killed at intervals ranging from 8 to 198 days
    after the last dose. The highest concentration of 113Sn was found in
    the liver but the brain also contained measurable amounts. In rats,
    any absorbed triphenyltin chloride was rapidly distributed through the
    tissues of the body including the brain. Tin was eliminated relatively
    slowly and could be detected in the brain 38 days after a single dose
    (Heath, 1963).

        Only trace quantities of tricyclohexyltin hydroxide were found in
    the tissues of rats and dogs fed up to 12 mg/kg bodyweight per day, in
    the diet, for periods ranging from 45 days to 2 years (FAO/ WHO,

    6.2.3  Excretion

        When ethyltin trichloride was administered intraperitoneally to
    rats, it was excreted almost exclusively in the urine; binary
    excretion was negligible. When diethyltin was administered
    intraperitoneally it was eliminated as diethyl- and ethyltin in both
    faeces and urine. Diethyltin was excreted in the bile (Bridges et al.,
    1967). Rats that had initially received a diet containing triethyltin
    and had retained approximately 0.7 mg triethyltin in their tissues
    were then given a normal diet; 12 days later, no triethyltin could be
    detected in the tissues (Cremer, 1957). The route of excretion was not

        The elimination of triphenyltin from the body is slow (Stoner,
    1966). Its persistence in guineapigs is suggested by the similarity
    between the amounts consumed by those dying on diets containing 25 and
    50 mg/kg and the acute oral LD50. In studies on guineapigs using
    113Sn-labelled triphenyltin, the concentration of triphenyltin that

    had entered the brain after a single oral dose did not decrease during
    the first 10 days. In rats, triphenyltin disappeared more rapidly,
    having a half-time of about 3 days in the brain (Heath, 1963, 1965).
    Triphenyltin acetate labelled with 113Sn was slowly excreted in the
    urine of lactating sheep given oral doses of the compound at the rate
    of 10 mg/day for 20 days. The milk confined small amounts of tin
    (about 1 µg/litre) in both organic and inorganic forms (Herok & Götte,

        The biological half-time of tricyclohexyltin hydroxide in rats was
    5-40 days, when the compound had been included in the diet over a
    prolonged period. The brain was one of the tissues from which the
    compound was removed most slowly (FAO/WHO, 1971).

    6.2.4  Biotransformation

        In some early studies on the metabolic degradation of organotin
    compounds, it was suggested that destannylation (carbon-tin bond
    cleavage) was the major result of this biotransformation. For example,
    triethyl tin was detected in the tissues of rabbits and rats given
    tetraethyltin intravenously (Cremer, 1957, 1958). The liver was the
    organ most active in this conversion. Bridges et al. (1967) reported
    that dealkylation of diethyltin occurred in both the gut and tissues
    of the rat. Although Herok & Götte (1963) found that after
    administration of triphenyltin acetate labelled with 113Sn small
    amounts of inorganic tin were present in the milk of sheep, Stoner
    (1966) considered that triphenyltin was not readily transformed in the
    body. Dicyclohexyltin oxide and trace amounts of cyclohexylstannoic
    acid were identified as metabolites in rats and dogs treated with
    tricyclohexyltin hydroxide (FAO/WHO, 1971). Blair (1975) concluded
    that tricyclohexyltin hydroxide undergoes metabolism in animals by
    scission of cyclohexyl groups from the atom.

        More recent studies using tributyltin acetate showed primary
    biological oxidation reactions in the hydroxylation of carbon-hydrogen
    bonds that are alpha, ß, gamma and delta to the tin atom (Fish et al.,
    1976). This type of reaction was already assumed by Casida et al.
    (1971), although no carbon-hydroxylated metabolites could be
    identified when triethyltin derivatives were biologically oxidized
     in vitro to monoethyl derivatives.

        Fish et al. (1975) treated tributyltin acetate with rat liver
    microsomes (a mono-oxygenase enzyme system) in the presence of NADPH,
    and obtained alpha and ß hydroxylated metabolites in yields of 24% and
    50%, respectively. An  in vivo study with [1-14C]-tetrabutyltin
    showed the occurrence of similar reactions in mice (Kimmel et al.,
    1977). The alpha-hydroxyl metabolite is unstable and undergoes a
    cleavage reaction at pH = 7.4 to give 1-butanol and a dibutyltin
    derivative. A ß-elimination reaction in acidic media transforms the
    ß-hydroxyl derivatives rapidly into 1-butane and a dibutyl derivative
    (Fish et al., 1976).

        Studies on the  in vitro metabolism of tricyclohexyltin compounds
    indicated that carbon-hydroxylation of the cyclohexyl group was a
    major metabolic reaction (Fish et al., 1976; Kimmel et al., 1977).

        When [113Sn] -triphenyltin acetate was subjected to  in vitro
    biological oxidation, the phenyl group was not biotransformed, but in
     in vivo studies, rats were found to metabolize triphenyltin acetate
    into diphenyl- and phenyltin derivatives (Kimmel et al., 1977).


    7.1  Inorganic Tin Compounds

        Although tin is present in small amounts in most animal and human
    tissues, it is uncertain whether it is an essential element for
    mammals. However, recent results indicate that tin is an essential
    nutrient for the growth of the rat. Both inorganic and organotin
    compounds at concentrations similar to those present in feeds were
    found to stimulate growth rate in rats maintained on purified amino
    acid diets (Table 11) (Schwarz, 1971; 1974; Schwarz et al., 1970). The
    authors concluded that tin, as an essential element, could have a
    function at the active site of some metal-dependent enzymes; however,
    this has still to be confirmed.

        Compared with most organotin derivatives, inorganic tin and its
    salts are not highly toxic, mainly because of their poor absorption
    and rapid tissue turnover (Barnes & Stoner, 1959; Cheftel, 1967;
    Hiles, 1974; National Academy of Sciences, Washington 1973). The
    systemic toxicity of some simple tin salts is difficult to assess
    because of the irritant properties of their solutions.

    7.1.1  Effects on the Skin

        The effects of 1% tin(II) chloride and 0.25% tin(II) fluoride
    solutions, applied to the abraded skin of rabbits, were examined by
    Stone & Willis (1968). Both compounds induced intraepidermal pustules
    with complete destruction of the epidermis but the stratum corneum
    remained intact. No injury occurred when the solutions were applied to
    intact skin.

    7.1.2  Respiratory system effects

        According to Robertson (1960), intratracheal administration of
    50 mg of metallic tin dust to rats was well tolerated and no fibrosis
    was produced within one year of exposure.

        Exposure of guineapigs by inhalation, to tin(IV) chloride (3 mg/
    litre for 10 min, daily, for "several months") produced only transient
    irritation of the nose and eyes (Pedley, 1927).

        Table 11.  The effect of tin(IV) sulfate on the growth of rats in a trace-element-controlled

                        Dose level        No. of    Average daily   Increase
    Compound            (µg of tin/kg)    animals   weight gain        (%)     p-value

    control                  --             5b      1.10±0.05c         --      --
    tin (IV) sulfate        500             8       1.37±0.10           2      .02
    tin (IV) sulfate       1000             8       1.68±0.10          53      .001
    tin (IV) sulfate       2000             8       1.75±0.10          59      .001

    a  From: Schwarz et al. (1970).
    b  2 control rats died during the 26-29 days of the experiment.
    c  mean ± standard error.


    7.1.3  Effects on the gastrointestinal system

        Soluble tin salts are gastric irritants. This explains the signs
    of acute poisoning occasionally observed in man and in experimental
    animals following consumption of food containing high concentrations
    of tin (de Groot et al, 1973). However, the concentrations required to
    elicit an acute gastrointestinal reaction have not been determined
    reliably. Beney et al. (1971) reported signs of illness in 3/10 cats
    after ingestion of 5 ml/kg body weight of fruit juice containing a tin
    concentration of 1370 mg/litre, and in 1/11 cats receiving the same
    dose of fruit juice containing tin at a concentration of 540 mg/litre.
    However, no adverse effects were recorded in cats receiving a similar
    amount of juice containing a tin concentration of about 500 mg/litre
    or in dogs given juice with a tin concentration of 1400 mg/litre.

    7.1.4  Effects on the liver

        A 3-fold increase in haem oxygenase (EC activity in
    the liver of rats was observed 16 h after a single subcutaneous
    injection of tin(II) chloride dihydrate (SnCl22H2O) at doses ranging
    from 5.6 to 56.4 mg/kg body weight. Cytochrome P-450 mediated drug
    metabolism and the content of cytochrome P-450 were reduced by one
    third. These effects on the liver increased by about 15-20%, when the
    compound was administered intraperitoneally (Kappas & Maines, 1976).

        Tin chloride, oxalate, or sulfate added to the diet at a
    concentration of 10 g/kg for 4 and 13 weeks resulted in homogenous
    liver cell cytoplasm and hyperplasia of the bile duct in rats. The
    liver changes were more distinct after 13 weeks administration.
    Similar, although milder, hepatic alterations were seen after
    administration of tin chloride, oxalate, or orthophosphate at a
    concentration of 3 g/kg of dietb (de Groot et al., 1973).

        Increased incidence of fatty degeneration in the liver was noted
    by Schroeder et al. (1968) in female but not in male rats, when the
    animals were given tin in the form of tin(II) chloride at a dose of
    5 mg/litre in drinking water, from weaning until their natural death.


    a  The numbers within parentheses following the names of enzymes
       are those assigned by the Enzyme Commission of the Joint IUPAC-IUB
       Commission on Biochemical Nomenclature.
    b  Tables for the approximate conversion of concentrations in diet
       to mg/kg body weight per day are given in Nelson (1954).

    7.1.5  Effects on the kidney

        Renal damage was produced in rats by single intravenous and
    intraperitoneal doses of sodium pentafluorostannite (NaSn2F5) and
    tin(II) chloride dihydrate (SnCl22H2O) (Conine et al., 1973, 1975;
    Yum et al, 1976). A single intraperitoneal injection of sodium
    pentafluorostannite at 35 mg/kg body weight or of tin(II) chloride
    dihydrate at 44.4 mg/kg produced extensive necrosis of epithelial
    cells mainly involving proximal tubules. The extent of the necrosis
    was thought to be related to the tin moiety of the compound because
    damage of the same magnitude could not be produced by administration
    of sodium fluoride (Yum et al., 1976).

        Studies in which rats received single subcutanous injections of
    tin(II) chloride dihydrate in doses ranging from 5.6-56.4 mg/kg body
    weight revealed a 20 to 30-fold increase in the haem oxidation
    activity in the kidney, 16 h after administration. This effect was
    already noticeable at the lowest dose (5.6 mg/kg) and was found to be
    dose-related (Kappas & Maines, 1976).

        Conine et al. (1976) administered daily oral doses of sodium
    pentafluorostannite for 15 or 30 days to rats at rates of 20, 100, and
    175 mg/kg body weight. The highest dose caused degenerative changes in
    the proximal epithelium of the kidneys that were similar to those
    observed in chronic fluoride poisoning (Lindemann et al., 1959), and
    affected about 15-20% of the 30 rats that were killed. Most of the 8
    animals in the 175 mg/kg group that died spontaneously during the
    experiment displayed necrosis of the proximal tubular epithelium
    similar to that previously reported to be caused by tin (Yum et al.,

        Exposure of rats to tin(II) chloride at a concentration of 5 mg of
    tin/litre of drinking water, for life, produced vacuolar changes in
    the renal tubules of animals of both sexes (Schroeder et al., 1968).

    7.1.6  Effects on the blood-forming organs

        When tin(II) (as chloride, orthophosphate, sulfate, oxalate, or
    tartrate) was given in the diet to Wistar rats of both sexes at
    concentrations of 3 and 10 g/kg for 4 weeks, food intake was reduced,
    growth was retarded and slight anaemia developed. The signs of anaemia
    included a reduction in haemoglobin levels of about 10% and
    corresponding reductions in haematocrit values, erythrocyte counts,
    and serum iron concentration (de Groot et al., 1973). Dietary
    supplements of iron had a markedly protective effect (de Groot, 1973;
    de Groot et al., 1973). The authors suggested that tin compounds might
    inhibit haemopoiesis, possibly by interfering with the intestinal
    absorption of iron. An alternative mechanism by which tin salts could
    cause mild gastrointestinal bleeding was not investigated.

        A dose-related decrease in haemoglobin concentrations was noted in
    rats after daily oral treatment, for 15 days, with sodium
    pentafluorostannite at 100 and 175 mg/kg body weight. Administration
    of 20 mg/kg per day did not affect the haemoglobin level (Conine et
    al., 1976).

    7.1.7  Central nervous system effects

        High doses of inorganic tin compounds seem to affect the central
    nervous system producing such effects as ataxia, muscular weakness,
    and the depression of the central nervous system. These signs were
    observed by Conine et al., (1975) after oral administration to rats of
    sodium pentafluorostannite and tin(II) chloride dihydrate in single
    doses of the order of the median lethal dose (LD50). According to de
    Groot et al. (1973), feeding rats with tin(II) chloride at a
    concentration of 10 g/kg diet for 13 weeks, resulted in a spongy state
    of the white matter of the brain. Ataxia, hind-leg paralysis, and
    death were also observed in rats by Mamontova (1940) following daily
    subcutaneous injections of 3 mg of tin(II) citrate for 5-6 months.

    7.1.8  Effects on the reproductive system and the fetus

        There is one report indicating that tin(II) chloride might have an
    effect on the reproductive system. De Groot et al. (1973) noted
    testicular degeneration in rats after prolonged feeding with this
    compound (10 g/kg of food, for 13 weeks).

        Inorganic tin compounds have not been shown to be fetotoxic.
    Theuer et al. (1971) gave groups of pregnant rats sodium
    pentafluorostannite, sodium pentachlorostannite, and tin(II) fluoride
    corresponding to tin levels in the diet of 125, 250, and 500 mg/kg.
    The rats were killed on day 20 of gestation. No effects were seen in
    the fetuses; tin concentrations in the fetuses were about 1 mg/kg
    compared with approximately 0.65 mg/kg in control fetuses, indicating
    a rather low transplacental transfer.

    7.1.9  Carcinogenicity and mutagenicity

        Few reports are available concerning the carcinogenicity of
    inorganic tin compounds. Walters & Roe (1965) administered either
    sodium chlorostannate at 1 or 5 g/litre of drinking water or tin(II)
    oleate at 5 g/kg of diet to mice, for up to one year; the survivors
    were then killed. The incidence of lymphomas, hepatomas, or pulmonary
    adenomas did not increase with any of the regimens.

        Roe et al. (1965) reported 3 malignant tumours in 30 August rats
    that survived for 1 year or more on a diet containing sodium
    chlorostannate at a concentration of 20 g/kg, whereas a control group
    of 33 rats did not exhibit any case of malignant tumours. One tumour
    was an adenocarcinoma of mammary origin, another a pleomorphic sarcoma
    in the uterus, and the third, an adenoma-carcinoma in the jaw region.
    The difference was not statistically significant. No tumours were seen
    in another group of 27 rats surviving on a diet containing tin(II)
    2-ethylhexoate at a concentration of 5-10 g/kg.

        Administration of tin(II) chloride to rats and mice at 5 mg/litre
    in drinking water throughout their life-time did not produce any
    increase in the incidence of tumours compared with a control group
    consisting of an equal number of animals (Kanisawa & Schroeder, 1969).

        Studies concerning the mutagenicity of inorganic tin compounds
    were not available to the Task Group,

    7.1.10  Other effects

        Growth retardation in rats has been reported after the
    administration of high doses of various tin compounds. Dietary levels
    of tin as tin(II) oxalate, orthophosphate, chloride, sulfate, and
    tartrate at 3 and 10 g/kg for 4 weeks caused inhibition of growth in
    rats and oedema and atrophy of the pancreas (de Groot et al., 1973).
    Daily administration, by garage, of sodium pentafluorostannite at 100
    and 175 mg/kg body weight, for 30 days, resulted in a dose-related
    retardation of growth in rats (Conine et al., 1976). Administration of
    tin(II) chloride at a concentration of 5 mg of tin per litre of
    drinking water reduced the life span of female rats, whereas the
    longevity of male rats was unaffected (Schroeder et al., 1968).

    7.1.11  Effective doses and dose rates  Lethal doses

        The median lethal doses (LD50) for 2 inorganic tin compounds are
    given in Table 12. A marked difference between the oral and parenteral
    LD50 values can be explained by the low absorption of tin compounds.

        Daily intravenous administration of 3.3-4.2 mg of sodium tin
    citrate per kg body weight provoked death in rabbits in 7-8 days,
    whereas at a dose of 2.5 mg/kg, death occurred only after 15 or more
    days (Mamontova, 1940).

        In studies on 6 rats, subcutaneous injection of 3 mg of tin
    citrate/animal, per day, killed all the animals in 5-6 months. Similar
    administration of the same compound in doses of 2 mg/kg body weight
    produced vomiting, diarrhoea, weight loss, ataxia, hind-leg paralysis,
    and death within 5 months (Mamontova, 1940).

        Table 12.  Median lethal doses (LD50) of tin(II) chloride dihydrate (SnCl22H2O) and sodium
               pentafluorostannite (NaSn2F5)a

                             Sodium pentafluorostannite
                                                                   Tin(II) chloride dihydrate
    Route            male mice      male rats      female rats     male rats (LD50, mg/kg)
                     (LD50, mg/kg)  (LD50, mg/kg)  (LD50, mg/kg)

    intravenous         18.9           12.9           12.9                    29.3
    intraperitoneal     80.9           75.4           65.0                   258.4
    oral (fasted)      --b            223.1          218.7                  2274.6
    (fed)              592.9          573.1          --b                    3190.1

    a  From: Conine et al. (1975).
    b  no data.
  Minimum effective and no-observed-effect doses

        Some information on effective doses has been given in the sections
    describing the effects. However, the following information may also be
    of interest.

        De Groot et al. (1973) reported a normal growth rate in Wistar
    rats that had received tin(IV) oxide, tin(II) sulfide, or tin(II)
    oleate at dietary levels up to 10 g/kg for 4 weeks; haematological
    data were also normal except for an increase in the haematocrit in
    male rats fed with the highest concentration of tin(II) sulfide. The
    weight and the gross and macroscopic appearance of the liver, kidney,
    heart, and spleen were also normal.

        When a similar experiment was conducted with tin(II) chloride for
    13 weeks, the no-observed-effect concentration in food appeared to be
    1 g/kg, if the diet were supplemented with iron (de Groot et al.,
    1973). This is equivalent to a dose rate of about 20-30 mg tin/kg body
    weight per day, for 90 days.

        No effect on growth was observed by Conine et al. (1976), when
    sodium pentafluorostannite was administered orally to rats at a dose
    rate of 20 mg/kg body weight per day for 30 days.

        Oral administration of sodium tin citrate in dose rates ranging
    from 100-150 mg/kg body weight per day for 1 year did not produce any
    noticeable signs of poisoning in rats (Mamontova, 1940). Similarly
    rats fed a diet containing either sodium chlorostannate at 20 g/kg or
    tin(II) 2-ethyl hexoate at 5-10 g/kg for one year did not show any
    pathological changes in the gastrointestinal tract, kidneys, or liver
    (Roe et al., 1965).

        Mice that received tin in the form of sodium chlorostannate at a
    concentration of 1 or 5 g/litre in drinking water or tin in the form
    of tin(II) oleate in the diet at a concentration of 5 g/kg during
    their lifetime did not show any adverse effects (Waiters & Roe, 1965).

        Mice and rats (Schroeder & Balassa, 1961; Schroeder et al., 1968)
    given tin(II) chloride in drinking water at a concentration of 5 mg of
    tin/litre grew normally throughout their life. The life span of mice
    of both sexes and of male rats was not affected but that of female
    rats was shorter and there was an increased incidence of fatty
    degeneration of the liver (section 7.1.4). Vacuolar changes in the
    renal tubules were apparent in rats of both sexes (section 7.1.5).

    7.2  Organotin Compounds

        Distinction should be made between the effects of di-, tri-, and
    tetrasubstituted organotin compounds. The principal toxicological
    difference is that some trisubstituted compounds have a specific
    effect on the central nervous system producing cerebral oedema (Barnes
    & Stoner, 1958; Torack et al., 1969), whereas disubstituted compounds
    do not produce this effect but are potent irritants that can induce an
    inflammatory reaction in the bile duct (Barnes & Magee, 1958).
    Toxicologically, the tetrasubstituted compounds resemble
    trisubstituted compounds, which are, generally, more toxic than the
    mono- and disubstituted derivatives.

    7.2.1  Effects on the skin and eyes

        Dermal application of dibutyltin dichloride at 10 mg/kg body
    weight per day for a period of 12 days, caused severe local damage and
    also bile duct injury in rats and mice. Guineapigs were more
    resistant, showing little reaction to daily applications of 120 mg/kg
    on 5 successive days (Barnes & Stoner, 1958).

        An aqueous solution of bis(tributyltin) oxide applied to the
    shaved skin (30 x 60 mm) of rats at concentrations of 0.36-0.95 mg/kg
    body weight produced slight local irritation lasting 2-3 weeks
    (Pelikan & Cerny, 1968b). At higher doses (1.40-185 mg/kg), marked
    inflammation developed into skin necrosis. Severe effects on the eyes
    were also observed with bis(tributyltin) oxide (Pelikan & Cerny,

        Triphenyltin hydroxide was reported not to irritate rabbit skin or
    sensitize the skin of guineapigs (Marks et al., 1969). However, it was
    found to be extremely irritating to the eyes, even after brief
    exposure, and could cause corneal opacity (Marks et al., 1969).

        A solution of triphenyltin acetate in oil at a dose of 150 mg/kg
    body weight caused a skin reaction in rats (Klimmer, 1964). Doses of
    tricyclohexyltin hydroxide at 1.2-60 mg/kg body weight per day,
    applied to the skin of rabbits over a 3-week period, produced distinct
    reactions locally but did not result in any systemic ill effects
    (FAO/WHO, 1971, p. 527)a

    7.2.2  Respiratory system effects

        Pulmonary congestion and oedema were observed in rats after single
    intravenous administrations of solutions of diethyl-, di-propyl-,
    diisopropyl-, and dipentyltin dichloride (20 mg/kg body weight), in
    0.05 ml of polyoxyethylene sorbitin monoleate, whereas in the case of
    dibutyltin dichloride, 10 mg/kg was enough to cause this effect
    (Barnes & Stoner, 1958). Petechial and ecchymotic haemorrhages in the
    trachea and larynx were observed in sheep after intrarumenal
    administration of tricyclohexyltin hydroxide at 500 mg/kg body weight.
    Congestion was present in the dorsal portion of all pulmonary lobes at
    a dose as low as 150 mg/kg (Johnson et al., 1975).

    7.2.3  Effects on the gastrointestinal system

        A single dose of butyltin trichloride, butyltin- S,S',S"-tris
    (2-ethylhexylmercaptoacetate), butylstannoic acid, and butyl
    thiostannoic acid at 4000 mg/kg body weight, administered by stomach
    tube to mice, produced various degrees of submucosal, subserosal, and
    intra-luminar gastrointestinal hemorrhage within 24 h (Pelikan &
    Cerny, 1970b). Similar administration of dioctyltin- S,S'-bis
    (2-ethylhexyl-mercaptoacetate) produced dilatation of the stomach,
    which was filled with gas. The stomach walls appeared ischaemic
    whereas the intestinal walls were hyperaemic, and traces of blood were
    found in the contents of the small stomach. Similar, but more
    pronounced findings were recorded after administration of dioctyltin-


    a  Unpublished reports on triphenyltin compounds and tricyclohexyltin
       hydroxide were abstracted in  1970 Evaluations of Some Pesticide
        Residues in Food (FAO/WHO, 1971). The proprietary data were
       submitted to the WHO by the manufacturers. Page numbers given in the
       text refer to the FAO/WHO publication, which also contains
       information with reference to authors and manufacturers.

    bis-(butylmercaptoacetate), although no traces of blood were seen in
    the stomach. Treatment with dioctyltin bis(2-ethylhexyl-
    mercaptoacetate) resulted in large amounts of liquid in the stomach
    contents, and slightly hyperaemic stomach walls; other findings were
    similar to those produced by the other 2 dioctyltin compounds,
    dioctyltin bis(dodecylmercaptide) and octyltin tris(2-ethylhexyl-
    mercaptoacetate) (Pelikan & Cerny, 1970a). Ingestion of dibutyltin
    dichloride at a dose of 50 mg/kg body weight per day for one week,
    caused a temporary dilatation of the stomach in rats due to
    accumulation of fluid, and diarrhoea (Barnes & Stoner, 1958).
    Intrarumenal administration of tricyclohexyltin hydroxide at 150 mg/kg
    body weight resulted in fluid diarrhoea in sheep which persisted up to
    death. Necropsy findings included mild enteritis and colitis
    characterized by severe hyperaemia and oedema (Johnson et al., 1975).
    Gastroenteritis occurred in rats receiving an oral dose of
    tricyclohexyltin hydroxide of 25 mg/kg body weight per day for 19 days
    (FAO/WHO, 1971, pp. 527-528).

    7.2.4  Effects on the liver and bile duct

        Steatosis of hepatocytes and enlargement of the liver were seen
    within 24 h of administration to mice through a stomach tube, of a
    single dose of butylstannoic acid, butyltin trichloride, butyltin
    tris(2-ethylhexylmercaptoacetate), or butylthiostannoic acid, each at
    a dose of 4000 mg/kg body weight (Pelikan & Cerny, 1970b). In rats, a
    single oral dose of dibutyl,tin dichloride at 50 mg/kg body weight
    produced congestion and inflammation especially in the lower part of
    the bile duct (Barnes & Magee, 1958; Gaunt et al., 1968). When this
    dose of dibutyltin dichloride was given on 3 successive days, the
    lesion was more severe involving also the proximal part of the bile
    duct and the portal blood vessels. Necrotic areas were seen in the
    liver. In some cases, bile escaped from the injured duct into pancreas
    and peritoneum. The authors considered that death occurring 5 days
    after the 3 successive doses was the result of a general toxic effect
    of this compound, whereas death occurring later was secondary to bile
    duct and liver damage. Changes in the pancreas were inflammatory and
    confined to areas surrounding the bile duct. In surviving rats,
    examined 6-12 months after receiving 3 daily doses of 50 mg/kg, the
    bile duct was shorter and thicker than normal with fibrosis in the
    wall. A similar reaction in the bile duct was seen after a single
    intravenous administration of 5 mg/kg body weight, and after a dermal
    application of 10 mg/kg body weight. The effects on mice of oral doses
    of dibutyltin dichloride at 20-50 mg/kg body weight were similar to
    those seen in rats, although liver damage appeared to be more
    widespread. Repeated doses of this compound at 20-50 mg/kg body weight
    killed rabbits, but did not cause bile duct or liver injury;
    guineapigs, however, tolerated such doses without any signs of adverse
    effects (Barnes & Magee, 1958). It has been suggested that bile duct
    injury occurs only in species in which the bile duct and the
    pancreatic duct have a common course (Kimbrough, 1976).

        Daily doses of dibutyltin dichloride at 0.1 and 1.0 mg/kg body
    weight, for 6 months, caused intoxication in rabbits with dystrophic
    changes in the liver (Mazaev & Korolev, 1969). Dioctyltim- S,S'-bis
    (2-ethylhexylmercaptoacetate), diootyltin- S,S'-bis
    (butylmercaptoacetate), and diootyltin bis(dodecyl-mercaptide) at an
    oral dose of 4000 mg/kg body weight produced steatosis of the
    hepatocytes in mice (Pelikan & Cerny, 1970a). Nikonorow et al. (1973)
    reported a significant increase in the mean liver weight of rats after
    oral administration of dioctyltin- S,S'-bis(isoctylmercaptoacetate)
    at 20 mg/kg body weight per day, for 3 months.

        A single oral dose of tributyltin acetate, benzoate, chloride,
    laurate, or oleate at 500 mg/kg body weight produced fatty
    infiltration of the liver in mice (Pelikan & Cerny, 1968a) and
    triphenyltin acetate at a dietary level of 10 mg/kg produced fatty
    degeneration of the liver in guineapigs, when administered over a
    2-year period (FAO/WHO, 1971, p. 341). Cholangitis was reported in
    rats after administration of tricyclohexyltin hydroxide at a dietary
    level of 400 mg/kg for 90 days (Shirasu, 1970). Similarly, both intra-
    and extrahepatic cholangitis was noted in rats that had received
    tri-cyclohexyltin hydroxide at 25 mg/kg body weight per day, for 19
    days (FAO/WHO, 1971, pp. 527-528).

    7.2.5  Effects on the kidney

        Some degree of fatty degeneration of the renal cortical tubular
    epithelium was seen on histological examination of mice that had
    received a single oral dose (4000 mg/kg body weight) of butyltin
    tin- S,S',S"-tris(2-ethylhexylmercalytoacetate), butylstannoic acid,
    or butylthiostannoic acid, but not in animals given butyltin
    trichloride. The structure of the renal tissue was unchanged.
    Macroscopically, all compounds produced slight hyperaemia in the
    kidneys (Pelikan & Cerny, 1970b).

        Dioctyltin- S,S'-bis(2-ethylhexylmercaptoacetate) and
    dioctyltin- S,S'-bis(butylmercaptoacetate) administered at the same
    rate and by the same route produced a similar slight fatty
    degeneration of the renal cortical tubular epithelium in mice (Pelikan
    & Cerny, 1970a). Feeding rats with an organotin stabilizer,
    dioctyltin- S,S'-bis(isooctyl mercaptoacetate) at a dietary level of
    200 mg/kg for 12 months produced an increase in kidney weight in
    female rats only (Nikonorow et al., 1973). Mazaev & Korolev (1969)
    also reported dystrophic changes in the kidneys in rats treated with
    dibutyltin dichloride at 0.1 and 1.0 mg/kg body weight.

        Haemorrhages were reported in the kidneys of mice after single
    administrations (gavage) of tributyltin benzoate, chloride, laurate,
    and oleate at 500 mg/kg body weight. Hyperaemia of the kidney was seen
    in all groups, whereas tubular cells containing lipids were observed
    only in mice that had received laurate or oleate. Renal changes were
    not reported in mice that were similarly dosed with tributyltin
    acetate (Pelikan & Cerny, 1968a). Congestion of the glomeruli and mild
    toxic nephrosis were observed in rats receiving a dietary level of
    tricyclohexyltin hydroxide of 400 mg/kg for 3 months (Shirasu, 1970).
    Similarly, toxic nephrosis was reported in rats after administration
    of tricyclohexyltin hydroxide at a daily dose of 25 mg/kg body weight
    for 19 days (FAO/WHO, 1971, pp. 527-528).

    7.2.6  Effects on the lymphatic tissues and immunological effects

        Small necrotic areas were observed in the germinal centres of the
    splenic follicles of mice after a single administration, through a
    stomach tube, of 4000 mg/kg body weight of butyltin- S,S',S"-tris-
    (2-ethylhexylmercaptoacetate), butylthiostannoic acid, and
    butyl-stannoic acid, (Pelikan & Cerny, 1970b); dioctyltin- S,S'-bis
    (2-ethyl-hexylmercaptoacetate), and dioctyltin- S,S'-bis(butyl-
    mercaptoacetate) (Pelikan & Cerny, 1970a).

        Seinen & Willems (1976) reported that the main action of
    di-octyltin dichloride, given to rats at dietary levels of 50 and
    150 mg/ kg, was on the thymus, the weight of which was significantly
    reduced during the experiment. In subsequent experiments, feeding rats
    with dioctyltin dichloride or dibutyltin dichloride at dietary levels
    of 50, or 150 mg/kg for 6 weeks, resulted in a dose-dependent
    reduction in the weight of the thymus Land thymus-dependent peripheral
    lymphoid organs (Seinen et al., 1977a). The delayed type
    hypersensitivity was decreased and the allograft rejection was delayed
    when the same compounds were given in the same way to rats.
    Furthermore, it was reported that both these compounds decreased the
    survival rate of rat and human thymocytes in  in vitro studies
    (Seinen et al., 1977b). The effects of diethyltin dichloride and
    dipropyltin dichloride on rat lymphoid organs were similar but less
    pronounced. However, other dialkyltin compounds such as dimethyltin
    dichloride, didodecyltin dibromide, and dioctadecyltin dibromide, as
    well as octyltin trichloride, trioctyltin chloride, and tetraoctyltin
    did not cause atrophy of lymphoid tissues (Seinen et al., 1977a). The
    rat proved more sensitive to the action of di-octyltin dichloride and
    dibutyltin dichloride on lymphoid organs than the mouse and the
    guineapig in which no atrophy of the lymphoid organs was produced.
    (Seinen et al., 1977a).

        Studies on triphenyltin acetate have been reviewed by the FAO/ WHO
    (1971, pp. 327-366). In guineapigs, a dietary level of 15 mg/kg for 77
    days produced a decrease in plasma cells in the spleen and in the
    mesenteric, cervical, axillary, and popliteal lymph nodes. After
    feeding the same dose to female guineapigs for 104 days, a reduction

    in immune response to tetanus toxoid stimulation was observed. In
    another experiment, a decrease in the number of lymphocytes and
    leukocytes accompanied by histological changes in the lymphatic
    tissues, such as atrophy of the white pulp of the spleen, was seen in
    guineapigs at dietary levels of 5 mg/kg in females and 10 mg/kg in
    males administered, for 12 weeks. A decrease in the number of
    leukocytes was also reported in dogs after 8 weeks on a dietary level
    of triphenyltin hydroxide of 25 mg/kg and 8 weeks on 50 mg/kg.

    7.2.7  Haematological effects

        Decreases in the numbers of erythrocytes and reticulocytes were
    reported in rats after daily administration of an oral dose of
    dibutyltin sulfide at 0.1 mg/kg body weight for 6 months (Mazaev &
    Slepning, 1973). A mild anaemia was noted in rats that had received
    dibutyltin dichloride for 3 months at a dietary level of 80 mg/kg, but
    a level of 40 mg/kg did not produce this effect (Gaunt et al., 1968).

         In vitro studies of the haemolytic activity of trialkyltin
    compounds indicated that the most haemolytic organotin compounds were
    the alkyltin derivatives with alkyl groups of 3-6 carbon atoms
    (Byington et al, 1974). Decreases in the percentage haemoglobin and in
    the number of erythrocytes were reported in guinea-pigs treated with
    triphenyltin acetate at a dietary level of 10 mg/kg for 4 months
    (FAO/WHO, 1971, p. 337). A reduction in haemoglobin and leukocytes was
    also seen in rats after 12 weeks on a dietary level of triphenyltin
    hydroxide of 50 mg/kg (FAO/WHO, 1971, pp. 337-333).

    7.2.8  Central nervous system effects

        Intoxication in animals by lower trialkyltin compounds is
    manifested as generalized weakness progressing to paralysis, sometimes
    accompanied by generalized tremor. In rabbits, typical reactions to a
    lethal dose (5 mg/kg body weight) of triethyltin sulfate administered
    intravenously are prostration, flaccid paralysis, and encephalopathy
    (Stoner et al, 1955). These responses resemble those observed in human
    subjects, accidentally poisoned with triethyltin compounds. Daily
    intraperitoneal injections of triethyltin sulfate at 5 mg/kg body
    weight in saline solution resulted in death in rats within 3 days.
    Diffuse haemorrhagic encephalopathy was found in the brain (Suzuki,
    1971). Rats maintained on a dietary level of triethyltin hydroxide of
    20 mg/kg displayed weakness in the hind legs after one week. The
    weakness reached a maximum at 3-4 weeks, when about half of the rats
    died, but the signs disappeared in one week, when normal diet was
    restored. Some of the rats showed signs of becoming resistant to the
    substance. At a dietary level of 40 mg/kg, the recovery process was

    unaltered but, at 80 mg/kg, the rats developed generalized muscular
    tremors that resembled those seen in acute trimethyltin poisoning
    (Stoner et al, 1955). This course of events, including the development
    of resistance to triethyltin hydroxide at a dietary level of 20 mg/kg
    was corroborated by Magee et al. (1957), who was also able to produce
    a specific lesion of the central nervous system (CNS) by feeding rats
    with a dietary level of triethyltin hydroxide of 20 mg/kg. The lesion
    consisted of an oedema extending throughout the white matter. It was
    microscopically visible after 3 days of exposure and progressed to a
    maximum at about 2 weeks. After 4 months of normal diet, the changes
    in the brain and spinal cord disappeared. Electronmicroscopic studies
    of this lesion in rabbits disclosed that the myelin sheaths split to
    form clefts and vacuoles in which the fluid responsible for the oedema
    accumulated (Aleu et al., 1963). The triethyltin-induced lesion of the
    CNS is different from those produced by alkyl derivatives of lead,
    antimony, bismuth, and mercury, which cause damage to the nerve cells,
    but appears to be similar to that produced in rats by exposure to
    hexachlorophene (Kimbrough & Gaines, 1971). When 5 mg of triethyltin
    sulfate per litre of drinking water was administered to newborn rats
    and their mothers for 4 months, all young rats were asymptomatic,
    whereas the mothers showed paralysis of posterior limbs, severe
    cerebral oedema, and status spongiosus of the white matter (Suzuki,
    1971). Hedges & Zaren (1969) described papilloedema in monkeys
    following a single intraperitoneal dose of triethyltin acetate of
    0.1 mg/kg, body weight administered as a 5% solution. Oedema of the
    white matter of the brain extended through the chiasma and orbital
    optic nerve to the retrolaminar area, but the papilloedema was not due
    to extension of the intramyelinic tin oedema of the nerves through the
    lamina. Papilloedema does not develop in the cat when similarly
    treated, in spite of profound swelling of the intracerebral white
    matter, chiasma, and the orbital optic nerve as far as the
    retrolaminar portion.

        Tricyclohexyltin hydroxide appears to be a depressant for the
    central nervous system, although it is not as potent as triethyltin
    acetate and cerebral oedema does not occur (FAO/WHO, 1971, p. 526).
    Johnson et al. (1975) studied the acute toxicity of tricyclohexyltin
    hydroxide in sheep by intrarumenal injection of doses ranging from 15
    to 750 mg/kg body weight. Central nervous depression was observed at
    50 mg/kg body weight.

        Because of the enzymatic conversion of tetraalkyltin compounds by
    hepatic microsomal enzymes (section 6.2.4), these compounds act in a
    similar way to trialkyltin compounds. The toxicity of tetraalkyltin
    compounds in mice and clogs was studied by Caujolle and his colleagues
    (1954). Tetraethyltin was the most active, tetramethyltin slightly
    less toxic, and for the higher members of the series, the toxicity
    decreased with increasing molecular weight. The toxic effects of
    tetramethyltin differed from those of the other members of the series
    and the dominant findings were tremors and hyperexcitability. The

    major effects of the other members of the tetraalkyltin series were
    muscular weakness and paralysis followed by respiratory failure.
    Development of the signs of poisoning were noticeably slow following
    administration of tetraalkyltin compounds and death was often delayed.
    Intravenous administration of tetraethyltin at 25 mg/kg produced a
    slight increase in the respiratory rate and vasodilatation as
    immediate effects, but after 1.5-2 h, prostration with muscular
    weakness was noted. The later effects resembled those seen after
    administration of triethyltin; the mode of death was also similar
    (Stoner et al., 1955).

    7.2.9.  Effects on reproduction and the fetus

        Few studies of the effects of disubstituted organotin compounds on
    reproduction have been reported. Nikonorow et al. (1973) reported
    toxic effects of dioctyltin- S,S'-bis(isooctylmercaptoacetate) on the
    embryo and fetus at daily oral doses of 20 and 40 mg/kg body weight,
    administered for about 3 months. A distinct increase in the incidence
    of fetal deaths was observed. Teratogenic effects were not found.

        Investigations on triphenyltin hydroxide have yielded variable
    results. In 2 investigations on rats, oral dose rates of 20 mg/kg per
    day for less than 4 weeks produced histologically evident
    abnormalities in the testes and ovaries. Diminution in the size of the
    testes and less advanced maturation of the germinal epithelium was
    seen in rats receiving triphenyltin hydroxide at a rate of 5 mg/kg for
    90 days, although a 3-generation reproduction study at this dietary
    level failed to demonstrate any adverse effect on the reproductive
    indices (FAO/WHO, 1971, pp. 332-333). In another experiment (Gaines &
    Kimbrough, 1968), dietary levels of up to 200 mg/kg over a 276-day
    period caused a reversible reduction in fertility in male rats which
    was considered to be due to a pronounced decrease in food intake, that
    was later reversed. No gross abnormalities were seen in the offspring
    of these males when mated with untreated females. In 3 later
    experiments (FAO/WHO, 1971, p. 333) in which weanling animals were fed
    the compound in their diets at doses of up to 25 mg/kg, the previously
    reported change in testicular development could not be confirmed.

        In a 3-generation study in which rats produced 2 litters per
    generation, animals continuously received a dietary level of
    tricyclohexyltin hydroxide of up to 100 mg/kg (corresponding to 4-6 mg
    test compound/kg body weight per day for an adult rat). No evidence of
    any adverse effects on reproduction could be found and examination of
    the fetuses did not reveal any indication of teratogenic effects
    (FAO/WHO, 1971, p. 524). No evidence of teratogenic effects from
    tricyclohexyltin hydroxide was obtained in a study in which pregnant
    rabbits received up to 3 mg/kg body weight per day from the 8th to
    16th day of gestation (FAO/WHO, 1971, p. 524). In a study in which
    diets containing tricyclohexyltin hydroxide were fed to Japanese
    quail, no evidence of ill effects on egg fertility or hatchability was
    seen at a dietary level of 1 mg/kg.

        Effects observed at a dietary level of 10 mg/kg were of doubtful
    significance but a dietary level of 100 mg/kg had definite effects on
    fertility, egg production, hatchability, and embryonic mortality
    (FAO/WHO, 1971, pp. 523-524).

    7.2.10  Carcinogenicity

        In an 18-month study, mice were given an oral dose (stomach tube)
    of 0.46 mg/kg body weight per day of triphenyltin acetate between the
    ages of 7 and 28 days and thereafter a dietary level of 1206 mg/kg.
    There was no statistically significant increase in tumours compared
    with a control group (Innes et al., 1969). In a 2-year study on rats
    receiving tricyclohexyltin hydroxide at concentrations up to 12 mg/kg
    body weight (section 7.2.3), the pattern of tumour incidence
    throughout both the control and test groups appeared to be random and
    did not suggest a dose-response relationship (FAO/WHO, 1971, p. 527).
    Reports of experiments specifically designed to investigate the
    carcinogenicity of other compounds were net available to the Group.

    7.2.11  Effects on chromosomes

        Mazaev & Slepnina (1973) reported an increased percentage of
    chromosomal aberrations in bone marrow cells and also an increased
    mitotic index in cells of the small intestine mucosa of rats that had
    received dibutyltin sulfide at 0.1 mg/kg body weight per day
    administered by intubation over a period of 6 months. Doses of less
    than 0.1 mg/kg body weight per day did not cause poisoning and did not
    have any effect on the chromosomes or somatic cells.

    7.2.12  Other effects

        A reduction in weight gain, mainly related to reduced food intake,
    has been recorded in various species given organotin compounds. In
    rats, a dietary level of dibutyltin dichloride of 80 mg/kg
    administered for 90 days caused growth retardation and decreased food
    intake (Gaunt et al., 1968). Triphenyltin acetate given to guineapigs
    at dietary levels exceeding 5 mg/kg for 2 years, caused a dose-related
    inhibition of growth rate (FAO/WHO, 1971, p. 341). A dietary level of
    tricyclohexyltin hydroxide of 25 mg/kg for 90 days, caused a slight
    reduction in weight gain in female rats (Shirasu, 1970), and dogs
    receiving the same compound in their diet at a level of 12 mg/kg for 6
    months also lost weight; some animals that totally refused the food
    died from starvation (FAO/WHO, 1971, pp. 526-527).

        Severe cardiovascular changes were demonstrated electro-
    cardiographically in sheep after intrarumenal administration of
    tricyclohexyltin hydroxide at doses greater than 150 mg/kg body weight
    (Johnson et al., 1975).

    7.2.13  Mechanisms o[ action

        There have been relatively few studies of the biochemical effects
    of dialkyltin compounds, which do not cause cerebral oedema. In acute
    toxicity experiments on the rat, diethyltin compounds did not affect
    the sodium and potassium contents of the central nervous system but
    caused a decrease in its water con, tent (Magee et al, 1957).

        The action of a homologous series of disubstituted
    organotin-compounds from dimethyl- to dioctyltin have been examined;
    most of them inhibit mitochondrial respiration by preventing the
    oxidation of keto acids, presumbly via the inhibition of alpha-keto
    oxidase activity, leading to the accumulation of pyruvate (Aldridge,
    1976; Piver, 1973).

        Of the trisubstituted compounds, triethyltin compounds have been
    the most closely examined in relation to the mechanism by which they
    cause ill effects. Trimethyl- and triethyltin compounds are potent
    inhibitors of oxidative phosphorylation in the mitochondria for which
    these compounds have a high binding affinity (Aldridge, 1958; Aldridge
    & Street, 1964, 1970, 1971). In a later study by Aldridge (1976),
    triorganotin compounds were stated to derange mitochondrial function
    in 3 different ways, namely by secondary responses caused by discharge
    of a hydroxyl-chloride gradient across mitochondrial membranes, by
    interaction with the basic energy conservation system involved in the
    synthesis of ATP, and by an interaction with mitochondrial membranes
    causing swelling and disruption.

        Using a 113Sn-labelled triethyltin compound, Rose (1969)
    identified a pair of histidine residues on guineapig liver
    mitochondria as the binding site for triethyl compounds. Thus, one
    molecule of rat haemoglobin binds 2 molecules of triethyltin; the
    binding sites are located in the globin.

        Stockdale et al. (1970) showed that the order of effectiveness for
    the organotin compounds in inhibiting coupled respiration was tributyl
    > tripropyl > triphenyl > trimethyl. Two separate effects were
    suggested:  (a) an oligomycin-like inhibition of coupled
    phosphorylation; and  (b) an alteration of hydroxide exchange across
    lipid membranes producing uncoupling, swelling, and reduction of
    intramitochondrial substrate and phosphate concentrations followed by
    structural damage.

    7.2.14  Effective doses and dose rates  Lethal doses

        The median lethal doses for some mono-, di-, tri-, and
    tetrasubstituted organotin compounds are given in Tables 13, 14, 15,
    and 16.a Trimethyl and triethyltin compounds, administered orally,
    are more toxic than the higher homologues of the trialkyltin group.
    The oral toxicity diminishes progressively from tripropyltin to
    trioctyltin compounds (Barnes & Stoner, 1958). This is probably
    because of poorer absorption of higher trialkyltin compounds from the
    gastrointestinal tract, as judged from the difference between the oral
    and intraperitoneal toxicity of higher trisubstituted alkyltin
    compounds (Stoner et al., 1955). The intraperitoneal toxicity of
    various trialkyltin compounds does not differ to any large extent. In
    rats, Stoner et al. (1955) found that triethyltin sulfate was equally
    toxic after intravenous, intraperitoneal, and oral administration. The
    lethal dose per kg body weight given intravenously or
    intraperitoneally was 10 mg/kg, causing death within 4-5 days. A dose
    of 40 mg/kg body weight killed the rat in 2 h. The oral LD50 for
    tricyclohexyltin hydroxide (Table 15) for most species, appears to be
    between 100 and 1000 mg/kg body weight, while the intraperitoneal and
    intravenous routes yield LD50 values below 20 mg/kg. The difference
    between oral and parenteral toxicity reflects the poor absorption of
    tricyclohexyltin hydroxide from the gastrointestinal tract.

        In rats and dogs fed with tricyclohexyltin hydroxide, the
    metabolites, dicyclohexyltin oxide and traces of cyclohexylstannoic
    acid have been identified. Dicyclohexyltin oxide and
    cyclohexylstannoic acid also constitute a small portion of the
    residues on fruit as a result of photodecomposition (FAO/WHO, 1971,
    pp 522, 534). The median lethal dose of these metabolites may
    therefore be of interest. The LD50 of dicyclohexyltin oxide in the
    rat appears to be about 350 mg/kg body weight, whereas the LD50 value
    of cyclohexylstannoic acid in this species is probably ten times
    higher (FAO/WHO, 1971, pp. 524-526).

        Only a small amount of data is available concerning the acute
    toxicity of tetraalkyltin compounds. The median lethal dose for
    tetraethyltin is given in Table 16.


    a  Additional data on the toxicity of organotin compounds may be
       found in a proposal for the United Nations classification and hazard
       grouping of organotin compounds submitted by the expert from the
       Netherlands to the Committee of Experts on the Transport of Dangerous
       Goods of the United Nations Economic and Social Council
       (EN/CN.2/CONF.5/R.607 of November 1976).

        Table 13.  Acute oral toxicity of some mono-organotin compounds in various animal species

                                      Medium lethal
    Trivial name of compound          dose                Species       Reference
                                      (LD50, mg/kg)

    butylstannoic acid                > 6000              mouse         Pelikan & Cerny (1970b)
    butyltin trichloride              1400                mouse
                                      2140                rat           Marhold (1972)
    butyltin-S,S'S"-tris              1520                mouse         Pelikan & Cerny (1970b)
    octyltin trichloride              4600                mouse         Klimmer (1969)
    octyltin-S,S',S"-tris             1500                rat (male)    Pelikan & Cerny (1970a)

                                                                                                  Minimum effective and no-observed-effect doses

        When dibutyltin dichloride was fed to rats for 90 days at dietary
    levels of 10, 20, 40, and 80 mg/kg, the no-observed effect level was
    40 mg/kg, equivalent to 2 mg/kg body weight per day (Gaunt et al.,
    1968). When dibutyltin was administered to rats for 6 months, the
    no-observed-effect level was 20 mg/kg diet (Barnes & Stoner, 1958).
    Dibutyltin sulfide, administered to rats at oral doses of 1.0, 0.1,
    0.01, and 0.001 mg/kg body weight, per day for 7 months, was tolerated
    without any detected adverse effects up to a dose o.f 0.01 mg/kg per
    day but the higher levels of 0.1 and 1.0 mg/kg per day caused
    intoxication (Mazaev & Korolev, 1969). By comparison, the toxicity of
    dioctyltin compounds was relatively low (Klimmer, 1969). Thus,
    dioctyltin did not produce any injury in rats, mice, or guineapigs at
    oral doses up to 400 mg/kg body weight per day when given for 3-4
    successive days, nor were there any ill effects when it was added to
    the daily diet of rats for 4 months at a rate of 200 mg/kg (Barnes &
    Stoner, 1958).

        Table 14.  Acute toxicity of some diorganotin compounds in various animals

                                             Medium lethal dose
    Trivial name of compound                 (LD50,    mg/kg)         Species                 Reference

    dibutylin di(2-ethylhexoate)              200      (oral)       rat (male)           Calley et al. (1967)
    dibutyltin di(butyl maleate)              120      (oral)       rat                  Klimmer (1969)
    dibutyltin di(nonylmaleate)               170      (oral)
    dibutyltin dichlorlde                     100      (oral)       rat (male)           Klimmer (1969)
                                              182      (oral)       rat (male)           Mazaev et al. (1971)
                                              112      (oral)       rat (female)
                                               35      (oral)       mouse
                                              190      (oral)       guineapig
                                              150      (oral)       rat                  Marhold (1972)
    dibutyltin-S,S'-bis                       150      (oral)       rat (male)           Klimmer (1969)
    (2-ethylhexylmercaptoacetate)             175      (oral)                            Klimmer (1969)
    dibutyltin dilaurate                      243      (oral)       rat                  Marhold (1972)
                                               45      (oral)       rat                  Marhold (1972)
    dibutyltin oxide                          520      (oral)       rat (male)           Klimmer (1969)
                                               39.9    (i.p.)a      rat (female)         Robinson (1969)
                                               24      (oral)       mouse                Mazaev & Slepnina (1973)
    dibutyltin sulfide                        145      (oral)       rat (male)
                                              150      (oral)       rabbit
                                              180      (oral)       rat (female)
                                              800      (i.p.)       rat (female)         Robinson (1969)
                                            > 800      (i.p.)       rat (female)         Robinson (1969)
    dioctyltin acetate                       2030      (oral)       rat                  Klimmer (1969)
    diocyltin dibutylmaleate                 3750      (oral)       mouse                Pelikan et al. (1970)
    (butylmercaptoacetate)                   1140      (oral)       white mouse          Pelikán & Cerny (1970a)
    dioctyltin bis
    (dodecylmercaptide)                      4000      (oral)       white mouse
    dioctyltin bis
    (2-ethylhexylmaleate)                   2760/      (oral)       rat (male)           Klimmer (1969)

    Table 14.  (contd).

                                             Medium lethal dose
    Trivial name of compound                 (LD50, mg/kg)          Species              Reference

    dioctyltin-S,S'-bis                      2010      (oral)       white mouse          Pelikan & Cerny (1970a)
    dioctyltin-S,S'-bis                      3700      (oral)       rat (male)           Klimmer (1969)
    dioctyltin-S,S'-(1,4-                    2950      (oral)       rat (male)
    dioctyltin dichloride                   5500/
                                             8500      (oral)       rat (male)
    dioctyltin dilaurate                     6450      (oral)       rat (male)
                                              800      (i.p.)       rat (female)         Robinson (1969)
    dioctyltin di(1,2-
    propylene-glycolmaleate)                 4775      (oral)       rat (male)           Klimmer (1969)
    dimercaptoacetate)                        880      (oral)       rat (male)
    dioctyltin maleate                       4500      (oral)       rat (male)
    ß-mercapto-propanoate                   1850/
                                             2050      (oral)       rat (male)
    dioctyltin oxide                         2500      (oral)       rat (male)
    dioctyltin mercaptoacetate                945      (oral)       rat (male)

    a  intraperitoneal

    Table 15.  Acute toxicity of some triorganotin compounds in various animals

    Trivial name                    Medium lethal dose
    of compound                      (LD50, mg/kg)      Species         Reference

    oxide)-1-triethyl-               9.8     (i.p.)       rat               Ignatjeva (1968)
    stannyloxy)ethane                9.6     (i.p.)       mouse             Ignatjeva (1968)
    (1-propynyl)formal              10.7     (i.p.)       rat               Ignatjeva (1968)
    acetylene                        9.9     (i.p.)       mouse             Ignatjeva (1968)
                                     9.1     (i.p.)       rat               Ignatjeva (1968)
    propyne                         11.8     (i.p.)       mouse             Ignatjeva (1988)
                                    11.4     (i.p.)       rat               Ignatjeva (1968)
    triethyltin acetate              4       (oral)       rat (female)      Stoner (1966)
    triethyltin chloride             5       (i.p.)       rat (female)      Robinson (1969)
    triethyltin sulfate              5.7     (i.p.)       rat (male)        Stoner (1966)
                                     5.3     (i.p.)       guineapig         Stoner (1966)
    tributyltin acetate             46       (oral)       white mouse       Pelikan & Cerny (1968a)
                                    99       (oral)                         J. Pharm. Sci. (1967)
                                   133       (oral)       rat (male)        Klimmer (1969)
    tributyltin benzoate           108       (oral)       white mouse
                                                                            Pelikan & Cerny (1968a)
                                   132       (oral)       rat               Arzneimittelforsch. (1969)
    tributyltin chloride           117       (oral)       white mouse       Pelikan & Cerny (1968a)
                                   129       (oral)       rat               Manhold (1972)
    tributyltin laurate            180       (oral)       white mouse       Pelikan & Cerny, (1968a)
    tributyltin oleate             195       (oral)       rat               Klimmer (1969)
    tributyltin salicylate         137       (oral)       rat (male)        Klimmer (1969)

    Table 15.  (contd).

    Trivial name                    Medium lethal dose
    of compound                      (LD50, mg/kg)        Species         Reference

    bis(tributyltin oxide)         112-      (oral)       rat (male)        Klimmer (1969)
                                   180       (oral)       rat               Truhaut et al. (1976)
                                   234       (oral)       rat               Sheldon (1975)
                                   194       (oral,       rat (male)        Elsea & Paynter (1958)
                                   148       (oral,       rat (male)        Elsea & Paynter (1958)
                                    11.7     (dermal)     albino rabbit     Elsea & Paynter (1958)
                                    10.0     (oral)       white mouse       Pelikan & Cerny (1969)
    trihexyltin acetate           1000       (oral)       rat               Barnes & Stoner (1958)
    trioctyltin chloride        10 000       (oral)       rat (male)        Klimmer (1969)
    triphenyltin acetate            21       (oral)       guineapig         Klimmer (1963)
                                    24       (oral)       guineapig         Kimbrough (1976)
                                   136       (oral)       rat               Klimmer (1963)
                                    81       (oral)       mouse (male)      FAO/WHO (1971)
                                     7.9     (i.p.)       mouse (male)      Stoner (1966)
                                   136       (oral)       rat (male)        Klimmer (1964)
                                   491       (oral)       rat (female)      Stoner (1966)
                                   450       (dermal)     rat (male)        Klimmer (1963)
                                     8.5     (i.p.)       rat (female)      Stoner (1966)
                                    11.9     (i.p.)       rat (female)      Stoner (1966)
                                    13.2     (i.p.)       rat (male)        Klimmer (1964)
                                    21       (oral)       guineapig
                                                          (male)            Klimmer (1964)
                                     3.7     (i.p.)       guineapig
                                                          (male)            Stoner (1966)

    Table 15.  (contd).

    Trivial name                    Medium lethal dose
    of compound                      (LD50, mg/kg)     Species          Reference

    triphenyltin acetate             5.3     (i.p.)       guineapig
    cont'd.                                               (male)            Klimmer (1964)
                                    30-      (oral)       rabbit (male)     Klimmer (1964)
    triphenyltin chloride           80       (oral)       rat (male)        FAO/WHO (1971)
                                   135       (oral)       rat (female)      FAO/WHO (1971)
    triphenyltin hydroxide         245       (oral)       mouse (male)      FAO/WHO (1971)
                                   209       (oral)       mouse (female)
                                                                            FAO/WHO (1971)
                                   240       (oral)       rat (male)        Gaines & Kimbrough (1968)
                                   360       (oral)       rat (female)      Gaines & Kimbrough (1968)

                                    27.1     (oral)       guineapig         FAO/WHO (1971)
                                    31.1     (oral)       guineapig         FAO/WHO (1971)
                                   171       (oral)       rat (male)        Marks et al. (1969)
                                   268       (oral)       rat (female)      Marks et al. (1969)
    tricyclohexyltin               710a      (oral)       mouse-            FAO/WHO (1971)
    hydroxide                                             peromyscus
                                  1070a      (oral)       mouse-swiss       FAO/WHO (1971)
                                   540       (oral)       rat               FAO/WHO (1971)
                                    13       (i.p.)       rat               FAO/WHO (1971)
                                   780       (oral)       guineapig         FAO/WHO (1971)

    Table 15.  (contd).

    Trivial name                    Medium lethal dose
    of compound                      (LD50, mg/kg)      Species         Reference

    tricyclohexyltin                 9       (i.p.)       guineapig         FAO/WHO (1971)
    hydroxide                      500-      (oral)       rabbit            FAO/WHO (1971)
    cont'd.                       1000
                                 > 126       (i.p.)       rabbit            FAO/WHO (1971)
                                   150a      (oral)       sheep             Johnson et al. (1975)
                                    14       (i.v.)c      dog               FAO/WHO (1971)
                                     6       (i.v.)       cat               FAO/WHO (1971)

    a  approximate lethal dose
    b  intraperitoneal
    c  intravenous


        Table 16.  Acute oral toxicity of some tetraorganotin compounds in various animal species

    Trivial name       Medium lethal dose   Species        Reference
    of compound        (LD50, mg/kg)

    tetraethyltin           40.0            mouse          Skackova (1967)
                            15.0            rat
                            40.0            guineapig
                             7.0            rabbit
                            40              mouse          Mazaev et al. (1971)
                             9.0            rat
                            40.0            guineapig
                             7.0            rabbit
    tetrabutyltin         6000              rat            Skackova (1967)

        Data on effective doses of trisubstituted organotin compounds are
    available only for triphenyltin derivatives and tricyclohexyltin
    hydroxide. Triphenyltin acetate was administered, by gavage, to groups
    of rats at doses equivalent to dietary levels of 5, 10, 25, and
    50 mg/kg for up to 17 days. While no adverse effects were found at the
    25 mg/kg level, the 50 mg/kg level resulted in the death of animals,
    mainly as a result of infection (Klimmer, 1964). In a 2-year study on
    rats fed diets containing concentrations of triphenyltin hydroxide of
    up to 10 mg/kg, the no-observed-effect level was about 2 mg/kg
    (equivalent to about 0.1 mg/kg body weight per day) (FAO/WHO, 1971,
    pp. 341-342). In another 2-year study in which groups of guineapigs
    were fed diets containing concentrations of triphenyltin acetate, up
    to 200 mg/kg, the no-observed-effect level was 5 mg/kg. At higher
    levels there was a dose-related increase in mortality and the
    occurrence of other effects such as inhibition of growth rate and
    fatty degeneration of the liver and heart (FAO/ WHO, 1971, p. 341).
    With respect to tricyclohexyltin hydroxide, no toxic effects were
    noted in rats receiving 12.5 mg/kg body weight daily for 19 days,
    whereas a rate of 25 mg/kg per day caused toxic effects (FAO/WHO,
    1971, pp. 527-528). Rats were fed on diets providing up to 12 mg/kg
    body weight per day of tricyclohexyltin hydroxide in a 2-year study;
    the no-observed-effect level was 3 mg/kg body weight per day (FAO/WHO,
    1971, p. 528). When dogs were fed tricyclohexyltin hydroxide in the
    diet at concentrations of up to 12 mg/kg body weight per day for 6-24
    months, many dogs refused the 12 mg/kg per day diet, causing weight
    loss and death from starvation. The no-observed-effect level was found

    to be about 0.75 mg/kg per day (FAO/WHO, 1971, pp. 526-527). Johnson
    et al. (1975) also reported the effects of thoroughly wetting the skin
    of yearling cattle, goats, and sheep with suspensions of
    tricyclohexyltin hydroxide. They found that cattle tolerated
    suspensions up to a concentration of 5 g/litre while anorexia was
    registered in some animals after spraying with a suspension of
    10 g/litre. Yearling goats and sheep tolerated suspensions of up to
    1 g/litre. Transitory anorexia and eye irritation developed after
    application of a suspension of 20 g/litre to the skin of goats.

        Few data are available on the effective dose levels of
    tetrasubstituted organotin compounds. Intravenous administration of
    tetraethyltin at 25 mg/kg body weight produced a slight increase in
    respiratory rate and vasodilatation as immediate effects, but, 1.5-2 h
    later, prostration with muscular weakness occurred. (Stoner et al.,


        There are comparatively few clinical observations and
    epidemiological data concerning the effects of inorganic tin compounds
    on man and even fewer on the effects of organotin compounds.

    8.1  Inorganic Tin Compounds

    8.1.1  Acute poisoning

        Some episodes of acute poisoning have been reported, mainly in
    association with the ingestion of fruit juices containing high
    concentrations of tin. The major symptoms and signs noted were nausea,
    vomiting, diarrhoea, fatigue, and headache. The concentrations of tin
    in the products thought to have been associated with the incidents
    were uncertain in many cases, but were probably in the range of
    300-500 mg/kg (Horio et al, 1967). Orange and apple juice, containing
    tin concentrations of 250-385 mg/kg were suspected of causing one
    incident (Benoy et al., 1971). Nausea, vomiting, and diarrhoea were
    recorded in individuals consuming-peach preserves that contained a tin
    concentration of 563 mg/kg, zinc at 1.5 mg/kg, cadmium at 0.1 mg/kg,
    lead at 0.16 mg/kg, copper at 1 mg/kg, nitrate at 93 mg/kg, nitrite at
    1.7 mg/kg, and chloride at 115 mg/kg (Nehring, 1972). Acute
    gastroenteritis followed ingestion of a fruit punch stored in a tin
    can and containing a tin concentration of 2000 mg/litre. First
    symptoms occurred after 1-2 h, the earliest and commonest being
    bloatedness, followed by severe nausea, stomach cramps, vomiting and,
    in one-third of the patients, mild diarrhoea (Warburton et al, 1962).
    Other similar outbreaks have involved canned cherries (Luff & Metcalf,
    1890), asparagus, herring (Schryver, 1909), and apricots (Savage,
    1939) with tin concentrations ranging from 300 to about 1000 mg/kg.

        An incident of acute intoxication after the ingestion of canned
    peaches was reported by Sverrsson (1975). It was unique in that about
    110 participants in a meeting received nothing else to eat or drink,
    except for the peaches. The report was based on questionnaires
    received from 85 persons, 76 (89%) of whom had fallen ill. About half
    of these had developed symptoms such as nausea, vomiting, and
    diarrhoea within 1 h. The majority became symptom-free after 24 h. The
    fruit contained a mean tin concentration of 533 mg/kg (range
    413-597 mg/kg) and the juice 369 mg/kg (range 298-405 mg/kg). Two out
    of 7 persons who had consumed only one quarter of the contents fell
    ill. The calculated intake of tin for these persons was 50 mg.

        In another report, canned tomato juice was associated with 113
    cases of acute gastroenteritis (Barker & Runte, 1972). In a small
    number of these cases, superficial erosion of the mucosa of the mouth
    was observed, while abdominal distension and cramps, and diarrhoea
    were quite common. The cans containing the juice showed complete
    corrosion of tin linings and this yielded a product containing a tin
    concentration of approximately 400 mg/kg. The crops of tomatoes, used
    to make this particular juice, had been grown in soil excessively
    treated with nitrate fertilizer and contained high levels of nitrate;
    complete corrosion of the lining of the cans occurred within
    approximately 6 months.

        Five human volunteers did not show any toxic signs after drinking
    fruit juices containing about 500 or 730 mg/kg of tin, but all had
    some gastrointestinal disturbance after drinking 5-7 ml/kg body weight
    of fruit juice containing a tin concentration of about 1400 mg/litre
    (Benoy et al., 1971). There was no evidence to indicate that the
    effects were due to the absorption of tin, the likeliest cause being
    local irritation of the mucous membranes of the alimentary tract.

    8.1.2  Prolonged exposure  Effects of inhalation

        The only available information on exposure by inhalation pertains
    to pneumoconiosis caused by the inhalation of tin(IV) oxide. This
    benign condition is termed stannosis.

        More than 200 cases of stannosis have been described (Bartak
    et al., 1948; Cutter et al., 1949; Dundon & Hughes, 1950; Oyanguren
    et al., 1958; Pendergrass & Pryde, 1948; Robertson & Whitaker, 1957;
    Schuler et al., 1958). The relative importance of exposure to tin
    fumes in the etiology of this disorder was emphasized by Dundon &
    Hughes (1950). The significance of the quantity of dust and the
    duration of exposure were stressed by Robertson & Whitaker (1957), who
    reviewed 121 cases.

        Pendergrass & Pryde (1948) noted stannosis in a man who, for 15
    years, had been bagging tin oxide material containing 96.5% tin(IV)
    oxide and small amounts of aluminium, iron, and sodium but not silica.
    Radiography revealed small dense shadows (denser than those of
    silicosis) resembling those of barytosis in both lungs. Bartak et al.,
    (1948) reported a similar case in a workman who had suffered from
    asthma for many years and who attended a furnace in which metallic tin
    was burnt to produce tin(IV) oxide. Necropsy of this man, who died
    from gastric carcinoma, revealed deposits of tin(IV) oxide in the

    lungs, lymph glands, liver, and spleen. Six other workmen with a
    similar radiographic appearance of the lungs, did not have any
    symptoms of asthma or signs of pulmonary dysfunction. Similar
    radiological findings were reported by Cutter et al. (1949) in 2 cases
    with nodules 1-2 mm in diameter unaccompanied by evidence of pulmonary
    dysfunction. Both had been working in a tin recovery department for 20

        Oyanguren et al., (1958) reported 10 cases of stannosis in workers
    involved in a process where tin ore concentrates were reduced to
    metal. The workers were exposed to dust with a high tin and a low
    silica content and to fumes rich in tin. None of the exposed workers
    had any disability and the vital capacity, maximal breathing and
    resting minute volume, and respiratory reserve were normal, as were
    the findings on the blood and urine. Radiological examination of these
    10 workers showed that the first alteration appeared to be increase of
    bronchovascular markings, with hilar thickening in the early stages;
    later, well-defined nodular elements appeared first in the middle
    third of the right and then of the left lung. These appeared to
    progress to the rest of the lung fields, and with continuous exposure,
    accumulation of tin(IV) oxide gave a metallic density to a part of the
    nodules, which subsequently acquired an appearance of lipoid droplets.
    In the later stages, the bronchovascular markings disappeared as the
    density of the shadows increased. The radiographic changes appeared
    after some 3-5 years of exposure (Schuler et al., 1958). Hlebnikova
    (1957) made a survey over a number of years of workers, who were
    exposed to condensation aerosols, formed during the smelting of tin
    and consisting mainly of tin(IV) oxide. The free silica concentration
    in the aerosols was not more than 1% and the total silica did not
    exceed 3%. The total dust concentration in air varied between 3 and
    70 mg/m3. Workers developed pneumoconiosis after 6 to 8 years of
    working at the smelter. The authors described 45 cases of
    pneumoconiosis in workers, who were employed at the smelter from 6 to
    20 years, Six of them were reported to have second degree
    pneumoconiosis. X-ray examination showed small spotty shadows, but
    there were no other symptoms or signs. The opacities seen on the
    radiographs were thought to be due to the accumulation of
    tin-containing dust and the development of connective tissue, This was
    confirmed by experiments on rats exposed to tin(II) oxide. No cases of
    pneumoconiosis were observed in 10 years, after the dust concentration
    had been reduced to 10 mg/m3. An important feature of stannosis is
    that fibrosis of the lung does not develop, providing that other
    agents such as silica are not present.  Effects of ingestion

        Packaged military rations were fed to 9 young male adult
    volunteers for successive 24-day periods. The average tin content of a
    control fresh diet was 13 mg/kg (in dry solids), while C-rations
    stored at 1°C contained a tin concentration of 33 mg/kg, and rations
    stored at 37°C contained 204 mg/kg. All the tin ingested was
    accounted for by faecal elimination. No toxic effects were noted
    (Calloway & McMullen, 1966). Dack (1955) reported a study in which 4
    subjects ate canned pumpkin containing a tin concentration of about
    380-480 mg/kg and canned asparagus containing a concentration of about
    360 mg/kg, for 6 days, with no apparent illness. In an earlier study,
    Mamontova (1940) did not observe any toxic manifestations in 4
    volunteers who, for a period of 30 days, consumed 250 g per day of
    canned fruit containing 212-250 mg of tin.

    8.2  Organotin Compounds

    8.2.1  Local effects

        Toxic lesions among laboratory and process workers handling di-
    and tributyltin compounds were reported by Lyle (1958). Most of the
    lesions were typical acute skinburns, caused by the colourless di- or
    tributyltin chlorides, which can come into contact with the skin
    without exposed workers being aware of it. This type of lesion
    developed 1 to 8 h following exposure. When the substance was washed
    off immediately, no lesion developed. A more diffuse, but less rapidly
    healing lesion, was caused by contact with clothes that had been
    moistened by vapour or liquid compounds. This subacute irritation was
    characterized by itching, affecting mostly the skin of the lower
    abdomen, thighs, and groin. On examination, an easily distinguishable
    erythematous eruption, was noted. Cessation of contact with the
    compound was followed by rapid healing. Following contact with the
    eye, lachrymation and severe suffusion of the conjunctivae appeared
    within a few minutes and persisted for 4 days. Immediate lavage of the
    eye did not prevent the development of the signs.

        Lyle (1958) also studied the skin lesions induced by butyltin
    compounds by applying various compounds on the skin of the back of the
    hands of 5 volunteers. Skin lesions could be produced by a single
    application of dibutyltin dichloride, and of the chloride, acetate,
    and oxide of tributyltin, while the diacetate, dilaurate, oxide, and
    maleate of dibutyltin and also tetrabutyltin failed to produce any
    lesions. No visible changes occurred for 2 go 3 h after application,
    although a swelling of the mouth of the hair follicles was noticeable.
    The follicular inflammation progressed during the following 8 h with
    only slight visible irritation of the skin between the openings of the
    follicles. On the second day, sterile pustules developed over the
    follicular openings, but remained small during the next 3 to 4 days.
    After one week, the lesions had practically disappeared.

        Symptoms experienced by female spray-painters working with a latex
    paint, to which was added a fungicidal solution containing 20%
    bis(tributyltin) oxide, ethylene oxide, ethanol, and water, were
    described by Landa et al. (1973). The symptoms were reported to appear
    "immediately" after the start of spraying and were experienced by all
    the women engaged in the work. The first sensations were irritation of
    the nasal mucosa and the conjunctivae. The exposure continued for
    another fortnight during which the symptoms and signs became more
    severe, and included bleeding from the nose and mucous discharges. An
    otorhinolaryngological examination revealed rhinitis with distinct
    hyperaemia and haemorrhages of the nasal septum. The workers reported
    that the symptoms were less severe during weekends. When the addition
    of the fungicidal solution was abandoned, the symptoms disappeared.
    One year later, identical symptoms were reported by 4 spray-painters
    using latex paint. An inquiry disclosed that the manufacturer had
    begun to use bis(tributyltin) oxide as a fungicidal additive since the
    banning of the use of mercury. The authors considered that the
    trialkyltin compound was responsible for the symptoms. Measurements
    performed later indicated that the concentrations of tin in the
    breathing were below 0. 05 mg/m3 air.

        Another description of local effects seen in workers handling
    triphenyltin acetate was given by Markicevic & Turko (1967). These
    workers were engaged in the formulation of a 20% solution of a
    fungicide. During the hottest summer days, subjects working in the
    dustiest places developed conjunctival irritation and irritation of
    the mucous membranes of the upper respiratory tract as well as of the
    skin, the hands and scrotum being particularly affected. Effects on
    the central nervous system were not registered. The signs disappeared
    rapidly after termination of exposure.

        A wettable powder formation containing 50% tricyclohexyltin
    hydroxide was examined for its irritation and sensitization potential.
    No adverse reactions were observed in 53 females after sensitization
    applications and a challenge application 20 days later of 0.5 ml of an
    emulsion (10 g/litre). Tricyclohexyltin hydroxide was reported not to
    be dermally irritating at a concentration of about 0.01 mg/kg body
    weight (FAO/WHO, 1971).

    8.2.2  Systemic effects  Effects of Dermal exposure

        In a recent review (NIOSH, 1976), a fatal case was described in
    which a 29-year-old woman was accidentally drenched in a slurry
    containing triphenyltin chloride, diphenyltin dichloride, hexane, and
    other unidentified compounds at a temperature of 79.4°C. On arrival at
    hospital, first-degree thermal burns covered 10% of her body. Second-
    and third-degree burns with 80-85% desquamated skin developed 12 h
    later. Death from renal failure occurred 12 days after the accident.
    However, the agent responsible for her symptoms and signs and for the
    death could not be identified from the data available.

        Mijatovic (1972) reported a case of systemic intoxication
    resulting from dermal contact with a compound containing triphenyltin
    acetate (60%) and manganese dithiocarbamate (15%). The subject,
    engaged in agricultural aviation, spilt the compound on his hands and
    chest while filling the aeroplane. The skin on his chest and abdomen
    was endured after 3 h and vesicles developed the following day. He
    experienced headache, nausea, epigastric pain, and general weakness.
    Clinically the liver transaminases (SGPT) were elevated, reaching a
    maximum one month later. Two months later the transaminases were
    returning to normal, but the patient had pains over the liver, which
    was tender and enlarged. The liver damage persisted for 2 years and
    the case was labelled chronic hepatitis. No liver biopsy was
    performed.  Effects of inhalation

        Acute intoxication caused by the inhalation of triphenyltin
    compounds has been reported in some instances. Three cases occurred in
    farmers treating beetroot plants with triphenyltin acetate which was
    inhaled (Guardascione & di Bosco, 1967). The symptoms started from a
    few minutes to about 2 h after the first exposure. After 2 hours of
    spraying, one subject felt a general malaise and severe headache and
    eventually lost consciousness. On admission to the hospital he had a
    diffuse tremor and a slightly depressed sensorium. All laboratory
    investigations during the 2-week hospitalization were normal. When
    mixing triphenyl tin acetate powder into a solution, a second subject
    experienced repeated flushes, nausea, and shortness of breath, which
    started only a few minutes after inhalation. During the 8-day hospital
    surveillance, the only pathological finding was glucosuria. A third
    subject suffered from severe headache, strong nausea, and epigastric
    pains. However, laboratory investigations were normal. The headache
    persisted for 2 days while the epigastric pains and the nausea
    disappeared after one day. All 3 subjects recovered completely.

        Horacek & Demcik (1970) reported a group poisoning involving 2
    pilots and 3 mechanics following the spraying of a formulation
    comprising 60% of triphenyltin acetate and 15° of manganese
    dithiocarbamate. Protective measures were found to be deficient and
    food was consumed with unwashed hands; thus, exposure by both
    inhalation and ingestion could have occurred. Furthermore, other
    pesticides containing copper, zinc, DDT, and organophosphates were
    handled during exposure to the formulation, but the authors considered
    these substances unlikely to be responsible for the symptoms
    experienced. Exposure to the formulation continued for 2 weeks before
    symptoms were recognized and continued for 2 further weeks. One pilot
    experienced gastric pain, diarrhoea, and dryness of the mouth with
    severe thirst that was not relieved by drinking. He also felt pressure
    over the chest and slight shortness of breath. Blurred vision was
    experienced after one week of exposure. Clinically hepatomegaly with a
    painful liver was noted. Liver transaminases (SGPT) were elevated and
    the highest recorded value was obtained 6 weeks later. Hyperglycaemia
    and glycosuria were also present. Eight weeks afterwards, liver biopsy
    revealed marked diffuse steathosis without any detected necrosis.
    Monthly follow-ups showed that hepatomegaly and steathosis persisted
    for one year. The second pilot suffered from heartburn, diarrhoea, and
    vision disturbances. Clinically a hepatomegaly and a slight
    hyperglycaemia were registered. The symptoms persisted for 4 weeks and
    the glycosuria and hepatomegaly for 6 weeks. Recovery was complete.
    The mechanics had symptoms that were less severe, comprising
    diarrhoea, headache, eye pains, blurred vision, epigastric pain, and

        A worker engaged in the manufacture of butyltin compounds was
    reported to suffer from a reduced sense of smell (Akatsuka et al.,
    1959). It was first observed after an exposure period of 16 months,
    and a further deterioration of the olfactory sense was established
    during the following 8 months. The state persisted without any noted
    improvement for 2 years. Other reported symptoms were headaches in the
    occipital region, nasal haemorrhages, lassitude, and a feeling of
    stiffness in the shoulders.

        In four eases of acute poisoning due to exposure to organotin
    vapours, patients were reported to have suffered from such symptoms as
    vertigo, headaches, nausea and vomiting, and visual disturbances.
    Clinically, stasis of the papilla was found and all patients displayed
    pathological findings on the electroencephalograms. These were
    reversible in 7-25 days, and all eases recovered clinically. The
    organotin compound or compounds responsible for the intoxications were
    not identified (Prüll & Rompel, 1976).  Effects of ingestion

        A most serious episode involving organotin poisoning occurred in
    1954 due to oral administration of a proprietary preparation used for
    the treatment of furonculosis, osteomyelitis, anthrax, and acne. The
    drug was responsible for about 100 deaths and a total of about 210
    intoxications. These numbers vary to some extent depending on the
    source of information: Alajouanine et al., (1958) reported a total of
    210 deaths whereas another source quotes 102 deaths and at least 100
    persons permanently affected ( Br. med. J., 1958). A total of about
    400 000 capsules was sold ( Br. med. J., 1958), and about 1000
    persons were believed to have taken the drug (Barnes & Stoner, 1959).
    However, the capsules consumed by the intoxicated subjects amounted
    only to about 7% of the lot distributed ( Br. med. J., 1958),
    implying that the majority of the capsules were consumed without any
    known adverse effects. The main ingredients of the preparation were
    diethyltin diiodide (15 mg/capsule) and linoleic acid
    (100 mg/capsule). It was suggested that ethyltin triiodide,
    triethyltin iodide, or tetraethyltin could have been present as
    impurities because of deficiencies in the manufacturing process or as
    metabolites formed under the influence of various physical factors
    (Rondepierre et al, 1958). A theory that diethyltin diiodide would
    have reacted with the isolinoleic component producing tetraethyltin
    was also presented (Lecoq, 1954). The symptoms and clinical findings
    described in victims by Alajouanine et al. (1958) seem to favour the
    hypothesis of a trialkyltin compound being the causal agent, probably
    acting synergistically with other constituents. The clinical data of
    201 cases including 98 deaths were reviewed by Alajouanine et al.
    (1958). The dominating symptom, reported in about 98% of the cases,
    was a diffuse headache, sometimes intolerably severe, and appearing a
    few days after medication was started. Nausea and vomiting occurred in
    73%, visual disturbances, mainly photophobia, but also double vision,
    colour-vision disturbances and, in a few cases, blindness were
    recorded in 33% of cases. Ophthalmoscopic findings included
    congestion, papilloedema (Druault-Toufesco, 1955), and in some cases,
    papillary stasis (Gayral et al., 1958; Pesme, 1955). Frequent symptoms
    and signs were urinary incontinence, vertigo, loss of weight, and
    abdominal pains. Absence of fever and a tendency towards hypothermia
    were also noted. Psychological disturbances or stupor were reported in
    70% of the cases. Other findings were meningeal irritation,
    somnolence, insomnia, convulsions, constipation, and bradycardia.
    Sometimes electroencephalograms were altered but did not suggest any
    localized lesion. Death occurred during coma or from respiratory or
    cardiac failure and in some cases during convulsions. It is probable

    that most of the symptoms and signs could be attributed to a cerebral
    oedema, the occurrence of which was established at autopsies and
    decompressive surgery (Cossa et al., 1958, Fontan et al., 1958). This
    cerebral oedema of the white matter appeared to be very similar to
    that produced experimentally by administration of a proprietary
    preparation containing an organotin compound, to mice and monkeys
    (Gruner, 1958). Macroscopically, the brain was oedematic but the
    microscopic findings were minor.

        It has been reported that only 10 out of 103 subjects, who
    survived, recovered completely: in the remainder, symptoms such as
    headaches and asthenia persisted for at least 4 years (Barnes &
    Stoner, 1959). Information on later, follow-up studies is not
    available. The lethal dose of the preparation was in some instances
    only about 25 capsules taken during one week. Ingestion of 3 capsules
    was enough to cause intoxication in a 9-year-old child (Fontan et al.,

    8.3  Treatment of Poisoning

        Dimercaprol has been suggested by Stoner et al. (1945) to be an
    effective antidote for dialkyltin poisoning. It has also been reported
    to completely prevent the accumulation of alpha-keto acids produced by
    dialkyltin compounds (Barnes & Stoner, 1959). Although dimercaprol
    protected rats against the general toxic effects of these compounds,
    it did not have any effect on the response to triethyltin compounds.
    This seems to be due to the fact that dialkytin compounds, at least up
    to the dihexyl derivatives, react readily with sulfhydryl groups and
    the trialkyltin compounds do not (Barnes & Magos, 1968),

        Studer et al. (1973) reported that steroid therapy (dexamethasone)
    appeared to diminish mortality and the severity of brain oedema in
    rats; there also appeared to be significant decreases in brain, liver,
    and blood levels of triethyltin bromide. The authors suggested that
    the beneficial effects of this steroid therapy might be partly due to
    enhanced excretion or catabolism of triethyltin bromide.

        Surgical decompression was considered to be the only treatment
    that offered any benefit in human cases of cerebral oedema caused by
    trialkyltin compounds (Alajouanine et al., 1958).


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    AMOS, M.D. & WILLIS, J. B. (1966) Use of high-temperature pre-mixed
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    ANALYTICAL METHODS COMMITTEE (1967) The determination of small amounts
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    BARNES, J. M. & MAGEE, P. N. (1958) The biliary and hepatic lesion
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    BARNES, R. D., BULL, A. T., & POLLER, R. C. (1973) Studies on the
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    BENNETT, R. L. & SMITH, H. A. (1959) Spectrophotometric determination
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    BERTINE, K. K. & GOLDBERG, E. D. (1971) Fossil fuel combustion and the
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    BOGEN, J. (1973) Trace elements in atmospheric aerosol in the
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        (in German).

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    BYINGTON, K. H., YEH, R. Y., & FORTE, L. R. (1974) The hemolytic
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    CALLEY, D. J., GUESS, W. L., & AUTIAN, J. (1967) Hepatotoxicity of a
        series of organotin esters.  J. Pharm. Sci., 56 (2): 240-243.

    CALLOWAY, D. H. & MCMULLEN, J. J. (1966) Fecal excretion of iron and
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    CASIDA, J. E., KIMMEL, E. C., HOLM, B., & WIDMARK, G. (1971) Oxidative
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    See Also:
       Toxicological Abbreviations