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    FAO Nutrition Meetings 
    Report Series No. 48A 
    WHO/FOOD ADD/70.39




    TOXICOLOGICAL EVALUATION OF SOME
    EXTRACTION SOLVENTS AND CERTAIN 
    OTHER SUBSTANCES




    The content of this document is the 
    result of the deliberations of the Joint 
    FAO/WHO Expert Committee on Food Additives 
    which met in Geneva, 24 June  -2 July 19701




    Food and Agriculture Organization of the United Nations
    World Health Organization


                   

    1 Fourteenth report of the Joint FAO/WHO Expert Committee on Food
    Additives, FAO Nutrition Meetings Report Series in press; Wld Hlth
    Org. techn. Rep. Ser., in press.


    TIN AND STANNOUS CHLORIDE

    Biological data

    Biochemical aspects

          Tin was discussed at the Tenth FAO/WHO Expert Committee on Food
    Additives in 1967 (FAO/WHO, 1967). It is still uncertain whether tin
    plays any essential biological role in the body. It is present in
    small amounts in all human and animal organs and normal adult man
    contains about 352 mg. Animals fed on tin-containing food may tend to
    accumulate a body load. Tin is poorly absorbed from the alimentary
    tract of dog, cat, rat, rabbit and man and is chiefly excreted by the
    faeces with additional slow elimination in the urine (Browning, 1969).
    Administration of 2 mg tin daily to rats in their drinking water was
    followed by 99% excretion in the faeces (Flinn & Inouye, 1928). More
    than 90% of tin tartrate was excreted in the faeces (Schryver, 1909).
    Tin tends to be retained in the liver, kidneys, bones, least in the
    brain (Browning, 1969). Tin is widely distributed after parenteral
    injection especially in the liver and spleen, where it deposits in the
    RES; most of it is excreted eventually in the urine and a little in
    the bile (Barnes & Stoner, 1959).

    Acute toxicity

    Tin itself, taken orally, is practically innocuous but inhaled dust or
    fumes causes benign symptomless pneumoconiosis. The inorganic salts
    are caustic but of low toxicity. The alkyl derivatives are highly
    toxic.

    The LD by i.v. injection appears to be 100 mg tin (Seifter &
    Rambousek, 1943), death occurring from CNS and G.I. tract injury. The
    spleen and liver appear mostly affected. Inorganic tin compounds have
    been used as antistaphylococcal agents and also mixed colloidal tin
    and tin stearate (Kelmer et al., 1931). No toxic effects have been
    reported.

                                                                               

    Compound               Animal   Route   LD50        Reference
                                            mg/kg 
                                            bodyweight
                                                                               

    Sodium tin citrate     mouse    oral    2700        Ministry of Health and
                                                        Welfare, Japan, 1969
                                                                               


    Observations in man

          Chronic industrial exposure to tin dust or fumes causes benign
    pneomoconiosis (Pendergrass & Pryde, 1948). Stannic oxide deposits in
    the lung with little absorption owing to insolubility (Browning,
    1969).

          Fifteen students were reported to have been poisoned following
    the consumption of canned orange beverages in 1963 and a further 81
    cases were reported elsewhere. The symptoms observed were vomiting,
    diarrhoea, fatigue and headache. Tin content of random samples of cans
    from the same manufacturers ranged from about 75 to 500 ppm. Eight
    cases were reported in 1969 following ingestion of canned tomato
    juice. Analysis of a number of cans from the same lot as those
    containing the juice consumed by these cases showed a tin content of
    156-247 ppm (Kojima, 1969). (In view of the wide variation in the tin
    content in the lots it was considered possible that the tomato juice
    consumed actually came from cans containing tin approaching or
    exceeding the upper limit stated.)

    Long-term studies

          Rat

          A group of 13 male end 17 female rats were fed on a diet
    containing 2% chlorostannate for over one year. 16 males and 17
    females acted as controls. Mammary adenocarcinoma, one uterine sarcoma
    and one adenocarcinoma near the jaw occurred in the test group. The
    difference in tumour incidence was probably not significant (Roe ef
    al., 1965).

          Mouse

          Groups of mice received over several generations sodium
    chlorostannate either at 1000 or 5000 ppm Sn in their drinking water
    or stannous oleate in their diet at 5000 ppm. No adverse effects were
    noted nor was there any difference in tumour incidence between test
    and control groups (Walters & Roe, 1965).

    STANNOUS CHLORIDE

    Acute toxicity

                                                                             

    Animal          Route     LD50           LD100          Reference
                              mg/kg          mg/kg 
                              bodyweight     bodyweight
                                                                             

    mouse           oral       1 200           40           Calvery, 1942; 
                                                            Le Breton, 1962

    rat             oral         700           -            Calvery, 1942

    rabbit          oral      10 000           40           Eckardt, 1909; 
                                                            Le Breton, 1962

    guinea-pig      oral                       60           Le Breton, 1962
                                                                             

          Oral 4-6 g stannous chloride (200 mg/kg) produced severe
    gastrointestinal symptoms; r.m. injection caused convulsions and
    paralysis (Deschiens et al., 1956).

          Tin accumulated mainly in the liver, the kidneys and the heart. A
    1% solution of SnCl2, when applied for 18 hours to dermal scratches
    in rabbits, produced a reaction with intra-epidermal pustules but none
    on intact skin.  Probably some interference with enzymes occurs (Stone
    & Willis, 1968).

    Short-term studies

          Groups of guinea-pigs received additional 770 mg Sn/kg bodyweight
    in their diet for five months without any abnormalities being
    observed. At autopsy no accumulation of tin was found (Schwartze &
    Clarke, 1927).

          Cat

          Three cats survived for 390-612 days on 40 mg/kg tin salts
    (Lehmann, 1902).

          Dog

          One dog given 500 mg/kg stannous chloride daily developed
    paralysis after 14 months (Lehmann, 1902).

    Comments

          The inorganic salts of tin are of low acute toxicity and the
    available short-term tests do not point to any significant
    abnormalities. Moreover, most inorganic tin salts are excreted in the
    faeces. Experience with tin contamination resulting from the canning
    of a multiplicity of food items, especially at low pH, points to an
    absence of untoward effects except in special circumstances. Studies
    on the effect of inorganic tin salts are in progress.

    Evaluation

          The available data do not permit the establishment of a formal
    ADI and this will have to await the outcome of the studies presently
    in progress. There is no reason at present to depart from the
    assessment given in the tenth report of the Joint FAO/WHO Expert
    Committee that the maximum safe dietary level of tin is unknown, but
    that it is probably much higher than the current level of exposure.
    The usual amounts present in food do not appear to pose any
    toxicological problem.

    REFERENCES

    Barnes, J. M. & Stoner, H. B. (1959) Pharmacol. Rev., 11, 211

    Browning, E. (1969) Toxicity of Industrial Metals, Butterworths,
    London

    Calvery, H. 0. (1942) Food Res., 7, 313

    Deschiens, R., Bertrand, D. & Romand, R. (1956) C.R. Acad. Sci.
    (Paris), 243, 2178

    Eckardt, A. (1909) Zeitschr. f. Untersuchung d. Nahr.-u
    Genussmittel., 18, 193

    FAO/WHO (1967) FAO Nutrition Meeting Report Series No. 43, Wld 
    Hlth Org. techn. Rep. Ser., 373

    Flinn, F. B. & Inouye, J. M. (1928) J. Amer. med. Ass., 90, 1070

    Kojima, K. (1969) Unpublished data submitted to WHO

    Kolmer, J. A., Brown, H. & Harkins, M. J. (1931) J. Pharmacol., 43,
    515

    Le Breton, R. (1962) Tin Toxicology, Thesis, Univ. of Paris

    Lehmann, K. B. (1902) Arch. Hyg (Berl.), 45, 88

    Ministry of Health & Welfare, Japan (1969) Unpublished data submitted
    to WHO

    Pendergrass, E. P. & Pryde, A. W. (1948) J. industr. Hyg., 30, 119

    Roe, F. J. C., Boyland, E. & Millican, K, (1965) Food Cosmet.
    Toxicol., 3, 277

    Schryver, B. S. (1909) J. Hyg. (Lond.), 9, 253

    Schryver, E. W. & Clarke, W. F, (1927) J. Pharmacol. exp. Ther.,
    31, 224

    Seifter, J. & Rambousek, E. S. (1943) J. Lab. clin. Med., 28, 1344

    Stone, O. J. & Willis, C. J. (1968) Toxicol. appl. Pharmacol., 13,
    332

    Walters, M. & Roe, F. J. C. (1965) Food Cosmet. Toxicol., 3, 271
    


    See Also:
       Toxicological Abbreviations
       Tin and stannous chloride (WHO Food Additives Series 1)
       Tin and stannous chloride (WHO Food Additives Series 17)