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)