FAO Meeting Report No. PL/1965/10/1
    WHO/Food Add./27.65


    The content of this document is the result of the deliberations of the
    Joint Meeting of the FAO Committee on Pesticides in Agriculture and
    the WHO Expert Committee on Pesticide Residues, which met in Rome,
    15-22 March 19651

    Food and Agriculture Organization of the United Nations
    World Health Organization

    1 Report of the second joint meeting of the FAO Committee on
    Pesticides in Agriculture and the WHO Expert Committee on Pesticide
    Residues, FAO Meeting Report No. PL/1965/10; WHO/Food Add./26.65


    Chemical name

           Triphenyltin acetate          Triphenyltin hydroxide



    Empirical formulae

           C20H18O2Sn                    C18H16OSn

    Structural formulae



    Biochemical aspects

           After ingestion of triphenyltin by cows or sheep, the compound 
    is largely excreted with the faeces (Bügemann et al., 1964; Herok &
    Götte, 1961). Three sheep given 10 mg daily of 113Sn-triphenyltin
    acetate for 20 days were killed respectively 28, 52 and 218 days after
    the beginning of the treatment. 113Sn was found in the milk (average
    concentration 0.0017 ppm) during the treatment but 17 days after
    withdrawal of the compound its concentration in the milk was near
    detectable limits. Tin was present in the milk in at least two forms
    other than triphenyltin acetate. During the treatment, the
    concentration of 113Sn in the blood and in the wine were 2.9 µg/l and
    7.5 µg/l respectively. In the sheep killed at 28 days, liver, kidney,
    lungs, pancreas, gall-bladder and brain contained a greater amount of
    113Sn than other organs. After 218 days the amount of 113Sn found in
    the liver was still greater than in other organs (Herok & Götte,

           Work on rats given 113Sn-triphenyltin showed that absorbed
    triphenyltin was rapidly distributed through the tissues of the body
    including the brain. Triphenyltin was eliminated relatively slowly and
    it could be detected in the brain 38 days after a single dose (Heath,

           In vitro studies have shown that triphenyltin inhibits
    oxidative phosphorylation by isolated liver mitochondria and the
    adenosine triphosphatase activity of brain microsomes (50% inhibition
    by concentrations of 1 × 10-6M and 1 × 10-5M respectively) (W. N.
    Aldridge, quoted by Stoner, 1965).

           The oxygen consumption of cerebral slices of brains from rats in
    a moribund condition due to triphenyltin was within normal limits (J.
    E. Cremer, quoted by Stoner, 1965).

           Studies on the effect of tin compounds on plants are in 
    progress in several laboratories. It has been shown that in the 
    presence of light and air several by-products of triphenyltin acetate 
    can be formed, such as diphenyltin and finally insoluble tin (Kroller,
    1960). The tin content from the leaves can be transferred to the 
    ground. However, when 113Sn-triphenyltin acetate or hydroxide was 
    applied to potato foliage, no translocation of 113Sn from leaves 
    to tubers could be demonstrated above the limit of determination of 
    0.0001 ppm. Tin could be detected in the haulm, where the percentage 
    of the original compound decreased for 20 days (Anon., 1964). It has 
    also been shown that triphenyltin has no systemic action when applied
    to celeriac and sugar-beet (Herok & Götte, 1963).

    Acute toxicity

    Animal              Route        LD50 mg/kg   References

    Mouse               Oral          81-93.3     Anon., 1961

    Mouse          Intraperitoneal        7.9     Stoner, 1965

    Rat                 Oral            136*      Klimmer, 1964

    Rat                 Oral            491**     Stoner, 1965

    Rat            Intraperitoneal       13.2     Klimmer, 1964

    Rat            Intraperitoneal        8.5     Stoner, 1965

    Guinea-pig          Oral             21       Klimmer, 1964

    Guinea-pig     Intraperitoneal        5.3     Klimmer, 1964

    Guinea-pig     Intraperitoneal        3.7     Stoner, 1965

    Animal              Route        LD50 mg/kg   References

    Rabbit              Oral            30-50     Klimmer, 1964

    Rabbit         Intraperitoneal       10       Klimmer, 1964

    *  In tylose.
    ** In arachis oil.

    In all species the main action of these organo-tin compounds is
    thought to be on the central nervous system.

           Cat. Intravenous administration of triphenyltin acetate at a
    dose of 1 mg/kg produced an increase in blood-pressure and a short
    interruption of respiration followed by stimulation of respiration and
    clonic contractions of the limb muscles. Repeated administration of
    1-2 mg/kg at 20-60 minute intervals led to arterial hypotension. A
    decrease in the effect of noradrenaline on blood-pressure was also
    found. Death took place after 4-14 mg/kg of triphenyltin acetate from
    paralysis of the respiratory centres (Tauberger, 1963).

    Short-term studies


           (a) Triphenyltin acetate. Groups of 20-25 rats given
    triphenyltin acetate by stomach-tube at doses equivalent to 5, 10, 25
    and 50 ppm for 107-170 days. At 50 ppm 70% of the rats died in 7.49
    days. Nervous symptoms, as well as blood, urinary or histopathological
    changes were not observed at these lower dose levels (Klimmer, 1964).

           In other experiments on rats no deaths occurred during a 
    10-week period on 200 ppm triphenyltin acetate. These rats were then 
    put on a diet containing 300 ppm and 5 out of 6 rats died after a 
    further 117-168 days (Stoner, 1965).

           Groups of young rats, 10 of each sex, were given respectively 
    0, 5, 10, 25 and 50 ppm of triphenyltin acetate for 12 weeks. Decrease 
    of food intake and growth inhibition were recorded at 50 ppm as well 
    as growth inhibition in males at 25 ppm. At 10 ppm and above the 
    number of leucocytes in the blood was decreased and at 50 ppm the 
    haemoglobin was reduced. At the highest level there was a decrease of 
    the organ/heart weight ratio for the pituitary and pancreas in all 
    animals and uterus and ovary in the females. The same ratio for the 
    thyroid was decreased in all the females as well as in the males at 
    25 and 50 ppm. The water content of the brain in males and spinal cord
    in females was significantly increased but only at 50 ppm. No
    histological studies are yet available on this material (Verschuuren &
    van Esch, 1964).

           (b) Triphenyltin hydroxide. Groups of 10 or 20 rats of both
    sexes were given 0, 5, 20, 50 and 100 ppm of triphenyltin hydroxide
    for 28 days. Food intake and body growth were depressed at 20 ppm and
    above. Death-rates were 9/10 at 100 ppm; 9/20 at 50 ppm and 1/20 at
    both 20 and 5 ppm (van Esch & Arnoldussen, 1962).

           Groups of 10 rats of each sex were given respectively 0, 5, 10 
    or 25 ppm of triphenyltin hydroxide in the diet for 12 weeks. The food
    intake was comparable to the controls. The females showed growth
    inhibition after six weeks but they recovered in spite of continuing
    treatment. Growth in males was comparable to the controls. In the
    females blood leucocytes were decreased. No significant changes in
    water content were found in nervous tissues. At 25 ppm decrease of the
    thyroid weight was noticed (Verschuuren et al., 1962). In a similar
    experiment in which 10 rats of each sex were given 50 ppm of the same
    compound, the following features were noticed: decreased food intake,
    growth inhibition in both sexes, decrease in weight of the thyroid,
    pituitary, uterus, ovary, prostate and pancreas as well as decrease of
    haemoglobin and leucocytes. The water content increased in the spinal
    cord but not in the brain. No histopathological details of these
    studies are yet available (Verschuuren & van Esch, 1964).


           (a) Triphenyltin acetate. In one experiment, 50 ppm led to the
    death of all of nine animals in 17-31 days. In other experiments only
    a group of 5 guinea-pigs given 1 ppm for 392 days did not show an
    increased mortality rate. Even at 1 ppm food intake was reduced. When
    death occurred it was preceded by loss of weight and generalized
    weakness (Stoner, 1965). Neither in these experiments nor in others
    (acute and short-term) in which guinea-pigs and rats have been treated
    with triphenyltin has a significant increase in the water content of
    the central nervous system been found nor the characteristic
    histological lesion in the white matter produced by triethyltin (Magee
    et al., 1957) been seen (Stoner, 1965).

           In other experiments, groups of guinea-pigs, 10 of each sex, 
    were given respectively 5, 10, 20 and 50 ppm of triphenyltin acetate 
    for 12 weeks. In all groups, but for the males given 5 ppm, growth 
    inhibition was obvious. At the end of the treatment no animals at 50 
    ppm were alive; in the other groups the survival rates were: 20 ppm, 
    8/10 males and 8/10 females; 10 ppm, 9/10 males and 10/10 females; 5 
    ppm, 9/10 males and 10/10 females. In all the groups the Hb content of 
    the blood as well as the total number of leucocytes and erythrocytes 
    was decreased in comparison to untreated controls. Also basophilic
    "stippling" in erythrocytes was noted and only in the experimental
    group. At 20 and 50 ppm a significant increase of brain water was
    noticed (Verschuuren & van Esch, 1964).

           (b) Triphenyltin hydroxide. Groups of 3 males and 3 females
    were given 0, 1, 2.5, 5 and 20 ppm of triphenyltin hydroxide for three

    weeks. No changes in the growth rate nor the water content nor
    histology of the nervous system were observed (Verschuuren & van Esch,

           Groups of 10 males and 10 females were given 2.5, 5, 10 or 20 ppm
    for 12 weeks. Growth inhibition was observed at the highest
    dose-level. Hb and total leucocytes were decreased in all groups. The
    organ/body-weight ratio of spleen, thymus, uterus and testes were
    decreased and those of kidney and brain were increased, but no
    increase in the water content of the nervous system was observed. In
    another experiment in which 10 animals of each sex were given 50 ppm
    of triphenyltin hydroxide, all the animals died within six weeks and
    showed a significant increase of brain weight and water content of the
    brain and spinal cord. No histological details are yet available on
    these studies (Verschuuren & van Esch, 1964).

    Long-term studies

           No long-term experiments are so far reported.

    Comments on experimental studies reported

           Triphenyltin appears to be a non-systemic fungicide for celeriac,
    sugar-beet and potatoes. Although some toxicological data are now
    available they are insufficient to establish a no-effect level in a
    sensitive species of animal. There are many unresolved problems
    concerning this compound notably concerning its action on the nervous
    system. The meeting was informed that work on these problems was in
    progress. Until detailed reports of these studies are to hand no
    statement can be made about the acceptability of these compounds to


    Anon. (1961) Unpublished data from Sankyo Co., Ltd.

    Anon. (1964) Unpublished data from Philips-Duphar

    Brügemann, J., Berth, K. & Nieser, K. H. (1964) Zbl. Vet. Med.,
    11, 4

    van Esch, G. J. & Arnoldussen, A. M. (1962) Unpublished report of the
    National Institute of Public Health, Utrecht, Tox 39/62

    Heath, D. F. (1963) Radiation and radioisotopes applied to insects
    of agricultural importance, IAEA, Vienna, p. 185

    Herok, J. & Götte, H. (1961) Symp radioisotopes in animal biology,
    Mexico City, p. 177

    Herok, J. & Götte, H. (1963) Internal J. Appl. Radiation and
    Isotopes, 14, 461

    Klimmer, O. R. (1964) Zbl. Vet. Med., 11, 29

    Kroller, E. (1960) Dtsch Lebensmitt Rdsch., 7, 190

    Magee, P. N., Stoner, H. B. & Barnes, J. M. (1957) J. Path. Bact.,
    73, 107.

    Stoner, H. B. (1965) To be published

    Tauberger, G. (1963) Med. Exp., 9, 393

    Verschuuren, H. G. & van Esch, G. J. (1964) Unpublished report of the
    National Institute or Public Health, Utrecht

    Verschuuren, H. G. van Esch, G. J. & Arnoldussen, A. M. (1962)
    Unpublished report of the National Institute of Public Health, 161/162

    See Also:
       Toxicological Abbreviations
       Triphenyltin compounds (CICADS 13, 1999)