Tin - Toxicology of Metals - page 834

Leukopenia is the most prominent feature of triphe-
nyltin poisoning accompanied by a decrease in the size
of the spleen, thymus, and lymph nodes (Stridh et al .,
1999; Vos et al ., 1984b). Benzene metabolite of triphe-
nyltin seems to be responsible for lymphocyte death
(Stridh et al ., 1999). Secondary Fanconi syndrome has
been observed in guinea pigs after painting tributyl-
tin on their skin (Mori et al ., 1984). Microcytic anemia
has been observed in rats exposed to 80-320 mg/kg
tributyltin oxide (Krajnc et al ., 1984). In erythrocytes,
tributyltin >10

1970). More than 100 deaths and more than 200 cases of
illness occurred in France in 1954 because of ingestion
of a preparation containing diethyltin diiodide and tri-
ethyltin monoiodide. The doses of diethyltin were esti-
mated to be from 45-675 mg in nonfatal cases and from
380-675 mg in fatal cases (Barnes and Stoner, 1959).
Severe headache, vertigo, visual abnormalities, paraly-
sis, and convulsions have been reported after only a
few days of exposure. Death occurred from coma, res-
piratory, or cardiac failure. A pronounced edema of
white matter of the brain had been seen in fatal cases. mol/L induces hemolysis associated

with intercalated within the lipid membrane multi-
molecular tin-containing aggregates, which transform
red cells into crenellated spheres (Byington et al ., 1974;
Gray et al ., 1986; Porvaznik et al ., 1986).
Triphenyltin, tripropyltin, and tributyltin com-
pounds are extremely immunotoxic to rats (Snoeij
et al ., 1985; Vos and Krajnc, 1983). Both triphenyltin and
tributyltin have been shown to induce thymus atrophy
and suppression of T cell-induced immune responses
(Seinen et al ., 1979; Snoeij et al ., 1985). Triphenyltin intra-
peritoneally injected into mice for 14 days inhibited the
T-cell-dependent humoral and cellular (induction of
cytotoxic T-cell or induction of delayed hypersensitiv-
ity) immune response (Nishida et al ., 1990). The lower
molecular weight diethyltin and dipropyltin produced
less pronounced effects, whereas octyltin and diocta-
decyltin did not cause immunotoxic effects.

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7.3 Mechanism of Action
Because of lipophilicity, organotin compounds can
be regarded as membrane active, and the cell mem-
brane is an initial site of activation (Tobin and Cooney,
1999). Indeed, it has been shown that tributyltin alters
the plasma membrane/cytoplasm complex, decreases
plasma membrane potential of the murine erythro-
leukemic cell, and causes cell death (Zucker et al .,
1988). Organotins may affect lipid bilayers by alter-
ing membrane fl uidity (Ambrosini et al ., 1996). In a
number of studies, the mitochondrion has been iden-
tifi ed as a target of triorganotins. The major action of
organotins is associated with interference with mito-
chondrial energy production, including interruption
of oxidative phosphorylation, changes in permeability
of outer mitochondrial membrane, and suppression of
enzyme activity (Boyer, 1989; Stridh et al ., 2001). More-
over, triorganotins increase calcium fl ux in mitochon-
dria attributed to organotin toxicity (Miura et al ., 1997;
Viviani et al ., 1995). It has been shown that triphenyltin
affects calcium homeostasis through impairment of cal-
cium infl ux through voltage-gated calcium channels,
inhibition of Ca 2+ -ATPase activity, and calcium uptake
of sarcoplasmic reticulum (Miura et al ., 1997; Viviani
et al ., 1995). Furthermore, tributyltin induced caspase
activation and apoptosis in human peripheral blood
lymphocytes without affecting the CD8+ T-cell popu-
lation (Stridh et al ., 2001). Triphenyltin at 0.1-1

7.2.2.2 Human
There are no human studies available on chronic
low-level exposure to organotin compounds. How-
ever, some case reports describe various health effects
after accidental exposure to tributyltin and triphenyltin
compounds. Patients, who had been exposed mainly to
cutaneous absorption, developed acute nephropathy
and disorders of the central nervous system (Colosio
et al ., 1991; Manzo et al ., 1981; Prull and Rompel, 1970;
Wax and Dockstader, 1995). Exposure to triphenyltin
causes spontaneous involuntary movement of hands,
facial twitching, and crying. Some of the patients expe-
rienced diplopia, drowsiness, giddiness, vertigo, bidi-
rectional nystagmus, impairment of calculation ability,
and disorientation in time and place (Lin et al ., 1998).
In addition to CNS abnormalities, delayed periph-
eral neuropathy, hepatitis, and leukopenia have been
monitored 6 and 9 days after consumption of triphe-
nyltin. Two case reports of triphenyltin poisoning
indicated leukopenia, a decrease in responsiveness of
neutrophils, elevated hepatic enzymes, hepatomegaly,
and central nervous system effects (encephalopathy
and delayed neuropathy) (Colosio et al ., 1991; Lin et al .,
1998). Liver damage has been reported in people using
triphenyltin acetate as a spray (Horacek and Demcik,

µ mol/L,

as well as tributyltin at 0.5-5 mol/L, also triggers

caspase activation and induces apoptosis in Jurkart T
lymphocytes. Both compounds at 1

µ

mol/L can induce
phosphorylation and activation of MAPK kinases,
which transmit extracellular signals into the nucleus
and result in cell death (Yu et al ., 2000). However, at
high concentrations, triphenyltin and tributyltin inhib-
ited caspase activity causing necrotic cell death (Stridh
et al ., 1999). Genotoxicity of a number of organotin
compounds has been reported by various methods
(Ghosh et al ., 1990; Hamasaki et al ., 1993). Organotin
compounds inhibit microtubule assembly through
direct interaction with tubulin (Jensen et al ., 1991).

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