Tin - Toxicology of Metals - page 828

Similar to butyltins, orally administrated dodecyltin,
octyltin, and phenyltin compounds are eliminated
almost exclusively through feces, with only a small
amount in urine (Eckert. et al ., 1992; IPCS, 1999; Pen-
ninks et al ., 1987). Approximately 10% of dioctyltin is
excreted in the urine, whereas <1% of triphenyltin
is excreted in urine, mainly as unchanged parent com-
pound. Ethyltin trichloride administered intraperito-
neally was excreted almost exclusively in the urine in
rats, whereas diethyltin is excreted through the bile
(Bridges et al ., 1967; Cremer, 1957). Carboxyethyltin,
after daily intravenous administration, was detected
mainly in urine, suggesting a rapid excretion of the
parent compound without any metabolism (Penninks
and Seinen, 1985b). However, daily gavage of 15 mg/
kg carboxyethyltin resulted in excretion in urine and
feces as a result of fast hydrolysis of the parent com-
pound in the gastrointestinal tract. Therefore, excre-
tion of organotins depends on their chemical structure,
solubility (hydrophilic or hydrophobic nature), and
mode of administration.

system (Fish, 1984; Iwai et al ., 1981; Ueno et al ., 1995).
However, debutylation of dibutyltin to monobutyltin
by microsomal monooxygenase system is considerably
slower than that of tributyltin to dibutyltin (Kannan
et al ., 1996a). Isolated rat liver microsomes metabolize
tributyltin to hydroxybutyldibutyltin derivatives with
further oxidation to 1-butanol, 1-butane, and ketones.
Tributyltin is metabolized more rapidly than triphe-
nyltin. Phenyltins biodegrade through sequential
dephenylation with cleavage of the tin-carbon bond
by biological, ultraviolet, chemical, or thermal mecha-
nisms (Stasinakis et al ., 2005). Triphenyltin is metabo-
lized by the cytochrome P450 enzyme system (Suzuki
et al ., 1992), but it can convert cytochrome P450 into
cytochrome P420 and thereby affect the function of the
monooxygenase system (Prough et al ., 1981). The meta-
bolic products are less toxic than parental compounds.
In humans, the cytochrome P 450 system enzymes are
not involved in dealkylation and dearylation of orga-
notins (Ohhira et al ., 2003b).

5.2.4 Biological Half-Life

6 LEVELS IN TISSUE AND
BIOLOGICAL FLUIDS

For triphenyltin, the biological half-life has been esti-
mated to be approximately 3 days in rat brain and is
considerably longer in guinea pig. The half-life of tin
in the liver and kidneys has been estimated as 3-4 days
after oral absorption of diethyltin chloride in rats, but is
longer in muscles and bone. The half-life of injected bis-
tributyltin oxide in mice is approximately a few days
with an initial rapid elimination followed by a slow
elimination rate of 3-4 weeks, similar to inorganic tin
(Brown et al ., 1977). For tricyclohexyltin, half-life ranges
from 5-40 days with slow removal from the brain.

The average concentration of tin in urine is approxi-
mately 4.2-42.2 nmol/L and in hair is approximately
0.42-3.37 nmol/g. The average concentration of tin
in blood of normal subjects is 0.14 mg/L and is found
mainly in the erythrocytes (Baselt et al ., 1989). Tissue
analysis has shown that tin is present in lungs, adrenal
glands, and liver at concentrations of 37, 23, and 23 mg/
kg, respectively. The highest amount of tin (in dry ash)
has been found in the cecum (130 mg/kg), ileum (79 mg/
kg), rectum (57 mg/kg), and sigmoid colon (45 mg/kg)
(Schroeder et al ., 1964). Inorganic tin does not accu-
mulate in soft tissues with increasing age (Baselt et al .,
1989). A dose-dependent increase in the tin content of
the tibia and kidneys of weanling rats has been reported
after administration of tin in the diet ranging from 1-
2000

5.2.5 Biotransformation

The metabolism of organotin compounds deter-
mines their environmental fate and tissue retention.
Although in both aerobic and anaerobic conditions,
organotins (such as tributyltin) biodegrade through
a sequential dealkylation process to inorganic tin, the
addition of organic nutrients in soil can slow down
the process of degradation (Shizhong et al ., 1989). The
exposure of Chlorella vulgaris to tributyltin results in
rapid biosorption with sequential degradation to dib-
utyl- and monobutyltin (Tsang et al ., 1999). The reac-
tion rates for the cleavage of carbon bonds are greater
for tributyltin to dibutyltin than that for dibutyltin to
monobutyltin or monobutyltin to inorganic tin. Recent
evidence demonstrates that toxicity of butyltin com-
pounds decreases with degradation (Suzuki et al ., 1992;
Whalen et al ., 1999). Butyltins are metabolized by the
microsomal cytochrome P450 enzyme hydroxylation

g/g diet (Johnson and Greger, 1985).
Concentrations of organotin compounds in organ-
isms are very high near sources such as ports, pleasure-
boat marinas, shipyards, and much-traveled shipping
routes. The bioconcentration factors for triphenyltin
have been found to be 2090 in carp kidney and in the
range of 80,000-440,000 in the crab hepatopancreas
(Kannan et al ., 1995b; Tsuda et al ., 1987). The levels of
triphenytyl in mussels and samples of sea birds from
coastal areas of Japan are approximately 0.45

µ

µ g/g and

0.05 g/g, respectively. In fi sh from the same coastal

areas, the maximum concentration of triphenyltin has
been reported to be 2.6

µ

g/g
in 1995. Butyltin compounds in the tissue of mussels

µ g/g in 1989 and 0.25 µ