Tin: Environmental Pollution and Health Effects

F Cima, Università di Padova, Padova, Italy

& 2011 Elsevier B.V. All rights reserved.

Cationic Sn is absorbed onto proteins, changing their

Abbreviations
conformation, or is incorporated into proteins; rat liver
ACT azocyclotin
metallothionein contains approximately 0.3% Sn. At pH
DBT dibutyltin
above 6, SnX2 are easily oxidized and are strong reducing
DET diethyltin
agents. Bivalent tin can be in the ionic form, but stannic
DMT dimethyltin
compounds are covalent and the ionic form of tetravalent
FBTO fenbutatin oxide
tin does not exist.
MBT monobutyltin
Both of the tin valence states form a large number of
MET monoethyltin
stable inorganic compounds, while stannic tin can form a
MMT monomethyltin
volatile hydride (SnH4) and a number of toxicologically
TBT tributyltin
important organometallic compounds in which the stannic
TBT-MMA tributyltin methyl methacrylate
form is covalently attached to one or more carbon atoms.
copolymer
The most common inorganic compounds of tin are
TBTO tributyltin oxide
stannous chloride (SnCl2), stannous oxide (SnO), stannous
TCHT tricyclohexyltin
fluoride (SnF2), stannic chloride (SnCl4), and stannic oxide
TET triethyltin
(SnO2). In the organic compounds of tin, there are one to
TMT trimethyltin
four covalent carbon–tin bonds; therefore, there are mono-
TPT triphenyltin
, di-, tri-, and tetraorganotin compounds. These are clas-
TPTA triphenyltin acetate
sified as R4Sn, R3SnX, R2SnX2, and RSnX3, where R is an
TPTC triphenyltin chloride
alkyl or aryl group (e.g., methyl, ethyl, butyl, octyl, phenyl,
TPTH triphenyltin hydroxide
or cyclohexyl group) and X is an anionic group (e.g.,
chloride, fluoride, oxide, hydroxide, carboxylate, or
thiolate). The tin–carbon bond is stable to water, atmos-
phere, and heat (at least to 200 1C), whereas UV radiation,
Introduction strong acid, and electrophilic reagents cleave the bond.
Solubility in water varies greatly with R and X in
Physical and Chemical Properties RnSnX4n depending on their relative numbers.
Tin (Sn) (atomic number 50, atomic mass 118.69, melting
point 231.9 1C, density 5.8–7.3, boiling point 2602 1C)
Production and Uses
belongs to Group IV A of the periodic table. In its
most common form, tin is a lustrous silver-white metal, Even if there are some naturally occurring organotin
insoluble in water, tetragonal (tin white), and white compounds, mostly produced by biomethylation of
rhombic (tin brittle) when it is warmed at 200 1C with a inorganic ion, most of organotins entering the environ-
density of 6.4. When tin is cooled below 13.2 1C, it is ment are man-made products. The production of tributyl
slowly converted to another enantiotropic form called species is approximately 4000 tons per year, used as wood
gray tin or a-tin, cubic. Tin compounds are found in the preservatives, antifoulants, and disinfectant biocides, by
environment with tin possessing an oxidation state of þ 2 comparison, the total organotin production is more than
or þ 4, but the trivalent forms are unstable. Therefore, 60 000 tons per year. On the whole, both inorganic and
tin forms two series of compounds, the stannous com- organotin compounds have extensive industrial uses,
pounds SnX2 of bivalent tin and the stannic compounds but of the tin total prepared, 7% is for organometallic
SnX4 of tetravalent tin. Cationic Sn2þ and Sn4þ are tin compounds with major environmental aspects and
stable, whereas anionic stannite and stannate are insol- toxicological properties. Their successful employment
uble and stable. Tin does not exist in ionized form, but has been due to their advantage over the very effective
rather in colloidal complexes. Although ubiquitous, tin is mercury compounds of being degraded to relatively
one of the least abundant elements on the earth’s crust, harmless inorganic tin compounds.
occurring mainly as tinstone or cassiterite (SnO2) and in Currently, inorganic tin compounds are in extensive
complex sulfides (stannite), up to 3 ppm as tin both in industrial use, such as in the manufacture of tin-plated
the earth’s crust and in seawater. Sn2þ combines weakly containers for food and equipment in the dietary
with dithiol groups, whereas Sn4þ combines more readily. industry; in solders and other alloys, such as bronze and

351
352 Tin: Environmental Pollution and Health Effects
brass, pewter (in processes developed by the Sumerians
since 2000 BC), and babbitt; and in more specialized
alloys, such as dental amalgams and the titanium alloys
used in aircraft engineering. Tin-electrodeposited coat-
ings are used in electronic and engineering components,
and tin is also used in foil and collapsible tubes.
Some tin(II) compounds, such as SnCl2, are used in tin
galvanizing; as reducing agents in the manufacture of
polymers, toothpaste, ceramics, porcelain, enamel, drill
glass, and ink; as pigments in the ceramic and textile
industry (tin violet); in the weighting of silk; and as
mordants in dyeing. SnO is used in making tin salts for
chemical reagents for plating (tin plate and tin sheet).
SnF2 is the additive whether in fluoride toothpastes and
dental washes or in certain industrial processes and a
polishing powder for steel. Tin(IV) compounds, such as
SnCl4 and SnO2, are used as a stabilizer for perfumes,
and as a catalyst in certain industrial processes and a
polishing powder for steel, respectively. SnO2 is used in
glass manufacture (float glass) and glazed pottery and as a
bronzing agent for wood coloring and frame gilding.
The industrial applications are listed in Table 1.
Because of such wide applications, tin has been designated
as the third most important pollutant in the environment.
Therefore, several studies have focused on the increasing
amounts of both organic and inorganic tin present in the
environment. Most of the researches describing the
environmental distribution of organotins have under-
standably focused on the spread of the antifoulant
Table 1 Industrial use of organotins
Compound Use
R4Sn Intermediates in the synthesis of other organotins
R3SnX Agriculture fungicides
Antifeedants
Acaricides
Antifoulants – biocides
Wood preservatives – fungicides
Miticides, ovicides
Stone preservatives – disinfectants
Hospital and veterinary disinfectants
Surface-modifying and -curing agents
Bacteriostats, antimicrobials
Laundry sanitizers
Mildewcides
Rodent repellents
Molluscicides
R2SnX2 Heat and light stabilizers for rigid PVC
Homogeneous catalysts for RTV silicones
Precursors for forming SnO2 films on glass
Polyurethane foams and transesterification
reactions
Anthelmintics for poultry
RSnX3 Heat stabilizers for rigid PVC
Homogeneous catalysts for transesterification
reactions
Precursors for forming SnO2 films on glass
tributyltin (TBT), its methyl methacrylate copolymer
(TBT-MMA), and their breakdown products in the mar-
ine
environment, where the first known effect was the devel-
opment of male sexual characteristics in female mollusks,
namely, imposex. This malformation causes sterilization
and reproduction failures in these invertebrates, leading to
their local extinction. The relative persistence of butyltins,
combined with their affinity for biological tissues, has led
to their widespread occurrence in mollusks, arthropods,
tunicates, and vertebrates, including teleosts and marine
mammals. The toxicology of these compounds is discussed
in more detail in the following text.
Environmental Distribution and
Biogeochemistry
The regional distribution of tin in the earth’s crust is
uneven. Tin bound to the soils and sediments is relatively
immobile, but may be released into the atmosphere from
windstorms, roads, and farming activities. Continental
dust flux, volcanic emission, and forest fires release
approximately 5000 tons of tin, whereas the contribution
of anthropogenic sources, such as burning of fossil fuels
(coal or oil) or waste incineration, and the production
of tin, organotins, iron, steel, and nonferrous metals, is
approximately 10 times higher.
Therefore, tin exists in the atmosphere as gases and
fumes and attached to dust particles, which, in turn, can
be spread by wind or washed out by rain. The contri-
bution of atmospheric pollution to the daily tin intake of
humans is less than 1 mg per person.
The concentration of tin in water, such as rivers,
estuaries, and oceans (both at surface and deep inside),
is generally less than 5 ng Sn l1. At first, the use of
organotin biocides, especially when they are added to
water to control snails or are released from organotin-
coated ship bottoms, was not thought to lead to the sig-
nificant presence of organotins in water and sediments.
However, simple methyltins have been found in the en-
vironment, probably as a result of a process of bio-
methylation and demethylation (Figure 1, clockwise and
MeSn3+
Me2Sn2+
SnX3
SnX4
Me3Sn+
SnX2
Me4Sn
Figure 1 A section of the biogeochemical cycle of inorganic tin.
 Tin: Environmental Pollution and Health Effects
anticlockwise, respectively) of the inorganic tin biocycle.
Similarly, octyltins have not been reported away from
point source use. It is also assumed that monobutyltin
(MBT) and dibutyltin (DBT) found in the aquatic en-
vironment arise from demethylation of TBT rather than
direct input of the former species. In seawater, following
hydrolysis, TBT exists as a cation complexed to chloride,
carbonate, and hydroxide, and it is rapidly absorbed onto
suspended particulate material and hence, in due course,
sediment. Since this happens more rapidly than does
aqueous decay, TBT tends to be found in sediments on
removal from the water column. Actually, it has been
clearly demonstrated that TBT concentrations in sea-
water decline quite rapidly once the input of TBT is
reduced or eliminated, and the initial response rate is
usually less than 5 years. As TBT is quite lipophilic, it
would be expected to bioaccumulate. In fact, bioaccu-
mulation factors in various species range from 1000 to
30 000, and bioaccumulation to the surface microlayer
increases TBT concentrations over subsurface water two-
to tenfold. Recovery from sediments is much slower and
apparently variable. The water above the sediments tends
to clear rapidly, suggesting that, although there is a res-
ervoir of TBT in the sediment, it is not completely
available for the replenishment of TBT lost from the
water layer by nonuse and decay.
From several multivolume and monograph publi-
cations in recent years, the following deductions can be
made: (1) TBT decays sequentially to DBT and MBT;
(2) the organotin derivatives may be reduced, that is,
converted into hydrides, in the environment; (3) they
may also be biomethylated; (4) some are volatile, such as
tributyltin oxide (TBTO) and hydrides; and (5) landfill
sites make a contribution to organotin levels in the
environment. Moreover, it should be noted that, as for
most organometallics in the environment, except for
arsenic, there is no information on the TBT or any other
organotin counterion other than in the case of the
saturated tetraorganotin and the volatile hydrides and
TBT in seawater, where complexation with OH, Cl,
and CO3 2 takes place. One might speculate on the ex-
istence of organotin counterions, but there is no evi-
dence. Before legislation, or its effects becoming noticed,
water concentrations of TBT in polluted zones were
recorded at up to 1–2000 ng Sn l1. Surface microlayer
levels were up to 25 000–36 000 ng Sn l1. Sediment
levels of up to 5500 ng Sn g1 were noted, although levels
of hundreds of nanograms of Sn per gram were most
common. Sewage sludge had similar levels, with sewage
plant effluent up to 55 200 ng Sn l1.
It must be stressed that organotins released into
the environment are not stable, and their degradation is
accelerated by photochemical (abiotic) and biochemical
(biotic) processes that may take a few days or several
weeks. So the addition of organic nutrients in soil can
353
slow down the process of degradation, but anyway, the
reaction rates for the cleavage of carbon bonds for TBT
to DBT are greater than those for DBT to MBT or MBT
to inorganic tin as tin oxide, with a decrease in toxicity
along the two last steps in comparison with the parental
compound. Decay occurs by stepwise debutylation, with
UV and chemical or microbiological attack on the butyl
group leading to hydroxylation and loss of the butyl
group as butanol or butene. Generally, photolysis by
sunlight is the faster route to degradation in water, but it
seems not to be important at depth or on sediments,
where degradation is rather caused by bacteria or
macroalgae, for example, pseudomonads and chlorella,
whereas chemical reagent decay is not important in most
natural environments.
The opposite process is biological alkylation, mainly
biomethylation of inorganic tin ion to mono-, di-, tri-, and
tetramethyltin (in a lesser degree, bioethylation and bio-
methyl ethylation), which can contribute to the biocycling
of tin in the environment by increasing the volatility,
toxicity, adsorptivity, and mobility. In estuaries, the con-
centration of methyltin increases with salinity. The slow
methylation of trimethyltin to the water-insoluble, volatile
tetramethyltin contributes to the flux of organotin to the
atmosphere from which, after decomposition to lower
homologues, methyltin is removed with rainwater. There
is no compelling body of experimental data, but some
laboratory works have demonstrated that the main
mechanisms for methylation (methyl carbanion, methyl
carbonium ion) could be successful for tin. So methylco-
balamin, CH3I, and yeast, as the source of CH3, and
certain pseudomonads have been demonstrated to meth-
ylate tin. However, the normal redox range of environ-
mental sediments is sufficient to hydrogenate tin and other
metals; for example, in the electron carrier nicotinamide
adenine dinucleotide (NADþ), the NADþ/NADH has a
very negative redox couple (  0.32 V) and can transfer
hydrogen to many metals. A reasonable biogeochemical
cycle for organic tin and TBT as an example may be
constructed (Figure 2), even if little quantitative infor-
mation is available about fluxes, despite levels in water and
sediments having been well studied.
Exposure Routes and Metabolic
Pathways
Plants, animals, and humans have long been exposed to
inorganic tin. In general, the tin concentration is at least
100 times lower in forest vegetation, pasture, vegetables,
and cereals than in soil (less than 0.3 mg kg1), except
for lichen and moss, which concentrate tin to some
extent. For example, fresh asparagus and dried split peas
contain approximately 9 ppm Sn, whereas canned food
products may contain more Sn than do fresh products.
354 Tin: Environmental Pollution and Health Effects
Me4Sn BuSnH3 EtMe3Sn
+ Bu2SnH2 Et2Me2Sn
Me3Sn
Et3MeSn
Me2Sn2+
Et4Sn
MeSn3+
Landfill
Figure 2 The biogeochemical cycle of organic tin compounds. TBT as an example.
Tin accumulates in animal and human tissues in widely
varying amounts, according to the geographic region, the
kinds of dust or fumes inhaled and food ingested, and the
exposition length.
Long-term exposure to tin dust or fumes results in
accumulation of the particles of tin compounds in the
lung tissues, because these are poorly absorbed and
metabolized. Inorganic tin deposits in the lung because of
its insolubility and lack of absorption; thus lungs are the
main target organs for tin dust.
It is actually accepted that toxicity of inorganic tin
is very low, even if only a few toxicological studies
have been conducted. A precautionary limit value (time-
weighted average) for tin in air was set at 0.1 mg m3 in
1979 as a maximum workplace exposure, but afterward,
it was increased to up to 2 mg m3, regarding tin and
inorganic tin compounds, except tin hydrides. However,
the early limit value (TLV-TVA of 0.1 mg m3) remained
just confirmed for organic tin compounds, owing to their
higher toxicity, by the ACGIH, OSHA, and NIOSH.
The absorption of ingested inorganic tin is approxi-
mately 5% in animals, but 3% in humans from a diet
supplemented with 50 mg of Sn per day. Moreover,
stannous compounds are more readily absorbed from the
gastrointestinal tract than stannic compounds. In humans,
approximately 90% of a dose of soluble Sn compounds,
such as sodium tartrate, was found in the feces, indicating
poor absorption that is attributed to the absorption of
Sn by proteins coagulated in the gastrointestinal tract,
whereas tin sulfides, oxides, and soaps are negligibly
absorbed. At last, the bodies of newborn children contain
no Sn, but it is deposited rapidly during their early life,
Atmosphere
Bu4−nSnH4 SnH4
Bu4−nSnMe4
Bu4−nSnH4
Water
Bu4−nSnMe4
Bu3SnX Bu3Sn+ Bu2Sn2+ BuSn3+ SnO2
(TBT) (DBT) (MBT)
Sediment
Bu3Sn+ Bu2Sn2+ BuSn3+ SnO2
(TBT) (DBT) (MBT) SnH4
Bu3SnMe Me4SnH4−n
Bu2SnMe2 MenSnH(4−n)+
BuSnMe3
Bu4−nSnH4
so that tin is confirmed not to be an essential metal. The
estimated daily average intake of tin from food and water,
excluding canned food, is 1–8 mg, ranging from 2.9–1 mg
in 3-year-old children to 7.5 mg for female vegetarians in
industrialized countries. The increase in the total dietary
tin intake, estimated at 0.19 mg per day and observed in
1991 in the United Kingdom, has been due to greater
exposure to tin compounds and to canned food products,
since tissues from humans in other geographic areas do
not appreciably accumulate tin. The main sources of tin
are canned foods, cereal grains, dairy, meat, vegetables
licorice, and certain toothpastes. Vegetables grown on
soil high in tin contain less than 1 mg Sn kg1, and diets
consisting of fresh vegetables, meat, and cereals con-
tribute less than 1 mg to the daily tin intake. Likewise, the
tin accumulation in tissues of normal US adults may be
explained by the staple diet greatly based on canned food
products. In 1940, balance studies of Sn using tracer
amounts of radioactive Sn showed the absence of any
steady accumulation of Sn in American adults, but since
then, exposure to it has been considerably reduced in the
United States. On the basis of the above-mentioned
evidence, it has been claimed that intestinal transport
and barrier systems are present in humans and that an
efficient homeostatic mechanism is operative for Sn, but
evidently not functioning at higher doses.
However, the use of organotin pesticides does not
seem to have caused a substantial increase in the dietary
tin intake, although dietary exposure to organotin com-
pounds may result from the consumption of organotin-
contaminated meat and fish products. Since butyltin and
phenyltin compounds accumulate within the marine food
 Tin: Environmental Pollution and Health Effects
chain, they may eventually accumulate in aquatic food
products such as mollusks (their digestive gland as the
primary site of uptake), crabs, and fish. Moreover, the
finding of triphenyltin (TPT) in coastal fish, as well as
in open oceanographic fish, suggests biomagnifications
through the food chain. Thus, the average daily intake of
TPT by humans, estimated in Japan from a standard
market basket survey, has been determined as approxi-
mately 0.6–10.4 mg, and the daily consumption of TBT
ranges from 0.18 mg in the United Kingdom to 2.6 mg in
Korea. Moreover, butyltin compounds have been found
in cookies prepared with silicone-backed parchment, in
foodstuffs stored in containers made of PVC polymers,
and in several brands of wine. But the release of these
compounds, mainly monomethyltin (MMT), dimethyltin
(DMT), MBT, and DBT from PVC tubing used for
drinking water systems, has also been reported. By the
use of the predicted tolerable daily intake value for DBT
of 5 mg kg1 (as tin), an adult who weighs 60 kg and
consumes 2 l of drinking water per day can safely ingest
water with a DBT concentration of 150 mg l1 (as tin). So
far, there are no data on the levels of TPT in drinking
water. The possible contamination of DBT dilaurate has
been reported in poultry and turkey in the United States.
About the persistence in vegetable food, residues up to
0.3 mg kg1 were still found in potatoes and sugar beets
7 days after application.
Easily moving along the trophic chains, all the orga-
notins have an impact on natural aquatic environment,
particularly in estuarine and coastal ecosystems, leaching
out from various sources, as a result of chemical industry,
agriculture, and marine activities, but other sources
of environmental exposure include discard and sanitary
landfill disposal of plastic, PVC food wrapping, bottle,
and rigid potable water pipes. Their stable presence in
both freshwater and sea ecosystems represents a high risk
in provoking deleterious effects on biocenosis already at
low concentrations, such as 0.1–1.0 mg l1. In comparison
with inorganic tin compounds, organotins are more
rapidly bioaccumulated in tissues of organisms living in
the water–sediment interface, causing more severe, long-
term toxic effects on local epifauna with more reper-
cussions on biodiversity.
The potential risk of bioaccumulating organotin
compounds from dietary exposure depends mainly on
their liposolubility, which gives them easy access to the
various links of trophic chains. This risk is then high for
aquatic organisms because these compounds are of some
toxicological concern. Organotin residues in fish and
shellfish for human consumption are easily accumulated
in algae, thus interfering with their life cycle, and in
animals by dietary and branchial uptake from water into
the lipophilic compartments, whereas their elimination
from the body is slow, as reported in fish for butyltins and
TPT. Triethyltin (TET) and monosubstituted organotins
355
are more effective in growth inhibition of methanogenic
and sulfate-reducing bacteria than trisubstituted alkyl-
tins, but TBT-tolerant marine bacteria have also been
found.
Other marine species have been reported to accu-
mulate TBT up to 2% of their dry weight because
of their ability to dealkylate it, forming less toxic com-
pounds that may also be utilized as carbon source, or to
exclude the toxicants outside the cell. In vertebrates,
organotins accumulate in specific target organs, such as
brain, liver, kidney, and lymphatic tissues. Metabolites
can also be found in tissues, since the hepatic microsomal
system is able to metabolize TBT to DBT by a deal-
kylation process in mammals, in fish, and in tadpoles,
while cycloalkyltin compounds undergo a progressive
scission of cycloalkyl groups from the tin atom. Marine
vertebrates of the higher trophic chains, such as
cetaceans, tunas, and sharks, bioaccumulate great
amounts of butyltin compounds. In various marine in-
vertebrates, such as mollusks, organotin bioaccumulation
appears to be related to seasons and ship activities, and is
more rapid when animals feed microalgae, supporting the
hypothesis of the contaminant transfer through the
trophic chain. Mollusks show the highest concentrations
of organotins in their tissues relative to vertebrates,
probably because of the presence, in the latter, of enzyme
systems able to degrade TBT allowing the excretion of
its metabolites. Bivalves such as Mytilus edulis and Cras-
sostrea virginica accumulate organotins to the greatest
extent in gill tissue and metabolize these pollutants
slowly in comparison with gastropods, crustaceans, ech-
inoderms, and fish. On the contrary, organotin degrad-
ation is relatively inefficient in other edible mollusks
such as Mercenaria mercenaria and Mya arenaria; hence,
bioaccumulation and bioavailability represent a potential
risk to human health by their intake from contaminated
food. High levels of consumption of fish and mollusks
from contaminated areas may occur at typical levels of
0.01–1.0 mg l1, primarily as TBT and TPT, but levels in
shellfish may be higher.
Toxicity
Tin has not been shown to be an essential element in
humans, whereas only one report so far has claimed that
the growth of rats was enhanced by nearly 60% when
1–2 mg tin as tin sulfate was added to a highly purified
diet. At present, tin is considered an essential nutrient
for growth in the rat, since a tin-deficient diet leads to
reduced growth, alopecia or bilateral hair loss, hearing
loss, and reduced feeding efficiency. Moreover, dietary
tin deficiency can cause imbalances of essential metals,
causing an increase in calcium and a decrease in the
concentrations of zinc, copper, and manganese.
356 Tin: Environmental Pollution and Health Effects

Mechanisms of Toxicity caused an increase in micronucleated reticulocytes

(positive in both the Ames test and the comet assay).
Severe growth retardation, decreased food efficiency,
2. Carcinogenity: organotins inhibit the ability of natural
anemia because of hemopoiesis, inhibition by interfering
killer cells to bind to tumor cells, thereby predisposing
with the intestinal absorption of Fe, and a slight
to malignancy, and can initiate the multistage process
degeneration in the liver were observed in rats fed with
of carcinogenesis by influencing the steroid hormonal
66–99 mg Sn kg1 per day or more as stannous chloride,
metabolism (TBT); however, TBTO is classified as a
orthophosphate, sulfate, oxalate, or tartrate, but most of
group E carcinogen (evidence of noncarcinogenicity
these effects may be due to partial starvation. The
in humans), but TPT is the exception to this rule
stannous ion also interacts with N-type calcium channels
and is classified as B2 (probable human carcinogen) by
enhancing calcium transport into neurons. Interestingly,
the US EPA, whereas some DBT compounds seem to
the high toxicity of soluble inorganic tin compounds can
open a new horizon in their potential application in
be ameliorated by supplementary dietary iron and
metal-based chemotherapy as metallopharmaceutical
copper, according to the interactions between inorganic
exhibiting antitumor activity (as well as antimicrobial,
tin compounds and iron, copper, and zinc metabolism.
antituberculosis, and anti-inflammatory properties).
Moreover, tin toxicity may involve the inhibition of
3. Immunotoxicity: TBT 4 TPT cause atrophy of the
certain key enzymes. Evidence for this mechanism
thymus cortex and lymphoid tissues by apoptosis, with
of action is as follows: (1) the chronic administration of
consequent depletion of T lymphocytes in peripheral
stannous chloride causes, more effectively than stannic
blood: the thymolytic action may be due to the pri-
chloride, cardiac hypertrophy in stroke-prone hyper-
mary action of DBT on the maturation of immature
tensive rats; the tin-induced increase in left ventricular
thymocytes, whereas TPT may cause a depolymer-
heme oxygenase level, as well as cGMP content, has been
ization of thymocyte F-actin; moreover, organotins
accomplished by a decrease in left ventricular weight/
may involve cytoskeletal modification in addition to
bodyweight, potently as lead; (2) tin also inhibits
the perturbation of thymocyte calcium homeostasis,
glutathione transferase; and (3) the high-tin diet de-
enhanced glucocorticoid blood levels indicating a
presses copper status in rats, and the interaction between
permanently disturbed regulation of the hypothalamic–
copper and tin affects the levels of liver superoxide dis-
pituitary–adrenal axis leading to a higher susceptibility
mutase and glutathione peroxidase.
for cardiovascular and metabolic disorders including
Most of the chronic toxic effects of organotins are
obesity, insulin resistance, and type II diabetes.
often irreversible, dose and time dependent, since they,
4. Embryotoxicity: a low and controversial teratogenic
like detergents, may affect lipid bilayers by altering
potential appears in vertebrates, differently from
membrane fluidity. As they are lipophilic and amphi-
marine invertebrate bivalves, echinoderms, and tuni-
pathic, their major action is associated with interference
cates, whereas there are no studies in fetuses and
with mitochondrial energy production, including inter-
children whose mothers were exposed to organotins
ruption of oxidative phosphorylation, changes in per-
during pregnancy.
meability of outer mitochondrial membrane, and
suppression of enzyme activity. Moreover, they increase
calcium flux in mitochondria, so that two mechanisms
of toxic action have been proposed, that is, Ca2þ Differential Toxicity of Organotins
independent and Ca2þ dependent. However, they are
Tetra-, tri-, and diethyltin undergo dealkylation up to
linked and synergistic in triggering the cascade of sec-
monoethyl compounds; likewise, TBT is dealkylated to
ondary events that led to toxic activities, such as induced
di- and monobutyltin compounds. Phenyltin compounds
caspase activation and apoptosis or caspase inhibition
undergo dealkylation, mainly by microsome mono-
causing necrotic cell death.
oxygenase and P450 enzymes. On the basis of toxic
Combined mechanisms are involved in the following
effects, organotin derivatives can be divided into five
human delayed toxicological effects:
classes: (1) low-molecular-weight trialkyltin compounds,
1. Mutagenicity/genotoxicity: organotins inhibit micro- such as TMT and TET; (2) butyltin compounds, such
tubule assembly through direct interaction with as MBT, DBT, and TBT; (3) TPT compounds, such as
tubulin, and their mitotic activity increases with their triphenyltin acetate or Fentin acetate (TPTA), triphe-
lipophilicity; in chronic dietary studies, chromosomal nyltin chloride or Fentin chloride (TPTC), and triphe-
aberration has been reported in peripheral blood, nyltin hydroxide or Fentin hydroxide (TPTH);
such as chromatid and chromosome breaks and (4) phenyl-alkyltin compounds, such as fenbutatin oxide
gaps, dicentrics, increased sister-chromatid exchanges, or Lexitin or Torque (FBTO); and (5) cycloalkyltin
altered cell cycle kinetics, and induction of compounds, such as tricyclohexyltin or Cyhexatin or
aneuploidy (TBT 4 TPT), whereas mainly TPT Plictran (TCHT) and azocyclotin or Peroral (ACT).
 Tin: Environmental Pollution and Health Effects
All these compounds are known to be toxic at rela-
tively low levels, not only to marine invertebrates but
also to mammals and other animals, and the effect varies
according to the number and type of organic moiety
present. In general, their toxicity increases with the
number of alkyl or aryl groups attached (R). In view of
the biocidal use, the maximum toxic effect in RnSnX4n
is usually achieved for R3SnX, but unless X is toxic, it
does not have much effect on overall toxicity. Within
R3SnX, the nature of R profoundly affects toxicity to a
single species and relative toxicity to different species.
So, Et3SnX is most toxic to mammals, and Bu3SnX to
aquatic life, and increase in chain length of R decreases
toxicity. Therefore, the most toxic organotin compounds
are the trialkyltin compounds, followed by the dialkyl-
and monoalkyltin compounds, with the ethyl derivatives
in each group being reported as the most toxic. Of the
triorganotin compounds, TPT is moderately toxic, but
less toxic than the trialkyl compounds with shorter alkyl
chains, such as TMT compounds.
Owing to the negative impact on coastal ecosystems of
TBT, TPT, and their derivatives in antifouling paint
formulations against a wide spectrum of fouling organ-
isms (used concentrations: up to 3%), organotin com-
pounds were definitively banned by the International
Maritime Organization (IMO Resolution A.895(21),
25 November 1999) and then by the EU (ordinance No.
782/2003, 14 April 2003).
Toxicity in Animals
Metallic Sn and its inorganic salts are generally con-
sidered of low oral toxicity due to their poor alimentary
absorption, and reports of their toxicity are restricted
to experiments with laboratory animals and to limited
observations in humans.
It must be emphasized that metallic Sn or its inorganic
salts typically require large doses over prolonged periods
to produce toxicity, differently from organic tins that are
more highly toxic than inorganic compounds. Because tin
compounds are lipid soluble and stable in biologic
fluids at tissue pH, extensive penetration into the brain
and lodgment in the central nervous system can occur.
Metallic Sn is toxic only when given orally in large
doses, whereas the unstable stannic hydride gas, when
inhaled, is neurotoxic, but even though similar to arsine
gas, the effects are less severe because it does not
cause hemolysis. Insoluble Sn compounds are relatively
harmless, whereas cationic Sn compounds soluble in
water or dilute acids are gastric irritants, and can be very
toxic because of high absorption from the gastrointestinal
tract, but the acidity of Sn salt solutions and their irritant
properties complicate interpretations of Sn toxicity. Since
divalent Sn salts are more readily absorbed from the
gastrointestinal tract, they are more toxic than Sn4þ salts.
357
Besides, they can form more stable complexes with
SH compounds than Sn4þ, accounting for the greater
toxicity of Sn2þ compounds. In rats, there are marked
differences in the oral toxicity of various Sn compounds;
insoluble stannous compounds, such as the oxide, sulfide,
and oleate, and stannic oxide are relatively harmless at
levels up to 1% of the diet, but cationic Sn2þ compounds
of sulfate, chloride, and tartrate are toxic at dietary levels
above 0.3%.
Chronic Sn poisoning in rats causes moderate testi-
cular degeneration, severe pancreatic atrophy, acute
bronchopneumonia, enteritis, and neurological and renal
damage, but there are marked differences in the toxicity
of stannic and stannous oxide in rats when given orally as
regards growth retard. Lifetime intake of 5 ppm Sn2þ in
their drinking water by mice and rats causes fatty de-
generation of liver and increased incidence of vascular
changes in their renal tubules. Mammary adenocarci-
noma, uterine sarcoma, and adenocarcinoma near the jaw
occurred in rats that were fed with a diet containing 2%
chlorostannate for more than 1 year. Hepatocellular
adenoma or carcinoma occurred in mice, and histolytic
lymphomas in female mice (approximately 16%) fed
with 2 g kg1 of stannous chloride for a period of 105
weeks, but no adverse effects were noted nor was there
any difference in tumor incidence in a group of mice
receiving over several generations sodium chlorostannate
either at 1 or 5 g Sn kg1 in the drinking water or stan-
nous oleate at 5 g kg1 in the diet. In vitro researches have
shown that stannous chloride exposition resulted in loss
of cell liability and DNA damage in a dose-dependent
manner, which was linked to tin-mediated formation of
reactive oxygen species, suggesting that tin can interfere
with heme formation by competitive antagonism with
iron, zinc, and copper. Moreover, a genotoxic effect of
tin chloride has been shown with a tester strain of
Escherichia coli.
Organic tin compounds are more highly toxic than
inorganic compounds. Acute toxicity (LD50) was repor-
ted for experimental mammals and aquatic invertebrates
and vertebrates. Except for the three acaricides (ACT,
TCHT, FBTO), mice generally appear the most sensitive
species relative to other mammals, and the oral route
seems less dangerous because organotins undergo limited
gastrointestinal absorption. Among aquatic invertebrates,
the most sensitive species to TBT are the filter-feeding,
benthic ones, such as bivalve mollusks, bryozoans, and
tunicates. Among teleosts, marine ones appear more
sensitive to TBT than freshwater ones.
Human Toxicity
In humans, most of the local and systemic toxic effects
mentioned previously have been confirmed, such as
neurotoxicity by inhalation of tin hydride but no
358 Tin: Environmental Pollution and Health Effects

hemolysis, which, on the contrary, is caused by tetra- Table 2 Human toxicity of organotins
hydrogenated tin (SnH4). High-level intakes of inorganic Toxic effects Clinical findings Compound
tin compounds can cause skin rashes, stomach complaints, Local effects
nausea, vomiting, diarrhea, abdominal pain, headache, Skin irritation Erythematous All
and palpitations, whereas low level can result in fatigue, and lesion eruption
depression, low cardiac left output, low adrenals, shortness Contact dermatitis
of breath, asthma, headaches, and insomnia. Stannous Ulceration
Eye irritation Profuse lacrimation All
and stannic chloride at concentrations of 10–50 mmol l1
Eye inflammation
induce prolonged suppression of DNA synthesis in Photophobia
human lymphocytes. Stannic chloride was found to be a Blurred vision
potential clastogen showing an age-related elevation of Respiratory Breath shortness All
mitotic index, chromosome aberration, sister-chromatid damage Coughing
Wheezing
exchanges, and micronuclei formation in blood lympho-
Gastrointest- Pharyngitis TBT, TPTA
cyte cultures from tin miners. However, experimental inal irritation Nausea TBT, TPTA
studies have failed to find convincing evidence of muta- Vomiting TBT, TPTA
genicity, carcinogenicity, or teratogenicity of inorganic tin Hematemesis TBT, TPTA
compounds. Interestingly, cytotoxic antitumor properties Inappetence TBT, TPTA
Abdominal pain TBT, TPTA
of diorganotin complexes have been detected against some
Systemic effects
human tumor cell lines. In general, the organotin moiety, Neurological Smell disturbance TBT
the ligand, and the number of tin atoms appear to play an effects Hearing loss TMT
important role in determining the cytotoxic activity. Visual disturbance TMT
The main toxic effects of organotins causing en- Seizures TMT
Neural necrosis TMT, TET
vironmental pollution are summarized in Table 2.
Encephalopathy TPT
Cerebral edema TPT
Involuntary hand TPT
Epidemiology of Tin Exposure movements
Facial twitching TPT
Crying TPT
Inhalation of tin oxide dust is a hazard both in the deep Diplopia TPT
mining of tin and in molten metal refining, and a chronic Drowsiness TPT
industrial exposure to tin dust causes benign pneumo- Giddiness TPT
coniosis called stannosis. Inhaled tin hydride gas can Bidirectional TPT
cause damage to nerves. nystagmus
Calculation ability TPT
Inorganic tin compounds are comparatively harmless
impairment
than organotins because of their poor absorption, relative Time and place TPT
insolubility, and low retention in tissues, whereas non- disorientation
absorbable and inert motes of silver-white metal tin have Amnesia TMT, TPTA
been present even since fifth century BC as a component Headache TET, TBT
Delayed TPTA
of Diagora’s cosmetic eyewash. An epidemiological rela-
sensomotor
tionship of tin exposures has been shown with an increased polyneuropathy
risk of chronic renal failure, ischemic heart disease, and Cardiovascu- Vasodilatation TBTO
the metabolism of cholesterol, whereas an increase in lar effects Hypotension TBTO
plasma cholesterol has been related to a decrease in Heart failure TBTO
Hepatic Elevated hepatic TPT
copper status caused by tin concentrations similar to those effects enzymes
found in human diets. Indeed, there are several reports Elevated C-reactive TPTA
on outbreaks of food poisoning from tin contamination in protein
canned food – such as vomiting and diarrhea after con- Hepatomegaly TPTA
sumption of formulated orange juice containing 250– Hepatic TPTA
inflammation
390 mg Sn kg1, acute gastroenteritis after ingestion, dur-
Genitourinary Acute renal failure TPTA
ing a 3-month period, of canned tomato juice containing effects
135–405 mg Sn kg1, and nausea and diarrhea after Hematologic- Hemolysis TBT4TPT4
drinking orange juice containing tin at concentrations up al effects TET4DBT4
to 1.4 mg kg1 – but none on adverse effects after ingestion TMT ¼ MBT
Leucopoenia TPTA, TPT
of tin at doses of 1.6–2.9 mg per kg bodyweight per day.
In contrast, all organotins, particularly TMT and
TET, are better absorbed and more toxic than inorganic
 Tin: Environmental Pollution and Health Effects
tin compounds, even if they are probably absorbed
to a limited extent by skin and the gastrointestinal tract.
They easily cross the blood-brain barrier and placenta.
The tissue distribution of tin from these organometallic
compounds shows the highest concentration in the
bone, liver, kidney, and lung, with smaller amounts in the
muscle, spleen, heart, or brain. Short-term exposure to
powdered organotin compounds or as vapors or aerosol
by the inhalation route may cause severe organotin poi-
soning in humans.
There are no human studies available on chronic
low-level exposure to organotin compounds. Their
absorption, either through the skin or through the gas-
trointestinal tract, is generally limited, and few poison-
ings and deaths, except by TPT, have been reported as a
result of occupational exposure, such as manufacturing,
formulating, painting, and spraying. The manifestations
of poisoning are local or systemic, but there are no
specific antidotes and treatment involves decontamin-
ation and supportive therapies, whereas the long-term
human health effects due to low-level exposures are
unknown.
An outbreak of almost epidemic nature took place in
humans in France in 1954 because of ingestion of an
antibacterial preparation (Stalinon) for the treatment of
skin disorders containing diethyltin diiodide and TET
monoiodide: 102 fatalities occurred out of 217 cases
of contaminated subjects. The doses of diethyltin were
estimated to be from 45 to 675 mg in nonfatal cases and
from 380 to 675 mg in fatal cases. Severe headache,
vertigo, visual abnormalities, paralysis, and convulsions
have been reported after only a few days of exposure.
Death occurred from coma and respiratory or cardiac
failure, and a pronounced edema of white matter of the
brain persisted for years in survivors, although it has
always been seen in fatal cases.
Further Reading
Cima F, Craig PJ, and Harrington C (2003) Organotin compounds in the
environment. In: Craig PJ (ed.) Organometallic Compounds in the
Environment, 2nd edn., pp. 101--149. Chichester: Wiley.
359
Cima F, Marin MG, Da Ros L, and Ballarin L (1998) Marine invertebrates
as bioindicators of organotin contaminants: Immuno- and
embryotoxicity. Annali di Chimica 88: 517--527.
Cima F, Dominaci D, Mammi S, and Ballarin L (2002) Butyltins and
calmodulin: Which interaction? Applied Organometallic Chemistry
16: 182--186.
FAO (2005) Pesticide residues in food – 1991. Evaluations, Part 1 –
Residues. FAO Plant Production and Protection Paper 113/1, 337.
Geneva: World Health Organization.
Hoch M (2001) Organotin compounds in the environment: An overview.
Applied Geochemistry 16: 719--743.
Klevay IM (2000) Tin. In: Bogden JD and Klevay LM (eds.) Clinical
Nutrition of the Essential Trace Elements and Minerals: The Guide
for Health Professionals, pp. 251--271. Totowa, NJ: Humana Press.
Liu J, Goyer A, and Waalkes MP (2008) Tin (Sn). In: Klaassen C (ed.)
Casarett and Doull’s Toxicology: The Basic Science of Poisons, 7th
edn., pp. 969--970. New York: McGraw-Hill.
Magos L (1986) Tin. In: Friberg L, Nordberg GF, and Vouk VB (eds.)
Handbook on the Toxicology of Metals, 2nd edn., pp. 568--593.
Amsterdam: Elsevier.
Nath M (2008) Toxicity and the cardiovascular activity of organotin
compounds: A review. Applied Organometallic Chemistry 22:
598--612.
Ostrakhovitch EA and Cherian MG (2007) Tin. In: Nordberg GF, Fowler
BA, Nordberg M, and Friberg L (eds.) Handbook on the Toxicology of
Metals, 3rd edn., pp. 839--859. Burlington, MA: Academic Press –
Elsevier.
Pressel G (1988) Tin. In: Seiler HG and Sigel H (eds.) Handbook on
Toxicity of Inorganic Compounds, pp. 697--703. New York: Marcel
Dekker.
WHO (1996) Tin Trace Elements in Human Nutrition and Health.
Geneva: World Health Organization.
WHO (1999) Concise International Chemical Assessment Document
14: Tributyltin Oxide. Geneva: World Health Organization.
WHO (2001) Food Additives Series 46. Geneva: World Health
Organization.
Winship KA (1988) Toxicity of tin and its compounds. Adverse Drug
Reactions and Acute Poisoning Reviews 1: 19--38.
Relevant Websites
http://www.atsdr.cdc.gov/
Agency for Toxic Substances and Disease Registry (ATSDR).
http://www.pesticideinfo.org/Search_Chemicals.jsp
PAN Pesticides Database Chemicals.
http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?TOXLINE
Toxicology Data Network (TOXNET), NLM TOXLINE Search.