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The following study shows that the greatest concentration
of tin in the body is in the thymus gland. Since the thymus is a key
immune system gland, my suspicion is that tin may somehow be involved in
autoimmune diseases such as thyroid diseases.
|J Anal Toxicol 1986 Jan-Feb;10(1):6-9
Tin concentration in the thymus glands of rats and mice
and its relation to the involution of the gland.
Sherman LR, Masters J, Peterson R, Levine S
Tin is an ubiquitous element and thus enters mammals through the food chain.
It has never been found to be dysfunctional in either plants or animal
tissue and has been regarded as an innocuous background material. Of the
many organs and glands that have been analyzed for tin, only the thymus
gland exhibits an above average value for tin. A complete study on the tin
content in the thymus gland has never been published and this work is an
attempt to investigate this subject. Three types of rodents were used in
this study; inbred Lewis rats, inbred A/KI mice (a breast cancer prone
mouse) and outbred COBS mice (a cancer resistant mouse). The tin analysis of
the muscle, spleen, and thymus indicated constant values for the muscle and
spleen tissue, but an increase in the thymic tin concentration (ppm) with
age. Besides normal aging studies, the animals were administered the
disodium salt of dexamethasone-21-phosphate (dexa), which causes rapid loss
of lymphocytes from the spleen and thymus but has no effect upon the muscle.
Tin concentration in the muscles remained constant, showed a loss from the
spleen and an increase in the thymus gland. The increase indicates that the
tin was probably located in the medulla of the thymus, which may be the
active biochemical site for tin in rodents. When compared to the COBS mice,
the A/KI mice showed a non-statistical difference in tin content in the
muscle and spleen and statistically significant lower tin content in the
The following study suggests that tin toxicity can result in psychiatric
abnormalities such as psychosis.
|G Ital Med Lav Ergon 2000 Jan-Mar;22(1):52-61; discussion
[Occupational poisoning with psychiatric manifestations].
[Article in Italian]
Candura SM, Butera R, Gandini C, Locatelli C, Tagliani M, Fasola D, Manzo
Dipartimento di Medicina Preventiva, Universita degli Studi di Pavia.
Numerous occupational intoxications (acute, chronic and their sequelae) may
affect the central nervous system and result in a wide variety of
neuropsychiatric effects, ranging from subtle behavioural disturbances to
overt psychosis. Chemicals causing such manifestations include many metals
and organometals (Hg, Mn, Pb, Al, Sn), pesticides (organophosphates),
compounds utilised in the industrial setting as solvents or intermediates
(carbon disulfide, hydrocarbons and their halogenated derivatives), and
combustion products (carbon monoxide). Some types of toxic insults may not
be reflected in any clinical manifestation. However, this type of damage may
render the brain more vulnerable to additional insult or accelerate
physiological loss of neurones with ageing. Thus, occupational exposures to
chemicals (Al, Pb, organic solvents) might be involved in the causation of
neurodegenerative diseases--such as Alzheimer's disease--which are usually
labelled as "idiopathic". A careful occupational anamnesis is
crucial to diagnose work-related psychiatric manifestations
and--consequently--to interrupt the toxic exposure, to start therapy, and to
promote insurance compensation.
|Sangyo Eiseigaku Zasshi 1997 Jan;39(1):1-20
[Biological activity of tin and immunity].
[Article in Japanese]
Department of Hygiene and Preventive Medicine, Faculty of Health Sciences,
University of Shizuoka, Japan.
Tin generates a wide variety of biological activities deriving from its
chemical character. In this article, the biological activities of tin
compounds are reviewed with a focus on the connection with immunity. The
table of contents is as follows: Introduction, 1. Inorganic Tin and
Immunity, 2. Organic Tin and Immunity, 2.1. Immunotoxicity, 2.1.1.
Immunosuppression, 2.1.2. Thymus atrophy, 2.1.3. Changes in the membrane
surface antigens of T cells, 2.2. Antitumor activity, 2.3. Anti-inflammatory
action, 2.4. Tolerance manifestation of thymus atrophy, 3. Cellular and
Biochemical Aspects of the Activity Manifestation, 3.1. Intracellular
distribution of organotins 3.2. Effects on structure and function of Golgi
apparatus and endoplasmic reticulum, 3.3. Effects on physical properties of
phospholipid membrane, 3.4. Suppressive effects on cell proliferation
system, 3.5. Consideration, Conclusion. To sum up this article, tin
compounds (especially organotin compounds) act mainly on cellular immune
systems and the mechanism appears to be due to their hydrophobicity-dependent
intracellular distribution and their action on the phospholipid metabolism
including the inhibition of intracellular phospholipid transport between
organelles through an impairment of the structure and functions of the Golgi
apparatus and the endoplasmic reticulum (ER), and the consequent inhibition
of the membrane-mediated signal transduction system leading to DNA synthesis
via phospholipid turnover and Ca2+ mobilization.
The following study suggests that a tin deficiency might be involved in
|Int Dent J 1994 Feb;44(1 Suppl 1):107-18
The effect of stannous fluoride on dentinal
Thrash WJ, Dodds MW, Jones DL
Department of Community Dentistry, University of Texas Health Science Center
at San Antonio 78284-7917.
Many agents have shown varying degrees of effectiveness on pain resulting
from exposed dentine. One which has shown some promising results is stannous
fluoride (SnF2). The purpose of the following paper is twofold: to review
and summarise the clinical literature pertaining to the relative
effectiveness of solutions or gels containing SnF2 in controlling pain
associated with dentinal hypersensitivity; and to statistically re-evaluate
these studies in combination, in order to develop recommendations for the
optimal use of SnF2 for hypersensitivity. Seven blinded clinical studies
were identified and reviewed. Five of these compared 0.4 per cent SnF2 gel
solution to an identical placebo. One compared a 0.4 per cent SnF2 gel
solution and a 0.717 per cent F solution to an aqueous placebo. The final
study compared a 0.717 per cent F solution to an aqueous placebo.
Statistical power analysis and a combined meta-analysis were used to ensure
adequate internal consistency and to contribute to an overall consensus of
the efficacy across time. It was concluded that the 0.717 per cent F
solution provides a virtually immediate and definable effect, which seems to
continue for several months. This effect was present in all subjects used in
the study. This solution was applied directly to the sensitive area for one
minute and allowed to remain for 3-5 minutes. An additional one minute
application was applied if needed. The effect of the 0.4 per cent SnF2 gel
appears to be more gradual, perhaps involving a different mechanism of
action. This solution requires approximately two to four weeks of continuous
treatment to be effective. It was concluded that an effective strategy
involving the use of stannous fluoride gel includes the application of the
0.717 per cent F solution in the office, effectively providing immediate
relief. The patient would then use the 0.4 per cent SnF2 gel at home in
order to achieve the long-term effect. In order to control episodic pain
while the gel is developing its effect, a small amount of the 0.717 per cent
F solution could be given to the patient for occasional symptomatic
|J Toxicol Sci 1990 Dec;15 Suppl 4:125-51
The neurotoxicology and pathology of organomercury,
organolead, and organotin.
Department of Pathology, University of Arkansas for Medical Sciences, Little
The toxicities of many metals, such as mercury and lead, are known to man
since the dawn of civilization. Organic compounds of some heavy metals are
known to have a particular toxic impact on the central nervous system.
Organomercury, particularly alkyl-mercuric compounds (e.g. methylmercury),
has a selective effect on the granule cells of the cerebellum, the nerve
cells of the calcarine cortex, and the sensory neurons in the dorsal root
ganglia. The well known Minamata Bay disease is the result of a massive
epidemic episode of human exposure to alkylmercury contaminated food
sources. Mental retardation and other developmental defects are also known
to be a consequence of exposure to this toxic metal. Organic lead compounds
have been employed as gasoline additives and in other industrial purposes.
Unlike its inorganic counterpart, organolead compounds have a more prominent
impact on the central nervous system. Pathological changes of the brain stem
neurons have been described. Organotin compounds have been used in plastic
industries and as agricultural chemicals. Both trimethyl and triethyl tin
compounds are found to be extremely neurotoxic. Despite the similarity of
their chemical structures, trimethyl and triethyl tins have a diversely
different toxic property and effects. While triethyl tin is myelinotoxic,
producing edematous and vacuolar changes in the central myelin, trimethyl
tin is neurotoxic, producing prominent toxic changes in the neurons of the
limbic system (hippocampus, entorhinal cortex, etc.). The factors which
determine the specificity and selectivity of the neurotoxic impacts by
various organometals are still unknown. In view that most of the
organometals are still widely employed by many countries for industrial and
for agricultural purposes, caution must be made for their proper handling
and disposure to avoid undesirable exposures to workers and environmental
contamination of water sources and food-chain for the common public. Since
organometals are difficult to eliminate from the central nervous system,
injuries usually lead to permanent neurological deficits, such tragedies are
frequently long lasting and create not only a medical problem, but also a
social economical problem for the society.
|Thymus 1990 Jun;15(4):223-31
Tin and the thymus gland: a review.
Engineering and Science Technology Division, University of Akron, OH 44325.
Experimental studies over the last decade have suggested an association
between thymus immune and homeostatic function and exogenous tin. It has
been hypothesized that the thymus gland synthesizes and secretes one or more
tin bearing factors that enhance immune defenses against malignancy and
retard the gradual loss of immune capacity with senescence. This review
conciliates data from several divergent areas of research in order to
explore the rationale for the above concepts.
Tin in the thymus gland of dogs.
Sherman LR, Cardarelli NF
Department of Chemistry, University of Akron, OH 44325-0001.
The thymus glands from four mixed breed dogs were analyzed to determine
the water content, chloroform extractable fraction and residue. The thymi
samples were assayed for tin and compared to the tin in the spleen and
muscle tissue. The tin content in the thymus gland (29.4 ppm) was higher
than the muscle (14.9 ppm) or spleen (12.8 ppm). The tin content in the
lipid portion of the thymus was approximately four times greater than the
non-chloroform extractable fraction (primarily protein).
|Int J Rad Appl Instrum B 1992 Apr;19(3):297-301
m-[125I]iodoaniline: a useful reagent for radiolabeling
Khawli LA, Kassis AI
Department of Radiology (Nuclear Medicine), Harvard Medical School, Shields
Warren Radiation Laboratory, Boston, MA 02115.
Biotinyl-m-[125I]iodoanilide (BIA) was synthesized by coupling biotin to
m-[125I]iodoaniline via a mixed anhydride reaction. m-[125I]Iodoaniline was
produced from the tin precursor, which was prepared using a palladium
catalyzed reaction of hexabutylditin with m-bromoaniline. The radioiodinated
BIA derivative is characterized by a stable amide and/or intact ureido group
on the biotin molecule; it may thus be a useful carrier for targeting
radionuclides to avidin-conjugated antibodies previously localized on
|Pharmacology 1996 Mar;52(3):178-86
Effects of a series of metalloporphyrins on adrenal,
testicular and thyroid function in rats.
Drummond GS, Smith TJ, Kappas A
Rockefeller University Hospital, New York 10021, USA.
We have extended our earlier studies [Pharmacology 1986;34:9-16] on the
effects of certain synthetic heme analogues and cobalt chloride (CoCl2) on
endocrine functions mediated by the hypothalamic-pituitary axis to examine
specifically the ability of Sn-protoporphyrin (SnPP) and Sn-mesoporphyrin (SnMP)
to perturb adrenal, testicular and thyroid function since there is interest
in the use of Sn(tin)-porphyrins in the treatment of hyperbilirubinemia of
the newborn. SnPP and SnMP when administered to adult male rats did not
alter serum corticosterone, testosterone, thyroxine or triiodothyronine
levels when compared to control animals. In addition, administration of
exogenous adrenocorticotrophic hormone produced an increase in serum
corticosterone levels that was comparable in placebo-treated and SnPP- and
SnMP-treated animals. These studies involved doses of both compounds
substantially greater than those used clinically. The results clearly
indicate that SnMP, presently the compound of choice for use in newborns,
and SnPP do not in the doses studied impair adrenal, testicular and thyroid
function in vivo.
|Food Chem Toxicol 1990 Mar;28(3):179-96
Chronic toxicity and carcinogenicity of
bis(tri-n-butyltin)oxide (TBTO) in the rat.
Wester PW, Krajnc EI, van Leeuwen FX, Loeber JG, van der Heijden CA,
Vaessen HA, Helleman PW
National Institute of Public Health and Environmental Protection, Bilthoven,
In a 106-wk toxicity and carcinogenicity study, groups of 60 male and 60
female weanling Wistar rats were fed 0, 0.5, or 50 mg
bis(tri-n-butyltin)oxide (TBTO)/kg diet. In males, feed consumption was
increased in all treated groups and increased water consumption occurred at
5 and 50 mg/kg. During the second year, body weight decreased in the
50-mg/kg males, while the females in that group showed no weight gain.
Excess mortality was confined to the 50-mg/kg group towards the end of the
study. Haematological changes, comprising anaemia, lymphocytopenia and
thrombocytosis were noted mainly at the high-dose level. Also, signs of
decreased kidney function and increased plasma enzyme activities (alanine
aminotransferase, aspartate aminotransferase and alkaline phosphatase) were
noted. No effects on serum hormone concentrations (thyrotropin, follicle
stimulating hormone, luteinizing hormone or insulin) were observed, except
for a decrease in the free thyroxin:thyroxin ratio in both sexes at the
high-dose level. Higher serum IgM and IgA levels were present at 50 mg/kg,
while, in females, IgG was decreased. At 50 mg/kg, the ovaries, adrenals,
spleen (females), heart (males), pituitary, liver and kidneys were increased
in weight, but the thyroid weight was decreased in females. The total tin
concentrations in liver and kidneys showed a dose relationship and, in
general, the concentrations were similar after 1 and 2 yr. Non-neoplastic
histological alterations after 1 yr consisted of a decrease in the cell
height of the thyroid follicles in all dose groups, with a reduced number of
psammoma bodies at 50 mg/kg, a decrease in splenic iron content at 5
(females only) and 50 mg/kg, and a slight bile-duct activation. After 2 yr,
only the thyroid changes were still present. In addition, at 2 yr,
vacuolation and pigmentation of the proximal tubular epithelium and
nephrosis were enhanced at 50 mg/kg. The incidence of benign tumours of the
pituitary was significantly elevated and enhanced at 0.5 and 50 mg/kg. At 50
mg/kg increases in pheochromocytomas in the adrenal medulla and in
parathyroid adenomas (males) were noted, while adrenal cortical tumours were
decreased (males). There was a low, non-dose-related incidence of pancreatic
carcinoma. Other tumour rates were in line with control data. It is
concluded that lifetime feeding of 50 mg TBTO/kg diet induces toxicity in
various organ systems. An increase in some common tumours was found at the
high dose, probably due to hormonal or immunological changes.
|Radiology 1977 Aug;124(2):445-50
The effect of tin on the tissue distribution of
Ancri D, Lonchampt MF, Basset JY
When tin complex is administered prior to the injection of 99mTc-sodium
pertechnetate, the distribution of the tracer is altered such that: (a) the
concentration at foci of cerebral pathology is drastically reduced; (b) the
concentration in the stomach (mucus cells), thyroid and salivary glands, and
choroid plexus is greatly increased; and (c) there is a shift of the tracer
from the plasma to the red blood cells. Bone studies utilizing a tin complex
should be done after other organs have been evaluated.
|:Arch Toxicol 1981 Jul;47(4):263-8
Distribution of tin in the rat and disturbances in
the metabolism of zinc and copper due to repeated exposure to SnCl2.
Chmielnicka J, Szymanska JA, Sniec J
The effect of stannous chloride on tissue concentrations of zinc and
copper was studied in female rats. The animals were subjected to
repeated exposure to seven doses given every other day 2 mg Sn/kg,
subcutaneously. About 60% of tin 113Sn was retained in the body. Of this
amount, about 95% accumulated in the skin and hair. In the remaining
organs the tin concentrations corresponded to 2.57 to 0.0001% of the
retained dose. In comparison with the control group a 3-fold increase of
the content of zinc was found in the liver while a decrease were
revealed in the spleen, heart, brain, lungs, and especially in muscle. A
statistically significant decrease of the copper content was found in
the blood and brain.
The following study indicates a connection between tin and lithium.
|Org Lett 2000 Jun 1;2(11):1561-4
Synthesis and reactivity of conformationally locked
alpha-aminoorganostannanes and alpha-aminoorganolithiums. Discovery Of a
surprising configurational requirement for transmetalation.
Chambournier G, Gawley RE
Department of Chemistry, University of Miami, P.O. Box 249118, Coral Gables,
Florida 33124, USA.
[Medline record in process]
2-Tributylstannyl-N-methylpiperidines that are conformationally locked by a
4-tert-butyl substituent were evaluated in transmetalations (Sn-Li exchange)
and reactions with electrophiles. When the tin is equatorial,
transmetalation occurs smoothly as does reaction with carbonyl electrophiles.
Alkyl halides seem to undergo single electron transfer reactions, affording
nonselective alkylation products, along with products of radical
disproportionation. In a surprise, an axially oriented tin failed to
transmetalate, suggesting that a synclinal relationship between the nitrogen
lone pair and the carbon-tin bond is a requirement for transmetalation.
|J Immunol 1989 Dec 15;143(12):3981-7
Immune stimulatory properties of metalloporphyrins.
Novogrodsky A, Suthanthiran M, Stenzel KH
Rogosin Institute, Cornell University Medical College, New York 10021.
A possible approach to the immunotherapy of tumors is to stimulate either
specific or nonspecific immune responses in vivo. We recently found that
provision of a mitogenic signal to PBMC, by incubation with the oxidizing
mitogens, enhanced the effect of IL-2 in generating cytolytic activity. We
therefore searched for a mitogen that might safely be administered to
patients. The present study is an investigation of the mitogenic properties
of iron and tin (Sn)-protoporphyrin and their capacity to induce
cytotoxicity in human PBMC. These agents have been administered to humans
with little toxicity. Both iron- (hemin) and Sn-protoporphyrin induce
mitogenicity in peripheral T cells. This effect is markedly enhanced by low
concentrations of IL-2. Hemin and Sn-protoporphyrin, in combination with
IL-2, increase IL-2R on PBMC. Hemin alone, and to a greater extent in
combination with IL-2, induces cytotoxicity for NK-sensitive and NK-resistant
cell lines. Sn-protoporphyrin, a more potent mitogen than hemin, fails to
induce cytotoxicity, and has a marked inhibitory effect on cytotoxicity
induced by IL-2. Hemin and Sn-protoporphyrin stimulate TNF-alpha and IFN-gamma
production by PBMC. IL-2 is synergistic with the metalloporphyrins in
eliciting this effect. Metalloporphyrin-induced mitogenesis has a stringent
requirement for macrophages. Scavengers of oxygen-free radicals and
inhibitors of peroxidase inhibit mitogenicity induced by hemin but not that
induced by Sn-protoporphyrin. Hence, an oxidative event may mediate the
mitogenic effect of hemin. Our results indicate that hemin is an
immunostimulatory agent in vitro and the data warrant further evaluation of
its in vivo immunostimulatory and antitumor effect.
|Aust J Exp Biol Med Sci 1984 Apr;62 ( Pt 2):199-208
Organotin implications in anticarcinogenesis. Background
and thymus involvement.
Cardarelli NF, Quitter BM, Allen A, Dobbins E, Libby EP, Hager P, Sherman
A comprehensive study of the scientific literature regarding tin content in
normal and pathogenic human tissue has disclosed that various organotin
materials retard both the onset and growth of cancer in laboratory animals,
and decreased tissue tin in humans may be associated with tumour
development. Initial studies by the authors have shown that the thymus gland
of the mouse possesses a relatively high concentration of tin and is also
the major site of accumulation for 14C-labelled tri-n-butyltin fluoride (TBTF).
When mammary cancer-prone mice with transplanted tumours were orally dosed
continuously with this agent in their drinking water, the tumour growth rate
was significantly reduced. Both mouse mammary tumours and human lung tumours
show low tin content compared to normal body tissue.
The following study seems to suggest that tin (in combination with vinyl)
can facilitate the synthesis of estradiol. Since there is some evidence
that food from tin cans might be a facilitator of hyperthyroidism, at least in
cats, there might be some connection between tin from cans, and an increase in
estradiol (which seems to increase cadmium uptake). Also there is mention of
selenium-estradiol compounds, which I'd like to investigate further.
|Steroids 1996 Jun;61(6):384-9
Synthesis and estrogen receptor binding of (17 alpha,
20E)- and (17 alpha, 20Z)-21-phenylthio- and
Napolitano E, Fiaschi R, Herman LW, Hanson RN
Department of Pharmaceutical Sciences, Bouve College of Pharmacy and Health
Sciences, Northeastern University, Boston, Massachusetts 02115, USA.
Previous studies from our laboratory using 17 alpha-E- and 17 alpha-Z-halovinyl
estradiols demonstrated a marked enhancement of receptor binding by the
Z-isomers. This suggested tolerance at the 17 alpha-position was not
previously observed by investigations using 16 alpha and 17
alpha-substituted estradiols. Because of the synthetic access provided by
vinyl tin chemistry, we prepared the 17 alpha-E and Z-phenylthiovinyl
and phenylselenovinyl estradiols and compared their binding characteristics
to those of the previously reported 16 alpha/17 alpha-phenylseleno and
methylseleno estradiols. The results, in addition to demonstrating a facile
preparation of the target compounds, indicated that significant receptor
affinity was retained by these compounds (relative binding affinity =
24.5-117). The highest affinity was demonstrated by the 17 alpha-Z-phenylthiovinyl
estradiol 5a, which, by molecular modeling, exhibited a significantly
different molecular conformation from the corresponding 17 alpha-E-phenylthiovinyl
isomer or the 17 alpha-phenyl-thioethynyl analog. The current series
possessed better binding characteristics than the phenylseleno and
methylseleno estradiols but somewhat poorer binding than the 17 alpha-E/Z-halovinyl
series. The observations suggest that some steric limitations exist in a
portion of the 17 alpha-region, and that the region is better accessed by
compounds possessing Z-vinyl stereochemistry.
|J Steroid Biochem Mol Biol 1993 Nov;46(5):613-22
Synthesis, receptor binding and biodistribution of the
Ali H, Rousseau J, van Lier JE
MRC Group in the Radiation Sciences, Faculty of Medicine, University of
Sherbrooke, Quebec, Canada.
Radioiodinated 11 beta-methoxy-(17 alpha,20E)iodovinylestradiol (11
beta-OMe-IVE2) shows high estrogen receptor (ER)-mediated uterus uptake and
good potential as an ER-imaging agent. In order to examine the tolerance of
the ER for modification about the iodovinyl substituent, we prepared the (17
alpha,20Z-chloro)21-chloro-21-iodovinylestradiol (4a) and several
derivatives featuring 11 beta-methoxy (4b), 11 beta-ethoxy (4c) or 7
alpha-methyl (4d) substituents. All gem-dihalogen derivatives 4a-d were
prepared from the 17 alpha-chloroethynyl precursors. The intermediate
chlorostannylvinyl derivatives were obtained using tri-n-butyltin hydride
and palladium acetate catalyst. Compounds 4a and 4b were labeled with 125I
via their corresponding tin intermediates and their tissue distribution was
studied in immature female rats. Addition of a 21-Cl to the 17 alpha-ethynylestradiols
reduced ER binding affinity, except for the 11 beta-substituted analogs
which showed a pronounced increase. Surprisingly, addition of a 21-Cl to the
(17 alpha,20E)IVE2 resulted in increased ER binding affinities and augmented
ER-mediated uterus uptake, which may result from the pronounced increase in
the dipole moment of the molecule. Thus, further modifications at the C-21
position of IVE2 are well tolerated by the ER. However, addition of the
21-Cl also resulted in increased radioiodine uptake by the thyroid, much
slower blood clearance and lower uterus to blood/nontarget ratios,
suggesting increased in vivo instability of the C--I bond of the
gem-chlorine-iodine atoms which may reflect the increase in steric and