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Activity: Antifoulant,
Algaecide, Herbicide (Organotin)
Structure:
Adverse Effects:
Blood
Body Weight Decrease
Diabetes
Eye
Lung
Pancreas
Teratogen
Environmental
Table
5-1. Current U.S. Manufacturers of Selected Tin Compounds
ATOFINA
Chemicals, Inc. Specialty Chemicals Division Carrollton,
Kentucky
Derived from SRI 2003. SRI reports production of chemicals
produced in commercial quantities (defined as exceeding
5,000 pounds or $10,000 in value annually) by the companies
listed.
Ref:
DRAFT TOXICOLOGICAL PROFILE FOR TIN AND COMPOUNDS. U.S.
DEPARTMENT OF HEALTH AND HUMAN SERVICES. Public Health Service
Agency for Toxic Substances and Disease Registry. September
2003.
http://www.atsdr.cdc.gov/toxprofiles/tp55.pdf
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Blood
(click
on for all fluorinated pesticides)
Abstract: Recent work in our laboratory has shown that oral administration
of triphenyltin fluoride (TPTF) evokes hypertriglyceridemia
in rabbits. The present experiments were conducted to elucidate
the mechanism of TPTF-induced hypertriglyceridemia in rabbits
by a combined biochemical and ultrastructural approach. After
a single TPTF administration, fasting blood glucose and plasma
triglyceride levels increased significantly (P less than 0.02)
for about 20 days. On the other hand, both plasma and adipose
tissue lipoprotein lipase (LPL) activity was markedly decreased
(P less than 0.001) during this period, and triglyceride production
rates on day 2 after TPTF administration was significantly decreased
(P less than 0.01). Density-gradient ultracentrifugation showed
a remarkable accumulation of chylomicron and VLDL in the composition
of plasma lipoproteins. Insulin injection to the hypertriglyceridemic
rabbits induced a significant recovery of the decreased plasma
LPL activity with a concomitant decrease of plasma triglyceride
levels, while abeyance of insulin injection resulted in a decrease
of LPL activity again. A significant inhibition of insulin release
in response to the loading of glucose, glucagon, or arginine was
observed in the TPTF rabbits (P less than 0.02). Inhibition of
glucagon release was also observed in the arginine-loading test
(P less than 0.01). Electron microscopic studies showed small
abnormalities in the pancreatic islets of TPTF-treated rabbits.
These findings suggest that TPTF inhibits
insulin release from rabbit islets, subsequently inducing diabetic
lipemia due to the insulin deficiency. Furthermore, it is possible
to provide a new animal model for diabetes and diabetic lipemia
by administration of TPTF to rabbits.
Ref: Diabetes 1981 Dec;30(12):1013-21.
Triphenyltin
fluoride (TPTF) as a diabetogenic agent. TPTF induces diabetic
lipemia by inhibiting insulin secretion from morphologically intact
rabbit B-cell. Manabe S, Wada O.
• Definition
of hypertriglyceridemia: Condition of elevated triglyceride
concentration in the blood; an inherited form occurs in familial
hyperlipoproteinaemia IIb and hyperlipoproteinaemia type IV.
It has been linked to higher risk of heart disease and arteriosclerosis.
•• see National
Institutes of Health Consensus Development Conference Statement
on Hypertriglyceridemia, September 27-29, 1983
Abstract.
Recent studies have demonstrated
that triphenyltin fluoride (TPTF)
inhibits collagen-induced aggregation and ATP secretion of rabbit
platelets in vivo [S. Manabe and O. Wada, J. Toxic. Sci. 6, 236
(1981)]. The aim of the present investigation was to test the
effects in vitro of TPTF on platelet aggregation and to elucidate
the mechanism of the inhibitory action by studying the release
and metabolism of arachidonic acid and the cyclic AMP contents
of rabbit platelets treated in vitro with TPTF. Although no inhibitory
effect of TPTF was found on sodium arachidonate-induced platelet
aggregation and ATP secretion, TPTF inhibited both reactions induced
by collagen. Triphenylarsine and triphenylantimony did not inhibit,
even at a concentration of 10(-3) M. The anti-aggregating concentration
(IC50) of TPTF was 6.0 x 10(-6) M against collagen. TPTF had no
inhibitory effect on the conversion of exogenous arachidonic acid
to malondialdehyde (MDA) by platelets, while the collagen-induced
production of arachidonate metabolites [MDA, 12-L-hydroxy-5,8,10-heptadecatrienoic
acid (HHT) and thromboxane B2] was remarkably inhibited by TPTF.
Furthermore, TPTF apparently inhibited the collagen-induced release
of arachidonic acid from platelets, although the formation of
phosphatidic acid was not inhibited. Total cyclic AMP content
after TPTF exposure was not changed significantly. These
results indicate that TPTF inhibited the collagen-induced arachidonic
acid release from platelet phospholipids, presumably by acting
on phospholipase A2. Furthermore, it seems unlikely that the inhibition
of arachidonic acid release by TPTF can be explained by the level
of cyclic AMP in platelets.
Ref: Triphenyltin fluoride
in vitro inhibition of rabbit platelet collagen-induced aggregation
and ATP secretion and blockade of arachidonic acid mobilization
from membrane phospholipids; by S Manabe et al. Biochem Pharmacol
1983 May 15;32(10):1627-34.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6305366&dopt=Abstract
Abstract.
Recent studies have demonstrated that triphenyltin fluoride (TPTF),
widely used as an agricultural chemical and a marine antifoulant,
inhibits collagen-induced platelet aggregation and ATP secretion
in rabbits ex vivo. The aim of the present investigation was to
elucidate the mechanism of the inhibitory action of TPTF by investigating
platelet malondialdehyde (MDA) formation, aggregation and ATP
secretion following the stimulation by various stimuli of rabbit
platelets treated in vitro with TPTF, other triphenyl metals and
aspirin. Although no inhibitory effect of TPTF was found on sodium
arachidonate-induced platelet aggregation and ATP secretion, TPTF
inhibited dose-dependently both platelet aggregation and ATP secretion
induced by collagen. The antiaggregating (IC50) concentration
of TPTF was 6.0 X 10(-6) M against collagen. In addition, TPTF
prevented the collagen-, and thrombin-induced formation of MDA,
but had little inhibitory effect on the conversion of exogenous
arachidonic acid to MDA in platelets. In contrast, aspirin (10(-3)
M) inhibited platelet aggregation, ATP secretion and MDA formation
induced by all the stimuli tested. Other triphenyl metals did
not any inhibitory effect on collagen-, and sodium arachidonate-induced
platelet aggregation and ATP secretion even at a final concentration
at 10(-3) M. These results suggest that
TPTF has a specific inhibitory effect on platelet aggregation
and ATP secretion by acting at some step(s) of platelet membrane
between the binding site of collagen and thrombin and the release
of arachidonic acid.
Ref: [The effect of triphenyltin
fluoride on aggregation, ATP secretion and malondialdehyde formation
of rabbit platelets in vitro]. [Article in Japanese]; by S Manabe
S et al. Sangyo Igaku 1983 Jan;25(1):15-22.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6865093&dopt=Abstract
Body
Weight Decrease
(click on for all fluorinated pesticides)
Abstract.
An
acute dust inhalation toxicity study using albino rats as experimental
animals was performed for the compound triphenyltin-fluoride.
The acute dust inhalation median lethal concentration of the test
compound is 0.29 milligrams per liter of air based on a four hour
exposure period. Untoward behavioral reactions exhibited by the
animals included gasping, bloody nasal discharge, bloody ocular
discharge, and weakness. Body weight gains
of the survivors of the 14 day observation period were less than
normal. Gross pathologic observation revealed
mild to severe focal discoloration of the lungs in all test animals.
Ref: Elliott CB (1972). Acute Dust Inhalation
Toxicity Study with Triphenyltin Fluoride in Albino Rats. M and
T Chemicals, Inc. (Unpublished report submitted to NIOSH), Rahway,
N. J., IBT No. N1632, 14 pages, 1 reference.
[Toxline abstract at Toxnet]
Diabetes
(click on for all fluorinated
pesticides)
Abstract: ...Recently
we found that a single oral administration of triphenyltin fluoride
to rabbits induces transient diabetes and diabetic lipemia by
inhibiting insulin secretion from morphologically normal pancreatic
B-cells...
Ref: Recent
progress in the study of analytical methods, toxicity, metabolism
and health effects of organotin compounds] by Wada O, Manabe
S, Iwai H, Arakawa Y. Sangyo Igaku 1982 Jan;24(1):24-54.
Abstract:
... These findings suggest that TPTF inhibits
insulin release from rabbit islets, subsequently inducing diabetic
lipemia due to the insulin deficiency. Furthermore, it
is possible to provide a new animal model for diabetes and diabetic
lipemia by administration of TPTF to rabbits.
Ref: Triphenyltin
fluoride (TPTF) as a diabetogenic agent. TPTF induces diabetic
lipemia by inhibiting insulin secretion from morphologically intact
rabbit B-cell by Manabe S, Wada O. Diabetes 1981 Dec;30(12):1013-21.
Abstract.
Phenyltin compounds have been used as agricultural chemicals and
marine antifoulants and studied from the stand-point of toxicity.
The in vivo mechanisms of toxicity and metabolism are not understood.
Oral administration of 100 mg/kg body wt
of tripheyltin fluoride (TPTF) to rabbits evoked hypertriglyceridemia.
The mechanism of TPTF-induced hypertriglyceridemia was
studied by following the time course of fasting blood glucose
(FBS), glucose tolerance tests, serum IRI (immunoreactive insulin),
serum lipids and lipoprotein lipase (LPL) activity and by determining
the influence of insulin on TPTF-induced hypertriglyceridemia.
The pancreatic islets, liver and kidney of the rabbits were also
examined histologically. After TPTF administration, FBS
and plasma triglyceride concentration were elevated significantly
(P < 0.02) forma postheparin lipolytic activity) and LPL in adipose
tissue decreased (P < 0.02), while chyromicron and VLDL (very
low density lipoproteins) increased. Insulin treatment
for 1 or 2 days increased LPL activity to the normal level but
withdrawal of insulin from the insulin-treated rabbits again resulted
in a decrease in LPL activity. A single
oral dose of TPTF evoked diabetic lipemia and glucose intolerance
due to insulin deficiency. The IRI level decreased before
and even after glucose infusion during these periods. Microscopic
examinations revealed no remarkable changes in the pancreas islets,
liver and kidney. Pancreatic B-cells contained normal amounts
of granules at the maximal hyperlipemic stage.
TPTF interfered with insulin release from rabbit beta-cells and/or
TPTF decreased the sensitivity of islets to release insulin in
response to increasing levels of blood glucose.
Ref: MANABE S and WADA O (1981). Transient
diabetic lipemia and reversible glucose intolerance in rabbits
after a single dose of triphenyltin fluoride. J JPN DIABETIC SOC;
24 (6). 669-677.
Eye
(click
on for all fluorinated pesticides)
Abstract: The acute
and chronic toxicities of anti fouling coatings were studied in
animals. The acute oral median lethal dose (LD50) was determined
for bis(tri-n-butyltin)oxide (56-35-9),
tributyltin-fluoride (1983-10-4) and triphenyltin-fluoride
(379-52-2) for rats and rabbits...
All were severe or extreme eye irritants
and most were moderate to severe skin irritants.
Ref: 1975
Journal of Paint Technology, Vol. 47, No. 600, pages
54-58. Effects Of Organotin Anti-Fouling Coatings On Man And His
Environment by Sheldon AW.
http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~AAAjCaaO4:1
Abstract.
An
acute dust inhalation toxicity study using albino rats as experimental
animals was performed for the compound triphenyltin-fluoride.
The acute dust inhalation median lethal concentration of the test
compound is 0.29 milligrams per liter of air based on a four hour
exposure period. Untoward behavioral reactions
exhibited by the animals included gasping, bloody nasal discharge,
bloody ocular discharge, and weakness. Body
weight gains of the survivors of the 14 day observation period
were less than normal. Gross pathologic
observation revealed mild to severe focal discoloration of the
lungs in all test animals.
Ref: Acute Dust Inhalation
Toxicity Study with Triphenyltin Fluoride in Albino Rats; by Elliott
CB. Source: M and T Chemicals, Inc. (Unpublished report submitted
to NIOSH), Rahway, N. J., IBT No. N1632, 14 pages, 1 reference,
1972. [Toxline abstract at Toxnet]
Lung
(click
on for all fluorinated pesticides)
Abstract.
An
acute dust inhalation toxicity study using albino rats as experimental
animals was performed for the compound triphenyltin-fluoride.
The acute dust inhalation median lethal concentration of the test
compound is 0.29 milligrams per liter of air based on a four hour
exposure period. Untoward behavioral reactions exhibited by the
animals included gasping, bloody nasal discharge, bloody ocular
discharge, and weakness. Body weight gains of the survivors of
the 14 day observation period were less than normal. Gross pathologic
observation revealed mild to severe focal
discoloration of the lungs in all test animals.
Ref: Elliott CB (1972). Acute Dust Inhalation
Toxicity Study with Triphenyltin Fluoride in Albino Rats.
M and T Chemicals, Inc. (Unpublished report submitted to NIOSH),
Rahway, N. J., IBT No. N1632, 14 pages, 1 reference.
[Toxline abstract at Toxnet]
Pancreas
(click
on for all fluorinated pesticides)
Abstract:
...Recently we found that a single oral administration of triphenyltin
fluoride to rabbits induces transient diabetes and diabetic lipemia
by inhibiting insulin secretion from morphologically normal pancreatic
B-cells...
Ref: [Recent
progress in the study of analytical methods, toxicity, metabolism
and health effects of organotin compounds] by Wada O, Manabe
S, Iwai H, Arakawa Y. Sangyo Igaku 1982 Jan;24(1):24-54
Teratogen
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on for all fluorinated pesticides)
2. Comment. American Hoechst Corporation disagrees with the Agency's
[US EPA] position that TPTH produces teratogenic effects and that
a NOAEL has not been determined in the two previously reviewed
rat teratogenicity studies [Refs. 5 and 46]. American Hoechst
and M&T Chemicals had the rat teratology study by Battelle
Columbus Laboratories [Ref. 3] peer reviewed by two independent
sources and submitted the results of those reviews. One
reviewer found that 2.8 mg/ kg/day was clearly a NOAEL for teratogenicity
while the second reviewer was unable to identify a no effect
level from the data available. In addition, American Hoechst submitted
the results of a teratology study of triphenyltin
fluoride (TPTF) that had been previously submitted to EPA.
The NOAEL for this study was 3.0 mg/kg/day.
Response. The submissions from American Hoechst Corporation do
not satisfactorily eliminate concerns regarding the teratogenicity
of TPTH because no new information was presented to the Agency.
Although these studies provided sufficient data to assure that
TPTH is not teratogenic in rats at dose levels up to and including
8.0 mg/kg/day, these studies did result in developmental and maternal
toxicity. Second, the registrant did not provide new information
indicating that a NOAEL exists in the two rat studies. Third,
the teratology study with TPTF also indicated hydroureter as a
fetal lesion. The initial reviewer of this study classified this
compound as a teratogen.
Ref: Federal Register: October 20, 2000.
Triphenyltin Hydroxide; Proposed Determination To Terminate Special
Review.
http://www.epa.gov/EPA-PEST/2000/October/Day-20/p27036.htm
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