Return to Index Page
Return to Abstracts

Activity: Antifoulant, Algaecide, Herbicide (Organotin)
Structure:

Adverse Effects:
Blood
Body Weight Decrease
Diabetes
Eye
Lung
Pancreas
Teratogen
Environmental

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 (click 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