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Comparative teratogenicity of di-n-butyltin diacetate with n-butyltin trichloride in rats

Abstract

Teratological tests were conducted on di-n-butyltin diacetate (DBTA), and n-butyltin trichloride (MBTC). Pregnant Wistar rats were treated orally with DBTA at doses of 0, 1.7, 5.0, 10.0, and 15.0 mg/kg/day or with MBTC at doses of 0, 50, 100, 200, and 400 mg/kg/day during days 7–17 of gestation. Cesarean sections were performed on day 20 of gestation. Thymic atrophy of the pregnant rats was observed in a dose-dependent manner by DBTA treatment. The incidence of dead or resorbed fetuses and total resorption fetuses increased at the highest dose of DBTA. The incidence of fetuses with external malformations, such as cleft mandible, cleft lower lip, ankyloglossia (tongue-tie) and schistoglossia (cleft tongue), increased in a dose-dependent manner by DBTA treatment. The incidence of fetuses with skeletal malformations such as anomaly of mandibular fixation, fused ribs, fused cervical vertebral arches and fused thoracic vertebral arches also increased at 10.0 and 15.0 mg/kg. However, MBTC, one of the main metabolites of di-n-butyltin, failed to show any evidence of teratogenic activity at any doses tested. The results indicate that DBTA has potent teratogenic effects on rat fetuses, and DBTA is different from MBTC with respect to teratogenic effects.

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References

  1. Boyer IJ (1989) Toxicity of dibutyltin, tributyltin and other organotin compounds to humans and to experimental animals. Toxicology 55:253–298

  2. Dawson AB (1926) A note on the staining of the skeleton of cleared specimen with alizarin red S. Stain Technol 1:123–125

  3. Dunnett CW (1964) New tables for multiple comparisons with a control. Biometrics 20:482–491

  4. Harino H, Fukushima M, Mori Y, Nakadoi T (1991) Distribution of organotin compounds in the harbor area of Osaka city. Ann Rep Osaka City Inst Pub Health Environ Sci 53:20–25

  5. Ishizaka T, Suzuki T, Saito Y (1989) Metabolism of dibutyltin dichloride in male rats. J Agric Food Chem 37:1096–1101

  6. Kato R (1977) Drug metabolism under pathological and abnormal physiological states in animals and man. Xenobiotica 7:25–92

  7. Kato T, Kitagawa S (1974) Effects of a new antibacterial sulfonamide (CS-61) on mouse and rat fetuses. Toxicol Appl Pharmacol 27:20–27

  8. Kimmel CA, Wilson JG (1973) Skeletal deviations in rats: malformations or variations? Teratology 8:309–316

  9. Laughlin Jr RB, Linden O (1987) Tributyltin—contemporary environmental issues. AMBIO 16:252–256

  10. Maguire RJ, Tkacz RJ, Chau YK, Bengert GA, Wong PTS (1986) Occurrence of organotin compounds in water and sediment in Canada. Chemosphere 15:253–274

  11. Maguire RJ (1987) Environmental aspects of tributyltin. Appl Organometal Chem 1:475–498

  12. Merkord J, Hennighausen G (1989) Acute pancreatitis and bile duct lesions in rats induced by dibutyltin dichloride. Exp Pathol 36:59–62

  13. Meyers-Schulte KJ (1990) 124Sn as a tracer of tributyltin degradation in seawater. Marine Chem 29:339–354

  14. Nau H, Scott Jr WJ (1986) Weak acids may act as teratogens by accumulating in the basic milieu of the early mammalian embryo. Nature 323:276–278

  15. Noda T, Morita S, Shimizu M, Yamano T, Yamada A (1988) Safety evaluation of chemicals for use in household products (VIII)—teratological studies on dibutyltin diacetate in rats. Ann Rep Osaka City Inst Publ Health Environ Sci 50:66–75

  16. Noda T, Morita S, Yamano T, Shimizu M, Nakamura T, Saitoh M, Yamada A (1991) Teratogenicity study of tri-n-butyltin acetate in rats by oral administration. Toxicol Lett 55:109–115

  17. Piver WT (1973) Organotin compounds: Industrial applications and biological investigation. Environ Health Perspect 4:61–79

  18. Rosenberg DW, Kappas A (1989) Actions of orally administered organotin compounds on heme metabolism and cytochrome P-450 content and function in intestinal epithelium. Biochem Pharmacol 38:1155–1161

  19. Schebek L, Andreae MO (1991) Methyl- and butyltin compounds in water and sediments of the Rhine river. Environ Sci Technol 25:871–878

  20. Scheffé H (1953) A Method for judging all contrasts in the analysis of variance. Biometrika 40:87–104

  21. Schweinfurth HA, Günzel P (1987) The tributyltins: mammalian toxicity and risk evaluation for humans. Oceans 4:1421–1431

  22. Seinen W, Vos JG, van Krieken R, Penninks A, Brands R, Hooykaas H (1977a) Toxicity of organotin compounds. III. Suppression of thymus-dependent immunity in rats by di-n-butyltin dichloride and di-n-octyltin dichloride. Toxicol Appl Pharmacol 42:213–224

  23. Seinen W, Vos JG, van Spanje I, Snoek M, Brands R, Hooykaas H (1977b) Toxicity of organotin compounds. II. Comparative in vivo and in vitro studies with various organotin and organolead compounds in different animal species with special emphasis on lymphocyte cytotoxicity. Toxicol Appl Pharmacol 42:197–212

  24. Seligman PF, Valkirs AO, Stang PM, Lee RF (1988) Evidence for rapid degradation of tributyltin in a marina. Marine Poll Bull 19:531–534

  25. Snoeij NJ, Penninks AH, Seinen W (1987) Biological activity of organotin compounds—an overview. Environ Res 44:335–353

  26. Stewart C, de Mora SJ (1990) A review of the degradation of tri(n-butyl)tin in the marine environment. Environ Technol 11:565–570

  27. Thain JE, Waldock MJ, Waite ME (1987) Toxicity and degradation studies of tributyltin (TBT) and dibutyltin (DBT) in the aquatic environment. Oceans 4:1398–1404

  28. Wilson JG (1965) in: Wilson JG, Warkany J (eds) Teratology—principles and techniques. University of Chicago Press, Chicago, pp 251–277

  29. World Health Organization (1990) Tributyltin compounds. Environ Health Cri 116, WHO, Geneva

  30. Yasuda M, Maeda H (1973) Significance of the lumbar ribs as an indicator in teratogenicity tests. Cong Anom 13:25–29

  31. Yermakoff JK, Fuller GC, Rodil JV (1979) An experimental model of hepatic fibrosis induced by the administration of dibutyltin dichloride. Toxicol Appl Pharmacol 49:31–40

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Noda, T., Yamano, T., Shimizu, M. et al. Comparative teratogenicity of di-n-butyltin diacetate with n-butyltin trichloride in rats. Arch. Environ. Contam. Toxicol. 23, 216–222 (1992). https://doi.org/10.1007/BF00212278

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Keywords

  • Cesarean Section
  • Diacetate
  • Main Metabolite
  • Trichloride
  • Teratogenic Effect