Toxicity of Tributyltin

Mechanistic studies have shown that TBT and certain other forms of trialkyltin have two distinct modes of toxic action in vertebrates. On the one hand they act as inhibitors of oxidative phosphorylation in mitochondria (Aldridge and Street 1964). Inhibition is associated with repression of ATP synthesis, disturbance of ion transport across the mitochondrial membrane, and swelling of the membrane. Oxidative phosphorylation is a vital process in animals and plants, and so trialkyltin compounds act as wide-ranging biocides. Another mode of action involves the inhibition of forms of cytochrome P450, which was referred to earlier in connection with metabolism. This has been demonstrated in mammals, aquatic invertebrates and fish (Morcillo et al. 2004, Oberdorster 2002). TBTO has been shown to inhibit P450 activity in cells from various tissues of mammals, including liver, kidney, and small intestine mucosa, both in vivo and in vitro (Rosenberg and Drummond 1983, Environmental Health Criteria 116). 

Of particular interest in the present context is that TBT can inhibit cytochrome-P450-based aromatase activity in both vertebrates and aquatic invertebrates (Morcillo et al. 2004, Oberdorster and McClellan-Green 2002). The conversion of testosterone to estradiol is catalyzed by aromatase, and so inhibition of the enzyme can, in principle, lead to an increase in cellular levels of testosterone. The significance of this is that many mollusks experience endocrine disruption when exposed to TBTs, 

Returning to the question of endocrine disruption, it is now known that over 100 species of gastropods worldwide suffer from a condition described as imposex, the development of male characteristics by females. It has already been established for some species (e.g., dog whelk) that TBT is the cause of this, and it is suspected that organotin compounds account for most cases of imposex worldwide (Matthiessen and Gibbs 1998). Some examples of masculinization of female gastropods caused by tributyltin are given in Table 8.4. 

Dog whelk (Nucella lapillus) Sting whelk (Ocenebra erinacea) Common whelk (Buccinum undatum) 

TBT causes imposex Development of penis blocks oviduct Similar effect to that observed in dog whelk Also causes imposex 

---

Stronkhorst, J., van Hattum, B., Bowmers, T. (1999). Bioaccrrmrrlation and toxicity of tributyltin to a burrowing heart mchin and an amphipod in spiked, silt marine sediments. Environmental Toxicology and Cherrristry, 18,2343-2351. 

While the preparations of l-(trimethylsilyl)indene and l-(trimethylstannyl)-indene have been reported,4 there are no available preparations of l-(tributyl-stannyl)indene. We chose the tributyl analog because of the decreased toxicity of tributyltin reagents vs. trimethyltin reagents.5 A preparation for the synthesis of Mg(C9H7)2, another indenyl transfer agent, has appeared in Inorganic Syntheses.6... 

Day, K.E., Maguire, R.J., Milani, D. and Batchelor, S.P. (1998) Toxicity of tributyltin to four species of freshwater benthic invertebrates using spiked sediment bioassays, Water Quality Research Journal of Canada 33 (1), 111-132. 

Arizzi Novelli A, Argese E, Tagliapietra D, Bettiol C, Volpi Ghirardini V. 2002. Toxicity of tributyltin and triphenyltin to early life-stages of Paracentrotus lividus (Echino-derma Echinoidea). Environ Toxicol Chem 21 859-864. 

Exposure of the marine sponge Geodia cydonium to nontoxic (non-apoptotic) concentrations of water pollutant tributyltin together with CLP (10 mcg/ml) led to apoptosis. Increased toxicity of tributyltin was at least partially attributed to inhibition of multixenobiotic resistance pump by CLP [60]. This important observation elucidates the potential effect of CLP in overcoming resistance against chemotherapeutic agents. 

Short- to medium-term exposure has shown neurotoxicity, developmental toxicity, immunotoxicity, and endocrine disruption to be relevant end-points. Table 24 summarizes the critical studies for each compound and identifies NOAELs or LOAELs. The degree of each of the toxic end-points differs across the group as a whole. For example, tributyltin is well established as an aromatase inhibitor, and dibutyltin appears to have some potency also (exact characterization of the endocrine disrupting capacity of dibutyltin alone is difficult because of the presence of tributyltin as an impurity). Monobutyltin and mono- and dioctyltins have no aromatase inhibiting capacity in in vitro tests. No data are available for this end-point for the methyltins. 

Lack of exposure data for most organotins together with limited toxicity information for marine organisms preclude the calculation of risk factors for the marine environment. For dibutyltin, measured concentrations in seawater reflect the use of tributyltin as a marine anti-foulant rather than the use of dibutyltin in plastics. It is therefore not possible to conduct a reliable risk assessment for the current uses of the compormd. 

Tin is comparable in its toxicological behavior to lead and mercury. Bivalent tin compounds generally are more toxic than the tetravalent compounds. Furthermore, organic tin compounds are more toxic than inorganic ones and the trialkyl analogs (triethyltin, trimethyltin, tributyltin) are the most toxic. As the number of carbon atoms attached to tin increases, the toxicity of the organic tin compounds rapidly declines9,77. 

U ren, S.C. 1983. Acute toxicity of bis(tributyltin)oxide to a marine copepod. Mar. Pollut. Bull. 14 303-306. U.S. Environmental Protection Agency (USEPA). 1986. Initiation of a special review of certain pesticide products containing tributyltins used as antifoulants availability of support document. Federal Register 51(5) 778-779. 

Ward, G.S., G.C. Cramm, P.R. Parrish, H. Trachman, and A. Slesinger. 1981. Bioaccumulation and chronic toxicity of bis(tributyltin)oxide (TBTO) tests with a salt water fish. Pages 183-200 in D.R. Branson and K.L. Dickson (eds.). Aquatic Toxicology and Hazard Assessment fourth conference. ASTM Spec. Tech. Publ. 737, American Society for Testing and Materials, Philadelphia, PA. 

Strecker reactions provide one of the most efficient methods for the synthesis of a-amino nitriles, which are useful intermediates in the synthesis of amino acids and nitrogen-containing heterocycles. Although classical Strecker reactions have some limitations, use of trimethylsilyl cyanide (TMSCN) as a cyano anion source provides promising and safer routes to these compounds.133-351 Consequently, we focused our attention on tributyltin cyanide (Bu3SnCN), because Bu3SnCN is stable in water and is also a potential cyano anion source. Indeed, the Strecker-type reactions of aldehydes, amines, and Bu3SnCN proceeded smoothly in water (Eq. 9).1361 It should be noted that no surfactants are required in this reaction. Furthermore, Complete recovery of the toxic tin compounds is also possible in the form of bis(tributyltin) oxide after the reaction is over. Since conversion of bis(tributyltin) oxide to tributyltin cyanide is known in the literature, this procedure provides a solution to the problem associated with toxicity of tin compounds. 

Duft M., U. Schulte-Oehlmann, M. Tillman, B. Marker , and J. Oehlmann (2003). Toxicity of triphenyltin and tributyltin to the freshwater mudsnail Potamopyrgus antipoderum in a new sediment biotest. Environmental Toxicology and Chemistry 22 145-152. 

---