Tributyltin endocrine disruption

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. 

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. 

Matthiessen, P. and P.E. Gibbs. 1998. Critical appraisal of the evidence for tributyltin-mediated endocrine disruption in mollusks. Environ. Toxicol. Chem. 17 37-43. 

The Stille protocol is now well established, and finds many uses in preparative chemistry. Especially, application to the synthesis of bioactive substances and functional materials is noteworthy. The choice of catalyst and solvent, however, is still remained veiled. If the reaction to be attempted is not well documented, one should first try to find the most suitable reaction conditions. Organotin compounds can be extremely toxic, and tributyltin compounds are recently suspected to be endocrine disrupters. The presence of even traces of organotin contaminants in organic products must be avoided, as far as possible. In spite of these problems, the Stille protocol will continue to be a favorite method for car-bon-carbon-bond formation, owing to the mildness of the reaction conditions and the functional tolerability of both substrates and reagents. 

It is known that many environmental endocrine-disrupting chemicals have weak estrogenic or antiestrogenic activity [111], or they act as androgens (e.g. tributyltin) or possess antiandrogenic activities (e.g. linuron, 3,4-dichloro-acetanilide etc.). Some chemicals can block the effects of male sex hormones, the androgens [112, 113, 115f]. These special chemicals are described in the next sections. 

Tributyltin (TBT) is one of the best-studied endocrine disrupting compounds in invertebrates (Oberdorster and Cheek 2000). Concentrations as low as 1 ng/1 of TBT can lead to the development of male sex organs in female snails. This imposex response has been identified in approximately 150 species of gastropods and is clearly due to an interference with some part of the molluskan endocrine system. The toxicity of TBT to gastopods has caused its regulation. 

Receptors Estrogen receptor Androgen receptor Phytoestrogens, endocrine disrupters (e.g. DDT, nonylphenol) Endocrine disrupters (e.g. tributyltin) Growth, development, Reproduction... 

The importance of organotins as environmental endocrine disrupters and their potential to adversely affect human health, has prompted the European Commission to identify tributyltin (TBT) as a priority hazardous substance. Organotin compounds are widely employed as stabilizers of polyvinyl chloride (PVC) polymers, and as industrial catalysts for polyurethane and silicone elastomers. Hence, they are present in water pipes, food packing materials, polyurethane foams and many other consumer products. The prominent toxicological feature of the organotins is their immunotoxicity, and the effect produced by di- and trialkyltins as well as triphenyltins. 

Tributyltin oxide H Endocrine disrupter Aquatic H Bioaccumulation H M H H... 

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