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The tributyltin species, the active ingredient in some antifouling paint formulations, is perhaps the most acutely toxic chemical to aquatic organisms ever deliberately introduced to water. It has been demonstrated to have an adverse effect on shellfish in France and England, and as a consequence the use of tributyltin‐containing antifouling paints has been restricted in these countries. Other countries have banned the use of tributyltin‐containing antifouling paints or are contemplating restrictions. This article reviews such environmental aspects of tributyltin as methods of analysis, toxicity, environmental occurrence, persistence and fate. Tributyltin concentrations in many locations may be high enough to cause chronic toxicity or harmful effects in some aquatic organisms, and in some locations the tributyltin concentrations may be high enough to be acutely toxic to some organisms. Biological degradation of tributyltin in water and sediment appears to be the most important factor limiting the persistence of tributyltin in aquatic environments. To some degree, then, the persistence of tributyltin in aquatic environments depends upon the nature of the ecosystem. Tributyltin exhibits low‐to‐medium persistence in water and moderate persistence in sediment. A summary is given of the regulatory status of tributyltin in some countries, and recommendations are made for further research.

A survey was conducted of water and sediment from across Canada in 1993-94 to assess the effectiveness of the 1989 regulation of antifouling uses of tributyltin (TBT) under the Canadian Pest Control Products Act. The survey was also designed to assess concentrations of 13 other organotin species in water and sediment, and in sewage treatment plant influents, effluents and sludges. The main conclusion is that the 1989 regulation has only been partially effective. It has had some effect in the reduction of TBT concentrations in fresh water, but not in sea water. It has had less effect in the reduction of TBT concentrations in sediment, probably because of the longer persistence of TBT in sediment than in water. In many locations the TBT concentration was high enough to cause acute and chronic toxicity to aquatic and benthic organisms. In some areas there may be potential for recycling TBT from contaminated sediments back into the water column. In addition, it appears that large harbours that handle ships legally painted with TBT-containing antifouling paints continued to experience ecotoxicologically significant TBT contamination. Other organotin species found appear to pose no acute or chronic hazards to fresh water or marine organisms, but nothing is known of their hazards to benthic organisms. The presence of monooctyltin and dioctyltin in sediments and sewage treatment plant influents, effluents and sludges is reported for the first time, and tripropyltin is quantified in sediments for the first time.

Compound 4 (PF-04971729) belongs to a new class of potent and selective sodium-dependent glucose cotransporter 2 inhibitors incorporating a unique dioxa-bicyclo[3.2.1]octane (bridged ketal) ring system. In this paper we present the design, synthesis, preclinical evaluation, and human dose predictions related to 4. This compound demonstrated robust urinary glucose excretion in rats and an excellent preclinical safety profile. It is currently in phase 2 clinical trials and is being evaluated for the treatment of type 2 diabetes.

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