Critical appraisal of the evidence for tributyltin-mediated endocrine disruption in mollusks

This article reviews the field and laboratory evidence for endocrine disruption in gastropod mollusks caused by tributyltin (TBT). Abundant and undisputed field data link TBT with an irreversible sexual abnormality of female neogastropod snails known as "imposex." This phenomenon is a masculinization process involving the development of male sex organs, notably a penis and a vas deferens; in certain species the imposition of a vas deferens disrupts oviducal structure and function, preventing normal breeding activity and causing population disappearance. In some species, oogenesis is supplanted by spermatogenesis. A related condition referred to as "intersex" has been reported in littorinid mesogastropods, and these too become unable to lay eggs. Field evidence clearly associates these syndromes with the use of TBT as an antifoulant, chiefly on boat hulls, and dose-related effects can be replicated in laboratory exposures to environmentally relevant concentrations of TBT compounds. It has now been established that imposer and intersex are forms of endocrine disruption caused by elevated testosterone titers that masculinize TBT-exposed females. The precise mechanism by which increased levels of testosterone are produced has not been fully described, but the weight of evidence suggests that TBT acts as a competitive inhibitor of cytochrome P450-mediated aromatase. Some recent data suggest that TBT may also inhibit the formation of sulfur conjugates of testosterone and its active metabolites, thus interfering with its excretion. In summary, TBT-induced masculinization in gastropods, imposer and intersex, is the dearest example of endocrine disruption described in invertebrates to date that is unequivocally linked to a specific environmental pollutant.