title: Changes in the metabolic elimination profile of testosterone following exposure of the crustacean Daphnia magna to tributyltin.
abstract: The biocide tributyltin has been found to cause the development of pseudohermaphroditic conditions in some neogastropod species. These abnormalities of the reproductive system have adversely affected the fecundity of some field populations of gastropods, resulting in local population declines. Current evidence suggests that tributyltin elicits these effects by interfering with the biotransformation of testosterone to other steroid derivatives, resulting in an elevation in endogenous testosterone or some of its bioactive derivatives. The purpose of the present study was to determine whether tributyltin altered testosterone metabolism in daphnids (Daphnia magna), a species commonly used in ecotoxicology testing. Exposure of daphnids to 1.2 microg (tin)/L caused a general increase in the rate of elimination of oxido-reduced, hydroxylated, and glucose-conjugated derivatives of testosterone. However, tributyltin exposure had no significant effect on the rate of elimination of the glucose-conjugated forms of the various oxido-reduced and hydroxylated derivatives of testosterone. As a result, the percentage of the oxido-reduced and hydroxylated metabolites of testosterone eliminated as glucose conjugates decreased with increasing tributyltin exposure levels. These results demonstrate that tributyltin causes alterations in testosterone metabolism in daphnids that would result in an increase in the production of oxido-reduced derivatives. These products are preferentially retained in the tissues of daphnids and are variously androgenic in vertebrates. The increased production of oxido-reduced derivatives of testosterone may be mechanically responsible for the masculinizing effects of tributyltin in some species and suggests that daphnids may be a suitable surrogate for evaluating the potential of chemicals to elicit this form of toxicity.
authors.affiliation: Department of Toxicology, North Carolina State University, Raleigh, North Carolina 27695-7633, USA. ga_leblanc@ncsu.edu
authors.forename: G A
authors.initials: GA
authors.lastname: LeBlanc
authors.forename: J B
authors.initials: JB
authors.lastname: McLachlan
mesh_terms: D015113:Androstane-3,17-diol / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism; D000735:Androstenedione / Q000032:analysis / Q000378:metabolism; D000818:Animals; D003621:Daphnia / Q000187:drug effects* / Q000378:metabolism*; D013196:Dihydrotestosterone / Q000032:analysis / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005947:Glucose / Q000378:metabolism; D006915:Hydroxytestosterones / Q000032:analysis / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism*; D014220:Trialkyltin Compounds / Q000633:toxicity*
chemical_list: D006915:Hydroxytestosterones; D014220:Trialkyltin Compounds; D013196:Dihydrotestosterone; D015113:Androstane-3,17-diol; D013739:Testosterone; D000735:Androstenedione; C011559:tributyltin; D005947:Glucose