title: A novel amphibian tier 2 testing protocol: a 30-week exposure of Xenopus tropicalis to the antiandrogen flutamide.
abstract: In 1996, the U.S. Congress mandated the development of a screening program for endocrine-disrupting chemicals (EDCs) using validated test systems. Subsequently, the Endocrine Disruptor Screening and Testing Advisory Committee recommended the development of a standardized amphibian assay for tier 2 testing of EDCs. For that reason, a tier 2 testing protocol using Xenopus (Silurana) tropicalis and a 30-week, flow-through exposure to the antiandrogen flutamide from stage 46 tadpoles through sexually mature adult frogs were developed and evaluated in this pilot study. The endpoints for this study included measurements of frog body lengths and weights, liver weights, ovary/egg mass weights, testicular and ovarian histopathology, plasma vitellogenin levels, and notes on any abnormalities observed at necropsy. Increasing exposure concentrations to flutamide caused significant increases in frogs with no recognizable gonadal tissue and increased body and liver weights in male frogs, whereas the body lengths and weights decreased significantly in female frogs. Important issues must be resolved before a tier 2 amphibian assay can be further developed and validated, including the establishment of baseline values in the controls for the parameters under study; the maintenance, measurement, and timing of exposure concentrations; and the development of additional biomolecular markers of effect. This study demonstrated the feasibility of conducting long-term EDC exposure studies using X. tropicalis.
authors: U.S. Army Center for Environmental Health Research, 568 Doughten Drive, Fort Detrick, Maryland 21702-5010, USA.
authors: Paul L
authors: PL
authors: Knechtges
authors: Robert L
authors: RL
authors: Sprando
authors: Karen L
authors: KL
authors: Porter
authors: Linda M
authors: LM
authors: Brennan
authors: Mark F
authors: MF
authors: Miller
authors: David M
authors: DM
authors: Kumsher
authors: William E
authors: WE
authors: Dennis
authors: Charles C
authors: CC
authors: Brown
authors: Eric D
authors: ED
authors: Clegg
mesh_terms: D000367:Age Factors; D000663:Amphibians; D000726:Androgen Antagonists / Q000009:adverse effects; D000818:Animals; D049628:Body Size; D052244:Endocrine Disruptors / Q000009:adverse effects*; D004781:Environmental Exposure; D004784:Environmental Monitoring / Q000379:methods*; D005260:Female; D005485:Flutamide / Q000009:adverse effects*; D008297:Male; D009929:Organ Size; D013997:Time Factors; D014819:Vitellogenins / Q000097:blood; D014981:Xenopus
chemical_list: D000726:Androgen Antagonists; D052244:Endocrine Disruptors; D014819:Vitellogenins; D005485:Flutamide