Showing papers by "Gerald T. Ankley published in 2003"
TL;DR: The studies indicate that 17‐β‐trenbolone is a potent androgen and reproductive toxicant in fish and further studies are warranted to assess potential ecological risk.
Abstract: Trenbolone acetate is a synthetic steroid that is extensively used in the United States as a growth promoter in beef cattle. The acetate is administered to livestock via slow-release implants; some is converted by the animal to 17-beta-trenbolone, a relatively potent androgen receptor agonist in mammalian systems. Recent studies indicate that excreted 17-beta-trenbolone is comparatively stable in animal waste, suggesting the potential for exposure to aquatic animals via direct discharge, runoff, or both. However, little is known concerning the toxicity of trenbolone to fish. Our goal was to assess the effects of 17-beta-trenbolone on reproductive endocrinology of the fathead minnow (Pimephales promelas). An in vitro competitive binding study with the fathead minnow androgen receptor demonstrated that 17-beta-trenbolone had a higher affinity for the receptor than that of the endogenous ligand, testosterone. Male and female fish were exposed for 21 d to nominal (target) concentrations of 17-beta-trenbolone ranging from 0.005 to 50 microg/L. Fecundity of the fish was significantly reduced by exposure to measured test concentrations > or = 0.027 microg/ L. The 17-beta-trenbolone was clearly androgenic in vivo at these concentrations, as evidenced by the de novo production in females of dorsal (nuptial) tubercles, structures normally present only on the heads of mature males. Plasma steroid (testosterone and beta-estradiol) and vitellogenin concentrations in the females all were significantly reduced by exposure to 17-beta-trenbolone. The 17-beta-trenbolone also altered reproductive physiology of male fathead minnows, albeit at concentrations much higher than those producing effects in females. Males exposed to 17-beta-trenbolone at 41 microg/L (measured) exhibited decreased plasma concentrations of 11-ketotestosterone and increased concentrations of beta-estradiol and vitellogenin. Overall, our studies indicate that 17-beta-trenbolone is a potent androgen and reproductive toxicant in fish. Given the widespread use of trenbolone acetate as a growth promoter, and relative stability of its metabolites in animal wastes, further studies are warranted to assess potential ecological risk.
378 citations
TL;DR: The hypothesis that aromatization of MT to ME2 contributes to the estrogenic effects in fathead minnows following exposure to this androgen is supported.
96 citations
TL;DR: This review provides a brief overview of four databases created for the purpose of developing QSARs for estimating toxicity of chemicals to aquatic organisms and an overview of expert systems that integrate chemical‐specific mode of action classification and associatedQSAR selection.
Abstract: The use of quantitative structure-activity relationships (QSARs) in assessing potential toxic effects of organic chemicals on aquatic organisms continues to evolve as computational efficiency and toxicological understanding advance. With the ever-increasing production of new chemicals, and the need to optimize resources to assess thousands of existing chemicals in commerce, regulatory agencies have turned to QSARs as essential tools to help prioritize tiered risk assessments when empirical data are not available to evaluate toxicological effects. Progress in designing scientifically credible QSARs is intimately associated with the development of empirically derived databases of well-defined and quantified toxicity endpoints, which are based on a strategic evaluation of diverse sets of chemical structures, modes of toxic action, and species. This review provides a brief overview of four databases created for the purpose of developing QSARs for estimating toxicity of chemicals to aquatic organisms. The evolution of QSARs based initially on general chemical classification schemes, to models founded on modes of toxic action that range from nonspecific partitioning into hydrophobic cellular membranes to receptor-mediated mechanisms is summarized. Finally, an overview of expert systems that integrate chemical-specific mode of action classification and associated QSAR selection for estimating potential toxicological effects of organic chemicals is presented.
78 citations
TL;DR: Depuration rates for DDT and its metabolites and high-Kow PAHs were much higher in organisms held in clean sediment relative to both water-only depuration and model predictions, suggesting that depuration inclean sediment may artificially accelerate depuration of hydrophobic compounds.
Abstract: Uptake of sediment-associated contaminants by the oligochaete Lumbriculus variegatus was evaluated after 1, 3, 7, 14, 28, and 56 d of exposure to a field-collected sediment contaminated with DDT and its metabolites, dichlorodiphenyldichloroethane (DDD) and dichlorodiphenyldichloroethylene (DDE), or to a field-collected sediment contaminated with polycyclic aromatic hydrocarbons (PAHs). Depuration of contaminants by oligochaetes in a control sediment or in water was also evaluated over a 7-d period after 28 d of exposure to the field-collected sediments. Accumulation of PAHs with a log octanol-water partitioning coefficient (log Kow) 5.6 or DDD and DDE typically exhibited a steady increase from day 1 to about day 14 or 28, followed by a plateau. Therefore, exposures conducted for a minimum of 14 to 28 d better reflected steady-state concentrations for DDT and its metabolites and for PAHs. Depuration rates for DDT and its metabolites and high-Kow PAHs were much higher in organisms held in clean sediment relative to both water-only depuration and model predictions. This suggests that depuration in clean sediment may artificially accelerate depuration of hydrophobic compounds. Comparisons between laboratory-exposed L. variegatus and oligochaetes collected in the field from these sediments indicate that results of laboratory tests can be extrapolated to the field with a reasonable degree of certainty.
43 citations
TL;DR: The utility of models based on either two‐dimensional or three‐dimensional molecular descriptions to predict binding potential of diverse chemical structures in large chemical inventories, with potential application in a tiered risk assessment scheme, is discussed.
Abstract: The demonstrated ability of a variety of structurally diverse chemicals to bind to the estrogen receptor has raised the concern that chemicals in the environment may be causing adverse effects through interference with nuclear receptor pathways. Many structure-activity relationship models have been developed to predict chemical binding to the estrogen receptor as an indication of potential estrogenicity. Models based on either two-dimensional or three-dimensional molecular descriptions that have been used to predict potential for binding to the estrogen receptor are the subject of the current review. The utility of such approaches to predict binding potential of diverse chemical structures in large chemical inventories, with potential application in a tiered risk assessment scheme, is discussed.
42 citations
TL;DR: The objective of the current study was to compare the performance of three different ELISAs for measuring fathead minnow VTG, and recommend the homologous fVTG assay is recommended to achieve accurate quantification of VTG levels infathead minnows.
Abstract: Measurement of vitellogenin (VTG) concentrations in the fathead minnow (Pimephales promelas) is currently being considered and evaluated for screening of endocrine active substances. One of the proposed methods, an enzyme-linked immunosorbent assay (ELISA) based on VTG from carp (Cyprinus carpio), was recently evaluated in an inter-laboratory ring test using whole body homogenates from juvenile fathead minnows. The objective of the current study was to compare the performance of three different ELISAs for measuring fathead minnow VTG: (1) a heterologous carp VTG (cVTG) ELISA used in the ring test, (2) a homologous fathead minnow VTG (fVTG) ELISA, and (3) a hybrid ELISA with the antibody developed for cVTG, but using fVTG for coating the plates and preparing standard curves. VTG was measured in whole body homogenates from juvenile fathead minnows exposed to 17α-ethynylestradiol (EE2; 10 ng/l) and whole body homogenates and plasma from adult fathead minnows exposed to 17β-estradiol (E2; 5 mg/kg; i.p.). The cVTG assay showed lower specificity for fathead minnow VTG in whole body homogenates and plasma from treated fish, compared to the fVTG assay. VTG concentrations in juvenile fathead minnow homogenates from the EE2-exposed group were approximately 50-fold higher when measured using the fVTG method compared to the cVTG method. Use of the homologous fVTG in the hybrid cVTG assay yielded VTG concentrations in the range of the fVTG assay but the low specificity persisted. The homologous fVTG assay is recommended to achieve accurate quantification of VTG levels in fathead minnows.
32 citations
TL;DR: Data indicate that methoprene and its degradation products are not potent development toxicants in X. laevis, and the fact that field applications of sustained-release formulations of meethoprene result in methopene concentrations that do not typically exceed 0.01 mg/l, suggests that concerns for meetinghoprene-mediated developmental toxicity to amphibians may be unwarranted.
30 citations
22 May 2003
30 citations
TL;DR: It is unlikely that retinoid mimics would produce the spectrum of limb malformations which recently have been observed in amphibians collected from the field, and suggests that other aspects of growth and development, which are not externally obvious, are more sensitive to retinoids than skeletal development.
26 citations
TL;DR: Although there may be slight differences in responses between the two temperatures tested here, this assay can be used to effectively determine the relative estrogenic activity of chemicals within the physiological temperature range of rainbow trout.
Abstract: The potential for temperature to influence estrogen-mediated responses in poikilothermicanimals suggested that temperature may be an important variable to consider when using an estrogen-responsive reporter gene in a rainbow trout cell line to test chemicals for estrogenic activity. Rainbow trout hepatoma cells (RTH 149) incubated at 11 or 18°C were cotransfected with an estrogen-responsive luciferase reporter plasmid and a plasmid containing a constitutively expressed rainbow trout estrogen receptor. The RTH-149 cells were then exposed to estradiol, with samples collected at 24-h intervals. The 72-h effective concentration for 50% maximal response (EC50) for estrogen-responsive luciferase activity at 11°C was 3.8 × 10−9 M and 7.4 × 10−10 M at 18°C. The efficacy of estradiol was lower at 11°C. The maximal response to estradiol in cells at 11°C was generally two- to threefold greater than controls (mean = 2.6-fold), whereas the maximal response at 18°C was three- to fourfold greater than controls (mean = 3.2-fold). Ethinylestradiol, a strong estrogen receptor agonist, was similar to estradiol in potency (relative potency = 0.8) and efficacy at the two temperatures. The EC50 of the weak estrogen receptor agonist 4-tert-pentylphenol was 7.6 × 10−7 M at 11°C and 6.9 × 10−7 M at 18°C; its potency relative to 17β-estradiol was not significantly different at the two temperatures, 0.00036 and 0.00054 at 11°C and 18°C, respectively. The estrogen-responsive reporter gene activity produced by 10−8 M estradiol was completely inhibited by the two estrogen hormone receptor antagonists, ZM 189,154 and ICI 182,780, at 10−6 M concentration of either antagonist. Although there may be slight differences in responses between the two temperatures tested here, this assay can be used to effectively determine the relative estrogenic activity of chemicals within the physiological temperature range of rainbow trout.
13 citations
TL;DR: The feasibility of use of time-to-effects as a basis for quantifying the relative toxicity of contaminated sediments is demonstrated and is demonstrated to be feasible.
TL;DR: The results indicate that all-trans RA is rapidly metabolized by these Ranid species to a variety of retinoids derivatives, several of which are known ligands for RA and retinoid receptors, and are capable of activating this signaling transduction pathway.