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1.
Toxicol Sci ; 100(2): 393-405, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17804863

ABSTRACT

The need to understand chemical uptake, distribution, and metabolism in embryonic and larval fish derives from the fact that these early life stages often exhibit greater sensitivity to xenobiotic compounds than do adult animals. In this study, a 6-h acute waterborne exposure immediately after fertilization was used to quickly load the egg with benzo[a]pyrene (BaP). This exposure was used to mimic the initial egg concentration of a persistent bioaccumulative toxicant that could result from maternal transfer. We used multiphoton laser scanning microscopy (MPLSM) in combination with conventional analytical chemistry methods to characterize the tissue distribution of BaP and its principal metabolites in medaka embryos and post-hatch larvae. Embryonic metabolism of BaP was evident by MPLSM prior to liver formation or heart development. A major product of this metabolism was identified by liquid chromatography/mass spectrometry as BaP-3-glucuronide. MPLSM showed that metabolites were sequestered within the yolk, biliary system, and gastrointestinal tract. When the gastrointestinal tract became patent a few days after hatch, the metabolites were rapidly eliminated. These findings indicate that some of the earliest embryonic tissues are metabolically competent and that redistribution of BaP and its metabolic products occurs throughout development. Rapid metabolism of BaP substantially reduces the body burden of parent chemical in the developing embryo, potentially reducing toxicity. It remains unclear whether metabolism of BaP in medaka embryos leads to the formation of DNA adducts associated with genotoxic effects or yields metabolites that later lead to other toxicity in juveniles or adults.


Subject(s)
Benzo(a)pyrene/pharmacokinetics , Embryo, Nonmammalian/metabolism , Larva/metabolism , Oryzias/metabolism , Water Pollutants/pharmacokinetics , Animals , Carbon Radioisotopes , Chromatography, High Pressure Liquid , Embryo, Nonmammalian/drug effects , Embryo, Nonmammalian/ultrastructure , Larva/drug effects , Larva/ultrastructure , Microscopy, Confocal , Microscopy, Fluorescence , Oryzias/embryology , Spectrometry, Mass, Electrospray Ionization , Tissue Distribution
2.
Environ Toxicol Chem ; 24(9): 2316-24, 2005 Sep.
Article in English | MEDLINE | ID: mdl-16193761

ABSTRACT

Perfluorooctanesulfonate (PFOS) is a widespread environmental contaminant emanating from the production and/or metabolism of fluorinated chemicals with a variety of applications. The goal of this work was to assess the toxicity and bioconcentration of PFOS in the fathead minnow (Pimephales promelas). Sexually mature fish were exposed via the water for 21 d to 0 (control), 0.03, 0.1, 0.3, or 1 mg PFOS/L, and effects on reproductive capacity and endocrinology were assessed. To determine possible developmental effects, a subset of embryos from parental exposures at each test concentration were held for an additional 24 d in the same PFOS treatments. A concentration of I mg PFOS/L was lethal to adults within two weeks. The 21-d 50% effect concentration (95% confidence interval) for effects on fecundity of the fish was 0.23 (0.19-0.25) mg PFOS/L. Exposure to PFOS caused various histopathological alterations, most prominently in ovaries of adult females. Adult males exposed to 0.3 mg PFOS/L for 21 d exhibited decreased aromatase activity and elevated concentrations of plasma 11-ketotestosterone and testosterone. No significant adverse effects on survival or growth were observed in developing fathead minnows held for 24 d at PFOS concentrations up to 0.3 mg/L. Adult fathead minnows readily accumulated PFOS from the water. The largest concentrations of PFOS were in blood, followed by liver and then gonad; for all tissues, females accumulated higher concentrations than males. Water and tissue concentrations of PFOS associated with effects in this study exceeded those reported for samples collected from the field by two to three orders of magnitude, suggesting that the current risk of PFOS on aspects of fish reproduction and development assessed in this study would be small.


Subject(s)
Alkanesulfonic Acids/toxicity , Biological Assay/methods , Chironomidae/metabolism , Environmental Monitoring/methods , Fluorocarbons/toxicity , Reproduction/drug effects , Alkanesulfonic Acids/blood , Alkanesulfonic Acids/chemistry , Animals , Cyprinidae , Dose-Response Relationship, Drug , Estradiol/pharmacology , Female , Fishes , Fluorocarbons/blood , Fluorocarbons/chemistry , Kinetics , Life Cycle Stages , Male , Ovary/drug effects , Risk , Sex Factors , Testosterone/toxicity , Time Factors , Tissue Distribution , Water
3.
Environ Toxicol Chem ; 23(11): 2745-55, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15559291

ABSTRACT

A number of recent monitoring studies have demonstrated elevated concentrations of perfluorooctanesulfonate (PFOS) in humans and wildlife throughout the world. Although no longer manufactured in the United States, the global distribution and relative persistence of PFOS indicates a need to understand its potential ecological effects. Presently, little is known concerning toxicity of PFOS in chronic exposures with aquatic species. Therefore, we evaluated the effects of PFOS on survival and development of the northern leopard frog (Rana pipiens) from early embryogenesis through complete metamorphosis. Exposures were conducted via water at measured PFOS concentrations ranging from 0.03 to 10 mg/L. Animals exposed to 10 mg/L began dying within approximately two weeks of test initiation. Survival was not affected by PFOS at lower concentrations; however, time to metamorphosis was delayed and growth reduced in the 3-mg/L treatment group. Tadpoles readily accumulated PFOS directly from water. Using a one-compartment bioaccumulation model, growth was shown to have a modest impact on steady-state PFOS concentrations. Variability in observed growth rates and the possible contribution of a size-dependent decrease in PFOS elimination rate contributed uncertainty to modeling efforts. Nevertheless, fitted uptake and elimination rate constants were comparable to those determined in earlier studies with juvenile rainbow trout. Overall, our studies suggest that R. pipiens is not exceptionally sensitive to PFOS in terms of either direct toxicity or bioconcentration potential of the chemical.


Subject(s)
Alkanesulfonic Acids/toxicity , Fluorocarbons/toxicity , Life Cycle Stages/drug effects , Rana pipiens/growth & development , Rana pipiens/physiology , Animals , Body Weight/drug effects , Larva/drug effects , Larva/growth & development , Lethal Dose 50 , Metamorphosis, Biological/drug effects , Thyroid Gland/drug effects , Thyroid Gland/pathology
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