Department Environmental Chemistry

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   publications => '15559,10470,7766,7441,7348,7259,6690,6691' (41 chars)
   libraryUrl => '' (0 chars)

array(8 items)
   0 => Snowflake\Publications\Domain\Model\Publicationprototypepersistent entity (uid=15559, pid=124)
      originalId => protected15559 (integer)
      authors => protected'Rösch, A.; Gottardi, M.; Vignet, C.; Cedergreen, N.; Ho
         llender, J.' (92 chars)
      title => protected'Mechanistic understanding of the synergistic potential of azole fungicides i
         n the aquatic invertebrate <i>Gammarus pulex</i>' (124 chars)
      journal => protected'Environmental Science and Technology' (36 chars)
      year => protected2017 (integer)
      volume => protected51 (integer)
      issue => protected'21' (2 chars)
      startpage => protected'12784' (5 chars)
      otherpage => protected'12795' (5 chars)
      categories => protected'' (0 chars)
      description => protected'Azole fungicides are known inhibitors of the important enzyme class cytochro
         me P450 monooxygenases (CYPs), thereby influencing the detoxification of co-
         occurring substances via biotransformation. This synergism in mixtures conta
         ining an azole has mostly been studied by effect measurements, while the und
         erlying mechanism has been less well investigated. In this study, six azole 
         fungicides (cyproconazole, epoxiconazole, ketoconazole, prochloraz, propicon
         azole, and tebuconazole) were selected to investigate their synergistic pote
         ntial and their CYP inhibition strength in the aquatic invertebrate <i>Gamma
         rus pulex</i>. The strobilurin fungicide azoxystrobin was chosen as co-occur
         ring substrate, and the synergistic potential was measured in terms of inter
         nal concentrations of azoxystrobin and associated biotransformation products
          (BTPs). Azoxystrobin is biotransformed by various reactions, and 18 BTPs we
         re identified. By measuring internal concentrations of azoxystrobin and its 
         BTPs with high-resolution tandem mass spectrometry in the presence and absen
         ce of azole fungicides followed by toxicokinetic modeling, we showed that th
         e inhibition of CYP-catalyzed biotransformation reactions indeed played a ro
         le for the observed synergism. However, synergism was only observed for proc
         hloraz at environmentally realistic concentrations. Increased uptake rate co
         nstants, an increase in the total internal concentration of azoxystrobin and
          its BTPs, in vivo assays for measuring CYP activities, and <i>G. pulex</i> 
         video-tracking suggested that the 2-fold increase in bioaccumulation, and, t
         hereby, the raised toxicity of azoxystrobin in the presence of prochloraz is
          not only caused by inhibited biotransformation but even more by increased a
         zoxystrobin uptake induced by hyperactivity.' (1792 chars)
      serialnumber => protected'0013-936X' (9 chars)
      doi => protected'10.1021/acs.est.7b03088' (23 chars)
      uid => protected15559 (integer)
      _localizedUid => protected15559 (integer)modified
      _languageUid => protectedNULL
      _versionedUid => protected15559 (integer)modified
      pid => protected124 (integer)
   1 => Snowflake\Publications\Domain\Model\Publicationprototypepersistent entity (uid=10470, pid=124)
      originalId => protected10470 (integer)
      authors => protected'Rösch,&nbsp;A.; Anliker,&nbsp;S.; Hollender,&nbsp;J.' (53 chars)
      title => protected'How biotransformation influences toxicokinetics of azole fungicides in the a
         quatic invertebrate <I>Gammarus pulex</I>' (117 chars)
      journal => protected'Environmental Science and Technology' (36 chars)
      year => protected2016 (integer)
      volume => protected50 (integer)
      issue => protected'13' (2 chars)
      startpage => protected'7175' (4 chars)
      otherpage => protected'7188' (4 chars)
      categories => protected'' (0 chars)
      description => protected'Biotransformation is a key process that can greatly influence the bioaccumul
         ation potential and toxicity of organic compounds. In this study, biotransfo
         rmation of seven frequently used azole fungicides (triazoles: cyproconazole,
          epoxiconazole, fluconazole, propiconazole, tebuconazole and imidazoles: ket
         oconazole, prochloraz) was investigated in the aquatic invertebrate <I>Gamma
         rus pulex</I> in a 24 h exposure experiment. Additionally, temporal trends o
         f the whole body internal concentrations of epoxiconazole, prochloraz, and t
         heir respective biotransformation products (BTPs) were studied to gain insig
         ht into toxicokinetic processes such as uptake, elimination and biotransform
         ation. By the use of high resolution tandem mass spectrometry in total 37 BT
         Ps were identified. Between one (ketoconazole) and six (epoxiconazole) BTPs 
         were identified per parent compound except for prochloraz, which showed exte
         nsive biotransformation reactions with 18 BTPs detected that were mainly for
         med through ring cleavage or ring loss. In general, most BTPs were formed by
          oxidation and conjugation reactions. Ring loss or ring cleavage was only ob
         served for the imidazoles as expected from the general mechanism of oxidativ
         e ring openings of imidazoles, likely affecting the bioactivity of these BTP
         s. Overall, internal concentrations of BTPs were up to 3 orders of magnitude
          lower than that of the corresponding parent compound. Thus, biotransformati
         on did not dominate toxicokinetics and only played a minor role in eliminati
         on of the respective parent compound, with the exception of prochloraz.' (1591 chars)
      serialnumber => protected'0013-936X' (9 chars)
      doi => protected'10.1021/acs.est.6b01301' (23 chars)
      uid => protected10470 (integer)
      _localizedUid => protected10470 (integer)modified
      _languageUid => protectedNULL
      _versionedUid => protected10470 (integer)modified
      pid => protected124 (integer)
   2 => Snowflake\Publications\Domain\Model\Publicationprototypepersistent entity (uid=7766, pid=124)
      originalId => protected7766 (integer)
      authors => protected'Kim,&nbsp;H.&nbsp;Y.; Jeon,&nbsp;J.; Hollender,&nbsp;J.&nbsp;I.; Yu,&nbsp;S.
         ; Kim,&nbsp;S.&nbsp;D.' (98 chars)
      title => protected'Aqueous and dietary bioaccumulation of antibiotic tetracycline in <I>D. magn
         a</I> and its multigenerational transfer' (116 chars)
      journal => protected'Journal of Hazardous Materials' (30 chars)
      year => protected2014 (integer)
      volume => protected279 (integer)
      issue => protected'' (0 chars)
      startpage => protected'428' (3 chars)
      otherpage => protected'435' (3 chars)
      categories => protected'tetracycline; D. magna; bioaccumulation; biomagnification; multigenerational
          exposure' (85 chars)
      description => protected'The potential bioaccumulation and distribution of antibiotics in non-target 
         organisms have been inadequately studied in spite of their widespread occurr
         ence in aquatic systems. We investigated the ability of tetracycline to bioa
         ccumulate through aqueous and dietary routes in an aquatic organism, the fre
         shwater crustacean <I>Daphnia magna</I>. <I>D. magna</I> was exposed to alga
         l food (<I>Pseudokirchneriella subcapitata</I>) contaminated with tetracycli
         ne for dietary uptake. Tetracycline was transferred to <I>D. magna</I> more 
         through aqueous uptake than through dietary uptake. The uptake rate constant
          of tetracycline for <I>D. magna</I> was <I>k</I><SUB>in,water</SUB> = 0.3
         3 ± 0.045 via the aqueous route and <I>k</I><SUB>in,food</SUB> = 0.16 
         ± 0.012 via the dietary route for 1.0 mg L<SUP>−1</SUP> tetracycline. 
         
         
         line were found for <I>D. magna</I>. The biomagnification factor of 0.19 ±
          0.04 indicates that magnification of tetracycline through the food web wil
         l not occur. The change in the internal concentration of the target compound
          was also studied for multigenerational (F1-F4) exposure. The internal conce
         ntration in <I>D. magna</I> showed a decreasing trend with increasing genera
         tions except for the parent generation. The bioaccumulation tendency showed 
         a biphasic change in multigenerational exposure.' (1492 chars)
      serialnumber => protected'0304-3894' (9 chars)
      doi => protected'10.1016/j.jhazmat.2014.07.031' (29 chars)
      uid => protected7766 (integer)
      _localizedUid => protected7766 (integer)modified
      _languageUid => protectedNULL
      _versionedUid => protected7766 (integer)modified
      pid => protected124 (integer)
   3 => Snowflake\Publications\Domain\Model\Publicationprototypepersistent entity (uid=7441, pid=124)
      originalId => protected7441 (integer)
      authors => protected'Jeon,&nbsp;J.&nbsp;H.; Kretschmann,&nbsp;A.; Escher,&nbsp;B.&nbsp;I.; Hollen
         der,&nbsp;J.' (88 chars)
      title => protected'Characterization of acetylcholinesterase inhibition and energy allocation in
          <I>Daphnia magna</I> exposed to carbaryl' (117 chars)
      journal => protected'Ecotoxicology and Environmental Safety' (38 chars)
      year => protected2013 (integer)
      volume => protected98 (integer)
      issue => protected'' (0 chars)
      startpage => protected'28' (2 chars)
      otherpage => protected'35' (2 chars)
      categories => protected'carbaryl; acetylcholinesterase inhibitor; immobilization; energy budget; Dap
         hnia magna; carbamates' (98 chars)
      description => protected'The inhibition of acetylcholinesterase (AChE) activity and energy allocation
          in the freshwater organism <I>Daphnia magna</I> exposed to carbaryl and pot
         ential recovery from the effects was examined. The binding of carbaryl-AChE 
         was characterized through <I>in vitro</I> assays. To evaluate the recovery f
         rom inhibition and the alteration in energy budget, <I>in vivo</I> exposure 
         and recovery regime tests were conducted. In comparison to diazoxon, the act
         ive metabolite of the insecticide diazinon, the stability of enzyme–carbar
         yl complex was fifteen times lower and the reactivity toward the active site
          was two times lower, resulting in approximately 30 times lower overall inhi
         bition rate than for diazoxon. The <I>in vitro</I> reactivation rate constan
         t of the inhibited enzyme and the <I>in vivo</I> recovery rate constant of A
         ChE activity were 1.9 h<SUP>−1</SUP> and 0.12 h<SUP>−1</SUP> for carba
         ryl, respectively, which are much higher than the corresponding rate constan
         ts for diazoxon. The lower AChE inhibition and greater reactivation/recovery
          rates are in accordance with the lower toxicity of carbaryl compared to dia
         zinon. Carbaryl exposure also altered the profile of the energy reserve: the
          decrease in lipid and glycogen and the increase in protein content resulted
          in the reduction of the total energy budget by about 45 mJ/g<SUB>ww</SUB>.
          This corresponds to 26 percent of the available energy, which might allocat
         e for external stressors. The mechanistic model of AChE inhibition is helpfu
         l to get an insight into (eco-)toxicological effects of AChE inhibitors on f
         reshwater crustaceans under environmentally realistic conditions.' (1661 chars)
      serialnumber => protected'0147-6513' (9 chars)
      doi => protected'10.1016/j.ecoenv.2013.09.033' (28 chars)
      uid => protected7441 (integer)
      _localizedUid => protected7441 (integer)modified
      _languageUid => protectedNULL
      _versionedUid => protected7441 (integer)modified
      pid => protected124 (integer)
   4 => Snowflake\Publications\Domain\Model\Publicationprototypepersistent entity (uid=7348, pid=124)
      originalId => protected7348 (integer)
      authors => protected'Jeon,&nbsp;J.; Kurth,&nbsp;D.; Ashauer,&nbsp;R.; Hollender,&nbsp;J.' (67 chars)
      title => protected'Comparative toxicokinetics of organic micropollutants in freshwater crustace
         ans' (79 chars)
      journal => protected'Environmental Science and Technology' (36 chars)
      year => protected2013 (integer)
      volume => protected47 (integer)
      issue => protected'17' (2 chars)
      startpage => protected'8809' (4 chars)
      otherpage => protected'8817' (4 chars)
      categories => protected'' (0 chars)
      description => protected'Exposure and depuration experiments for <I>Gammarus pulex</I> and <I>Daphnia
          magna</I> were conducted to quantitatively analyze biotransformation produc
         ts (BTPs) of organic micropollutants (tramadol, irgarol, and terbutryn). Qua
         ntification for BTPs without available standards was performed using an esti
         mation method based on physicochemical properties. Time-series of internal c
         oncentrations of micropollutants and BTPs were used to estimate the toxicoki
         netic rates describing uptake, elimination, and biotransformation processes.
          Bioaccumulation factors (BAF) for the parents and retention potential facto
         rs (RPF), representing the ratio of the internal amount of BTPs to the paren
         t at steady state, were calculated. Nonlinear correlation of excretion rates
          with hydrophobicity indicates that BTPs with lower hydrophobicity are not a
         lways excreted faster than the parent compound. For irgarol, <I>G.pulex</I> 
         showed comparable elimination, but greater uptake and BAF/RPF values than <I
         >D.magna</I>. Further, <I>G. pulex</I> had a whole set of secondary transfor
         mations that <I>D. magna</I> lacked. Tramadol was transformed more and faste
         r than irgarol and there were large differences in toxicokinetic rates for t
         he structurally similar compounds irgarol and terbutryn. Thus, predictabilit
         y of toxicokinetics across species and compounds needs to consider biotransf
         ormation and may be more challenging than previously thought because we foun
         d large differences in closely related species and similar chemical structur
         es.' (1523 chars)
      serialnumber => protected'0013-936X' (9 chars)
      doi => protected'10.1021/es400833g' (17 chars)
      uid => protected7348 (integer)
      _localizedUid => protected7348 (integer)modified
      _languageUid => protectedNULL
      _versionedUid => protected7348 (integer)modified
      pid => protected124 (integer)
   5 => Snowflake\Publications\Domain\Model\Publicationprototypepersistent entity (uid=7259, pid=124)
      originalId => protected7259 (integer)
      authors => protected'Jeon,&nbsp;J.; Kurth,&nbsp;D.; Hollender,&nbsp;J.' (49 chars)
      title => protected'Biotransformation pathways of biocides and pharmaceuticals in freshwater cru
         staceans based on structure elucidation of metabolites using high resolution
          mass spectrometry' (170 chars)
      journal => protected'Chemical Research in Toxicology' (31 chars)
      year => protected2013 (integer)
      volume => protected26 (integer)
      issue => protected'3' (1 chars)
      startpage => protected'313' (3 chars)
      otherpage => protected'324' (3 chars)
      categories => protected'' (0 chars)
      description => protected'So far, there is limited information on biotransformation mechanisms and pro
         ducts of polar contaminants in freshwater crustaceans. In the present study,
          metabolites of biocides and pharmaceuticals formed in <I>Gammarus pulex</I>
          and <I>Daphnia magna</I> were identified using liquid chromatography–high
          resolution mass spectrometry. Different confidence levels were assigned to 
         the identification of metabolites without reference standards using a framew
         ork based on the background evidence used for structure elucidation. Twenty-
         five metabolites were tentatively identified for irgarol, terbutryn, tramado
         l, and venlafaxine in <I>G. pulex</I> (21 via oxidation and 4 via conjugatio
         n reactions) and 11 metabolites in <I>D. magna</I> (7 via oxidation and 4 vi
         a conjugation reactions), while no evidence of metabolites for clarithromyci
         n and valsartan was found. Of the 360 metabolites predicted for the four par
         ent compounds using pathway prediction systems and expert knowledge, 23 prod
         ucts were true positives, while 2 identified metabolites were unexpected pro
         ducts. Observed oxidative reactions included N- and O-demethylation, hydroxy
         lation, and N-oxidation. Glutathione conjugation of selected biocides follow
         ed by subsequent reactions forming cysteine conjugates was described for the
          first time in freshwater invertebrates.' (1332 chars)
      serialnumber => protected'0893-228X' (9 chars)
      doi => protected'10.1021/tx300457f' (17 chars)
      uid => protected7259 (integer)
      _localizedUid => protected7259 (integer)modified
      _languageUid => protectedNULL
      _versionedUid => protected7259 (integer)modified
      pid => protected124 (integer)
   6 => Snowflake\Publications\Domain\Model\Publicationprototypepersistent entity (uid=6690, pid=124)
      originalId => protected6690 (integer)
      authors => protected'Kretschmann,&nbsp;A.; Ashauer,&nbsp;R.; Hitzfeld,&nbsp;K.; Spaak,&nbsp;P.; H
         ollender,&nbsp;J.; Escher,&nbsp;B.&nbsp;I.' (118 chars)
      title => protected'Mechanistic toxicodynamic model for receptor-mediated toxicity of diazoxon, 
         the active metabolite of diazinon, in <I>Daphnia magna</I>' (134 chars)
      journal => protected'Environmental Science and Technology' (36 chars)
      year => protected2011 (integer)
      volume => protected45 (integer)
      issue => protected'11' (2 chars)
      startpage => protected'4980' (4 chars)
      otherpage => protected'4987' (4 chars)
      categories => protected'' (0 chars)
      description => protected'The organothiophosphate diazinon inhibits the target site acetylcholinestera
         se only after activation to its metabolite diazoxon. Commonly, the toxicity 
         of xenobiotics toward aquatic organisms is expressed as a function of the ex
         ternal concentration and the resulting effect on the individual level after 
         fixed exposure times. This approach does not account for the time dependency
          of internal processes such as uptake, metabolism, and interaction of the to
         xicant with the target site. Here, we develop a mechanistic toxicodynamic mo
         del for <I>Daphnia magna</I> and diazoxon, which accounts for the inhibition
          of the internal target site acetylcholinesterase and its link to the observ
         able effect, immobilization, and mortality. The model was parametrized by ex
         periments performed in vitro with the active metabolite diazoxon on enzyme e
         xtracts and in vivo with the parent compound diazinon. The mechanism of acet
         ylcholinesterase inhibition was shown to occur irreversibly in two steps via
          formation of a reversible enzyme–inhibitor complex. The corresponding kin
         etic parameters revealed a very high sensitivity of acetylcholinesterase fro
         m <I>D. magna</I> toward diazoxon, which corresponds well with the high toxi
         city of diazinon toward this species. Recovery of enzyme activity but no rec
         overy from immobilization was observed after in vivo exposure to diazinon. T
         he toxicodynamic model combining all in vitro and in vivo parameters was suc
         cessfully applied to describe the time course of immobilization in dependenc
         e of acetylcholinesterase activity during exposure to diazinon. The threshol
         d value for enzyme activity below which immobilization set in amounted to 40
         % of the control activity. Furthermore, the model enabled the prediction of 
         the time-dependent diazoxon concentration directly present at the target sit
         e.' (1826 chars)
      serialnumber => protected'0013-936X' (9 chars)
      doi => protected'10.1021/es1042386' (17 chars)
      uid => protected6690 (integer)
      _localizedUid => protected6690 (integer)modified
      _languageUid => protectedNULL
      _versionedUid => protected6690 (integer)modified
      pid => protected124 (integer)
   7 => Snowflake\Publications\Domain\Model\Publicationprototypepersistent entity (uid=6691, pid=124)
      originalId => protected6691 (integer)
      authors => protected'Kretschmann,&nbsp;A.; Ashauer,&nbsp;R.; Preuss,&nbsp;T.&nbsp;G.; Spaak,&nbsp
         ;P.; Escher,&nbsp;B.&nbsp;I.; Hollender,&nbsp;J.' (124 chars)
      title => protected'Toxicokinetic model describing bioconcentration and biotransformation of dia
         zinon in <I>Daphnia magna</I>' (105 chars)
      journal => protected'Environmental Science and Technology' (36 chars)
      year => protected2011 (integer)
      volume => protected45 (integer)
      issue => protected'11' (2 chars)
      startpage => protected'4995' (4 chars)
      otherpage => protected'5002' (4 chars)
      categories => protected'' (0 chars)
      description => protected'A toxicokinetic model for <I>Daphnia magna</I>, which simulates the internal
          concentration of the insecticide diazinon, its detoxification product 2-iso
         propyl-6-methyl-4-pyrimidinol, and its active metabolite diazoxon, is presen
         ted. During in vivo exposure to diazinon with and without inhibition of cyto
         chrome P450 by piperonyl butoxide, the parent compound as well as its metabo
         lites were quantified with high-performance liquid chromatography–tandem m
         ass spectrometry (LC-MS/MS) in extracts of <I>D. magna</I>. Rate constants o
         f all relevant toxicokinetic steps were obtained by modeling the time course
          of the internal concentrations with a multicomponent first-order kinetics m
         odel. When cytochrome P450 was inhibited, the kinetic bioconcentration facto
         r (BCF) of diazinon increased from 17.8 to 51.0 mL<B>·</B>g<SUB>ww</SUB><SU
         P>–1</SUP>. This clearly indicates that diazinon is biotransformed to a hi
         gh degree by cytochrome P450 in <I>D. magna</I>. The dominant elimination st
         ep of diazinon was shown to be its oxidative dearylation to pyrimidinol (62%
          of total elimination) with a corresponding rate constant of 0.16 h<SUP>–1
         </SUP>. In contrast, oxidative activation to diazoxon with a rate constant o
         f 0.02 h<SUP>–1</SUP> amounted to only 8% of the total elimination. During
          exposure to diazinon, the active metabolite diazoxon could be detected only
          in very low concentrations (approximately 0.5% of the parent compound), pre
         sumably due to a very fast reaction with the target site acetylcholinesteras
         e. During the exposure experiments (no feeding of daphnids), an exponential 
         decline of the lipid content in <I>D. magna</I> with a first-order rate cons
         tant of 0.013 h<SUP>–1</SUP> was observed. For short exposure times (≤24
          h), this had only a minor influence on the determined TK parameters. Such a
          TK model containing detailed biotransformation processes is an important to
         ol for estimation of the toxic potential of chemicals, particularly, when ac
         tive metabolites are for...' (2023 chars)
      serialnumber => protected'0013-936X' (9 chars)
      doi => protected'10.1021/es104324v' (17 chars)
      uid => protected6691 (integer)
      _localizedUid => protected6691 (integer)modified
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      _versionedUid => protected6691 (integer)modified
      pid => protected124 (integer)