Department Environmental Toxicology

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   0 => Snowflake\Publications\Domain\Model\Publicationprototypepersistent entity (uid=18923, pid=124)
      originalId => protected18923 (integer)
      authors => protected'Stadnicka-Michalak, J.; Schirmer, K.' (46 chars)
      title => protected'In vitro-in vivo extrapolation to predict bioaccumulation and toxicity of ch
         emicals in fish using physiologically based toxicokinetic models' (140 chars)
      journal => protected'In: Seiler, T.-B.; Brinkmann, M. (Eds.), In situ bioavailability a
         nd toxicity of organic chemicals in aquatic systems' (127 chars)
      year => protected2022 (integer)
      volume => protected0 (integer)
      issue => protected'' (0 chars)
      startpage => protected'229' (3 chars)
      otherpage => protected'258' (3 chars)
      categories => protected'PBTK model; fish growth; lethality; integrated testing design; predictive mo
         deling; chemical risk assessment; fish cell lines; toxicokinetics and toxico
         dynamics' (160 chars)
      description => protected'Out of the >107 million chemicals already registered with the Chemical Ab
         stracts Services, less than 0.5% are being regulated, and even fewer are eva
         luated for their safety. Consequently, a new paradigm in risk assessment is 
         urgently needed. It should encompass faster and less costly methods and redu
         ce the number of animals needed for testing. One proposal is to combine comp
         utational modeling with small-scale bioassay methods. This chapter describes
          the methods that link in vitro bioassays using fish cells with physiologica
         lly based toxicokinetic (PBTK) modeling in order to predict the acute toxici
         ty, bioaccumulation, and impact of chemicals on fish growth. The main focus 
         is on PBTK modeling; thus all the model equations and parameters available f
         or eight fish species as well as suggestions for possible software implement
         ation will be provided. The PBTK model described here can account for respir
         atory and dietary uptake routes and for chemical biotransformation processes
         .' (989 chars)
      serialnumber => protected'' (0 chars)
      doi => protected'10.1007/7653_2019_34' (20 chars)
      uid => protected18923 (integer)
      _localizedUid => protected18923 (integer)modified
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      _versionedUid => protected18923 (integer)modified
      pid => protected124 (integer)
   1 => Snowflake\Publications\Domain\Model\Publicationprototypepersistent entity (uid=15007, pid=124)
      originalId => protected15007 (integer)
      authors => protected'Stadnicka-Michalak, J.; Knöbel, M.; Županič, A.; Schirmer,
          K.' (84 chars)
      title => protected'A validated algorithm for selecting non-toxic chemical concentrations' (69 chars)
      journal => protected'ALTEX: Alternatives to Animal Experimentation' (45 chars)
      year => protected2018 (integer)
      volume => protected35 (integer)
      issue => protected'1' (1 chars)
      startpage => protected'37' (2 chars)
      otherpage => protected'50' (2 chars)
      categories => protected'fish cell lines and embryos; in vitro; bioassays; toxicology; animal testing
          alternatives' (89 chars)
      description => protected'The maximal chemical concentration that causes an acceptably small or no eff
         ect in an organism or isolated cells is an often - sought - after value in t
         oxicology. Existing approaches to derive this value have raised several conc
         erns; thus, it is often chosen case - by - case based on personal experience
         . To overcome this ambiguity, we propose an approach for choosing the non - 
         toxic concentration (NtC) of a chemical in a rational, tractable way. We dev
         eloped an algorithm that identifies the highest chemical concentration which
          causes no more than 10% effect (≤ EC10) including the modeled 95% confide
         nce intervals and considering each of the measured biological replicates; an
         d whose toxicity is not significantly different from no effect.The developed
          algorithm was validated in two steps: by comparing its results with measure
         d and modeled data for 91 dose - response experiments with fish cell lines a
         nd/or zebrafish embryos; and by measuring actual effects caused by NtCs in a
          separate set of experiments using a fish cell line and zebrafish emb ryos. 
         The algorithm provided an NtC that is more protective than NOEC (No - Observ
         ed - Effect - Concentration), NEC (modeled No - Effect Concentration), EC10 
         and Benchmark Dose (BMD). Despite focusing on small scale bioassays here, th
         is study indicates that the NtC algorithm could be used in various systems. 
         Its application on the survival of zebrafish embryos and on metabolic activi
         ty in cell lines showed that NtCs can be applied to different effect measure
         ments, time points and levels of biological organization. The algorithm is a
         vailable as Matlab and R code, and as a free, user friendly online applicati
         on.' (1675 chars)
      serialnumber => protected'1868-596X' (9 chars)
      doi => protected'10.14573/altex.1701231' (22 chars)
      uid => protected15007 (integer)
      _localizedUid => protected15007 (integer)modified
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      _versionedUid => protected15007 (integer)modified
      pid => protected124 (integer)
   2 => Snowflake\Publications\Domain\Model\Publicationprototypepersistent entity (uid=9224, pid=124)
      originalId => protected9224 (integer)
      authors => protected'Stadnicka-Michalak, J.; Schirmer, K.; Ashauer, R.' (64 chars)
      title => protected'Toxicology across scales: cell population growth in vitro predicts reduced f
         ish growth' (86 chars)
      journal => protected'Science Advances' (16 chars)
      year => protected2015 (integer)
      volume => protected1 (integer)
      issue => protected'7' (1 chars)
      startpage => protected'1' (1 chars)
      otherpage => protected'8' (1 chars)
      categories => protected'' (0 chars)
      description => protected'Environmental risk assessment of chemicals is essential but often relies on 
         ethically controversial and expensive methods. We show that tests using cell
          cultures, combined with modeling of toxicological effects, can replace test
         s with juvenile fish. Hundreds of thousands of fish at this developmental st
         age are annually used to assess the influence of chemicals on growth. Juveni
         les are more sensitive than adult fish, and their growth can affect their ch
         ances to survive and reproduce. Thus, to reduce the number of fish used for 
         such tests, we propose a method that can quantitatively predict chemical imp
         act on fish growth based on in vitro data. Our model predicts reduced fish g
         rowth in two fish species in excellent agreement with measured in vivo data 
         of two pesticides. This promising step toward alternatives to fish toxicity 
         testing is simple, inexpensive, and fast and only requires in vitro data for
          model calibration.' (931 chars)
      serialnumber => protected'' (0 chars)
      doi => protected'10.1126/sciadv.1500302' (22 chars)
      uid => protected9224 (integer)
      _localizedUid => protected9224 (integer)modified
      _languageUid => protectedNULL
      _versionedUid => protected9224 (integer)modified
      pid => protected124 (integer)
   3 => Snowflake\Publications\Domain\Model\Publicationprototypepersistent entity (uid=9060, pid=124)
      originalId => protected9060 (integer)
      authors => protected'Stadnicka-Michalak, J.; Tanneberger, K.; Schirmer, K.; Ashaue
         r, R.' (86 chars)
      title => protected'Measured and modeled toxicokinetics in cultured fish cells and application t
         o <I>in vitro - in vivo</I> toxicity extrapolation' (126 chars)
      journal => protected'PLoS One' (8 chars)
      year => protected2014 (integer)
      volume => protected9 (integer)
      issue => protected'3' (1 chars)
      startpage => protected'e92303 (10 pp.)' (15 chars)
      otherpage => protected'' (0 chars)
      categories => protected'' (0 chars)
      description => protected'Effect concentrations in the toxicity assessment of chemicals with fish and 
         fish cells are generally based on external exposure concentrations. External
          concentrations as dose metrics, may, however, hamper interpretation and ext
         rapolation of toxicological effects because it is the internal concentration
          that gives rise to the biological effective dose. Thus, we need to understa
         nd the relationship between the external and internal concentrations of chem
         icals. The objectives of this study were to: (i) elucidate the time-course o
         f the concentration of chemicals with a wide range of physicochemical proper
         ties in the compartments of an <I>in vitro</I> test system, (ii) derive a pr
         edictive model for toxicokinetics in the <I>in vitro</I> test system, (iii) 
         test the hypothesis that internal effect concentrations in fish (<I>in vivo<
         /I>) and fish cell lines (<I>in vitro</I>) correlate, and (iv) develop a qua
         ntitative <I>in vitro</I> to <I>in vivo</I> toxicity extrapolation method fo
         r fish acute toxicity. To achieve these goals, time-dependent amounts of org
         anic chemicals were measured in medium, cells (RTgill-W1) and the plastic of
          exposure wells. Then, the relation between uptake, elimination rate constan
         ts, and log K<SUB>OW</SUB> was investigated for cells in order to develop a 
         toxicokinetic model. This model was used to predict internal effect concentr
         ations in cells, which were compared with internal effect concentrations in 
         fish gills predicted by a Physiologically Based Toxicokinetic model. Our mod
         el could predict concentrations of non-volatile organic chemicals with log K
         <SUB>OW</SUB> between 0.5 and 7 in cells. The correlation of the log ratio o
         f internal effect concentrations in fish gills and the fish gill cell line w
         ith the log K<SUB>OW</SUB> was significant (r>0.85, p = 0.0008, F-test). Thi
         s ratio can be predicted from the log K<SUB>OW</SUB> of the chemical (77% of
          variance explained), comprising a promising model to predict lethal effects
          on fish based on <I>in ...' (2015 chars)
      serialnumber => protected'' (0 chars)
      doi => protected'10.1371/journal.pone.0092303' (28 chars)
      uid => protected9060 (integer)
      _localizedUid => protected9060 (integer)modified
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      _versionedUid => protected9060 (integer)modified
      pid => protected124 (integer)
   4 => Snowflake\Publications\Domain\Model\Publicationprototypepersistent entity (uid=7026, pid=124)
      originalId => protected7026 (integer)
      authors => protected'Stadnicka,&nbsp;J.; Schirmer,&nbsp;K.; Ashauer,&nbsp;R.' (55 chars)
      title => protected'Predicting concentrations of organic chemicals in fish by using toxicokineti
         c models' (84 chars)
      journal => protected'Environmental Science and Technology' (36 chars)
      year => protected2012 (integer)
      volume => protected46 (integer)
      issue => protected'6' (1 chars)
      startpage => protected'3273' (4 chars)
      otherpage => protected'3280' (4 chars)
      categories => protected'' (0 chars)
      description => protected'Quantification of chemical toxicity continues to be generally based on measu
         red external concentrations. Yet, internal chemical concentrations have been
          suggested to be a more suitable parameter. To better understand the relatio
         nship between the external and internal concentrations of chemicals in fish,
          and to quantify internal concentrations, we compared three toxicokinetic (T
         K) models with each other and with literature data of measured concentration
         s of 39 chemicals. Two one-compartment models, together with the physiologic
         ally based toxicokinetic (PBTK) model, in which we improved the treatment of
          lipids, were used to predict concentrations of organic chemicals in two fis
         h species: rainbow trout (<em>Oncorhynchus mykiss</em>) and fathead minnow (
         <em>Pimephales promelas</em>). All models predicted the measured internal co
         ncentrations in fish within 1 order of magnitude for at least 68% of the che
         micals. Furthermore, the PBTK model outperformed the one-compartment models 
         with respect to simulating chemical concentrations in the whole body (at lea
         st 88% of internal concentrations were predicted within 1 order of magnitude
          using the PBTK model). All the models can be used to predict concentrations
          in different fish species without additional experiments. However, further 
         development of TK models is required for polar, ionizable, and easily biotra
         nsformed compounds.' (1387 chars)
      serialnumber => protected'0013-936X' (9 chars)
      doi => protected'10.1021/es2043728' (17 chars)
      uid => protected7026 (integer)
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