Search: WFRF:(Suciu Ilinca) >
New Approach Method...
New Approach Methods (NAMs) Supporting Read-Across : Two Neurotoxicity AOP-based IATA Case Studies
-
- van der Stel, Wanda (author)
- Leiden Univ, Leiden Acad Ctr Drug Res, Div Drug Discovery & Safety, Leiden, Netherlands.
-
- Carta, Giada (author)
- Vrije Univ Amsterdam, Dept Chem & Pharmaceut Sci, Div Mol & Computat Toxicol, AIMMS, Amsterdam, Netherlands.
-
- Eakins, Julie (author)
- Cyprotex Discovery Ltd, Alderley Park, Macclesfield, Cheshire, England.
-
show more...
-
- Delp, Johannes (author)
- Univ Konstanz, Dept Inaugurated Doerenkamp Zbinden Fdn, Chair In Vitro Toxicol & Biomed, Constance, Germany.
-
- Suciu, Ilinca (author)
- Univ Konstanz, Dept Inaugurated Doerenkamp Zbinden Fdn, Chair In Vitro Toxicol & Biomed, Constance, Germany.;Univ Konstanz, Konstanz Res Sch Chem Biol, Constance, Germany.
-
- Forsby, Anna (author)
- Stockholms universitet,Institutionen för biokemi och biofysik,Stockholm Univ, Dept Biochem & Biophys, Stockholm, Sweden.
-
- Cediel Ulloa, Andrea (author)
- Uppsala universitet,Miljötoxikologi
-
- Attoff, Kristina (author)
- Stockholms universitet,Institutionen för biokemi och biofysik,Stockholm Univ, Dept Biochem & Biophys, Stockholm, Sweden.
-
- Troger, Florentina (author)
- Univ Vienna, Dept Pharmaceut Chem, Vienna, Austria.
-
- Kamp, Hennicke (author)
- BASF, Ludwigshafen, Germany.
-
- Gardner, Iain (author)
- Certara UK Ltd, Sheffield, S Yorkshire, England.
-
- Zdrazil, Barbara (author)
- Univ Vienna, Dept Pharmaceut Chem, Vienna, Austria.
-
- Moné, Martijn J. (author)
- Leiden Univ, Leiden Acad Ctr Drug Res, Div Drug Discovery & Safety, Leiden, Netherlands.
-
- Ecker, Gerhard F. (author)
- Univ Vienna, Dept Pharmaceut Chem, Vienna, Austria.
-
- Pastor, Manuel (author)
- Univ Pompeu Fabra, Dept Expt & Hlth Sci, Barcelona, Spain.
-
- Gómez-Tamayo, Jose Carlos (author)
- Univ Pompeu Fabra, Dept Expt & Hlth Sci, Barcelona, Spain.
-
- White, Andrew (author)
- Unilever, Sharnbrook, Beds, England.
-
- Danen, Erik H. J. (author)
- Leiden Univ, Leiden Acad Ctr Drug Res, Div Drug Discovery & Safety, Leiden, Netherlands.
-
- Leist, Marcel (author)
- Univ Konstanz, Dept Inaugurated Doerenkamp Zbinden Fdn, Chair In Vitro Toxicol & Biomed, Constance, Germany.
-
- Walker, Paul (author)
- Cyprotex Discovery Ltd, Alderley Park, Macclesfield, Cheshire, England.
-
- Jennings, Paul (author)
- Vrije Univ Amsterdam, Dept Chem & Pharmaceut Sci, Div Mol & Computat Toxicol, AIMMS, Amsterdam, Netherlands.
-
- Bennekou, Susanne Hougaard (author)
- Tech Univ Denmark DTU, Natl Food Inst, Lyngby, Denmark.
-
- van de Water, Bob (author)
- Leiden Univ, Leiden Acad Ctr Drug Res, Div Drug Discovery & Safety, Leiden, Netherlands.
-
show less...
-
Leiden Univ, Leiden Acad Ctr Drug Res, Div Drug Discovery & Safety, Leiden, Netherlands Vrije Univ Amsterdam, Dept Chem & Pharmaceut Sci, Div Mol & Computat Toxicol, AIMMS, Amsterdam, Netherlands. (creator_code:org_t)
- 2021
- 2021
- English.
-
In: Altex. - : ALTEX Edition. - 1868-596X .- 1868-8551. ; 38:4, s. 615-635
- Related links:
-
https://doi.org/10.1...
-
show more...
-
https://doi.org/10.1...
-
https://uu.diva-port... (primary) (Raw object)
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
https://urn.kb.se/re...
-
show less...
Abstract
Subject headings
Close
- Read-across approaches are considered key in moving away from in vivo animal testing towards addressing data-gaps using new approach methods (NAMs). Ample successful examples are still required to substantiate this strategy. Here we present and discuss the learnings from two OECD IATA endorsed read-across case studies. They involve two classes of pesticides - rotenoids and strobilurins - each having a defined mode-of-action that is assessed for its neurological hazard by means of an AOP-based testing strategy coupled to toxicokinetic simulations of human tissue concentrations. The endpoint in question is potential mitochondrial respiratory chain mediated neurotoxicity, specifically through inhibition of complex I or III. An AOP linking inhibition of mitochondrial respiratory chain complex I to the degeneration of dopaminergic neurons formed the basis for both cases but was deployed in two different regulatory contexts. The two cases also exemplify several different read-across concepts: analogue versus category approach, consolidated versus putative AOP, positive versus negative prediction (i.e., neurotoxicity versus low potential for neurotoxicity), and structural versus biological similarity. We applied a range of NAMs to explore the toxicodynamic properties of the compounds, e.g., in silico docking as well as in vitro assays and readouts - including transcriptomics - in various cell systems, all anchored to the relevant AOPs. Interestingly, although some of the data addressing certain elements of the read-across were associated with high uncertainty, their impact on the overall read-across conclusion remained limited. Coupled to the elaborate regulatory review that the two cases underwent, we propose some generic learnings of AOP-based testing strategies supporting read-across.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Keyword
- in vitro
- mitochondrial toxicity
- neurotoxicity
- PBK-modelling
- uncertainty analysis
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
-
Altex
(Search for host publication in LIBRIS)
To the university's database
- By the author/editor
-
van der Stel, Wa ...
-
Carta, Giada
-
Eakins, Julie
-
Delp, Johannes
-
Suciu, Ilinca
-
Forsby, Anna
-
show more...
-
Cediel Ulloa, An ...
-
Attoff, Kristina
-
Troger, Florenti ...
-
Kamp, Hennicke
-
Gardner, Iain
-
Zdrazil, Barbara
-
Moné, Martijn J.
-
Ecker, Gerhard F ...
-
Pastor, Manuel
-
Gómez-Tamayo, Jo ...
-
White, Andrew
-
Danen, Erik H. J ...
-
Leist, Marcel
-
Walker, Paul
-
Jennings, Paul
-
Bennekou, Susann ...
-
van de Water, Bo ...
-
show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Basic Medicine
-
and Pharmacology and ...
- Articles in the publication
-
Altex
- By the university
-
Stockholm University
-
Uppsala University