3.9. Toxicokinetics and Metabolism

Coecke, Sandra; Blaauboer, Bas J.; Elaut, Greetje; Freeman, Stuart; Freidig, Andreas P.; Gensmantel, Nigel P.; Hoet, Peter; Kapoulas, Vassilios M.; Ladstetter, Bernhard; Langley, Gill; Leahy, David E.; Mannens, Geert; Meneguz, Annarita; Monshouwer, Mario; Nemery, Benoît; Pelkonen, Olavi; Pfaller, Walter; Prieto, Pilar; Proctor, Nick; Rogiers, Vera; Rostami‐Hodjegan, Amin; Sabbioni, E.; Steiling, W.; Sandt, J.J.M. van de

doi:10.1177/026119290503301s15

Cited by 21 publications

(10 citation statements)

References 54 publications

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“…Concerns raised in evaluations of metabolism could necessitate synthesis of specific metabolites that would then be tested in the main toxicity-pathway assays. In the development of the European Centre for the Validation of Alternative Methods, there has been extensive discussion of the challenges of capturing the possible toxicity of metabolites so as not to miss ultimate toxicities of substances with in vitro testing (Coecke et al, 2005, 2006). …”

Section: Components Of the Visionmentioning

confidence: 99%

Toxicity Testing in the 21st Century: A Vision and a Strategy

Krewski

Acosta

Andersen

et al. 2010

Journal of Toxicology and Environmental Health, Part B

812

475

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With the release of the landmark report Toxicity Testing in the 21st Century: A Vision and a Strategy, the U.S. National Academy of Sciences, in 2007, precipitated a major change in the way toxicity testing is conducted. It envisions increased efficiency in toxicity testing and decreased animal usage by transitioning from current expensive and lengthy in vivo testing with qualitative endpoints to in vitro toxicity pathway assays on human cells or cell lines using robotic high-throughput screening with mechanistic quantitative parameters. Risk assessment in the exposed human population would focus on avoiding significant perturbations in these toxicity pathways. Computational systems biology models would be implemented to determine the dose-response models of perturbations of pathway function. Extrapolation of in vitro results to in vivo human blood and tissue concentrations would be based on pharmacokinetic models for the given exposure condition. This practice would enhance human relevance of test results, and would cover several test agents, compared to traditional toxicological testing strategies. As all the tools that are necessary to implement the vision are currently available or in an advanced stage of development, the key prerequisites to achieving this paradigm shift are a commitment to change in the scientific community, which could be facilitated by a broad discussion of the vision, and obtaining necessary resources to enhance current knowledge of pathway perturbations and pathway assays in humans and to implement computational systems biology models. Implementation of these strategies would result in a new toxicity testing paradigm firmly based on human biology.

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Section: Components Of the Visionmentioning

confidence: 99%

Toxicity Testing in the 21st Century: A Vision and a Strategy

Krewski

Acosta

Andersen

et al. 2010

Journal of Toxicology and Environmental Health, Part B

812

475

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“…More recently, a complete mathematical theory based on this new interpretation was developed by B. Coecke, who analyzed the "seemingly acausal flow of information" in the language of functional programing. Coecke's theory was formulated independently of the physicality of the system [8,9]. Coecke also applies his method to several quantum algorithms, such as logic gate teleportation [10] and entanglement swapping [11], and reproduces faithfully the results obtained using the usual tensor product treat- * email address : mlafores@iqc.ca ment of multipartite quantum mechanical systems.…”

Section: Introductionmentioning

confidence: 83%

“…In his work [8,9], B. Coecke renders the acausal flow of information unconditional by claiming that, in all cases, the state is sent backward in time at the Bell measurement, but depending on the measurement outcome, the information sent backward in time is altered.…”

Section: Bennett and Schumacher Interpretationmentioning

confidence: 99%

Time-reversal formalism applied to maximal bipartite entanglement: Theoretical and experimental exploration

2006

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Within the context of quantum teleportation, a proposed interpretation of bipartite entanglement describes teleportation as consisting of a qubit of information evolving along and against the flow of time of an external observer. We investigate the physicality of such a model by applying time reversal to the Schrödinger equation in the teleportation context. To do so, we first present the theory of time reversal applied to the circuit model. We then show that the outcome of a teleportationlike circuit is consistent with the usual tensor product treatment and is therefore independent of the physical quantum system used to encode the information. Finally, we illustrate these concepts with a proof-of-principle experiment on a liquid-state NMR quantum-information processor. The experimental results are consistent with the interpretation that information can be seen as flowing backward in time through entanglement.

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“…Thus the aim here is to review the available evidence on the necessity for inclusion of mammalian metabolic competence into the in vitro EAS/ED test system designs, and to suggest constructive ways of bringing these together, rather than duplicating the work that is already being done on the development and validation of tests for endocrine disruption and for kinetics and metabolism of chemicals [12,13]. The possibilities for in vitro testing of metabolism in a more general context, and with regard to cosmetics have already been addressed by the European Centre for the Validation of Alternative Methods (ECVAM).…”

mentioning

confidence: 99%

The Use of Metabolising Systems for In Vitro Testing of Endocrine Disruptors

Jacobs¹,

Janssens²,

Bernauer

et al. 2008

CDM

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Legislation and prospective legislative proposals in for instance the USA, Europe, and Japan require, or may require that chemicals are tested for their ability to disrupt the hormonal systems of mammals. Chemicals found to test positive are considered to be endocrine active substances (EAS) and may be putative endocrine disruptors (EDs). To date, there is still little or no experience with incorporating metabolic and toxicokinetic aspects into in vitro tests for EAS. This is a situation in sharp contrast to genotoxicity testing, where in vitro tests are routinely conducted with and without metabolic capacity. Originally prepared for the Organisation of Economic Cooperation and Development (OECD), this detailed review paper reviews why in vitro assays for EAS should incorporate mammalian systems of metabolism and metabolic enzyme systems, and indicates how this could be done. The background to ED testing, the available test methods, and the role of mammalian metabolism in the activation and the inactivation of both endogenous and exogenous steroids are described. The available types of systems are compared, and the potential problems in incorporating systems in in vitro tests for EAS, and how these might be overcome, are discussed. Lastly, some recommendations for future activities are made.

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3.9. Toxicokinetics and Metabolism

Cited by 21 publications

References 54 publications

Toxicity Testing in the 21st Century: A Vision and a Strategy

Toxicity Testing in the 21st Century: A Vision and a Strategy

Time-reversal formalism applied to maximal bipartite entanglement: Theoretical and experimental exploration

The Use of Metabolising Systems for In Vitro Testing of Endocrine Disruptors

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