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Interviewing Frederik-Jan van Schooten, Associate Editor for Toxicology Research

Toxicology research Associate Editor Frederik-Jan van SchootenFrederik-Jan van Schooten is a Professor of Genetic Toxicology at Maastricht University Medical Centre and is the Head of Department for the Department of Health Risk Analysis and Toxicology. As part of the Toxicology Research Editorial Board and one of the journal’s Associate Editors we took this opportunity to ask him a few questions:

1.         What led you to specialise in toxicology?

For the past 30 years I have been working in the field of chemical carcinogenesis and genetic toxicology. From the beginning of my scientific career it has fascinated me how chemical carcinogens induce cancer through damaging DNA and disrupting cellular control, especially how people differ in their response. The question why certain people have an increased susceptibility to chemical exposure and have an enhanced risk of getting cancer is intriguing to me. In toxicology it all comes together; chemical structures, biochemistry, biology, individual susceptibility for disease, and of course how to implement all this knowledge into assessing risks and onto policy making.

2.         What do you think are the most important developments in the field of toxicology at the moment?

Toxicology has grown into a real multidisciplinary discipline. It is not anymore describing phenomena by, for instance, treating animals with a chemical carcinogen and then counting the number of tumours that ultimately arise. Nowadays it is strongly orientated towards molecular mechanisms behind chemical exposures leading to disease by making use of state of the art technologies such as genomics, proteomics and metabolomics. Next to that is the emerging arena of the exposome that is the analytical challenge to judge a person’s lifetime exposure. An important development is the importance of knowing at what time during life we are exposed and especially the prenatal exposure window is increasingly becoming of interest via epigenetic imprinting. The following quote is still inspiring me: “What is it that is not a poison? All things are poisons and nothing is without poison. It is the dose only that makes a thing not a poison.” Who said this a long time ago? Right; Paracelsus, 1493-1541.

3.         How do you envisage toxicology research developing in the future?

Toxicology is developing into a real important and modern field of science that is highly relevant for society. It integrates all modern insights in science and the gained knowledge is increasingly important for an array of societal applications including refinement of risk assessment, replacement of animals in chemical testing and also applications in translational medicine by judging side effects of therapeutics.

4.         You’re one of the Associate Editors for Toxicology Research. What excites you most about your new role?

To say it bluntly, it is my desire to help to make Toxicology Research one of the leading journals dealing with chemical exposures and its effects in ecosystems to humans. I think that science should not be restricted to certain disciplines and that we can learn when crossing borders. And that we should use our imagination and creativity as much as possible to find solutions for the global environmental and societal problems we are facing. I am very proud to be part of a team that has the ambition to go beyond our self-imposed boundaries. Therefore I encourage the scientists to let loose their creativity and submit these papers to this inter-disciplinary journal.

5.         What advice would you give to the students who will be the next generation of scientists?

Research is very exciting. When I was a PhD student I remember how I biked to work in the morning, wondering what my experiment in the lab that night had done. I know that students first have to study hard to gain knowledge before becoming a scientist and sometimes this can be boring. But I advise them to push through because science is so exciting. Once a scientist, many times during the course of their experiments they may face troubles but it is very rewarding when the expectations come true. So, don’t give up because we need young and gifted people.

6.         If you weren’t a scientist, what would you be?

If possible something in a creative direction; perhaps an artist or actor. However I cannot imagine not being in science.

If you would like to submit an article to Toxicology Research, to be handled by Frederik-Jan, you can do so here on our submissions platform.

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Review: Mechanisms of lead and manganese neurotoxicity

It has been shown that exposure to high levels of lead and manganese in both children and adults can cause cognitive and behavioural deficits. While both metals having distinct neurological effects, each with different brain targets and modes of action, they do share a key similarity in that they both disrupt synaptic transmission.

In this review Tomas R. Guilarte and April P. Neal summarise the toxicokinetics of lead and manganese; describing their neurotoxic mechanisms and discussing the commonalities in their neurotoxicity.

Mechanisms of lead and manganese neurotoxicity
April P. Neal and Tomas R. Guilarte
DOI: 10.1039/C2TX20064C

Fancy writing a review article?  Have a topic in mind that will benefit the community? Send us your suggestions!

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Toxicology Research issue 1, 2013, available online now!

The first issue of Toxicology Research for 2013 has arrived!

In this issue we have: An editorial from Nigel Gooderham, Editor in Chief and Richard Kelly, Managing Editor, looking back on 2012 and looking forward to 2013.

3 reviews:
S-Methyl-L-cysteine sulphoxide: the Cinderella phytochemical?

William M. B. Edmands, Nigel J. Gooderham, Elaine Holmes and Stephen C. Mitchell

In vitro models for liver toxicity testing
Valerie Y. Soldatow, Edward L. LeCluyse, Linda G. Griffith and Ivan Rusyn

Novel in vitro and mathematical models for the prediction of chemical toxicity
Dominic P. Williams et al.

3 Papers:

Triclosan interferes with the thyroid axis in the zebrafish (Danio rerio)
Patrícia I. S. Pinto, Eduarda M. Guerreiro and Deborah M. Power

Assessing confidence in predictions made by knowledge-based systems
Philip N. Judson, Susanne A. Stalford and Jonathan Vessey

Adult human exocrine pancreas differentiation to hepatocytes – potential source of a human hepatocyte progenitor for use in toxicology research
Matthew C. Wright et al.

Read all of these articles for free today.

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All articles published in 2012 and 2013 are free to access.

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Safer blood clotting agents for open wounds

New toxicity results show that foams would be safer than the currently used clays as materials to stem blood flow in open wounds.

Blood loss is one of the leading causes of death in both military and civilian casualties. Currently, aluminosilicate layered clays, such as kaolin clay, are used as haemostatic agents (agents that encourage the blood to clot) in dressings to prevent fatalities. These clays have varying degrees of cytotoxicity and can be difficult to remove from wounds, which can lead to thrombosis. Recently, one clay product has been removed from use for this reason.

Haemostatic agents are added to wound dressings to encourage the blood to clot

Now, scientists in Singapore and the US, led by Daniele Zink from the Institute of Bioengineering and Nanotechnology in Singapore and Galen Stucky from the University of California, Santa Barbara, have found, using in vitro tests, that a silica mesocellular foam (MCF-26) is 1–2 orders of magnitude less toxic to human cells than the clays, whereas its potency in promoting blood clotting is similar.

‘MCF-26 would be effective and safer than currently used haemostatic agents,’ says Zink. She adds that the clay particles in their tests to compare the two materials adhered to cell surfaces and were taken up into the cells’ cytoplasm. The MCF-26 was not taken up and was easy to remove.

Read the full story in Chemistry World

And read the Toxicology Research paper, for free here:

Cytotoxicity and potency of mesocellular foam-26 in comparison to layered clays used as hemostatic agents
Yao Li, April M. Sawvel, Young-Si Jun, Sara Nownes, Ming Ni, Damien Kudela, Galen D. Stucky and Daniele Zink
DOI: 10.1039/C2TX20065A

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In vitro models for liver toxicity testing

In this review Ivan Rusyn, University of North Carolina, and co-workers present an overview of various traditional and novel liver-derived in vitro systems for hepatotoxicity testing. Examples of such systems include:

  • Primary hepatocytes cultures,
  • Immortalized cell lines,
  • Co-cultures of hepatocytes with liver non-parenchymal cells,
  • Bioartificial livers.

Rusyn et al. discuss the benefits and disadvantages associated with using traditional in vitro systems whilst also examining the usefulness of the novel in vitro liver models for toxicity testing.

Want to know more? Read the entire review for free….

In vitro models for liver toxicity testing
Valerie Y. Soldatow, Edward L. LeCluyse, Linda G. Griffith and Ivan Rusyn
DOI: 10.1039/C2TX20051A

Interested in liver toxicology? You may also be interested in these related articles:

Role of innate and adaptive immunity during drug-induced liver injury

Novel in vitro and mathematical models for the prediction of chemical toxicity

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Using transcriptomics to detect genotoxic and non-genotoxic renal carcinogens

Currently there is no in vitro system for the reliable detection of non-genotoxic carcinogens and the tests currently available for the detection of genotoxic carcinogens can have a low specificity. As such there is a need for the development of quick, cheap, sensitive and specific methods to detect the carcinogenic potential of chemicals.

In this paper Katarzyna M. Bloch (Liverpool John Moores University) and colleagues use toxicogenomics and NRK-52E cell lines to try and develop an in vitro system in renal cells to detect the carcinogenic potential of chemicals to the kidney.

Interested? Read the paper for free…

Detection of genotoxic and non-genotoxic renal carcinogens in vitro in NRK-52E cells using a transcriptomics approach
Katarzyna M. Bloch, Noreen Yaqoob, Andrew Evans, Robert Radford, Paul Jennings, Jan J. W. A Boei, Tara McMorrow, Craig Slattery, Michael P. Ryan, Hans Gmuender, Joost H. M. van Delft and Edward A. Lock
DOI: 10.1039/C2TX20023F

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Issue 3 of Toxicology Research: free to read online now

Issue 3 of Toxicology Research is here and ready for you to get your hands on.

On the front cover is a Paper from Gopal Chakrabarti and co-workers presenting the investigation into the target oriented molecular mechanism of the toxicity of acenaphthenequinone, a polyaromatic hydrocarbon present in diesel exhausts. Chakrabarti et al.demonstrate that acenaphthenequinone targets the microtubule cytoskeleton, and simultaneously activates mitochondria dependent cell death.

Acenaphthenequinone induces cell cycle arrest and mitochondrial apoptosis via disruption of cellular microtubules

Amlan Das, Diptiman Choudhury, Subhendu Chakrabarty, Abhijit Bhattacharya and Gopal Chakrabarti

Also featuring in this issue:

A review by C. David Williams and Hartmut Jaeschke on the role of innate and adaptive immunity during drug-induced liver injury

A paper from Ted Lock et al. using toxicogenomics to try and develop an in vitro system in renal cells to detect the carcinogenic potential of chemicals to the kidneys.

Detection of genotoxic and non-genotoxic renal carcinogens in vitro in NRK-52E cells using a transcriptomics approach
Edward A. Lock et al.

For all this and more, read the issue now for free…

Like what you read?

Submit your work to Toxicology Research now.
Ensure you keep up to date with the latest research published in the journal: sign up for the contents alerts and newsletter.

All articles published in 2012 and 2013 are free to access.

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Interview with Editorial Board member Dr William Pennie

Toxicology Research would like to welcome its newest member of the Editorial Board, Dr William Pennie, who has kindly answered a few questions to introduce himself to you, our readers.

1.    What led you to specialise in toxicology?
While I was at the NIH I had an interest in nuclear hormone receptor biology and in particular transcriptional regulation events mediated by these receptors. I was trained as a molecular biologist and never had any formal education in toxicology. When I was making the transition from academia to industry around 15 years ago, there were some very interesting scientific challenges in understanding the biology of xenoestrogens, particularly predicting tissue and species-specific effects associated with undesirable estrogenic activity.  This was a really easy transition for me to enter industry and to work at a phenomenally well-regard industrial lab (Central Toxicology Laboratory of Zeneca, in Macclesfield UK). Before I knew it I was drawn into biology problems that just happened to be labelled toxicology! My career then brought me closer to the realm of investigative toxicology, understanding the mechanisms by which individual compounds can cause adverse effects but more recently my interest in toxicology has been identifying multi-disciplinary solutions to the challenge of attempting to predict toxicity in the drug discovery process.

2.    What do you think are the most important developments in the field of toxicology at the moment?
The last few years have seen some concerted efforts in better data curation and accessibility across industry, academia and government labs. This has the promise of being very enabling, and could be fundamental in providing those of us looking to identify broad mechanisms of toxicity with well-curated compound lists we can use to mine for mechanisms and validate hypotheses. There have also been some very interesting developments in building panels of mechanistic screens that bring together assay developers, computational modellers and libraries of well-annotated compounds. The initiative of ToxCast and the IMI work are examples of this paradigm.

3.    What excites you most about your new role on the Editorial Board of Toxicology Research?
I love the idea of us helping to encourage a multi-disciplinary approach to understanding toxicity. I think we have an opportunity to encourage manuscripts that try to relate chemistry space to mechanism to phenotype. I’m fond of saying “multi-disciplinary problems need multi-disciplinary solutions” so perhaps Toxicology Research will give us an opportunity to help catalyze science that transcends any individual discipline.

4.    How do you envisage Toxicology Research developing in the future?
Like my previous example I’d love to see the journal help scientists to appreciate problems from multiple angles. I can easily imagine a future issue being of equal interest to toxicologists, pharmacologists, chemists and PKPD modellers.

5.    What advice would you give to the students who will be the next generation of scientists?
Develop collaborations with others as soon as possible. Almost everything I’ve been associated with doing in my career benefitted from collaborators with a different perspective or who bring a unique skill set to the table.

6.    If you weren’t a scientist, what would you be?
That’s a tough one! Since starting on my career path I’ve never been drawn to anything else but I certainly had aspirations to be a musician when I was in high school! All I was missing was musical talent. Seriously though,  I find that science just continues to become more satisfying the longer you spend working on it.

Toxicology Research is accepting submissions. All articles will be free to access until the end of 2013. Please contact the editorial office if you have any questions about the journal.

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Role of innate and adaptive immunity during drug-induced liver injury

Drug-induced liver injury (DILI) is a major concern in human health. Idiosyncratic DILI (IDILI) is highly variable in its time to onset and no one clear hypothesis exists to explain the mechanism, although there is a general belief that most cases of IDILI involve some immune mediated component. The most common cause of DILI is acetaminophen (APAP) overdose, and although mechanistically APAP-induced liver injury appears to be fundamentally different from IDILI, there are potential critical events shared between APAP-induced liver injury and IDILI.

In this review C. David Williams and Hartmut Jaeschke, University of Kansas Medical Center:

- Compare the existing hypotheses for potential causes of IDILI and discuss the potential roles of immune involvement in DILI;
- Compare and contrast what is known about the mechanisms of APAP-induced liver injury and IDILI;
- Describe the strategies and methods currently being used to study APAP-induced liver injury.

Read the full review for free or have a browse around the Toxicology Research website to see the latest accepted articles.

Role of innate and adaptive immunity during drug-induced liver injury
C. David Williams and Hartmut Jaeschke
DOI: 10.1039/C2TX20032E

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Novel in vitro and mathematical models for the prediction of chemical toxicity

Current in vitro test systems are poor at predicting the toxicity of chemicals/drugs entering the systemic circulation, particularly to the liver. Such systems fall short for several reasons:
(1) Physiological differences between cells currently used and human hepatocytes in their natural state
(2) Lack of physiological integration with other cells/systems within organs, required to amplify the initial toxicological lesion into overt toxicity
(3) An inability to assess how low level cell damage may develop into overt organ toxicity in some people
(4) Failure to consider systemic effects.

This review by Dominic P. Williams and colleagues presents an in-depth look at how combining technology, such as bioartificial livers (BALs), and mathematical models can allow the design of in vitro systems that can mimic the in vivo systems more accurately. This would allow the testing of theoretical hypothesis testing and a reduction of in vivo animal testing.

For the complete, detailed discussion read this review for free by following the link below….

Novel in vitro and mathematical models for the prediction of chemical toxicity
Dominic P. Williams, Rebecca Shipley, Marianne J. Ellis, Steve Webb, John Ward, Iain Gardner and Stuart Creton
DOI: 10.1039/C2TX20031G

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