Publications

Empirical Comparison of Genotoxic Potency Estimations: The In Vitro DNA-Damage ToxTracker Endpoints versus the In Vivo Micronucleus Assay

Wills J. W. et al. (2021)

Genetic toxicology is an essential component of compound safety assessment. In the face of a barrage of new compounds, higher throughput, less ethically divisive in vitro approaches capable of effective, human-relevant hazard identification and prioritisation are increasingly important.

Read more

Wills J. W. et al. (2021) Genetic toxicology is an essential component of compound safety assessment. In the face of a barrage of new compounds, higher throughput, less ethically divisive in vitro approaches capable of effective, human-relevant hazard identification and prioritisation are increasingly important....

Mode of action assessment of the genotoxic properties of antimony and its compounds evaluated in the ToxTracker assay

Boreiko, C. J., et al. (2021)

Antimony (Sb) and its compounds are negative in gene mutation assays in bacteria and cultured mammalian cells but positive in some assays for clastogenicity and/or DNA damage.

Read more

Boreiko, C. J., et al. (2021) Antimony (Sb) and its compounds are negative in gene mutation assays in bacteria and cultured mammalian cells but positive in some assays for clastogenicity and/or DNA damage. ...

The in vitro ToxTracker and Aneugen Clastogen Evaluation extension assay as a tool in the assessment of relative genotoxic potential of e-liquids and their aerosols

Czekala, L., et al. (2021)

In vitro (geno)toxicity assessment of electronic vapour products (EVPs), relative to conventional cigarette, currently uses assays, including the micronucleus and Ames tests.

Read more

Czekala, L., et al. (2021) In vitro (geno)toxicity assessment of electronic vapour products (EVPs), relative to conventional cigarette, currently uses assays, including the micronucleus and Ames tests....

A Case Study with Triazole Fungicides to Explore Practical Application of Next-Generation Hazard Assessment Methods for Human Health

van der Ven, L. T. M., et al. (2020)

The ongoing developments in chemical risk assessment have led to new concepts building on integration of sophisticated nonanimal models for hazard characterization. Here we explore a pragmatic approach for implementing such concepts, using a case study of three triazole fungicides, namely, flusilazole, propiconazole, and cyproconazole.

Read more

van der Ven, L. T. M., et al. (2020) The ongoing developments in chemical risk assessment have led to new concepts building on integration of sophisticated nonanimal models for hazard characterization. Here we explore a pragmatic approach for implementing such concepts, using a case study of...

Aneugen Versus Clastogen Evaluation and Oxidative Stress-Related Mode-of-Action Assessment of Genotoxic Compounds Using the ToxTracker Reporter Assay

Brandsma, I., et al. (2020)

Understanding the mode-of-action (MOA) of genotoxic compounds and differentiating between direct DNA interaction and indirect genotoxicity is crucial for their reliable safety assessment. ToxTracker is a stem cell-based reporter assay that detects activation of various cellular responses that are associated with genotoxicity and cancer.

Read more

Brandsma, I., et al. (2020) Understanding the mode-of-action (MOA) of genotoxic compounds and differentiating between direct DNA interaction and indirect genotoxicity is crucial for their reliable safety assessment. ToxTracker is a stem cell-based reporter assay that detects activation of various cellular responses that are associated with...

ToxTracker Reporter Cell Lines as a Tool for Mechanism-Based (geno)Toxicity Screening of Nanoparticles-Metals, Oxides and Quantum Dots

McCarrick, S., et al. (2020)

The increased use of nanoparticles (NPs) requires efficient testing of their potential toxic effects. A promising approach is to use reporter cell lines to quickly assess the activation of cellular stress response pathways. This study aimed to use the ToxTracker reporter cell lines to investigate (geno)toxicity of various metal- or metal oxide NPs and draw general conclusions on NP-induced effects, in combination with our previous findings.

Read more

McCarrick, S., et al. (2020) The increased use of nanoparticles (NPs) requires efficient testing of their potential toxic effects. A promising approach is to use reporter cell lines to quickly assess the activation of cellular stress response pathways. This study aimed to use the ToxTracker reporter...

Application of the adverse outcome pathway framework to genotoxic modes of action

Sasaki, J. C., et al. (2020)

In May 2017, the Health and Environmental Sciences Institute’s Genetic Toxicology Technical Committee hosted a workshop to discuss whether mode of action (MOA) investigation is enhanced through the application of the adverse outcome pathway (AOP) framework. As AOPs are a relatively new approach in genetic toxicology, this report describes how AOPs could be harnessed to advance MOA analysis of genotoxicity pathways using five example case studies.

Read more

Sasaki, J. C., et al. (2020) In May 2017, the Health and Environmental Sciences Institute's Genetic Toxicology Technical Committee hosted a workshop to discuss whether mode of action (MOA) investigation is enhanced through the application of the adverse outcome pathway (AOP) framework. As AOPs are...

A comparison of classical and 21st century genotoxicity tools: A proof of concept study of 18 chemicals comparing in vitro micronucleus, ToxTracker and genomics-based methods (TGx-DDI, whole genome clustering and connectivity mapping)

Allemang, A. et al. (2020)

A key step in the risk assessment process of a substance is the assessment of its genotoxic potential. Irrespective of the industry involved, current approaches rely on combinations of two or three in vitro tests and while highly sensitive, their specificity is thought to be limited.

Read more

Allemang, A. et al. (2020) A key step in the risk assessment process of a substance is the assessment of its genotoxic potential. Irrespective of the industry involved, current approaches rely on combinations of two or three in vitro tests and while highly sensitive, their specificity...

An approach for the extract generation and toxicological assessment of tobacco-free ‘modern’ oral nicotine pouches

Bishop, E. et al. (2020)

Tobacco-free ‘modern’ oral nicotine pouches (MOPs), are similar in appearance and use to Swedish-style snus, but without tobacco. There are few identified methods to create test samples for toxicologically assessment of MOPs in vitro. In this study we present a simple method for the extraction of pouch material in cell culture media, providing consistent nicotine concentration and easy in vitro assessment.

Read more

Bishop, E. et al. (2020) Tobacco-free 'modern' oral nicotine pouches (MOPs), are similar in appearance and use to Swedish-style snus, but without tobacco. There are few identified methods to create test samples for toxicologically assessment of MOPs in vitro. In this study we present a simple...

A Next-Generation Risk Assessment Case Study for Coumarin in Cosmetic Products

Baltazar, M. T., et al. (2020)

Next-Generation Risk Assessment is defined as an exposure-led, hypothesis-driven risk assessment approach that integrates new approach methodologies (NAMs) to assure safety without the use of animal testing. These principles were applied to a hypothetical safety assessment of 0.1% coumarin in face cream and body lotion.

Read more

Baltazar, M. T., et al. (2020) Next-Generation Risk Assessment is defined as an exposure-led, hypothesis-driven risk assessment approach that integrates new approach methodologies (NAMs) to assure safety without the use of animal testing. These principles were applied to a hypothetical safety assessment of 0.1% coumarin in...

Towards grouping concepts based on new approach methodologies in chemical hazard assessment: the read-across approach of the EU-ToxRisk project

Escher, S. E., et al. (2019)

Read-across is one of the most frequently used alternative tools for hazard assessment, in particular for complex endpoints such as repeated dose or developmental and reproductive toxicity. Read-across extrapolates the outcome of a specific toxicological in vivo endpoint from tested (source) compounds to “similar” (target) compound(s)

Read more

Escher, S. E., et al. (2019) Read-across is one of the most frequently used alternative tools for hazard assessment, in particular for complex endpoints such as repeated dose or developmental and reproductive toxicity. Read-across extrapolates the outcome of a specific toxicological in vivo endpoint from tested...

High variability in toxicity of welding fume nanoparticles from stainless steel in lung cells and reporter cell lines: the role of particle reactivity and solubility

McCarrick, S., et al. (2019)

Millions of people in the world perform welding as their primary occupation resulting in exposure to metal-containing nanoparticles in the fumes generated. Even though health effects including airway diseases are well-known, there is currently a lack of studies investigating how different welding set-ups and conditions affect the toxicity of generated nanoparticles of the welding fume.

Read more

McCarrick, S., et al. (2019) Millions of people in the world perform welding as their primary occupation resulting in exposure to metal-containing nanoparticles in the fumes generated. Even though health effects including airway diseases are well-known, there is currently a lack of studies investigating how different...

The mechanism-based toxicity screening of particles with use in the food and nutrition sector via the ToxTracker reporter system

Brown, D. M., et al. (2019)

The rapid expansion of the incorporation of nano-sized materials in consumer products overlaps with the necessity for high-throughput reliable screening tools for the identification of the potential hazardous properties of the nanomaterials. The ToxTracker assay (mechanism-based reporter assay based on embryonic stem cells that uses GFP-tagged biomarkers for detection of DNA damage, oxidative stress and general cellular stress) is one such tool, which could prove useful in the field of particle toxicology allowing for high throughput screening.

Read more

Brown, D. M., et al. (2019) The rapid expansion of the incorporation of nano-sized materials in consumer products overlaps with the necessity for high-throughput reliable screening tools for the identification of the potential hazardous properties of the nanomaterials. The ToxTracker assay (mechanism-based reporter assay based on...

Mechanistic insight into reactivity and (geno)toxicity of well-characterized nanoparticles of cobalt metal and oxides

Cappellini, F., et al. (2018)

An increasing use of cobalt (Co)-based nanoparticles (NPs) in different applications and exposures at occupational settings triggers the need for toxicity assessment. Improved understanding regarding the physiochemical characteristics of Co metal NPs and different oxides in combination with assessment of toxicity and mechanisms may facilitate decisions for grouping during risk assessment.

Read more

Cappellini, F., et al. (2018) An increasing use of cobalt (Co)-based nanoparticles (NPs) in different applications and exposures at occupational settings triggers the need for toxicity assessment. Improved understanding regarding the physiochemical characteristics of Co metal NPs and different oxides in combination with assessment of toxicity...

Genotoxic and mutagenic properties of Ni and NiO nanoparticles investigated by comet assay, γ-H2AX staining, Hprt mutation assay and ToxTracker reporter cell lines

Åkerlund, E., et al. (2018)

Nickel (Ni) compounds are classified as carcinogenic to humans but the underlying mechanisms are still poorly understood. Furthermore, effects related to nanoparticles (NPs) of Ni have not been fully elucidated.

Read more

Åkerlund, E., et al. (2018) Nickel (Ni) compounds are classified as carcinogenic to humans but the underlying mechanisms are still poorly understood. Furthermore, effects related to nanoparticles (NPs) of Ni have not been fully elucidated. ...

Good cell culture practices & in vitro toxicology

Eskes, C., et al. (2017)

Good Cell Culture Practices (GCCP) is of high relevance to in vitro toxicology. The European Society of Toxicology In Vitro (ESTIV), the Center for Alternatives for Animal Testing (CAAT) and the In Vitro Toxicology Industrial Platform (IVTIP) joined forces to address by means of an ESTIV 2016 pre-congress session the different aspects and applications of GCCP.

Read more

Eskes, C., et al. (2017) Good Cell Culture Practices (GCCP) is of high relevance to in vitro toxicology. The European Society of Toxicology In Vitro (ESTIV), the Center for Alternatives for Animal Testing (CAAT) and the In Vitro Toxicology Industrial Platform (IVTIP) joined forces to address...

An integrative test strategy for cancer hazard identification

Luijten, M., et al. (2016)

Assessment of genotoxic and carcinogenic potential is considered one of the basic requirements when evaluating possible human health risks associated with exposure to chemicals. Test strategies currently in place focus primarily on identifying genotoxic potential due to the strong association between the accumulation of genetic damage and cancer.

Read more

Luijten, M., et al. (2016) Assessment of genotoxic and carcinogenic potential is considered one of the basic requirements when evaluating possible human health risks associated with exposure to chemicals. Test strategies currently in place focus primarily on identifying genotoxic potential due to the strong association...

The Vitotox and ToxTracker assays: A two-test combination for quick and reliable assessment of genotoxic hazards

Ates, G., et al. (2016)

To ensure safety for humans, it is essential to characterize the genotoxic potential of new chemical entities, such as pharmaceutical and cosmetic substances. In a first tier, a battery of in vitro tests is recommended by international regulatory agencies.

Read more

Ates, G., et al. (2016) To ensure safety for humans, it is essential to characterize the genotoxic potential of new chemical entities, such as pharmaceutical and cosmetic substances. In a first tier, a battery of in vitro tests is recommended by international regulatory agencies. ...

Emerging metrology for high-throughput nanomaterial genotoxicology

Nelson, B. C., et al. (2016)

The rapid development of the engineered nanomaterial (ENM) manufacturing industry has accelerated the incorporation of ENMs into a wide variety of consumer products across the globe. Unintentionally or not, some of these ENMs may be introduced into the environment or come into contact with humans or other organisms resulting in unexpected biological effects. It is thus prudent to have rapid and robust analytical metrology in place that can be used to critically assess and/or predict the cytotoxicity, as well as the potential genotoxicity of these ENMs.

Read more

Nelson, B. C., et al. (2016) The rapid development of the engineered nanomaterial (ENM) manufacturing industry has accelerated the incorporation of ENMs into a wide variety of consumer products across the globe. Unintentionally or not, some of these ENMs may be introduced into the environment or...

The Extended ToxTracker Assay Discriminates Between Induction of DNA Damage, Oxidative Stress, and Protein Misfolding

Hendriks, G., et al. (2016)

Chemical exposure of cells may damage biomolecules, cellular structures, and organelles thereby jeopardizing cellular homeostasis. A multitude of defense mechanisms have evolved that can recognize specific types of damaged molecules and will initiate distinct cellular programs aiming to remove the damage inflicted and prevent cellular havoc.

Read more

Hendriks, G., et al. (2016) Chemical exposure of cells may damage biomolecules, cellular structures, and organelles thereby jeopardizing cellular homeostasis. A multitude of defense mechanisms have evolved that can recognize specific types of damaged molecules and will initiate distinct cellular programs aiming to remove the damage...

Mechanism-based genotoxicity screening of metal oxide nanoparticles using the ToxTracker panel of reporter cell lines

Karlsson, H. L., et al. (2014)

The rapid expansion of manufacturing and use of nano-sized materials fuels the demand for fast and reliable assays to identify their potential hazardous properties and underlying mechanisms. The ToxTracker assay is a recently developed mechanism-based reporter assay based on mouse embryonic stem (mES) cells that uses GFP-tagged biomarkers for detection of DNA damage, oxidative stress and general cellular stress upon exposure.

Read more

Karlsson, H. L., et al. (2014) The rapid expansion of manufacturing and use of nano-sized materials fuels the demand for fast and reliable assays to identify their potential hazardous properties and underlying mechanisms. The ToxTracker assay is a recently developed mechanism-based reporter assay based on mouse...

Cellular-signaling pathways unveil the carcinogenic potential of chemicals

Hendriks, G., et al. (2013)

Most of the current in vitro carcinogenicity assays assess the potential carcinogenic properties of chemicals through the detection of inflicted DNA damage or subsequent chromosome damage and gene mutations. Unfortunately, these assays generally do not provide mechanistic insight into the reactive properties of a chemical.

Read more

Hendriks, G., et al. (2013) Most of the current in vitro carcinogenicity assays assess the potential carcinogenic properties of chemicals through the detection of inflicted DNA damage or subsequent chromosome damage and gene mutations. Unfortunately, these assays generally do not provide mechanistic insight into the reactive...

The ToxTracker assay: novel GFP reporter systems that provide mechanistic insight into the genotoxic properties of chemicals

Hendriks, G., et al. (2012)

People are exposed to an ever-increasing number of chemical compounds that are developed by industry for a wide range of applications. These compounds may harmfully react with different cellular components and activate specific defense mechanisms that provide protection against the toxic, mutagenic, and possibly oncogenic consequences of exposure.

Read more

Hendriks, G., et al. (2012) People are exposed to an ever-increasing number of chemical compounds that are developed by industry for a wide range of applications. These compounds may harmfully react with different cellular components and activate specific defense mechanisms that provide protection against the toxic,...

Sensitive DsRed fluorescence-based reporter cell systems for genotoxicity and oxidative stress assessment

Hendriks, G., et al. (2011)

Various in vitro test systems have been developed for genotoxic risk assessment in early drug development. However, these genotoxicity tests often show limited specificity, and provide limited insights into the mode of toxicity of the tested compounds. To identify genes that could serve as specific biomarkers for genotoxicity or oxidative stress, we exposed mouse embryonic stem (ES) cells to various genotoxic and oxidative stress-inducing compounds and performed genome-wide expression profiling.

Read more

Hendriks, G., et al. (2011) Various in vitro test systems have been developed for genotoxic risk assessment in early drug development. However, these genotoxicity tests often show limited specificity, and provide limited insights into the mode of toxicity of the tested compounds. To identify genes that...