Publications & Documents

This Adverse Outcome Pathway (AOP) describes the linkage between Deiodinase 1 inhibition and increased mortality via reduced posterior swim bladder inflation. The swim bladder is a gas-filled organ found in many bony fish species and typically consists of two gas-filled chambers. The posterior chamber inflates during early development (embryo), while the anterior chamber inflates during late development (larva). Both chambers are important for fish to control buoyancy and the anterior chamber has an additional role in hearing. This AOP is part of a network of 5 AOPs describing how disruption of the thyroid hormone system can affect developmental processes involved in swim bladder inflation. The network includes three molecular initiating events representing the inhibition of enzymes that are important for thyroid hormone synthesis and activation. It describes how inhibition of thyroperoxidase and/or deiodinase, leads to reduced swim bladder inflation, resulting in reduced swimming performance, increased mortality and ultimately, decreased population trajectory in fish. This AOP network is currently mainly based on experimental evidence from studies on fish species with a two-chambered swim bladder. This AOP is referred to as AOP 157 in the Collaborative Adverse Outcome Pathway Wiki (AOP-Wiki).

This Adverse Outcome Pathway (AOP) describes the linkage between Deiodinase 2 inhibition and increased mortality via reduced anterior swim bladder inflation. The swim bladder is a gas-filled organ found in many bony fish species and typically consists of two gas-filled chambers. The posterior chamber inflates during early development (embryo), while the anterior chamber inflates during late development (larva). Both chambers are important for fish to control buoyancy and the anterior chamber has an additional role in hearing. This AOP is part of a network of 5 AOPs describing how disruption of the thyroid hormone system can affect developmental processes involved in swim bladder inflation. The network includes three molecular initiating events representing the inhibition of enzymes that are important for thyroid hormone synthesis and activation. It describes how inhibition of thyroperoxidase and/or deiodinase, leads to reduced swim bladder inflation, resulting in reduced swimming performance, increased mortality and ultimately, decreased population trajectory in fish. This AOP network is currently mainly based on experimental evidence from studies on fish species with a two-chambered swim bladder. This AOP is referred to as AOP 156 in the Collaborative Adverse Outcome Pathway Wiki (AOP-Wiki).

This Adverse Outcome Pathway (AOP) describes the linkage between uncoupling of oxidative phosphorylation (OXPHOS) and growth inhibition via decreased cell proliferation. The mitochondrial OXPHOS machinery is a key physiological process responsible for producing the primary cellular energy, adenosine triphosphate (ATP). Uncoupling of OXPHOS is a well-known mechanism of action of many chemicals and can affect many ATP-dependent biological functions. Cell proliferation in particular, as a major process to achieve organismal growth, is positively correlated with the cellular ATP level and highly susceptible to energy depletion. This AOP causally links uncoupling of OXPHOS to growth inhibition, through ATP depletion and reduced cell proliferation with strong weight of evidence support. This AOP is of high regulatory relevance, as it is considered applicable to both human health and ecological risk assessments. The AOP also forms the core of a larger AOP network addressing uncoupling of OXPHOS mediated growth inhibition. This AOP is referred to as AOP 263 in the Collaborative Adverse Outcome Pathway Wiki (AOP-Wiki).

This Adverse Outcome Pathway (AOP) describes the linkage between Deiodinase 1 inhibition and increased mortality via reduced anterior swim bladder inflation. The swim bladder is a gas-filled organ found in many bony fish species and typically consists of two gas-filled chambers. The posterior chamber inflates during early development (embryo), while the anterior chamber inflates during late development (larva). Both chambers are important for fish to control buoyancy and the anterior chamber has an additional role in hearing. This AOP is part of a network of 5 AOPs describing how disruption of the thyroid hormone system can affect developmental processes involved in swim bladder inflation. The network includes three molecular initiating events representing the inhibition of enzymes that are important for thyroid hormone synthesis and activation. It describes how inhibition of thyroperoxidase and/or deiodinase, leads to reduced swim bladder inflation, resulting in reduced swimming performance, increased mortality and ultimately, decreased population trajectory in fish. This AOP network is currently mainly based on experimental evidence from studies on fish species with a two-chambered swim bladder. This AOP is referred to as AOP 158 in the Collaborative Adverse Outcome Pathway Wiki (AOP-Wiki).

This Adverse Outcome Pathway (AOP) describes the linkage between binding to proteins involved in protection against oxidative stress and impairment in learning and memory. Production, binding and degradation of Reactive Oxygen Radicals are tightly regulated in the body, and an imbalance between production and protection may cause oxidative stress, which is common to many toxicity pathways. Oxidative stress may lead to an imbalance in glutamate neurotransmission, which is involved in learning and memory. Oxidative stress may also cause cellular injury and death. During brain development and in particular during the establishment of neuronal connections and networks, such perturbations may lead to functional impairment in learning and memory. The weight-of-evidence supporting the relationship between the key events described in this AOP is based mainly on developmental effects observed after an exposure to mercury, a heavy metal known for its strong affinity to many proteins having anti-oxidant properties. This AOP is referred to as AOP 17 in the Collaborative Adverse Outcome Pathway Wiki (AOP-Wiki).

This Adverse Outcome Pathway (AOP) describes the linkage between Thyroperoxidase inhibition and increased mortality via reduced anterior swim bladder inflation. The swim bladder is a gas-filled organ found in many bony fish species and typically consists of two gas-filled chambers. The posterior chamber inflates during early development (embryo), while the anterior chamber inflates during late development (larva). Both chambers are important for fish to control buoyancy and the anterior chamber has an additional role in hearing. This AOP is part of a network of 5 AOPs describing how disruption of the thyroid hormone system can affect developmental processes involved in swim bladder inflation. The network includes three molecular initiating events representing the inhibition of enzymes that are important for thyroid hormone synthesis and activation. It describes how inhibition of thyroperoxidase and/or deiodinase, leads to reduced swim bladder inflation, resulting in reduced swimming performance, increased mortality and ultimately, decreased population trajectory in fish. This AOP network is currently mainly based on experimental evidence from studies on fish species with a two-chambered swim bladder. This AOP is referred to as AOP 159 in the Collaborative Adverse Outcome Pathway Wiki (AOP-Wiki).

This Adverse Outcome Pathway (AOP) describes the linkage between Chitin synthase 1 inhibition and mortality in arthropods. In order to grow and develop, arthropods need to shed their exoskeleton (or cuticle) periodically and replace it with a new one in a process called molting. Successful molting, and therefore a successful development necessitates stability and integrity of the cuticle to support muscular contractions involved in the shedding of the old cuticle. Arthropods heavily rely on chitin synthesis as chitin is one of the main constituents of the cuticle. The cuticular chitin synthase (CHS-1) is the key enzyme in the biosynthetic pathway and arthropods are therefore especially dependent on its proper function. The present AOP describes the effects of CHS-1 chemical inhibition on the molting process leading to increased mortality in arthropods. Knowledge gaps still exist in the process and this AOP may help guiding assay development for further experimental studies, addressing these gaps. This AOP is referred to as AOP 360 in the Collaborative Adverse Outcome Pathway Wiki (AOP-Wiki).

This Test Guideline, covering nanomaterials spanning from 1 nm to 1000 nm, is intended for particle size and particle size distribution measurements of nanomaterials. The TG includes the following methods: Atomic Force Microscopy (AFM), Centrifugal Liquid Sedimentation (CLS)/Analytical Ultracentrifugation (AUC), Dynamic Light Scattering (DLS), Differential Mobility Analysis System (DMAS), (Nano)Particle Tracking Analysis (PTA/NTA), Small Angle X-Ray Scattering (SAXS), Scanning Electron Microscopy (SEM), and Transmission Electron Microscopy (TEM). For measuring the diameter and length of fibres, analysing images captured with electron microscopy is currently the only method available.

This Test Guideline describes an in vivo erythrocyte Pig-a gene mutation assay (hereafter called the Pig-a assay) which uses an endogenous mammalian gene, the phosphatidylinositol glycan class A gene (Pig-a), as a reporter of somatic-cell gene mutation. In vivo gene mutation tests, such as the Pig-a assay, are especially relevant for assessing mutagenicity because physiological factors, such as absorption of the test chemical from the site of exposure, distribution of the test chemical throughout the test system via systemic circulation, and in vivo metabolism and DNA repair processes, all contribute to the mutagenic responses. The Pig-a assay can be performed with commonly used strains of rats or mice and the test can be conducted without euthanizing the animals. These properties facilitate integration of the Pig-a assay into many in vivo rodent testing protocols.