Applicability of generic PBK modelling in chemical hazard assessment: A case study with IndusChemFate

Toxicology is moving away from animal testing towards in vitro tools to assess chemical safety. This new testing framework requires a quantitative method, i.e. kinetic modelling, which extrapolates effective concentrations in vitro to a bioequivalent human dose in vivo and which can be applied on “high throughput screening” of a wide variety of...

Systemic PFOS and PFOA exposure and disturbed lipid homeostasis in humans: what do we know and what not?

Associations between per- and polyfluoroalkyl substances (PFASs) and increased blood lipids have been repeatedly observed in humans, but a causal relation has been debated. Rodent studies show reverse effects, i.e. decreased blood cholesterol and triglycerides, occurring however at PFAS serum levels at least 100-fold higher than those in humans....

A high throughput screening system for predicting chemically-induced reproductive organ deformities

There is a great need for alternative testing methods for reproductive toxicants that are practical, fast, cost-effective and easy to interpret. Previously we followed a pragmatic approach using readily available tests, which was successful in predicting reproductive toxicity of chemicals [13]. This initial battery still contained apical tests...

The ChemScreen project to design a pragmatic alternative approachto predict reproductive toxicity of chemicals

There is a great need for rapid testing strategies for reproductive toxicity testing, avoiding animal use.The EU Framework program 7 project ChemScreen aimed to fill this gap in a pragmatic manner prefer-ably using validated existing tools and place them in an innovative alternative testing strategy. In ourapproach we combined knowledge on...

Evaluation of an alternative in vitro test battery for detecting reproductive toxicants in a grouping context

Previously we showed a battery consisting of CALUX transcriptional activation assays, the ReProGlo assay, and the embryonic stem cell test, and zebrafish embryotoxicity assay as 'apical' tests to correctly predict developmental toxicity for 11 out of 12 compounds, and to explain the one false negative [7]. Here we report on applying this battery...

Evaluation of an alternative in vitro test battery for detecting reproductive toxicants

The application of alternative methods in developmental and reproductive toxicology is challenging in view of the complexity of mechanisms involved. A battery of complementary test systems may provide a better prediction of developmental and reproductive toxicity than single assays. We tested twelve compounds with varying mechanisms of toxic...

Developmental immunotoxicity of ethanol in an extended one-generation reproductive toxicity study

The susceptibility of developing immune system to chemical disruption warrants the assessment of immune parameters in reproductive and developmental testing protocols. In this study, a wide range of immune endpoints was included in an extended one-generation reproduction toxicity study (EOGRTS) design to determine the relative sensitivity of...

Next-generation text-mining mediated generation of chemical response-specific gene sets for interpretation of gene expression data

Background: Availability of chemical response-specific lists of genes (gene sets) for pharmacological and/or toxic effect prediction for compounds is limited. We hypothesize that more gene sets can be created by next-generation text mining (next-gen TM), and that these can be used with gene set analysis (GSA) methods for chemical treatment...

Di-n-octyltin dichloride (DOTC) induced developmental immunotoxicity in male rats after juvenile exposure

Developmental immunotoxicity of di-n-octyltin dichloride (DOTC) in an extended one-generation reproductive toxicity study

Developmental immunotoxicity assessment is considered ready for inclusion in developmental toxicity studies. Further evaluation of proposed and additional assays is needed to determine their utility in assessing developmental immunotoxicity. In this study, a wide range of immunological parameters was included in an extended one-generation...

Developmental immunotoxicity of methylmercury: The relative sensitivity of developmental and immune parameters

Current developmental and reproductive toxicity protocols include only a limited set of parameters for effects on the developing immune system. In this study, a wide range of immunological parameters were included in a pre- and postnatal developmental toxicity study. Dose-response data were compared to determine the relative sensitivity of...

The use of in vitro toxicity data and physiologically based kinetic modeling to predict dose-response curves for in vivo developmental toxicity of glycol ethers in rat and man

At present, regulatory assessment of systemic toxicity is almost solely carried out using animal models. The European Commission's REACH legislation stimulates the use of animal-free approaches to obtain information on the toxicity of chemicals. In vitro toxicity tests provide in vitro concentration-response curves for specific target cells,...

Early gene expression changes during embryonic stem cell differentiation into cardiomyocytes and their modulation by monobutyl phthalate

The Embryonic Stem cell Test (EST) is an in vitro alternative test designed for the prediction of embryotoxicity. The endpoint of the test is the interference with mesoderm-derived cardiac muscle differentiation observed under the microscope as beating muscle foci. The relative subjectivity of this endpoint, as well as the applicability domain...

Relative developmental toxicity of glycol ether alkoxy acid metabolites in the embryonic stem cell test as compared with the in vivo potency of their parent compounds

The embryonic stem cell test (EST) has been proposed as an in vitro assay that might reduce animal experimentation in regulatory developmental toxicology. So far, evaluation of the EST was not performed using compounds within distinct chemical classes. Evaluation within a distinct class of chemically related compounds can define the usefulness...

Effecten van anaesthetica op de vroege ontwikkeling van de geslachtscellen van de rat