Assessing Modes of Toxic Action of Organic Cations in Cell-Based Bioassays: the Critical Role of Partitioning to Cells and Medium Components.

High-throughput cell-based bioassays can fulfill the growing need to assess the hazards and modes of toxic action (MOA) of ionic liquids (ILs). Although nominal concentrations () are typically used in an bioassay, freely dissolved concentrations () are considered a more accurate dose metric because they account for chemical partitioning processes and are informative about MOA. We determined the of IL cations in AREc32 and AhR-CALUX assays using both mass balance model (MBM) prediction and experimental quantification.

Fish early-life stage toxicity and environmental relevance: what does high-dose toxicity testing tell us?

The early-life stage (ELS) toxicity syndrome for fish is well described and has been reported in hundreds of toxicity studies. It is generally characterized by a reduced heart rate, yolk sac and pericardial edemas, and various morphological abnormalities, the most common being spinal curvature. For many of those studies, it appears that the ELS toxicity syndrome is the result of nonspecific (baseline) toxicity that occurs at aqueous and whole-body concentrations that are just below lethal concentrations.

A combination of high-throughput in vitro and in silico new approach methods for ecotoxicology hazard assessment for fish.

Fish acute toxicity testing is used to inform environmental hazard assessment of chemicals. In silico and in vitro approaches have the potential to reduce the number of fish used in testing and increase the efficiency of generating data for assessing ecological hazards. Here, two in vitro bioactivity assays were adapted for use in high-throughput chemical screening.

Role of Suspended Particulate Matter for the Transport and Risks of Organic Micropollutant Mixtures in Rivers: A Comparison between Baseflow and High Discharge Conditions.

The partition dynamics of organic micropollutants between water and suspended particulate matter (SPM) in riverine ecosystems differs between dry and wet weather, as demonstrated at two sites at the Ammer River, Germany. One site was impacted by a wastewater treatment plant (WWTP) and the other by runoff of a mixed agricultural/urban area. Liquid and gas chromatography coupled to high-resolution mass spectrometry were used to quantify 415 organic chemicals, and their mixture effects were characterized with three in vitro bioassays indicative of the activation of the aryl hydrocarbon (AhR) and peroxisome proliferator-activated (PPARγ) receptors and the oxidative stress response.

MLinvitroTox reloaded for high-throughput hazard-based prioritization of high-resolution mass spectrometry data.

MLinvitroTox is an automated Python pipeline developed for high-throughput hazard-driven prioritization of toxicologically relevant signals detected in complex environmental samples through high-resolution tandem mass spectrometry (HRMS/MS). MLinvitroTox is a machine learning (ML) framework comprising 490 independent XGBoost classifiers trained on molecular fingerprints from chemical structures and target-specific endpoints from the ToxCast/Tox21 invitroDBv4.1 database.