Review of Data Sources, QSARs and Integrated Testing Strategies for Aquatic Toxicity

This review collects information on sources of aquatic toxicity data and computational tools for estimation of chemical toxicity aquatic to aquatic organisms, such as expert systems and quantitative structure-activity relationship (QSAR) models. The review also captures current thinking of what constitutes an integrated testing strategy (ITS) for this endpoint. The emphasis of the review is on the usefulness of the models and for the regulatory assessment of chemicals, particularly for the purposes of the new European legislation for the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), which entered into force on 1 June 2007. Effects on organisms from three trophic levels (fish, Daphnia and algae) were subject of this review. In addition to traditional data sources such as databases, papers publishing experimental data are also identified. Models for narcoses, general (global) models as well as models for specific chemical classes and mechanisms of action are summarised. Where possible, models were included in a form allowing reproduction without consultation with the original paper. This review builds on work carried out in the framework of the REACH Implementation Projects, and was prepared as a contribution to the EU funded Integrated Project, OSIRIS.JRC.I.3-Toxicology and chemical substance

Alternative methods for regulatory toxicology – a state-of-the-art review

This state-of-the art review is based on the final report of a project carried out by the European Commission’s Joint Research Centre (JRC) for the European Chemicals Agency (ECHA). The aim of the project was to review the state of the science of non-standard methods that are available for assessing the toxicological and ecotoxicological properties of chemicals. Non-standard methods refer to alternatives to animal experiments, such as in vitro tests and computational models, as well as animal methods that are not covered by current regulatory guidelines. This report therefore reviews the current scientific status of non-standard methods for a range of human health and ecotoxicological endpoints, and provides a commentary on the mechanistic basis and regulatory applicability of these methods. For completeness, and to provide context, currently accepted (standard) methods are also summarised. In particular, the following human health endpoints are covered: a) skin irritation and corrosion; b) serious eye damage and eye irritation; c) skin sensitisation; d) acute systemic toxicity; e) repeat dose toxicity; f) genotoxicity and mutagenicity; g) carcinogenicity; h) reproductive toxicity (including effects on development and fertility); i) endocrine disruption relevant to human health; and j) toxicokinetics. In relation to ecotoxicological endpoints, the report focuses on non-standard methods for acute and chronic fish toxicity. While specific reference is made to the information needs of REACH, the Biocidal Products Regulation and the Classification, Labelling and Packaging Regulation, this review is also expected to be informative in relation to the possible use of alternative and non-standard methods in other sectors, such as cosmetics and plant protection products.JRC.I.5-Systems Toxicolog

IMPACTS OF WASTEWATER EFFLUENTS AND SEASONAL TRENDS ON LEVELS OF EMERGING CONTAMINANTS IN TWO COLD-REGION RIVERS

Emerging contaminants such as pharmaceutical drugs have been detected in waters across the globe and are of concern for human and aquatic ecosystems health. Most pharmaceuticals are found at trace concentrations, but the continuous use and potential accumulation of some of these compounds can potentially lead to effects in aquatic organisms. The principal aim of this research was to enhance our understanding of the environmental risks associated with pharmaceuticals as one group of emerging contaminants. Many pharmaceuticals are ionizable organic chemicals (IOCs), which makes their environmental and toxicological behavior particularly challenging to predict due to their partitioning mechanism which is useful to estimate the distribution of the chemical. Therefore, the objective of this thesis was to evaluate the hypothesis that uptake and effects of IOCs in aquatic organisms are influenced by the interaction between environmental, physicochemical, and biological factors. To this end, first, field studies were conducted during spring, summer, and fall of 2021 on water (diffusive gradient in thin film and conventional grab) and sediments at four locations including upstream and downstream of the wastewater treatment plants (WWTPs) of the cities of Saskatoon and Regina in the South Saskatchewan River and Wascana Creek, Saskatchewan, Canada, respectively. Second, seven representative antipsychotic pharmaceuticals were measured in water, sediment, and fish samples up- and downstream of the City of Regina WWTP. Data collected from this research effort indicate contamination with antipsychotic pharmaceuticals, with the potential to adversely impact exposed organisms. Third, non-target chemical analysis was conducted in water, sediments, and fish samples, at the two locations in Wascana Creek and throughout the three seasons. Data collected from non-target analysis indicated that pharmaceuticals, rubber components and personal care products were the priority pollutants in all the matrices and their transcriptomics changes were also supported by the qPCR analysis. Finally, transcripts of several genes of interest were determined in brain and liver samples from in fathead minnow (Pimephales promelas) exposed to the wastewater effluents in Wascana Creek during summer and fall in 2021, using a qPCR gene expression array (the EcoToxChips). The integrative approach used in this study, strongly supports the need to combine chemical analysis with transcriptomics-based approaches as useful tools for assessing of complex mixtures of contaminants in wastewater discharges and their effects in aquatic organisms. This research provides a better understanding of the risks that pharmaceuticals may pose to aquatic organisms under varying environmental conditions and thereby aid in better protecting aquatic ecosystems in the future