Comparative assessment of the sensitivity of fish early-life stage, daphnia and algae to the chronic ecotoxicity of xenobiotics - perspectives for alternatives to animal testing

No-observed-effect concentrations (NOECs) are used in environmental hazard classification and labeling of chemicals and their environmental risk assessment. They are typically obtained using standard tests such as the fish early-life stage (FELS) toxicity test, the chronic Daphnia reproduction test, and the algae growth inhibition test. Given the demand to replace and reduce animal tests, we explored the impact of the FELS toxicity test on the determination of effect concentrations by comparing the FELS toxicity test and the Daphnia and algae acute or chronic toxicity tests. Lowest-observed-effect concentrations (LOECs) were used instead of NOECs for better comparison with median lethal or effect concentration data. A database of FELS toxicity data for 223 compounds was established. Corresponding Daphnia and algae toxicity tests were identified using established databases (US Environmental Protection Agency ECOTOX, Organisation for Economic Co-operation and Development QSAR Toolbox, eChemPortal, EnviroTox, and OpenFoodTox). Approximately 9.5% of the investigated compounds showed a 10-fold higher sensitivity with the FELS toxicity test in comparison with the lowest effect concentrations obtained with any of the other tests. Some of these compounds have been known or considered as endocrine disrupting, or are other non-narcotic chemicals, indicating that the higher sensitivity in the FELS toxicity test is related to a specific mechanism of action. Targeting these mechanisms by alternative test systems or endpoints, using fish embryos for instance, may allow reduction or replacement of the FELS toxicity test or may allow us to prioritize compounds for conduction of the FELS toxicity test

Characterisation of data resources for in silico modelling: benchmark datasets for ADME properties.

Introduction: The cost of in vivo and in vitro screening of ADME properties of compounds has motivated efforts to develop a range of in silico models. At the heart of the development of any computational model are the data; high quality data are essential for developing robust and accurate models. The characteristics of a dataset, such as its availability, size, format and type of chemical identifiers used, influence the modelability of the data. Areas covered: This review explores the usefulness of publicly available ADME datasets for researchers to use in the development of predictive models. More than 140 ADME datasets were collated from publicly available resources and the modelability of 31selected datasets were assessed using specific criteria derived in this study. Expert opinion: Publicly available datasets differ significantly in information content and presentation. From a modelling perspective, datasets should be of adequate size, available in a user-friendly format with all chemical structures associated with one or more chemical identifiers suitable for automated processing (e.g. CAS number, SMILES string or InChIKey). Recommendations for assessing dataset suitability for modelling and publishing data in an appropriate format are discussed

Scanning electron microscopy image representativeness: morphological data on nanoparticles.

A sample of a nanomaterial contains a distribution of nanoparticles of various shapes and/or sizes. A scanning electron microscopy image of such a sample often captures only a fragment of the morphological variety present in the sample. In order to quantitatively analyse the sample using scanning electron microscope digital images, and, in particular, to derive numerical representations of the sample morphology, image content has to be assessed. In this work, we present a framework for extracting morphological information contained in scanning electron microscopy images using computer vision algorithms, and for converting them into numerical particle descriptors. We explore the concept of image representativeness and provide a set of protocols for selecting optimal scanning electron microscopy images as well as determining the smallest representative image set for each of the morphological features. We demonstrate the practical aspects of our methodology by investigating tricalcium phosphate, Ca3 (PO4 )2 , and calcium hydroxyphosphate, Ca5 (PO4 )3 (OH), both naturally occurring minerals with a wide range of biomedical applications

Cadmium pigments in consumer products and their health risks

© 2018 Elsevier B.V. Cadmium is a toxic heavy metal that has been increasingly regulated over the past few decades. The main exposure routes for the general public are the consumption of certain foods and the inhalation of cigarette smoke. However, additional exposure may occur through the current and historical use of the metal in consumer products. In this paper, the uses of Cd in consumer goods are reviewed, with the focus on brightly-coloured Cd sulphide and sulphoselenide pigments, and measurements of Cd in historical and contemporary products ascertained by XRF are reported. Cadmium is encountered across a wide range of contemporary plastic products, mainly because of the unregulated recycling of electronic waste and polyvinyl chloride. However, concentrations are generally low (<100 μg g−1), conforming with current limits and posing minimal risk to consumers. Of greater concern is high concentrations of pigmented Cd (up to 2% by weight) in old products, and in particular children's toys that remain in circulation. Here, tests conducted suggest that Cd migration in some products exceeds the Toy Safety Directive limit of 17 μg g−1 by an order of magnitude. The principal current use of Cd pigments is in ceramic products where the metal is encapsulated and overglazed. Leaching tests on new and secondhand items of hollowware indicate compliance with respect to the current Cd limit of 300 μg L−1, but that non-compliance could occur for items of earthenware or damaged articles should a proposed limit of 5 μg L−1 be introduced. The greatest consumer risk identified is the use of Cd pigments in the enamels of decorated drinking glasses. Thus, while décor is restricted to the exterior, any enamel within the lip area is subject to ready attack from acidic beverages because the pigments are neither encapsulated nor overglazed. Glass bottles decorated with Cd-based enamel do not appear to represent a direct health hazard but have the propensity to contaminate recycled glass products. It is recommended that decorated glassware is better regulated and that old, brightly-coloured toys are treated cautiously

Thresholds of Toxicological Concern for Cosmetics-Related Substances: New Database, Thresholds, and Enrichment of Chemical Space

A new dataset of cosmetics-related chemicals for the Threshold of Toxicological Concern (TTC) approach has been compiled, comprising 552 chemicals with 219, 40, and 293 chemicals in Cramer Classes I, II, and III, respectively. Data were integrated and curated to create a database of No-/Lowest-Observed-Adverse-Effect Level (NOAEL/LOAEL) values, from which the final COSMOS TTC dataset was developed. Criteria for study inclusion and NOAEL decisions were defined, and rigorous quality control was performed for study details and assignment of Cramer classes. From the final COSMOS TTC dataset, human exposure thresholds of 42 and 7.9 μg/kg-bw/day were derived for Cramer Classes I and III, respectively. The size of Cramer Class II was insufficient for derivation of a TTC value. The COSMOS TTC dataset was then federated with the dataset of Munro and colleagues, previously published in 1996, after updating the latter using the quality control processes for this project. This federated dataset expands the chemical space and provides more robust thresholds. The 966 substances in the federated database comprise 245, 49 and 672 chemicals in Cramer Classes I, II and III, respectively. The corresponding TTC values of 46, 6.2 and 2.3 μg/kg-bw/day are broadly similar to those of the original Munro dataset

Characterization of Emissions from a Desktop 3D Printer

3D printers are currently widely available and very popular among the general public. However, the use of these devices may pose health risks to users, attributable to air-quality issues arising from gaseous and particulate emissions in particular. We characterized emissions from a low-end 3D printer based on material extrusion, using the most common polymers: acrylonitrile-butadiene-styrene (ABS) and polylactic acid (PLA). Measurements were carried out in an emission chamber and a conventional room. Particle emission rates were obtained by direct measurement and modeling, whereas the influence of extrusion temperature was also evaluated. ABS was the material with the highest aerosol emission rate. The nanoparticle emission ranged from 3.7.10(8) to 1.4.10(9) particles per second (# s(-1)) in chamber measurements and from 2.0.10(9) to 4.0.10(9) # s(-1)in room measurements, when the recommended extruder temperature was used. Printing with PLA emitted nanoparticles at the rate of 1.0.10(7) # s(-1) inside the chamber and negligible emissions in room experiments. Emission rates were observed to depend strongly on extruder temperature. The particles' mean size ranged from 7.8 to 10.5 nanometers (nm). We also detected a significant emission rate of particles of 1 to 3nm in size during all printing events. The amounts of volatile organic and other gaseous compounds were only traceable and are not expected to pose health risks. Our study suggests that measures preventing human exposure to high nanoparticle concentrations should be adopted when using low-end 3D printers.Peer reviewe

Identification and Description of the Uncertainty, Variability, Bias and Influence in Quantitative Structure-Activity Relationships (QSARs) for Toxicity Prediction

Improving regulatory confidence in, and acceptance of, a prediction of toxicity from a quantitative structure-activity relationship (QSAR) requires assessment of its uncertainty and determination of whether the uncertainty is acceptable. Thus, it is crucial to identify potential uncertainties fundamental to QSAR predictions. Based on expert review, sources of uncertainties, variabilities and biases, as well as areas of influence in QSARs for toxicity prediction were established. These were grouped into three thematic areas: uncertainties, variabilities, potential biases and influences associated with 1) the creation of the QSAR, 2) the description of the QSAR, and 3) the application of the QSAR, also showing barriers for their use. Each thematic area was divided into a total of 13 main areas of concern with 49 assessment criteria covering all aspects of QSAR development, documentation and use. Two case studies were undertaken on different types of QSARs that demonstrated the applicability of the assessment criteria to identify potential weaknesses in the use of a QSAR for a specific purpose such that they may be addressed and mitigation strategies can be proposed, as well as enabling an informed decision on the adequacy of the model in the considered context

Are We Speaking the Same Language? Recommendations for a Definition and Categorization Framework for Plastic Debris

Embargo until 04 Jan 2020The accumulation of plastic litter in natural environments is a global issue. Concerns over potential negative impacts on the economy, wildlife, and human health provide strong incentives for improving the sustainable use of plastics. Despite the many voices raised on the issue, we lack a consensus on how to define and categorize plastic debris. This is evident for microplastics, where inconsistent size classes are used and where the materials to be included are under debate. While this is inherent in an emerging research field, an ambiguous terminology results in confusion and miscommunication that may compromise progress in research and mitigation measures. Therefore, we need to be explicit on what exactly we consider plastic debris. Thus, we critically discuss the advantages and disadvantages of a unified terminology, propose a definition and categorization framework, and highlight areas of uncertainty. Going beyond size classes, our framework includes physicochemical properties (polymer composition, solid state, solubility) as defining criteria and size, shape, color, and origin as classifiers for categorization. Acknowledging the rapid evolution of our knowledge on plastic pollution, our framework will promote consensus building within the scientific and regulatory community based on a solid scientific foundation.acceptedVersio

Cross-Sector Review of Drivers and Available 3Rs Approaches for Acute Systemic Toxicity Testing

Acute systemic toxicity studies are carried out in many sectors in which synthetic chemicals are manufactured or used and are among the most criticized of all toxicology tests on both scientific and ethical grounds. A review of the drivers for acute toxicity testing within the pharmaceutical industry led to a paradigm shift whereby in vivo acute toxicity data are no longer routinely required in advance of human clinical trials. Based on this experience, the following review was undertaken to identify (1) regulatory and scientific drivers for acute toxicity testing in other industrial sectors, (2) activities aimed at replacing, reducing, or refining the use of animals, and (3) recommendations for future work in this area

A ‘green’ approach to fixing polyacrylamide gels

Handling chemicals that require specific safety precautions and protections generates the need for hazardous waste removal and transportation costs. With the growing effort to reduce both cost per analysis and the environmental footprint of research, we report an effective alternative to the widely used methanol/acetic acid gel fixation solution. 1.0 M citric acid dissolved in 5% acetic acid (C3A) provides comparable results following both SDS-PAGE and two-dimensional gel electrophoresis, while also eliminating waste removal costs. •Citric acid dissolved in acetic acid replaces current gel fixative solution.•Cost per analysis is reduced and hazardous waste removal costs eliminated.•Environmental footprint of research is reduced