Development of surface plasmon resonance-based sensor for detection of silver nanoparticles in food and the environment

Silver nanoparticles are recognized as effective antimicrobial agents and have been implemented in various consumer products including washing machines, refrigerators, clothing, medical devices, and food packaging. Alongside the silver nanoparticles benefits, their novel properties have raised concerns about possible adverse effects on biological systems. To protect consumer’s health and the environment, efficient monitoring of silver nanoparticles needs to be established. Here, we present the development of human metallothionein (MT) based surface plasmon resonance (SPR) sensor for rapid detection of nanosilver. Incorporation of human metallothionein 1A to the sensor surface enables screening for potentially biologically active silver nanoparticles at parts per billion sensitivity. Other protein ligands were also tested for binding capacity of the nanosilver and were found to be inferior to the metallothionein. The biosensor has been characterized in terms of selectivity and sensitivity towards different types of silver nanoparticles and applied in measurements of real-life samples—such as fresh vegetables and river water. Our findings suggest that human MT1-based SPR sensor has the potential to be utilized as a routine screening method for silver nanoparticles, that can provide rapid and automated analysis dedicated to environmental and food safety monitoring

The impact of precision uncertainty on predictive accuracy metrics of non-animal testing methods

The ability of non-animal methods to correctly predict the outcome of in vivo testing in repeated applications is referred to as precision. Due to dichotomizing continuous read-outs into discrete “positive/negative” hazard data, non-animal methods can reveal discordant classifications if results are sufficiently close to a defined classification threshold. This paper explores the impact of precision uncertainty on the predictive accuracy of non-animal methods. Using selected non-animal methods for assessing skin sensitization hazard as case study examples, we explore the impact of precision uncertainty separately and in combination with uncertainty due to varying composition and size of experimental samples. Our results underline that discrete numbers on a non-animal method’s sensitivity, specificity, and concordance are of limited value for evaluation of its predictivity. Instead, information on the variability and the upper and lower limits of accuracy metrics should be provided to ensure a transparent assessment of a testing method’s predictivity, and to allow for a meaningful comparison of the predictivity of a non-animal method with that of an animal test.</p

A Critical Review of Adverse Outcome Pathway-Based Concepts and Tools for Integrating Information from Nonanimal Testing Methods: The Case of Skin Sensitization

Integrating information from in vitro, in silico, and in chemico methods into toxicity testing strategies has been widely considered the way of phasing out animal testing. At the same time, testing strategies using new approaches and methods shall provide adequate and relevant information about chemicals' hazardous properties. We reviewed objectives and requirements for guiding the process of data integration that are suggested in the scientific literature. Based on the existing approaches, we develop criteria for resource-efficient testing strategies, and we evaluate existing testing strategies for skin sensitization hazard and risk assessment under these criteria. We conclude that existing testing strategies—except two cases—still focus predominantly on maximizing toxicity information, but largely ignore resource efficiency criteria. Balancing information gained from testing strategies with its respective direct and indirect costs (including also welfare losses for society in case of unintended health or environmental damages) is a necessary condition to allow for transparent comparisons of their resource efficiency. Therefore, developing approaches for balancing information gains and costs should become an explicit part of the developmental process of nonanimal testing strategies to ensure that phasing out animal testing complies not only with regulatory information requirements but also with available resources

Evaluation of Polyurea-Crosslinked Alginate Aerogels for Seawater Decontamination

Polyurea-crosslinked Ca-alginate (X-Ca-alginate) aerogel beads (diameter: 3.3 mm) were evaluated as adsorbents of metal ions, organic solvents, and oils. They were prepared via reaction of an aromatic triisocyanate (Desmodur RE) with pre-formed Ca-alginate wet gels and consisted of 54% polyurea and 2% calcium. X-Ca-alginate aerogels are hydrophobic nanoporous materials (90% v/v porosity), with a high BET surface area (459 m2/g−1), and adsorb PbII not only from ultrapure water (29 mg/g−1) but also from seawater (13 mg/g−1) with high selectivity. The adsorption mechanism involves replacement of CaII by PbII ions coordinated to the carboxylate groups of the alginate backbone. After treatment with a Na2EDTA solution, the beads can be reused, without significant loss of activity for at least two times. X-Ca-alginate aerogels can also uptake organic solvents and oil from seawater; the volume of the adsorbate can be as high as the total pore volume of the aerogel (6.0 mL/g−1), and the absorption is complete within seconds. X-Ca alginate aerogels are suitable for the decontamination of aquatic environments from a broader range of inorganic and organic pollutants

Evaluation of non-Animal methods for assessing skin Sensitisation hazard : A Bayesian value-of-information analysis

This paper offers a Bayesian Value-of-Information (VOI) analysis for guiding the development of non-Animal testing strategies, balancing information gains from testing with the expected social gains and costs from the adoption of regulatory decisions. Testing is assumed to have value, if, and only if, the information revealed from testing triggers a welfare-improving decision on the use (or non-use) of a substance. As an illustration, our VOI model is applied to a set of five individual non-Animal prediction methods used for skin sensitisation hazard assessment, seven battery combinations of these methods, and 236 sequential 2-Test and 3-Test strategies. Their expected values are quantified and compared to the expected value of the local lymph node assay (LLNA) as the animal method. We find that battery and sequential combinations of non-Animal prediction methods reveal a significantly higher expected value than the LLNA. This holds for the entire range of prior beliefs. Furthermore, our results illustrate that the testing strategy with the highest expected value does not necessarily have to follow the order of key events in the sensitisation adverse outcome pathway (AOP)

Evaluation of Polyurea-Crosslinked Alginate Aerogels for Seawater Decontamination

Polyurea-crosslinked Ca-alginate (X-Ca-alginate) aerogel beads (diameter: 3.3 mm) were evaluated as adsorbents of metal ions, organic solvents, and oils. They were prepared via reaction of an aromatic triisocyanate (Desmodur RE) with pre-formed Ca-alginate wet gels and consisted of 54% polyurea and 2% calcium. X-Ca-alginate aerogels are hydrophobic nanoporous materials (90% v/v porosity), with a high BET surface area (459 m2/g−1), and adsorb PbII not only from ultrapure water (29 mg/g−1) but also from seawater (13 mg/g−1) with high selectivity. The adsorption mechanism involves replacement of CaII by PbII ions coordinated to the carboxylate groups of the alginate backbone. After treatment with a Na2EDTA solution, the beads can be reused, without significant loss of activity for at least two times. X-Ca-alginate aerogels can also uptake organic solvents and oil from seawater; the volume of the adsorbate can be as high as the total pore volume of the aerogel (6.0 mL/g−1), and the absorption is complete within seconds. X-Ca alginate aerogels are suitable for the decontamination of aquatic environments from a broader range of inorganic and organic pollutants

The borderline range of toxicological methods : Quantification and implications for evaluating precision

Test methods to assess the skin sensitization potential of a substance usually use threshold criteria to dichotomize continuous experimental read-outs into yes/no conclusions. The threshold criteria are prescribed in the respective OECD test guidelines and the conclusion is used for regulatory hazard assessment, i.e., classification and labelling of the substance. We can identify a borderline range (BR) around the classification threshold within which test results are inconclusive due to a test method's biological and technical variability. We quantified BRs in the prediction models of the non-animal test methods DPRA, LuSens and h-CLAT, and of the animal test LLNA, respectively. Depending on the size of the BR, we found that between 6% and 28% of the substances in the sets tested with these methods were considered borderline. When the results of individual non-animal test methods were combined into integrated testing strategies (ITS), borderline test results of individual tests also affected the overall assessment of the skin sensitization potential of the testing strategy. This was analyzed for the 2-out-of-3 ITS: Four out of 40 substances (10%) were considered borderline. Based on our findings we propose expanding the standard binary classification of substances into "positive"/"negative" or "hazardous"/"non-hazardous" by adding a "borderline" or "inconclusive" alert for cases where test results fall within the borderline range

Evaluation of non-Animal methods for assessing skin Sensitisation hazard : A Bayesian value-of-information analysis

This paper offers a Bayesian Value-of-Information (VOI) analysis for guiding the development of non-Animal testing strategies, balancing information gains from testing with the expected social gains and costs from the adoption of regulatory decisions. Testing is assumed to have value, if, and only if, the information revealed from testing triggers a welfare-improving decision on the use (or non-use) of a substance. As an illustration, our VOI model is applied to a set of five individual non-Animal prediction methods used for skin sensitisation hazard assessment, seven battery combinations of these methods, and 236 sequential 2-Test and 3-Test strategies. Their expected values are quantified and compared to the expected value of the local lymph node assay (LLNA) as the animal method. We find that battery and sequential combinations of non-Animal prediction methods reveal a significantly higher expected value than the LLNA. This holds for the entire range of prior beliefs. Furthermore, our results illustrate that the testing strategy with the highest expected value does not necessarily have to follow the order of key events in the sensitisation adverse outcome pathway (AOP).</p