Title: Cause-and-Effect Analysis as a Tool To Improve the Reproducibility of Nanobioassays: Four Case Studies
Authors: PETERSEN ELIJAH JHIRSCH CORDULAELLIOT JOHNATHANKRUG HARALD F.AENGENHEISTER LEONIEARIF ALI TALIBBOGNI ALESSIAKINSNER-OVASKAINEN AGNIESZKASARAH MAYWALSER TOBIASWICK PETERROESSLEIN MATTHIAS
Citation: CHEMICAL RESEARCH IN TOXICOLOGY vol. 33 no. 5 p. 1039-1054
Publisher: AMER CHEMICAL SOC
Publication Year: 2020
JRC N°: JRC111717
ISSN: 0893-228X (online)
URI: https://pubs.acs.org/doi/10.1021/acs.chemrestox.9b00165
https://publications.jrc.ec.europa.eu/repository/handle/JRC111717
DOI: 10.1021/acs.chemrestox.9b00165
Type: Articles in periodicals and books
Abstract: One of the challenges in using in vitro data to understand the potential risks of engineered nanomaterials (ENMs) is that results often differ or are even contradictory among studies. While it is recognized that numerous factors can influence results produced by nanobioassays, there has not yet been a consistently used conceptual framework to identify key sources of variability in these assays. In this paper, we use cause-and-effect analysis to systematically describe sources of variability in four key in vitro nanobioassays: the 2′,7′-dichlorofluorescein assay, an enzyme-linked immunosorbent assay for measuring interleukin-8, a flow cytometry assay (Annexin V/propidium iodide), and the Comet assay. These assays measure end points that can occur in cells impacted by ENMs through oxidative stress, a principle mechanism for ENM toxicity. The results from this analysis identify control measurements to test for potential artifacts or biases that could occur during conduct of these assays with ENMs. Cause-and-effect analysis also reveals additional measurements that could be performed either in preliminary experiments or each time the assay is run to increase confidence in the assay results and their reproducibility within and among laboratories. The approach applied here with these four assays can be used to support the development of a broad range of nanobioassays.
JRC Directorate:Health, Consumers and Reference Materials

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