Estimation and Uncertainty analysis of Dose Response in an inter-laboratory experiment

Published

November 13, 2011

Author(s)

Blaza Toman, Elijah J. Petersen, John T. Elliott

Abstract

An inter-laboratory experiment for the evaluation of toxic effects of NH2-polystyrene nanoparticles on living cells was performed with five participating laboratories. Previously published results in the field of nano toxicology have been contradictory, mostly due to challenges related to producing a reliable cytotoxicity assay protocol for use with nanomaterials. Specific challenges include reproducibility preparing nanoparticle dispersions, biological variability from testing living cell lines, and the potential for nano-related interference effects. In this experiment, such challenges were met by following a detailed experimental protocol and using a specially designed 96-well plate layout which incorporated a range of control measurements to assess multiple factors such as nanomaterial interference, pipetting accuracy, cell seeding density, and instrument performance. Detailed data analysis of these control measurements showed that good control of the experiments was attained by all participants in most cases. The main measurement objective of the study was the estimation of a dose response relationship between concentration of the nanoparticles and metabolic activity of the living cells, under several experimental conditions. The dose curve estimation was achieved by imbedding a three parameter logistic curve in a three level Bayesian hierarchical model, accounting for uncertainty due to all known experimental conditions as well as between laboratory variability. Computation was performed using Markov Chain Monte Carlo methods. The fit of the model was evaluated using Bayesian posterior predictive probabilities and found to be satisfactory.

Citation

Metrologia

Pub Type

Journals

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Keywords

uncertainty analysis, dose response, logistic, nanoparticles, toxicity.

Citation

Toman, B. , Petersen, E. and Elliott, J. (2011), Estimation and Uncertainty analysis of Dose Response in an inter-laboratory experiment, Metrologia, [online], https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=919392 (Accessed April 27, 2024)