Repeatability analysis of the Tetrahymena pyriformis population growth impairment assay

Abstract

Assessments necessary to ensure the safety of both humans and the environment are challenged by the sheer number of chemicals in use today. Chemical legislation, such as REACH, aims to use alternative methods to reduce the reliance on in vivo animal testing. Consequently, databases such as the TETRATOX database, containing data from the Tetrahymena pyriformis population growth impairment assay, have been used extensively to develop computational models which aid in priority setting and initial hazard assessments. To use any toxicological data, an assessment of quality is required. One important aspect of quality is the repeatability of the assay. This study considered TETRATOX assay data for 85 structurally and mechanistically diverse compounds. The repeatability of replicate determinations was assessed and factors relating to repeatability are discussed. Despite the majority of compounds demonstrating excellent repeatability, it was found that the mechanism of action is likely to be a modulating factor, with compounds acting via electrophilic mechanisms being more likely to exhibit reduced repeatability than those acting via narcotic mechanisms. It is evident from this study that the TETRATOX assay is a robust and highly repeatable assay, suitable for use in toxicological modelling studies and priority setting.

Keywords:

• repeatability
• Tetrahymena pyriformis
• mechanism of action
• toxicity
• quantitative structure–activity relationship (QSAR)

Acknowledgements

The funding of the European Union 6th Framework OSIRIS Integrated Project (GOCE-037017-OSIRIS) is gratefully acknowledged. The Office of Research and Graduate Studies of The University of Tennessee, College of Veterinary Medicine is gratefully acknowledged. Gratitude is expressed to all who have toiled to generate the data.