Toxicity ranking of heavy metals with screening method using adult Caenorhabditis elegans and propidium iodide replicates toxicity ranking in rat

The utility of any model system for toxicity screening depends on the level of correlation between test responses and toxic reactions in humans. Assays in Caenorhabditis elegans can be fast and inexpensive, however few studies have been done comparing toxic responses in this easily cultured nematode with data on mammalian toxicity. Here we report that a screening assay for acute toxicity, using adult C. elegans grown in axenic liquid culture, replicated LD50 toxicity ranking in rat for five metals. This assay utilized the COPAS Biosort and propidium iodide (PI) as a fluorescent indicator of morbidity and mortality after 30-h exposures. We found that chronic toxicity assays of 2-week treatment duration, followed by analysis of PI induced red fluorescence levels, produced less consistent results than the acute assays. However, other chronic toxicity endpoints were compound and concentration specific, including changes in vulval and gonadal morphology, intestinal thickness and integrity, and the presence of retained internal eggs in post-reproductive animals. Some of these endpoints reflect similar findings in mammals, indicating that measurements of morbidity and mortality in conjunction with morphology analyses in C. elegans may have the potential to predict mammalian toxic responses.

► Propidium iodide can be used as a fluorescent marker of morbidity and mortality in toxicity assays using Caenorhabditis elegans. ► Toxicity screen with C. elegans, propidium iodide (PI) and COPAS demonstrates the potential of this model to predict mammalian outcomes. ► C. elegans morphology analyses in conjunction with other types of testing can increase the sensitivity of toxicity screens.