title: A method to rank order water soluble compounds according to their toxicity using Caenorhabditis elegans, a Complex Object Parametric Analyzer and Sorter, and axenic liquid media.
abstract: Complex Object Parametric Analyzer and Sorter (COPAS) parameters Time of Flight (TOF) and Extinction (EXT) were utilized to assess growth and development in Caenorhabditis elegans exposed to (in order of decreasing toxicity) sodium arsenite, sodium fluoride, caffeine, valproic acid, sodium borate or DMSO in C. elegans Habitation Medium (CeHM) for 72h. Using multivariate statistical modeling and unique sub sampling procedures mean p-value ratios were calculated for each compound. Comparison of mean p-value ratios and/or the percent change in mean-p value ratios to controls were utilized to assess test compound toxicity. Using this assay 5 of the 6 compounds tested (83.3%) were correctly ranked according to their toxicity based on oral rat LD50 data. Test compounds were ranked from most toxic to least toxic as follows: sodium arsenite, sodium fluoride, sodium borate, valproic acid, caffeine and DMSO. Sodium borate was found to be more toxic than caffeine and valproic acid in this bioassay. This study suggests that axenic liquid culture may be used to expose large numbers of nematodes to water soluble toxicants and the COPAS parameters TOF and EXT may be used as functional biomarkers to assess a toxin's effect on growth and development in C. elegans.
authors.affiliation: Division of Toxicology, United States Food and Drug Administration, Center for Food Safety and Applied Nutrition, Office of Applied Research and Safety Assessment, Laural, MD 20708, United States. Robert.sprando@fda.hhs.gov
authors.forename: Robert L
authors.initials: RL
authors.lastname: Sprando
authors.forename: Nicholas
authors.initials: N
authors.lastname: Olejnik
authors.forename: Hediye Nese
authors.initials: HN
authors.lastname: Cinar
authors.forename: Martine
authors.initials: M
authors.lastname: Ferguson
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000254:growth & development; D006863:Hydrogen-Ion Concentration; D007928:Lethal Dose 50; D015233:Models, Statistical; D012995:Solubility; D018675:Toxicity Tests / Q000379:methods*