Assessing behavioral toxicity with Caenorhabditis elegans.

Behavior, even in simple metazoans, depends upon integrated processes at the subcellular, cellular, and organismal level, and thus is susceptible to disruption by a broad spectrum of chemicals. Locomotor behavior (movement) of the small free-living nematode Caenorhabditis elegans has proven to be useful in assessing toxicity. Recently reported observations suggest that behavioral change (reduced movement) occurs after 4 h of exposure to heavy metals, and that with abbreviated exposure, the concentration-response relationship for Pb (a known neurotoxic metal) differs from that for Cu. In this study, movement was evaluated after 4-h exposures for nine compounds from three chemical classes: organic pesticides, organic solvents, and heavy metals. Concentration-dependent reduction of movement was observed for all test compounds with the exception of mebendazole, for which test concentrations were limited by solubility. Within each chemical class, movement was more sensitive to the neurotoxic compounds than to substances not believed to be neurotoxic, as evidenced by behavioral effective concentration to reduce average worm movement to 50% of the control movement values (e.g., levamisole and chlorpyrifos < mebendazole, ethanol and acetone < dimethylsulfoxide, and Pb and Al < Cu). These observations are discussed as they relate to the use of acute behavioral tests in assessing general chemical toxicity, and the enhanced value of 4-h testing for the detection of neural toxicants.

The nematode Caenorhabditis elegans as a model of organophosphate-induced mammalian neurotoxicity.

Fifteen organic phosphate pesticides were tested by computer tracking for their acute behavioral toxicity with the nematode Caenorhabditis elegans. Thirteen of these 15 chemicals are used as insecticides and are anticholesterase agents. The other two chemicals are used as herbicides. EC50 values for each chemical were compared to the corresponding LD50 acute lethality value in rats and mice. Order of toxicity was found to be significantly correlated in comparisons of C. elegans to both rats and mice. Mechanistic investigations were conducted by assaying 8 of the 15 chemicals for anticholinesterase activity in C. elegans. Significant cholinesterase inhibition was confirmed for five chemicals that had displayed high behavioral toxicity, while three chemicals of low behavioral toxicity showed no significant decrease in cholinesterase activity. Toxicity for two chemicals that do not inhibit cholinesterase in mammals was linked to pH effects. Detailed comparison of individual chemicals and metabolic issues are discussed. These results have positive implications for the use of C. elegans as a mammalian neurological model and support the use of C. elegans in early rounds of chemical toxicity screening.

The effects of metals and food availability on the behavior of Caenorhabditis elegans.

Caenorhabditis elegans, a nonparasitic soil nematode, was used to assess the combined effects of metal exposures and food availability on behavior. Movement was monitored using a computer tracking system after exposures to Cu, Pb, or Cd while feeding was measured as a change in optical density (deltaOD) of bacteria suspensions over the exposure period. After 24-h exposures at high and low bacteria concentrations, movement was decreased in a concentration-dependent fashion by Pb and Cd but feeding reductions were not directly proportional to exposure concentrations. Copper exposure induced concentration-dependent declines in feeding and movement regardless of bacteria concentration. The impact of 24-h metal exposures was apparently reduced by increasing food availability. Therefore, exposures were shortened to 4 h in an attempt to minimize starvation effects on movement. Although nematodes were immobilized following 24 h of food depravation, worms deprived of food during the 4-h exposure continued to feed and move after exposure. A bead-ingestion assay after 4-h exposures was also used as an additional means of assessing the effects of metals on feeding behavior. Ingestion was significantly reduced by all concentrations of metals tested, indicating its sensitivity as a sublethal assay. Feeding (deltaOD) during exposures exhibited similar trends as ingestion but was slightly less sensitive, while movement was the least sensitive assay of 4-h metal exposures to C. elegans. Assessment of multiple sublethal endpoints allowed for the determination of the separate and interactive effects of metals and food availability on C. elegans behavior.