Baseline Narcosis for the Glass-Vial 96-h Growth Inhibition of the Nematode C. elegans and Its Use for Identifying Electrophilic and Pro-Electrophilic Toxicity.

The nematode Caenorhabditis elegans has been widely used as a model organism for assessing chemical toxicity. So far, however, a respective baseline narcosis reference has been lacking to predict narcosis-level toxicity and to identify excess-toxic compounds and associated mechanisms of action. Employing 22 organic narcotics that cover 7.2 units of their log K ow (octanol/water partition coefficient) from -1.20 to 6.03, a baseline narcosis model has been derived for a glass-vial 96-h growth inhibition test with C. elegans , both without and with correction for compound loss through volatilization and sorption. The resultant effective concentrations yielding 50% growth inhibition, EC 50 , vary by 6.4 log units from 5.04 · 10 -1 to 1.90 · 10 -7 mol/L (exposure-corrected). Application of the new model is illustrated through sensing the toxicity enhancement ( T e ) of four Michael-acceptor carbonyls driven by their reactive mode of action. Moreover, narcosis-level predicted vs experimental EC 50 of two α,β -unsaturated alcohols demonstrate the biotransformation capability of C. elegans regarding ADH (alcohol dehydrogenase). The discussion includes narcosis-level and excess-toxicity doses (critical body burdens) as well as chemical activities A 50 (at the EC 50 ) as compared to fish, daphnids, ciliates, bacteria, zebrafish embryo, and cell lines. Overall, the presently introduced model for predicting C. elegans baseline narcosis enables generating respective pre-test expectations, enriches experimental results by mechanistic information, and may complement 3Rs (reduce, refine, replace) test batteries through its ADH metabolic capacity.