| Title: | 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 |
| Author(s): | Saleem S; Bohme A; Schuurmann G; |
| Address: | "UFZ Department of Ecological Chemistry, Helmholtz Centre for Environmental Research, Permoserstrasse 15, 04318 Leipzig, Germany. Institute of Organic Chemistry, Technical University Bergakademie Freiberg, Leipziger Strasse 29, 09596 Freiberg, Germany" |
| ISSN/ISBN: | 1520-5851 (Electronic) 0013-936X (Linking) |
| Abstract: | "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 alpha,beta-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" |
| Keywords: | Animals *Zebrafish Caenorhabditis elegans *Stupor Biotransformation Aquatic Toxicity Dose In vitro Narcosis Nematodes; |
| Notes: | "MedlineSaleem, Sumaira Bohme, Alexander Schuurmann, Gerrit eng Research Support, Non-U.S. Gov't 2023/01/20 Environ Sci Technol. 2023 Jan 31; 57(4):1692-1700. doi: 10.1021/acs.est.2c05217. Epub 2023 Jan 19" |
