Comparing the Potency of Chemicals with Multiple Modes of Action in Aquatic Toxicology:  Acute Toxicity Due to Narcosis versus Reactive Toxicity of Acrylic Compounds

• Published in: Environmental science & technology Vol. 33; no. 17; pp. 3038 - 3043
• Main Authors: Freidig, Andreas P, Verhaar, Henk J. M, Hermens, Joop L. M
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 01.09.1999
• Subjects: acrylates; acrylic acid; Acrylics; Agnatha. Pisces; Animal, plant and microbial ecology; Applied ecology; Biological and medical sciences; Ecotoxicology, biological effects of pollution; Effects of pollution and side effects of pesticides on vertebrates; Fish; Fisheries; Fundamental and applied biological sciences. Psychology; glutathione; Mathematical models; methacrylates; methacrylic acid; Modal analysis; Pisces; Toxicity; Water pollution; Netherlands; Salmonidae; Aquatic environment; Vertebrata; Narcosis; Toxicity; Pisces; Acrylic acid; Acute; Mechanism of action; Oncorhynchus mykiss; Comparative study; Glutathione
• DOI: 10.1021/es990251b
• ISSN: 0013-936X

A series of acrylates and methacrylates was used to illustrate a strategy to compare the importance of two modes of action (MOA) and thereby identify the predominant cause of acute fish toxicity. Acrylic compounds are known to be Michael acceptors and may therefore react with glutathione (GSH), causing GSH-depletion in vivo (reactive mechanism). On the other hand, acrylates may also act by a nonspecific mechanism (narcosis). The following two, physiologically meaningful parameters were calculated in order to estimate the contribution of these two mechanisms to the overall acute toxicity:  (i) a lipid normalized body burden for narcosis and (ii) the potential degree of GSH depletion by chemical reactivity. The degree of GSH depletion was found to be related to the product of the reactivity toward GSH and the exposure concentration. This model was validated with four model compounds and an in vivo study. For both MOA, toxic ratios were calculated and compared for all chemicals in the series. The approach enables the comparison of the contribution to toxicity of chemicals with more than one MOA.