Harry W Broening1, Jane La Du2, Gregory J Carr1, J F Nash1, Lisa Truong2, Robert L Tanguay3. 1. The Procter & Gamble Company, Cincinnati, OH, USA. 2. Department of Environmental and Molecular Toxicology, The Sinnhuber Aquatic Research Laboratory, and the Environmental Health Sciences Center at Oregon State University, Corvallis, OR, USA. 3. Department of Environmental and Molecular Toxicology, The Sinnhuber Aquatic Research Laboratory, and the Environmental Health Sciences Center at Oregon State University, Corvallis, OR, USA. Electronic address: Robert.Tanguay@oregonstate.edu.
Abstract
BACKGROUND: Identifying chemicals with narcotic potency is an important aspect of assessing the safety of consumer products that may be accidentally ingested. A rapid and efficient assay of narcotic potency is desired for assessing chemicals with such suspected activity. OBJECTIVES: This purpose of this research was to develop a non-mammalian vertebrate, high throughput, neurobehavioral method to assess the narcotic potency of chemicals using larval zebrafish. METHODS: Larval zebrafish were acutely exposed to chemicals beginning at 5 days post fertilization (5 dpf). Locomotor activity, elicited by regular, periodic photostimulation, was quantified using a video tracking apparatus. Narcotic potency was determined as the molar concentration at which photostimulated locomotor activity was reduced by 50% (IC50). Toxicity was assessed based on observations of morbidity or mortality. Recovery was assessed following removal of test material by serial dilution and reassessment of photostimulated behavior 24 hr later (6 dpf). RESULTS: A total of 21 chemicals were assessed. Etomidate, a human narcotic analgesic agent, was used as a reference material. Investigating a series of eleven linear, primary alcohols (C6 to C16), a relationship between narcotic potency and carbon number was observed; narcotic potency increased with carbon number up to C12, consistent with historical studies. For a set of technical grade surfactants, nonionic surfactants (i.e., alcohol ethoxylates) were observed to be narcotic agents while anionic surfactants produced evidence of reduced locomotor activity only in combination with toxicity. Of the solvents evaluated, only ethanol exhibited narcotic activity with an IC50 of 261 mM and was the least potent of the chemicals investigated. Etomidate was the most potent material evaluated with an IC50 of 0.39 μM. CONCLUSIONS: The larval zebrafish neurobehavioral assay provides a method capable of estimating the narcotic potency of chemicals and can identify if toxicity contributes to observed neurobehavioral effects in the test organism.
BACKGROUND: Identifying chemicals with narcotic potency is an important aspect of assessing the safety of consumer products that may be accidentally ingested. A rapid and efficient assay of narcotic potency is desired for assessing chemicals with such suspected activity. OBJECTIVES: This purpose of this research was to develop a non-mammalian vertebrate, high throughput, neurobehavioral method to assess the narcotic potency of chemicals using larval zebrafish. METHODS: Larval zebrafish were acutely exposed to chemicals beginning at 5 days post fertilization (5 dpf). Locomotor activity, elicited by regular, periodic photostimulation, was quantified using a video tracking apparatus. Narcotic potency was determined as the molar concentration at which photostimulated locomotor activity was reduced by 50% (IC50). Toxicity was assessed based on observations of morbidity or mortality. Recovery was assessed following removal of test material by serial dilution and reassessment of photostimulated behavior 24 hr later (6 dpf). RESULTS: A total of 21 chemicals were assessed. Etomidate, a human narcotic analgesic agent, was used as a reference material. Investigating a series of eleven linear, primary alcohols (C6 to C16), a relationship between narcotic potency and carbon number was observed; narcotic potency increased with carbon number up to C12, consistent with historical studies. For a set of technical grade surfactants, nonionic surfactants (i.e., alcohol ethoxylates) were observed to be narcotic agents while anionic surfactants produced evidence of reduced locomotor activity only in combination with toxicity. Of the solvents evaluated, only ethanol exhibited narcotic activity with an IC50 of 261 mM and was the least potent of the chemicals investigated. Etomidate was the most potent material evaluated with an IC50 of 0.39 μM. CONCLUSIONS: The larval zebrafish neurobehavioral assay provides a method capable of estimating the narcotic potency of chemicals and can identify if toxicity contributes to observed neurobehavioral effects in the test organism.
Authors: Hugh C Hemmings; Myles H Akabas; Peter A Goldstein; James R Trudell; Beverley A Orser; Neil L Harrison Journal: Trends Pharmacol Sci Date: 2005-10 Impact factor: 14.819
Authors: Katerine S Saili; Margaret M Corvi; Daniel N Weber; Ami U Patel; Siba R Das; Jennifer Przybyla; Kim A Anderson; Robert L Tanguay Journal: Toxicology Date: 2011-11-15 Impact factor: 4.221
Authors: Michael Nguyen; Ester Yang; Nikhil Neelkantan; Alina Mikhaylova; Raymond Arnold; Manoj K Poudel; Adam Michael Stewart; Allan V Kalueff Journal: Behav Brain Res Date: 2013-08-12 Impact factor: 3.332