The Assessment of a Six Day Larval Zebrafish Model for Determining Acute Toxicity to Organophosphorus Compounds
Abstract
We developed a larval zebrafish acute toxicity screening tool for acetylcholinesterase (AChE)-inhibiting compounds. Our model uses the ability of the six day post-fertilization (DPF) larval zebrafish to produce AChE and various cytochrome P450 (CYP) metabolizing enzymes that activate or detoxify organophosphorus (OP) chemical species to modulate toxicity. We utilized 6 DPF Danio rerio embryos to examine nerve agent lethality and AChE inhibition relative to the OP pesticide parathion (PT). We also assessed the more active form of the CYP desulfonated OP, paraoxon (PT-O). We first compared the 24 h lethality response of D. rerio embryos to VX with their response to PT and PT-O. VX was observed to be 1000x more potent than PT. We then compared the AChE-inhibiting potential of VX relative to OPs when normalized to the lethal dose. VX induced a 100% inhibition of AChE. The -oxon derivative, PT-O, was notably more toxic than its parent compound. VX demonstrated lethality and AChE inhibition similar to that of active oxon rather than the parent pro-compound. This work demonstrates the ability of the 6 DPF zebrafish to be a competent model for nerve agent potency and measurement of AChE inhibition. These characteristics factor into operational risk assessments for traditional and emerging threat compounds.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2022
- Accession Number
- AD1172251
Entities
People
- Christopher S. Phillips
- Jennifer R. Horsmon
- Kyle P. Glover
- Michael G Feasel
- Sarah N. Davis
Organizations
- United States Army Soldier Systems Center