Derivation of an Effective Concentration for 50% of the Population (ECt50) for Whole Blood Acetylcholinesterase Inhibition by VX in the New Zealand White Rabbit
Abstract
This study established the effective concentration of O-ethyl-S-(2-diisopropylaminoethyl) methyl phosphonothiolate (VX) aerosol required to produce mild, moderate, and severe inhibition of whole blood acetylcholinesterase enzyme (WB-AChE) in the New Zealand white rabbit. A method was established by which an estimate for inhalation toxicity may be derived from known intravenous toxicity data for the rabbit. The calculated effective concentrations for 50 of the population for each severity level were as follows: mild (2150 inhibition), 6.6 mg min/m3 (95 confidence interval [CI], 4.310.1); moderate (5180 inhibition), 12.2 mg min/m3 (95 CI, 8.617.2); and severe (81100 inhibition), 23.2 mg min/m3 (95 CI, 12.742.3). We estimated that for the moderate severity level, the total VX dose administered was between 1.40 and 2.74 g/kg. For comparison, a previous study found an effective dose for 50 of the population that resulted in greater than 50 WB-AChE inhibition after intravenous delivery of VX in rabbits to be 1.37 g/kg. This represents a fairly accurate estimation of equipotent dosimetry between two differing routes of exposure.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2020
- Accession Number
- AD1092735
Entities
People
- Michael S. Horsmon
- Nicole M. Vincelli