title: Organophosphate nerve agent toxicity in Hydra attenuata.
abstract: The toxicity for analogues of sarin (GB), soman (GD), and VX was evaluated using Hydra attenuata as a model organism. The organophosphate nerve agent analogue simulants used in this investigation included the following: isopropyl p-nitrophenyl methylphosphonate (for GB); pinacolyl p-nitrophenyl methylphosphonate (for GD); and diisopropyl S-(2-diisopropylaminoethyl)phosphorothioate, diethyl S-(2-diisopropylaminoethyl)phosphorothioate, and diethyl S-(2-trimethylaminoethyl)phosphorothioate (for VX). The toxicity of each organophosphate nerve agent was assessed quantitatively by measuring the minimal effective concentration within 92 h in H. attenuata. There is a positive correlation between the molecular hydrophobicity of the compound and its ability to cause toxicity. Results from this study indicate the potential for application of this assay in the field of organophosphate chemical warfare agent detection, as well as for the prediction of toxicity of structurally similar organophosphate compounds. The minimal effective concentration for two of the VX analogues was 2 orders of magnitude more toxic than the analogue for GD and 4 orders of magnitude more toxic than the analogue for GB.
authors.affiliation: Department of Chemistry, P.O. Box 30012, Texas A&M University, College Station, Texas 77842-3012, USA.
authors.forename: Karin T
authors.initials: KT
authors.lastname: Lum
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Huebner
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Li
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Phillips
authors.forename: Frank M
authors.initials: FM
authors.lastname: Raushel
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001156:Artemia; D001681:Biological Assay; D002619:Chemical Warfare Agents / Q000633:toxicity*; D006829:Hydra / Q000187:drug effects*; D008958:Models, Molecular; D009946:Organothiophosphorus Compounds / Q000633:toxicity*; D012524:Sarin / Q000031:analogs & derivatives* / Q000633:toxicity*; D012999:Soman / Q000031:analogs & derivatives* / Q000633:toxicity*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013997:Time Factors; D018675:Toxicity Tests
chemical_list: D002619:Chemical Warfare Agents; D009946:Organothiophosphorus Compounds; D012524:Sarin; D012999:Soman; C009680:VX-agent