title: Comparative toxicity of fumigants and a phosphine synergist using a novel containment chamber for the safe generation of concentrated phosphine gas.
abstract: BACKGROUND
  With the phasing out of ozone-depleting substances in accordance with the United Nations Montreal Protocol, phosphine remains as the only economically viable fumigant for widespread use. However the development of high-level resistance in several pest insects threatens the future usage of phosphine; yet research into phosphine resistance mechanisms has been limited due to the potential for human poisoning in enclosed laboratory environments.
  
  
  RESULTS
  Here we describe a custom-designed chamber for safely containing phosphine gas generated from aluminium phosphide tablets. In an improvement on previous generation systems, this chamber can be completely sealed to control the escape of phosphine. The device has been utilised in a screening program with C. elegans that has identified a phosphine synergist, and quantified the efficacy of a new fumigant against that of phosphine. The phosphine-induced mortality at 20 degrees C has been determined with an LC(50) of 732 ppm. This result was contrasted with the efficacy of a potential new botanical pesticide dimethyl disulphide, which for a 24 hour exposure at 20 degrees C is 600 times more potent than phosphine (LC(50) 1.24 ppm). We also found that co-administration of the glutathione depletor diethyl maleate (DEM) with a sublethal dose of phosphine (70 ppm, <LC(5)), results in a doubling of mortality in C. elegans relative to DEM alone.
  
  
  CONCLUSIONS
  The prohibitive danger associated with the generation, containment, and use of phosphine in a laboratory environment has now been substantially reduced by the implementation of our novel gas generation chamber. We have also identified a novel phosphine synergist, the glutathione depletor DEM, suggesting an effective pathway to be targeted in future synergist research; as well as quantifying the efficacy of a potential alternative to phosphine, dimethyl disulphide.
authors.affiliation: School of Molecular and Microbial Sciences, University of Queensland, St. Lucia, Queensland, Australia.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Valmas
authors.forename: Paul R
authors.initials: PR
authors.lastname: Ebert
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects; D004220:Disulfides / Q000008:administration & dosage / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation / Q000379:methods; D004351:Drug Resistance; D004357:Drug Synergism; D005651:Fumigation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D008298:Maleates / Q000008:administration & dosage / Q000494:pharmacology; D010720:Phosphines / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D004220:Disulfides; D008298:Maleates; D010720:Phosphines; C021181:dimethyl disulfide; C044646:phosphine; C014476:diethyl maleate