Acute toxic effects of inhaled dichlorvos vapor on respiratory mechanics and blood cholinesterase activity in guinea pigs.

Using a modified noninvasive volume-displacement plethysmography system, we investigated the effects of inhaled dichlorvos (2,2-dimethyl-dichlorovinyl phosphate, or DDVP) vapor on the respiratory mechanics and blood cholinesterase activity of guinea pigs. Data revealed significant dose-dependent changes in several pulmonary parameters. Animals exposed to a DDVP concentration of 35 mg/m(3) did not show any significant changes in frequency, tidal volume, or minute ventilation. However, animals exposed to 55 mg/m(3) DDVP showed significantly decreased respiratory frequency and significantly increased tidal volume with no significant changes in minute ventilation. Similarly, animals exposed to 75 mg/m(3) DDVP showed significantly decreased respiratory frequency along with significantly increased tidal volume. The decreased respiratory frequency was large enough in the high exposure group to offset the increased tidal volume. This effect resulted in significantly decreased minute ventilation by the end of exposure, which remained attenuated 10 min after exposure. An analysis of whole-blood cholinesterase activity revealed significantly decreased activity for both acetylcholinesterase (AChE) and butyl-cholinesterase (BChE). Peak inhibition occurred for both enzymes at the end of exposure for all three concentrations and rapidly recovered within several minutes of exposure. Analysis of blood samples using gas chromatography-mass spectroscopy (GC-MS) revealed that minute ventilation may only play a minimal role in the dosimetry of inhaled DDVP vapor.

Generation, sampling, and analysis for low-level GB (Sarin) and GF (Cyclosarin) vapor for inhalation toxicology studies.

This study tested and optimized various methodologies to generate, sample, and characterize GB and GF test atmospheres in an inhalation chamber, particularly at low vapor levels. A syringe drive/spray atomization system produced vapor concentrations at a range of 1-50 mg/m3. A saturator cell was used to generate vapor at sub-lethal concentrations ranging from 1 mg/m3 down to low levels approaching the threshold limit value time-weighted average (TLV-TWA) of 0.0001 mg/m3 for GB. Both generation techniques demonstrated the ability to produce stable vapor concentrations over extended exposure periods. This capability was important to determine sublethal nerve agent effects, such as miosis, for inhalation toxicology studies. In addition, the techniques employed for producing and maintaining low-level agent vapor would lay the foundation for testing less volatile chemical warfare agents such as VX.