Low‐level exposure of guinea pigs and marmosets to sarin vapour in air: lowest‐observable‐adverse‐effect level (LOAEL) for miosis

Abstract

The purpose of this pilot study was to indicate, for low-level exposure of conscious guinea pigs and marmoset monkeys to sarin vapour in air, the lowest-observable-adverse-effect level (LOAEL) of sarin for miosis. This is the concentration x time (C.t) value (t = 5 h) of exposure at which miosis becomes significant. The ratio of pupil and iris diameters, measured on digital photographs taken on-line during exposure, was calculated as a measure for miosis. The exposure concentrations were in the range 7-150 microg x m(-3) and the exposure times needed to achieve significant miosis were in the range 10-300 min. Both vehicle- and pyridostigmine-pretreated animals were used in the experiments. The latter pretreatment resulted in ca. 30% inhibition of erythrocyte acetylcholinesterase in both species. In vehicle-pretreated guinea pigs and marmosets the pupil size was decreased significantly (P < 0.05) at sarin doses of 1.8 +/- 0.3 and 2.5 +/- 0.8 mg x min x m(-3), respectively. In pyridostigmine-pretreated guinea pigs and marmosets the pupil size was affected significantly (P < 0.05) at 1.8 +/- 0.5 and 3.0 +/- 0.8 mg x min x m(-3), respectively. Evidently there is no significant influence of pyridostigmine pretreatment on the LOAEL. These data were addressed in light of the recommended occupational and detection limits for sarin vapour in air. It was concluded that miosis will occur during low-level sarin exposure at levels that are not detectable by the currently fielded alarm systems, assuming that humans are as sensitive for sarin vapour in air as guinea pigs and marmosets.

Low levels of sarin affect the eeg in marmoset monkeys: a pilot study

“…The first signs appearing following whole-body exposure to low levels of sarin were miosis and EEG abnormalities. The results regarding miosis have been published elsewhere (Van Helden et al, 2003b). In this paper we present evidence indicating that the EEG is at least an order of magnitude more sensitive to sarin than the eye.…”

“…The first signs following exposure to low levels of sarin in that study were miosis and EEG abnormalities. The results regarding miosis have been presented in a separate paper (Van Helden et al, 2003b). The C·t value (LOAEL) at which the first significant miosis appeared was 2.5 ± 0.8 mg min m −3 for marmosets.…”

“…Evidently, the current alarm will not detect a risk of EEG abnormalities under these conditions of low-level exposure. In a previous publication we concluded also that there will be significant miosis before exposure to sarin will be detected (Van Helden et al, 2003b).…”

“…In this way photographs from both eyes could be taken every 10 min using a digital camera on a stand. Effects on the eye were published elsewhere (Van Helden et al, 2003b). The animals had learned to sit in the chair for several hours while watching video-films featuring marmosets.…”

Blood and Bronchoalveolar Lavage Fluid Acetylcholinesterase Levels Following Microinstillation Inhalation Exposure to Sarin in Guinea Pigs

“…In general, studies are lacking on the respiratory toxicity and lung injury following inhalation exposure to nerve agents. The few reports on the inhalation toxicity of sarin mainly focused on deducing the lethal concentrations, neurotoxic effects including neurobehavioral deficits, and acute/long-term low-dose effects as well as therapeutic evaluation (Allon et al, 2005;Anzueto et al, 1990;Bide & Risk, 2004;Husain et al, 1993;Mioduszewski et al, 2002;Sevelova et al, 2003;Spruit et al, 2000;Bartosova-Sevelova & Bajgar, 2005;Dabisch et al, 2005;Henderson et al, 2001Henderson et al, , 2002Kassa et al, 2004;van Helden et al, 2004bvan Helden et al, , 2004cKassa et al, 2001aKassa et al, , 2001bKassa et al, , 2002Kassa et al, , 2004Levy et al, 2004). Emerging studies have started to reveal respiratory toxicity induced by inhalation of chemical threat nerve agents Bajgar, 2004;Anthony et al, 2004;Bide & Risk, 2004;Benschop et al, 1998;van Helden et al, 2004b).…”