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

Abstract

The main purpose of this pilot study was to estimate the lowest observable adverse effect level (LOAEL) for the electroencephalogram (EEG) upon long-term, low-level exposure of vehicle-pretreated and pyridostigmine-pretreated marmoset monkeys to sarin vapour. This is the C.t value (t=5 h) of exposure at which the EEG becomes significantly different from that resulting from air exposure of the same animals. The LOAELs for effects on the EEG in vehicle- and pyridostigmine-pretreated marmosets appeared to be 0.2 and 0.1 mg min m(-3), respectively. Comparatively, the latter LOAEL values are at least an order of magnitude lower than the previously established LOAEL for miosis and only 2-5 times higher than the lowest observable effect level (LOEL) of bound sarin in blood. The second aim of the study was to analyse the EEG of the same marmosets again during a 5-h exposure to air 1 year after exposure to sarin vapour. All the marmosets still demonstrated significant (P <0.05) EEG differences. In most vehicle-pretreated marmosets the energy (microV2) per EEG band was higher than that observed 1 year earlier, which might indicate that neurons had become more sensitive to excitation. This phenomenon was less pronounced in pyridostigmine-pretreated animals. Visual examination of the EEG records revealed clear bursts of alpha frequencies (ca. 9 Hz), resembling sleep-spindles, that were present more frequently in both groups of exposed marmosets than in naive animals. These late changes in spindle oscillation might be the result of changes in the cholinergic system due to exposure to sarin vapour 1 year previously. In conclusion, EEG abnormalities persisting for more than 1 year may occur in humans during long-term (5 h) exposure to subclinical levels of sarin that are not detectable by the currently fielded alarm systems.

Recent research on Gulf War illness and other health problems in veterans of the 1991 Gulf War: Effects of toxicant exposures during deployment

“…Other studies showed reduced levels of acetylcholin-esterase (AChE) in the brains of animals given PB and exposed to stressors ( Baireddy, Mirajkar, Nallapaneni, Singleton, & Pope, 2007 ; Sinton, Fitch, Petty, & Haley, 2000 ). PB administered with the nerve agent sarin produced locomotor deficits ( Abou-Donia et al, 2002 ; Scremin et al, 2003 ), EEG abnormalities ( van Helden et al, 2004 ), changes in HRV ( Scremin et al, 2003 ) and increased markers of oxidative stress in urine ( Shih, Hulet, & McDonough, 2006 ).…”

Screening Pesticides for Neuropathogenicity

“…A review of this topic is beyond the scope of this manuscript. Nonguideline studies with monkeys [ 41 ] with sarin have been reported to produce long-lasting EEG changes that are claimed to confirm an earlier observation of changes in the human EEG patterns [ 42 ] following organophosphate exposure. The persons exposed to sarin (a potent cholinesterase inhibitor) gas in the Tokyo subway incident in the mid 1990s have been assessed periodically and reports indicate possible neurological effects either related to the gas itself of post traumatic stress disorder [ 56 – 58 ].…”

The Toxicity of Soman in the African Green Monkey (Chlorocebus aethiops)

“…For these reasons, there is a need to find an alternative monkey species to evaluate nerve agent toxicity and medical countermeasures against chemical warfare nerve agents. Two other NHP species, the cynomolgus monkey (Macaca fascicularis) (Carpentier et al 2001;Krummer et al 2002;Lenz et al 2005;Lallement et al 1997Lallement et al , 1998Lallement et al , 1999Lallement et al , 2000Lallement et al , 2002von Bredow et al 1991) and the common marmoset (Callithrix jacchus) (D'Mello and Scott 1986;Muggleton et al 2003;Wetherell and French 1991;van der Schans et al 2003;van Helden et al 1992van Helden et al , 2003van Helden et al , 2004avan Helden et al , 2004bBusker et al 1996;Philippens et al 2000), have been used in this regard. Both of these species have drawbacks.…”