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

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.

Biochemical and behavioral effects of soman vapors in low concentrations.

Soman belongs to the most dangerous nerve agents because of the low effectiveness of the presently available antidotes. Soman acts by inhibiting acetylcholinesterase (AChE) both peripherally and centrally, with a subsequent accumulation of neuromediator acetylcholine and other metabolic changes. From the data published in literature it can be concluded that exposure to nerve agents leading to acute effects or chronic exposure to nerve agents may lead to delayed and persistent adverse effects.

Retrospective detection of exposure to nerve agents: analysis of phosphofluoridates originating from fluoride-induced reactivation of phosphylated BuChE.

The utility was explored of a new approach to detect retrospectively exposure to nerve agents by means of conversion of the inhibitor moiety bound to the active site of the enzyme BuChE in plasma with fluoride ions into a phosphofluoridate which is subsequently analyzed by means of gas chromatography (GC). This quantifies >or=0.01% inhibition of BuChE and identifies the structure of the inhibitor except for the original leaving group.

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

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.

Toxicokinetics of the nerve agent (+/-)-VX in anesthetized and atropinized hairless guinea pigs and marmosets after intravenous and percutaneous administration.

In continuation of our investigations on the toxicokinetics of the volatile nerve agents C(+/-)P(+/-)-soman and (+/-)-sarin, we now report on the toxicokinetics of the rather nonvolatile agent (+/-)-VX. A validated method was developed to determine blood levels of (+/-)-VX by means of achiral gas chromatography at blood levels > or =10 pg/ml. The ratio of the two enantiomers of VX in blood could be measured at levels > or =1 ng/ml by using chiral HPLC in combination with off-line gas chromatographic analysis.

Long-term, low-level exposure of guinea pigs and marmosets to sarin vapor in air: lowest observable effect level.

Realistic scenarios for low-level exposure to nerve agents will often involve exposures over several hours to extremely low doses of agent. In order to expose animals to the lowest controllable concentrations of agent and to increase exposure times until a lowest observable effect level (LOEL) becomes measurable, a validated system was developed for exposing conscious animals to 0.05-1.

Immunochemical detection of sulfur mustard adducts with keratins in the stratum corneum of human skin.

As part of a program to develop methods for diagnosis of exposure to chemical warfare agents, we developed immunochemical methods for detection of adducts of sulfur mustard to keratin in human skin. Three partial sequences of keratins containing glutamine or asparagine adducted with a 2-hydroxyethylthioethyl group at the omega-amide function were synthesized and used as antigens for raising antibodies. After immunization, monoclonal antibodies were obtained with affinity for keratin isolated from human callus exposed to 50 microM sulfur mustard.