Effect of Pretreatment With Human Butyrylcholinesterase Scavengers on the Toxicokinetics and Binding of Nerve Agents in Guinea Pigs and Marmosets
Abstract
The effect of i.m. administered human butyryicholinesterase (HuBuChE) on the i.v. bolus and inhalation toxicokinetics of (+/-)-sarin in guinea pigs was studied. After i.m. administration of HuBuChE, the BuChE activity in blood gradually increased, reaching a maximum after 20-24 h, and remaining stable for about another 24 h. It was decided to study the effect of HuBuChE on the toxicokinetics of nerve agent at 24 h after administration of the enzyme. After iv. bolus administration of (+/-)-sarin, only the (-)-isomer was detectable in blood. The effect of HuBuChE- pretreatment (at a molar equivalent of 1.4 LD5O (i.v.) of C(+/-)P(+/-)-soman in the guinea pig) on the concentration-time profiles of (+/-)-sarin (2 LD5O) was not as dramatic as anticipated. The most pronounced effect on the blood concentration of (-)-sarin in HuBuChE-pretreated guinea pigs was observed in the first 10 min after administration of the toxicant. The area-under-the-curve of (-)-sarin from time 0 to 20 min was significantly lower in HuBuChE-pretreated animals. Furthermore, via fluoride-induced reactivation a significantly higher concentration of (j)-sarin bound in blood was demonstrated in these animals. After nose-only exposure to (+/-)-sarin vapor in air (ea. 2 LCt5O in 2 min) the effect of HuBuChE-pretreatment (at a molar equivalent of 0.5 LCt5O of C(+/-)P(+/-)-soman) on the toxicokinetics of (-)-sarin was also not as dramatic as anticipated. in vitro, HuBuChE showed only minor stereoselectivity towards the nerve agents (+/-)-sarin, (+/-)-VX and C(+/-)P(+/-)-soman.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2002
- Accession Number
- ADA406189
Entities
People
- Hendrik P. Benschop
- Jan P. Langenberg
- L. P. De Jong
- M. J. Van Der Schans
Organizations
- Prins Maurits Laboratorium TNO