Hendrik P. Benschop
Leiden University
AdductMedicinal chemistryChemistryToxicokineticsAtropineMoietyNerve agentGuinea pigAcetylcholinesteraseHemoglobinSomanSarinSulfur mustardHaptenToxicityAnesthesiaChromatographyBiochemistryStereochemistryPharmacology
83Publications
28H-index
2,262Citations
Publications 81
Newest
The oxime HI−6 is effective as an antidote in the soman poisoned (6–8LD50) rat, however, successfully treated animals subsequently show a gradual relapse of signs of poisoning and eventually die after several hours. The relapse is caused by the reappearance of soman at specific sites, after having been elsewhere in the body. Diaphragms isolated from poisoned rats successfully treated with HI−6 also showed a ‘secondary’ relapse of poisoning. Eight compounds chemically related to soman-soman-simul...
10 CitationsSource
The effects were investigated of structural variations of the soman simulator pinacolyl dimethylphosphinate on its efficacy to prevent secondary failure of oxime-induced recovery of neuromuscular transmission and death after soman intoxication. The simulators were administered prophylactically to atropinized, HI-6 treated rats, dosed with 6 or 8 × LD50 soman. In these new simulators the pinacolyl moiety was varied, the phosphonyl oxygen atom was replaced by sulphur, or the phosphorous-bound meth...
11 CitationsSource
#1Jan P. LangenbergH-Index: 19
Last. Hendrik P. BenschopH-Index: 28
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ln order to provide a quantitative basis for pretreatment and therapy of intoxications with sulfur mustard the toxicokinetics of this agent as well as its major DNA-adducts are being studied in male hairless guinea pigs for the intravenous, respiratory and percutaneous routes. A highly sensitive method for bioanalysis of the intact agent in blood and tissues was developed, involving gas chromatography with automated thermodesorption injection and mass-spectrometric detection. Deuterated sulfur m...
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 ap...
20 CitationsSource
A standard operating procedure has been developed for an immunoslotblot assay of sulfur mustard adducts to DNA in human blood and skin for use in a field laboratory. A minimum detectable level of exposure of human blood in vitro (≥ 50nM) sulfur mustard is feasible with the assay. In the case of human skin, a 1 s exposure to saturated sulfur mustard vapor (830 mg/m -3 ) could still be detected.
34 CitationsSource
#1Daan NoortH-Index: 29
#2A. FidderH-Index: 19
Last. J.R. SmithH-Index: 1
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A procedure for the modified Edman degradation of globin for determination of sulfur mustard adducts to the N-terminal valine residue in human hemoglobin has been developed for use under field laboratory conditions. The minimum detectable exposure level of human blood (in vitro) to sulfur mustard using this procedure is 100nM. The interindividual and intraindividual variabilities of the procedure were acceptable (standard deviation < 10% and < 20%, respectively). The procedure could be properly ...
24 CitationsSource
#1Jiri Bajgar (Military Medical Academy)H-Index: 19
#2Lucie Ševelová (Military Medical Academy)H-Index: 9
Last. Hendrik P. BenschopH-Index: 28
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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. Th...
32 CitationsSource
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 ≥0.01% inhibition of BuChE and identifies the structure of the inhibitor except for the original leaving group. A three-tiered approach was followed involving the five classica...
62 CitationsSource
#1Jiří Bajgar (Military Medical Academy)H-Index: 12
#2Lucie ŠevelováH-Index: 9
Last. Hendrik P. BenschopH-Index: 28
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SUMMARY The aim of this study was to demonstrate changes in acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities, tyrosine aminotransferase activity (TAT) and plasma corticosterone level, neuroexcitability and behavior following 24 hours and 4 weeks of soman sublethal inhalation exposure at low level. AChE activity in erythrocytes and BuChE activity in plasma was decreased (dependent on the concentration of soman) 24 h and 4 weeks after the exposure. Similar decrease in AChE ...
4 CitationsSource
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 × 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 ...
23 CitationsSource