Relative potency of albendazole and its sulfoxide metabolite in two in vitro tests for developmental toxicity: The rat whole embryo culture and the mouse embryonic stem cell test

Eckardt,K.; Kaltenhäuser,J.; Kilb,C.; Seiler,A.; Stahlmann,R.

doi:10.1016/j.reprotox.2012.05.037

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Relative potency of albendazole and its sulfoxide metabolite in two in vitro tests for developmental toxicity: The rat whole embryo culture and the mouse embryonic stem cell test

Eckardt,K.; Kaltenhäuser,J.; Kilb,C.; Seiler,A.; Stahlmann,R.

The benzimidazole carbamate albendazole (ABZ), a potent anthelmintic, is a teratogenic compound in rats. At present it is unclear to which degree this effect is caused by the parent compound or its major metabolite, albendazole sulfoxide (ASO). Both substances were studied separately and in combinations to mimic incomplete bioactivation in two in vitro tests: mouse embryonic stem cell test (EST) and rat whole embryo culture (WEC). In both assays, ABZ and mixtures with ASO induced detrimental effects at lower concentrations compared to ASO alone. While ABZ caused half-maximal effects on cardiomyocyte differentiation at a mean concentration of 0.26 ++M (EST) and dysmorphogenic development of rat embryos at 3.7 ++M (WEC), effective concentrations of ASO were similar in both assays (10-13 ++M). By using WEC and EST we demonstrate that ABZ exhibits stronger inherent embryotoxic potency although ASO might be the proximate teratogen in vivo because of higher plasma concentrations.

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Erschienen in:: Reproductive toxicology
Vol. 34, H. 3 (2012), S. 378-384
Band:: 34
Heft:: 3
Datum der Veröffentlichung:: 2012
DOI:: 10.1016/j.reprotox.2012.05.037
Sprache:: Englisch
Ressourcentyp:: Text
Schlagwörter:: 3; ACID; AGENT; AGENTS; Albendazole; Albendazole sulfoxide; analysis; animal; animal cell; animal experiment; animal experiments; ANIMAL-EXPERIMENTS; Animals; Antiparasitic Agents; article; ASSAY; assessment; behaviour; Berlin; bioassay; biology; cancer; CELL; Cell Differentiation; Cell Line; cell viability; CELL-LINE; CELLS; clinical; COMBINATION; comparative; comparison; COMPOUND; concentration; congresses; controlled study; cultivation; CULTURE; CULTURES; CYTOTOXICITY TEST; Design; development; developmental toxicity; DIFFERENTIATION; DISCOVERY; DOG; Dogs; domestic animals; DRUG; drug activity; drug potency; Drug Resistance; drug response; effect; EFFECTS; Embryo; embryo culture; embryo development; Embryo,Mammalian; embryonic stem cell; embryonic stem cell test; embryonic stem cells; embryos; embryotoxicity; EMBRYOTOXICITY TEST; EST; Experiments; Female; Fibroblasts; Food; food additives; german; Germany; growth; growth factor; GROWTH-FACTOR; heart muscle cell; Human; IC 50; In Vitro; in vitro study; in vitro test; In vitro tests; in vivo; IN-VITRO; IN-VIVO; inhibitor; international; line; Male; MECHANISM; metabolite; METABOLITES; method; methods; Mice; MIXTURE; MIXTURES; mode of action; model; molecular biology; MOUSE; murine; Myocytes,Cardiac; NO; nonhuman; parasitology; PATIENT; pharmaceutical; pharmacokinetics; pharmacology; PLASMA; PLASMA-CONCENTRATIONS; potential; PREDICT; protein; PROTOCOL; Rat; rats; Rats,Wistar; Rattus; reference; reproductive toxicology; Research; residue; RESIDUES; resistance; review; Risk; Risk Assessment; RISK-ASSESSMENT; SCIENCE; Software; standardization; Stem Cells; studies; study; SUBSTANCES; sulfoxide; Symposium; SYSTEM; technique; teratogenicity; TESTS; toxicity; toxicity testing; Toxicity Tests; toxicology; veterinary; VITRO; VIVO; WHO; Whole embryo culture; WISTAR RATS; Zebrafish
DDC-Sachgruppe der DNB:: 610 Medizin, Gesundheit, Ernährung
Link URL:: http://www.sciencedirect.com/science/article/pii/S0890623812001529
Einrichtung:: Bundesinstitut für Risikobewertung, Bundesinstitut für Risikobewertung (bis Juni 2014), Abteilung 9 - Experimentelle Toxikologie und ZEBET (bis Juni 2014), Fachgruppe 92 - ZEBET - Alternativmethoden zu Tierversuchen