Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8552491 | Reproductive Toxicology | 2018 | 31 Pages |
Abstract
The potential reproductive and developmental toxicity of the synthetic oligodeoxynucleotide (ODN) CpG 7909, a component of GSK's AS15 immunostimulant, was examined in rat and rabbit studies following intermittent intramuscular injections. Previous studies using subcutaneous and intraperitoneal injections in mice, rats and rabbits revealed that CpG ODNs induced developmental effects. To analyze the safety signal, GSK conducted additional animal studies using the intended clinical route of administration. CpG 7909 injections were administered intramuscularly to rats or rabbits 28 and 14Â days before pairing, on 4 or 5 occasions during gestation, and on lactation day 7. The No Observed Adverse Effect Level for female fertility, embryo-fetal and pre- and post-natal development was 4.2Â mg/kg in both species, approximately 500-fold higher than the anticipated human dose. In conclusion, the anticipated risk to humans is considered low for sporadic intramuscular exposure to CpG 7909.
Keywords
ODNCPG 7909FDANOAELNZWGlaxoSmithKlineGSKTLR9oligodeoxynucleotideCpGEFDHLSPNDEMAEuropean Medicines agencystandard deviationImmunostimulantinterleukinRabbitintraperitonealEmbryo-fetal developmentpost-natal dayWorld Health OrganizationFood and Drug AdministrationReproductive toxicitysafety signalIntramuscularPPNRatNo observed adverse effect levelbody weightWHOToll-like receptor 9
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Authors
Frédérique Delannois, Camille Planty, Giulia Giordano, Eric Destexhe, Dinesh Stanislaus, Fernanda Tavares Da Silva, Jens-Ulrich Stegmann, Karen Thacker, Lucie Reynaud, Nathalie Garçon, Lawrence Segal,