Studies with resVida (R) (a high purity trans-resveratrol) show that trans-resveratrol is a substance of low oral toxicity. An acceptable daily intake (ADI) in food of 450 mg/day has been defined, a level well beyond natural dietary intake of trans-resveratrol. The ADI was based on no-observed-adverse-effect-levels (NOAELs) of 750 mg/kg bw/day in 13-week developmental toxicity studies by the dietary route and a standard safety margin of 100. In studies by gavage, the kidney and bladder are target organs at very high dosages (2,000-3,000 mg/kg bw/day). Six-month studies in rat and rabbit models show no significant increase in toxicity in comparison to 4-week studies. Lower quoted NOAELs in gavage studies (ca. 300 mg/kg bw/day) potentially reflect more rapid bioavailability, but different dosage regimes complicate comparisons. Short-term studies show no genotoxicity in vivo. A 6-month mouse carcinogenicity model showed no increase in tumors. Clinical data support an ADI of at least 450 mg/day, and kinetic data from the DSM 13-week toxicity study also support the expectation of no increase in toxicity with longer term intake.
机构:
Univ Aix Marseille, INRA UMR 1260, F-13385 Marseille, France
Univ Aix Marseille, INSERM UMR 1062, F-13385 Marseille, France
Univ Aix Marseille, Fac Med La Timone, F-13385 Marseille, FranceUniv Aix Marseille, INRA UMR 1260, F-13385 Marseille, France
Amiot, Marie Josephe
Romier, Beatrice
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Univ Aix Marseille, INRA UMR 1260, F-13385 Marseille, FranceUniv Aix Marseille, INRA UMR 1260, F-13385 Marseille, France
Romier, Beatrice
Thi-Mai Anh Dao
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Univ Aix Marseille, Fac Med La Timone, F-13385 Marseille, FranceUniv Aix Marseille, INRA UMR 1260, F-13385 Marseille, France
Thi-Mai Anh Dao
Fanciullino, Raphaelle
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Univ Aix Marseille, Fac Pharm, Lab Pharmacocinet, F-13385 Marseille, FranceUniv Aix Marseille, INRA UMR 1260, F-13385 Marseille, France
Fanciullino, Raphaelle
Ciccolini, Joseph
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Univ Aix Marseille, Fac Pharm, Lab Pharmacocinet, F-13385 Marseille, FranceUniv Aix Marseille, INRA UMR 1260, F-13385 Marseille, France
Ciccolini, Joseph
Burcelin, Remy
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Univ Toulouse Paul Sabatier, INSERM U1048, F-31000 Toulouse, FranceUniv Aix Marseille, INRA UMR 1260, F-13385 Marseille, France
Burcelin, Remy
Pechere, Laurent
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Yvery SARL, F-13008 Marseille, FranceUniv Aix Marseille, INRA UMR 1260, F-13385 Marseille, France
Pechere, Laurent
Emond, Claude
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Univ Montreal, Quebec City, PQ, Canada
BioSimulat Consulting, Newark, DE USAUniv Aix Marseille, INRA UMR 1260, F-13385 Marseille, France
Emond, Claude
Savouret, Jean-Francois
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Univ Paris 05, INSERM UMRS Pharmacol Cartilage Destruct 747, F-75006 Paris, FranceUniv Aix Marseille, INRA UMR 1260, F-13385 Marseille, France
Savouret, Jean-Francois
Seree, Eric
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Univ Aix Marseille, INRA UMR 1260, F-13385 Marseille, France
Univ Aix Marseille, INSERM UMR 1062, F-13385 Marseille, France
Univ Aix Marseille, Fac Med La Timone, F-13385 Marseille, FranceUniv Aix Marseille, INRA UMR 1260, F-13385 Marseille, France
机构:
BIAL, Dept Res & Dev, P-4745457 S Mamede Do Coronado, Portugal
Univ Porto, Fac Med, Inst Pharmacol & Therapeut, Oporto, PortugalBIAL, Dept Res & Dev, P-4745457 S Mamede Do Coronado, Portugal
Vaz-da-Silva, M.
Loureiro, A. I.
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BIAL, Dept Res & Dev, P-4745457 S Mamede Do Coronado, PortugalBIAL, Dept Res & Dev, P-4745457 S Mamede Do Coronado, Portugal
Loureiro, A. I.
Falcao, A.
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4Hlth Consulting, Cantanhede, PortugalBIAL, Dept Res & Dev, P-4745457 S Mamede Do Coronado, Portugal
Falcao, A.
Nunes, T.
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BIAL, Dept Res & Dev, P-4745457 S Mamede Do Coronado, PortugalBIAL, Dept Res & Dev, P-4745457 S Mamede Do Coronado, Portugal
Nunes, T.
Rocha, J. -F.
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BIAL, Dept Res & Dev, P-4745457 S Mamede Do Coronado, PortugalBIAL, Dept Res & Dev, P-4745457 S Mamede Do Coronado, Portugal
Rocha, J. -F.
Fernandes-Lopes, C.
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BIAL, Dept Res & Dev, P-4745457 S Mamede Do Coronado, PortugalBIAL, Dept Res & Dev, P-4745457 S Mamede Do Coronado, Portugal
Fernandes-Lopes, C.
Soares, E.
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BIAL, Dept Res & Dev, P-4745457 S Mamede Do Coronado, PortugalBIAL, Dept Res & Dev, P-4745457 S Mamede Do Coronado, Portugal
Soares, E.
Wright, L.
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BIAL, Dept Res & Dev, P-4745457 S Mamede Do Coronado, PortugalBIAL, Dept Res & Dev, P-4745457 S Mamede Do Coronado, Portugal
Wright, L.
Almeida, L.
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机构:
BIAL, Dept Res & Dev, P-4745457 S Mamede Do Coronado, Portugal
Univ Porto, Fac Med, Inst Pharmacol & Therapeut, Oporto, PortugalBIAL, Dept Res & Dev, P-4745457 S Mamede Do Coronado, Portugal
Almeida, L.
Soares-da-Silva, P.
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机构:
BIAL, Dept Res & Dev, P-4745457 S Mamede Do Coronado, Portugal
Univ Porto, Fac Med, Inst Pharmacol & Therapeut, Oporto, PortugalBIAL, Dept Res & Dev, P-4745457 S Mamede Do Coronado, Portugal