Registration Dossier

Administrative data

genetic toxicity in vitro
Type of information:
experimental study
Adequacy of study:
other information

Data source

Reference Type:
other: EPAR Scientific discussion
Viread - EPAR Scientific discussion
Bibliographic source:
European Medicines Agency

Materials and methods

GLP compliance:

Test material



Target gene:
In vitro mouse lymphoma assay and an in vitro UDS test on rats hepatic cells.
Species / strainopen allclose all
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with and without
Species / strain:
other: rats hepatic cells

Results and discussion

Applicant's summary and conclusion

Interpretation of results (migrated information):

Mutagenicity: Ames test negative, mutagenic in the “in vitro” mouse lymphoma assay. Negative in “in vivo”
mouse micronucleus assay.
The mutagenic potential of tenofovir DF was evaluated in a standard battery of in vitro and in vivo
tests. Tenofovir DF was positive in the in vitro mouse lymphoma assay, equivocal in the Ames tests
(positive in one assay using the strain of Salmonella typhimurium TA 1535 with or without
activation). Tenofovir DF was negative in the in vivo micronucleus assay in mouse (doses up to 2000
mg/kg orally). To clarify these findings and complete the information on the genotoxicity of tenofovir
DF, additional in vitro and in vivo UDS test on rats hepatic cells have been performed in order to
assess the ability of tenofovir DF (or metabolites) to cause DNA damage by measuring UDS induced
in vivo in primary hepatocytes cultured in vitro. The tenofovir DF was considered as weakly positive
in this assay, showing that tenofovir can induce DNA damage and supporting the previous mutagenic
potential results. These results will have to be considered in the light of the final assessment of the
rodent carcinogenicity studies.