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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
other information

Data source

Reference
Reference Type:
other: EPAR Scientific discussion
Title:
Viread - EPAR Scientific discussion
Year:
2006
Bibliographic source:
European Medicines Agency

Materials and methods

GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat

Administration / exposure

Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
42 weeks
Doses / concentrations
Remarks:
Doses / Concentrations:
the highest doses were 1000 mg/kg in rats
Basis:

Control animals:
not specified

Results and discussion

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

In rats, the target organs were the gastro-intestinal tract (intestinal epithelial hypertrophy/slight to moderate intestinal hyperplasia) and kidney (renal tubular epithelial karyomegaly and pigment accumulation at dose of 30 mg/kg/day). It was suggested that gastro-intestinal lesions could be rodent specific occurring at the highest doses as no signs were reported in either monkeys or in dogs. It was agreed however that this finding should be further investigated. Changes in serum chemistry parameters, including dose-related slight to moderate changes in cholesterol, triglycerides, ALT, AST and creatinine were also reported in the 300 mg dose group. All these effects were reversible after treatment discontinuation. The no-observed effect-level (NOEL) determined was less than 30 mg/kg, and therefore no overall safety margins could be established.

Applicant's summary and conclusion

Conclusions:
NOEL (rat): < 30 mg/Kg./day
Target organs: bone, kidney.