Registration Dossier

Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: no OECD test method used

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
2005
Reference Type:
study report
Title:
Unnamed
Year:
2004

Materials and methods

Test guideline
Qualifier:
no guideline followed
Guideline:
other: not applicable
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

Results (fetuses)

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

Developmental toxicity (birth defects) – Skeletal malformations were reported in

mice and rats orally administered 800 mg/kg/day (40 and 80 times the maximum

human dose, respectively, based on surface area) (PDR, 2005). No drug-induced

changes were seen in either species at multiples of 8 (rats) or 4 (mice) times the

human exposure based on surface area. In another study, an increased frequency

of abdominal wall defects and skeletal abnormalities was observed in the

offspring of rats treated with 60 mg/kg/day (TERIS, 2004; Reprotox, 2005). In an

additional rat study, skeletal defects and decreased fetal weight were observed in

offspring following gestational exposure to ≥100 mg/kg/day. No birth defects

were reported in rabbits given 15 mg/kg/day, the maximum tolerated dose (about

3 times the maximum human dose, based on surface area) (PDR, 2005).

Applicant's summary and conclusion

Conclusions:
Developmental toxicity (birth defects) – Skeletal malformations were reported in
mice and rats orally administered 800 mg/kg/day (40 and 80 times the maximum
human dose, respectively, based on surface area) (PDR, 2005). No drug-induced
changes were seen in either species at multiples of 8 (rats) or 4 (mice) times the
human exposure based on surface area. In another study, an increased frequency
of abdominal wall defects and skeletal abnormalities was observed in the
offspring of rats treated with 60 mg/kg/day (TERIS, 2004; Reprotox, 2005). In an
additional rat study, skeletal defects and decreased fetal weight were observed in
offspring following gestational exposure to ≥100 mg/kg/day. No birth defects
were reported in rabbits given 15 mg/kg/day, the maximum tolerated dose (about
3 times the maximum human dose, based on surface area) (PDR, 2005).
Executive summary:

Developmental toxicity (birth defects) – Skeletal malformations were reported in

mice and rats orally administered 800 mg/kg/day (40 and 80 times the maximum

human dose, respectively, based on surface area) (PDR, 2005). No drug-induced

changes were seen in either species at multiples of 8 (rats) or 4 (mice) times the

human exposure based on surface area. In another study, an increased frequency

of abdominal wall defects and skeletal abnormalities was observed in the

offspring of rats treated with 60 mg/kg/day (TERIS, 2004; Reprotox, 2005). In an

additional rat study, skeletal defects and decreased fetal weight were observed in

offspring following gestational exposure to ≥100 mg/kg/day. No birth defects

were reported in rabbits given 15 mg/kg/day, the maximum tolerated dose (about

3 times the maximum human dose, based on surface area) (PDR, 2005).