Registration Dossier

Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
other: Inquiry result
Title:
Unnamed
Year:
2014

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
GLP compliance:
yes
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
other: Rat WIST HanIbm: WIST (SPF Quality)

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
other: Bi-distilled water containg 0.5 % carboxymethylcellulose and 0.1 % Tween 80
Details on exposure:
Method of administration or exposure: gavage
Frequency of treatment:
Dosing regime: 7 days/week
No. of animals per sex per dose:
Number of dams and doses
22 at 0 mg/kg or mg/l
22 at 100 mg/kg or mg/l
22 at 300 mg/kg or mg/l
22 at 1000 mg/kg or mg/l

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:no effects

Details on maternal toxic effects:
No female died and no reaction to treatment were observed in
any female of any group during the course of this study.
The evaluation of the food consumption data gave no
indication of test-article-related effects. The mean food
consumption was similar in all groups.
The mean body weight gain and the mean corrected body weight
gain (corrected for uterus) were similar in all groups. No
test-article-related differences were evident.
The reproduction data (mean number of implantation sites,
mean post-implantation loss and mean number of fetuses per
dam) of test-articled dams were similar to those of the
control dams.
All females in groups 1 and 4 were pregnant and had live
fetuses at Caesarean section. One female in group 2 and two
females in group 3 were not pregnant. Addtionally one female
in group 2 had three resorptions only. Isolated occurence
of females with total resorption is a common finding and was
therefore considered to be incidental.
There were no indication for treatment-related macroscopic
changes in any group. With the exception of one female with
dark red discolored ovaries, no abnormal findings were noted
in any female of any group.

Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (nominal)
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (nominal)
Basis for effect level:
other: other:

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
Effects on fetus - Gross:
The mean fetal body weights of all groups were nearly
identical.
Omphalocele was noted in one out of 235 fetuses of group 2.
No abnormal findings were noted in the 268 fetuses of group
1, in the 241 fetuses of group 3 or in the 261 fetuses of
group 4.
The evaluation of the sex ratios did not indicate
differences which were considered to be related to the
treatment with the test article.
Effects on fetus - Soft tissue:
No abnormal findings were noted in 128 fetuses of group 1,
in 113 fetuses of group 2, in 116 fetuses of group 3 or in
126 fetuses of group 4.
Effects on fetus - Skeletal:
Neither the frequency nor the type of the abnormal findings
indicated test article-related effects. A small number of
abnormal findings (mostly abnormally shaped sternebrae) were
noted in each group but they were not considered treatmentrelated.

No test article-related differences in the stage of skeletal
development amongst the fetuses of the vehicle control
(group 1) and those of groups 2, 3 or 4 were noted. The
statistically significant differences (mostly noted in group
4) demonstrate in all cases slightly higher stages of
skeletal development in group 4 than in the control group.
These findings were within the range of historical control
data and considered to be incidental.

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion