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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: comparable to guideline study with acceptable restrictions (e.g. test substance purity not indicated)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Santocure MOR (CP 15255)

Test animals

Species:
rat
Strain:
Sprague-Dawley

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
- M/F ratio per cage: 1:1
Duration of treatment / exposure:
from gestation day (GD) 6 through 15
Frequency of treatment:
daily
Duration of test:
study termination on GD 20
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 100, 300 and 1000 mg/kg bw/d
Basis:

No. of animals per sex per dose:
25 pregnant rats per dose group
Control animals:
yes, concurrent vehicle

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOAEL
Effect level:
100 mg/kg bw/day
Basis for effect level:
other: maternal toxicity
Dose descriptor:
LOAEL
Effect level:
300 mg/kg bw/day
Basis for effect level:
other: maternal toxicity

Results (fetuses)

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

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day
Basis for effect level:
other: fetotoxicity

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

Maternal observations:

Appearance and behavior:

a slight increase in hair loss was observed in the treatment groups when compared to the control group. A dose-related increase in the incidence and duration of matting and/or yellow staining of the anogenital and ventral haircoat regions was observed in the 300 mg/kg bw/d group (5/25) and in the 1000 mg/kg bw/d group (16/25) when compared to the control group (3/25). A dose-related increase in red staining of the anogenital region was also noted in the 300 mg/kg bw/g group (2/25) and in the 1000 mg/kg bw/d group (5/25) when compared to control (0/25).

Mortality:

No test substance related death; one death occured in the 1000 mg/kg bw/d group on gestation day 14 which attributed to a gavage error.survival was 100 % in the 0, 100 and 300 mg/kg bw/d dose groups.

Body weights:

There was no biologically meaningful difference in mean maternal body weight gain in the 100 mg/kg bw/d treatment group compared to control. A slight decrease in mean maternal body weight gain was noted in the 300 mg/kg bw/d group during gestation day 6 to 9 interval which resulted in a very slight decrease in weight gain over the treatment period when compared to control (-15 %). A mean body weight loss was observed during the first three days of treatment in the 1000 mg/kg bw/d group, which resulted in a slight to moderate reduction in mean body weight gain during the treatment period (-30 %).

Cesarean section observations:

No biologically meaningful or statistically significant differences were observed in the mean numbers of corpora lutea, total implantations, viable fetuses, early or late resorptions, postimplantation loss, mean fetal body weights, or mean fetal sex distribution in the treated groups when compared to the control group. Slight variations in the treatment group means (in particular the corpora lutea and postimplantation loss means) are found within the historical control ranges and are not considered meaningful differences.

Fetal morphological observations:

There were no biologically meaningful or statistically significant differences in the number of litters with malformations in the treated groups when compared to the control group. The slight increase in malformations in the 1000 mg/kg bw/d treatment group was due to a genetic anomaly (two fetuses with dwarfish) observed in the strain used in this laboratory. No biologically meaningful differences in the number of fetuses or litters with developmental or genetic variations were observed in the treated groups when compared to the control group.

Applicant's summary and conclusion