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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
Study period:
The experimental phase of the study started and the in vivo phase was completed as planned. However, due to delays explained in the attached justification, a draft report is not yet available.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
This information will be submitted later based on ECHA decision number TPE-D-2114479062-50-01/F.

The experimental phase of the study started and the in vivo phase was completed as planned. However, due to delays explained in the attached justification, a draft report is not yet available.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2020

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
liquid

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Italia S.p.A., Calco (Lecco), Italy
- Age at study initiation: females: 11 weeks, males: 13 weeks
- Housing: Before and after mating: up to 5 of one sex to a cage in clear polysulfone cages measuring 59.5x38x20 cm; During mating: 1 male to 1 female in clear polysulfone cages measuring 42.5x26.6x18.5 cm
- Diet (e.g. ad libitum): commercially available laboratory rodent diet (4 RF 21, Mucedola S.r.l., Via G. Galilei 4, 20019 Settimo Milanese (MI), Italy), ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: approximately 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 2°C
- Humidity (%): 55% ± 15%
- Air changes (per hr): 15 to 20 air
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
softened by reverse osmosis
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:
The required amount of the test item will be dissolved in the vehicle. The preparations will be made daily (concentrations of 10, 30 and 100 mg/mL), unless specified otherwise.
Concentrations will be calculated and expressed in terms of test item corrected for purity. During preparation and storage, the development of foam will be avoided.

dose volume: 10 mL/kg bw
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Analysis has been performed in a separate study in order to validate the analytical method and the preparation procedure and to verify the stability of the preparations (ERBC Study no. A3674). The preparation are stable for 28 days at room temperature and 7 days at 4°C. Samples of the preparations prepared during the current study (the first and the last week of treatment where possible) will be analysed to check the concentration. Chemical analysis will be carried out by the Analytical Chemistry Department.
Details on mating procedure:
- Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: 1:1
- Proof of pregnancy: vaginal plug / sperm in vaginal smear referred to as day 0 of pregnancy
Duration of treatment / exposure:
Day 5 through Day 19 post coitum
Frequency of treatment:
daily
Doses / concentrationsopen allclose all
Dose / conc.:
100 mg/kg bw/day
Dose / conc.:
300 mg/kg bw/day
Dose / conc.:
1 000 mg/kg bw/day
No. of animals per sex per dose:
25
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: Dose levels have been selected in consultation with the Sponsor, based on a previous preliminary, non GLP compliant study (ERBC Study No. Y0450).

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

Remarks on result:
other: The experimental phase of the study started and the in vivo phase was completed as planned. However, due to delays explained in the attached justification, a draft report is not yet available.

Maternal abnormalities

Abnormalities:
not specified

Results (fetuses)

Effect levels (fetuses)

Remarks on result:
other: The experimental phase of the study started and the in vivo phase was completed as planned. However, due to delays explained in the attached justification, a draft report is not yet available.

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion