Registration Dossier

Administrative data

Endpoint:
extended one-generation reproductive toxicity - basic test design (Cohorts 1A, and 1B without extension)
Type of information:
experimental study planned
Study period:
After approval by ECHA
Justification for type of information:
TESTING PROPOSAL ON VERTEBRATE ANIMALS

NON-CONFIDENTIAL NAME OF SUBSTANCE:
- Name of the substance on which testing is proposed to be carried out: 3-(trimethoxysilyl)propylamine


CONSIDERATIONS THAT THE GENERAL ADAPTATION POSSIBILITIES OF ANNEX XI OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION [please address all points below]:
- Available GLP studies: There are no reproductive toxicity studies in compliance with GLP available.
- Available non-GLP studies: There are no non-GLP reproductive toxicity studies available.
- Historical human data: No data available.
- (Q)SAR: No data available.
- In vitro methods: There are no validated in vitro test methods for reproductive toxicity.
- Weight of evidence: Insufficient data available.
- Grouping and read-across: A 90-day reproductive toxicity study with relevant reprotox endpoints for the analogous substance 3-aminopropyltriethoxysilane (CAS 919-30-2) was considered for read-across, however comparison with the 90-day oral repeated dose toxicity study available for 3-aminopropyltriethoxysilane, suggests that though there are similarities in effects, the differences are too great to support read-across.

CONSIDERATIONS THAT THE SPECIFIC ADAPTATION POSSIBILITIES OF ANNEXES VI TO X (AND COLUMN 2 THEREOF) OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION:
- There are no Column 2 adaptations for reproductive toxicity.

FURTHER INFORMATION ON TESTING PROPOSAL IN ADDITION TO INFORMATION PROVIDED IN THE MATERIALS AND METHODS SECTION:
- Details on study design / methodology proposed: An extended one-generation reproductive toxicity (OECD 443) will be conducted with 3-(trimethoxysilyl)propylamine. Doses will be carefully selected in order to avoid animal suffering due to local effects, and to avoid the secondary effects which may result from stress. The effects on oestrous cyclicity observed in the OECD 408 study, which may have been related to low and/or reduced body weight resulting from and therefore secondary to local effects will be clarified.

Data source

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 443 (Extended One-Generation Reproductive Toxicity Study)
Justification for study design:
SPECIFICATION OF STUDY DESIGN FOR EXTENDED ONE-GENERATION REPRODUCTION TOXICITY STUDY WITH JUSTIFICATIONS:

- Premating exposure duration for parental (P0) animals: At least 2 weeks
- Basis for dose level selection: A dose range-finding study will be conducted to determine doses or doses will be based on findings from a 90-day oral repeated dose toxicity study. Doses will be carefully selected in order to avoid animal suffering due to local effects, and to avoid the secondary effects which may result from stress.
- Inclusion/exclusion of extension of Cohort 1B: No extension of Cohort 1B will be included.
- Termination time for F2: Until weaning.
- Inclusion/exclusion of developmental neurotoxicity Cohorts 2A and 2B: Developmental neurotoxiciy Cohorts 2A and 2B will not be included.
- Inclusion/exclusion of developmental immunotoxicity Cohort 3: Developmental immunotoxicity Cohort 3 will not be included.
- Route of administration: Administration oral via gavage, to avoid reaction of substance with food.
- Other considerations, e.g. on choice of species, strain, vehicle and number of animals: The study will be performed in at least 20 rats per sex per dose.

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

Applicant's summary and conclusion