3-(trimethoxysilyl)propyl isocyanate

Toxicity to reproduction

Administrative data

Endpoint:

extended one-generation reproductive toxicity - with F2 generation (Cohorts 1A, and 1B with extension)

Type of information:

experimental study planned (based on read-across)

Study period:

Study ongoing. This information will be submitted later based on ECHA communication/decision number TPE-D-2114498375-34-01/F for the immediate disintegration product, 3-(trimethoxysilyl)propylamine (CAS 13822-56-5).

Justification for type of information:

TESTING PROPOSAL ON VERTEBRATE ANIMALS
The registered substance, 3-(trimethoxysilyl)propyl isocyanate (CAS 15396-00-6) is a trimethoxysilane with a propyl side-chain that has an isocyanate functional group at the opposite end from the trimethoxysilane group. The isocyanate group in 3-(trimethoxysilyl)propyl isocyanate (CAS 15396-00-6) hydrolyses very rapidly under physiological conditions (half-life 1 minute at 37°C and pH 7), forming an amine. Therefore, the substance hydrolyses very rapidly to give the immediate hydrolysis product, 3-(trimethoxysilyl)propylamine (CAS 13822-56-5). 3-(Trimethoxysilyl)propylamine (CAS 13822-56-5) has been predicted to hydrolyse rapidly under conditions relevant for oral exposure. The estimated hydrolysis half-life at pH 2 (relevant for oral exposure) and 37.5°C is approximately 5 seconds. Therefore, the test organism is expected to be mainly exposed to the hydrolysis products, 3-aminopropylsilanetriol and methanol.

NON-CONFIDENTIAL NAME OF SUBSTANCE:
- Name of the substance on which testing is proposed to be carried out : 3-(trimethoxysilyl)propylamine (CAS 13822-56-5)
- Name of the substance for which the testing proposal will be used [if different from tested substance] : 3-(trimethoxysilyl)propyl isocyanate (CAS 15396-00-6)

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 GLP studies available for the reproductive toxicity endpoint.
- Available non-GLP studies : There are no non-GLP studies available for the reproductive toxicity endpoint.
- Historical human data : None
- (Q)SAR : None
- In vitro methods : There are no validated in vitro methods that meet the Annex requirements
- Weight of evidence : Insufficient data
- Grouping and read-across : There are no suitable analogues with which to form a group for 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 applicable adaptations.

FURTHER INFORMATION ON TESTING PROPOSAL IN ADDITION TO INFORMATION PROVIDED IN THE MATERIALS AND METHODS SECTION:
- Details on study design / methodology proposed: Extended one-generation reproductive toxicity study conducted to OECD Test Guideline 443, without extension to cohort 1B, 2 or 3.

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 443 (Extended One-Generation Reproductive Toxicity Study)

GLP compliance:

yes

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

Test material information

Constituent 1

Reference substance name:

3-(trimethoxysilyl)propylamine

EC Number:

237-511-5

EC Name:

3-(trimethoxysilyl)propylamine

Cas Number:

13822-56-5

Molecular formula:

C6H17NO3Si

IUPAC Name:

3-Trimethoxysilylpropan-1-amine