Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
extended one-generation reproductive toxicity - basic test design (Cohorts 1A, and 1B without extension)
Type of information:
experimental study planned (based on read-across)
Study period:
After approval from ECHA. Following EU Commission request (SG-Greffe (2017) D/12522 - August 3, 2017) an extended one-generation reproductive toxicity test (EOGRT) (basic test) is proposed with no additional cohorts.
Justification for type of information:
TESTING PROPOSAL (BASED ON READ_ACROSS) ON VERTEBRATE ANIMALS

NON-CONFIDENTIAL NAME OF SUBSTANCE:
- Name of the substance on which testing is proposed to be carried out: Polysulfides, bis[3-(triethoxysilyl)propyl] (CAS 211519-85-6)

CONSIDERATIONS THAT THE GENERAL ADAPTATION POSSIBILITIES OF ANNEX XI OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION:
- Available GLP studies: A supporting, non-standard four-day uterine weight assay in mice following oral administration of the registered substance for 4 days (LPT, 1983) is available for the read-across substance (polysulfides, bis[3-(triethoxysilyl)propyl], 211519-85-6).
- Available non-GLP studies: There are no non-GLP studies available for the registration substance.
- Historical human data: No data available.
- (Q)SAR: No data available.
- In vitro methods: There are no validated alternative in vitro test methods for toxicity to reproduction endpoint.
- Weight of evidence: Insufficient data.
- Grouping and read-across: there is no reproductive toxicity data on the components of the reaction mass, such as Polysulfides and none38.

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 Column 2 adaptation of Annexes VI to X for toxicity to reproduction.

FURTHER INFORMATION ON TESTING PROPOSAL IN ADDITION TO INFORMATION PROVIDED IN THE MATERIALS AND METHODS SECTION:
- Details on study design / methodology proposed: Following EU Commission request (August 3, 2017) an extended one-generation reproductive toxicity Test (EOGRT) (basic study) is proposed with no additional cohorts.
- Based on the following information no additional cohorts are proposed:
- The ADME predicted data indicates accumulation does not occur.
- The data from toxicity studies show that the material is of no concern.
- DNT and DIT cohorts will not be required as there is no evidence to show any concern from the long-term toxicity studies.

Data source

Materials and methods

Test guideline
Qualifier:
according to guideline
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. No adverse findings were observed in relation to the reproductive organs in repeated dose tests.
- Basis for dose level selection: The doses will be based on a weight of evidnce from available toxicity tests conducted via the oral route, and if necessary, a dose range-finding study will be performed.
- Inclusion/exclusion of extension of Cohort 1B: The study design will not include extension of Cohort 1B. The substance does not display genotoxic effects in somatic cell mutagenicity tests in vivo which could lead to classifying it as Mutagen Category 2, and there are no indications that the internal dose for the substance and/or any of its metabolites will reach a steady state in the test animals only after an extended exposure, and there are no indications of one or more relevant modes of action related to endocrine disruption from available in vivo studies or non-animal approaches.
- Inclusion/exclusion of developmental neurotoxicity Cohorts 2A and 2B: The study design will not include Cohorts 2A and 2B. The available data for the substance do not indicate a particular concern to justify inclusion of the developmental neurotoxicity cohorts. For example, there were no adverse findings relating to the central nervous system, nerves or behaviour.
- Inclusion/exclusion of developmental immunotoxicity Cohort 3: The study design will not include Cohorts 3. The available data for the substance do not indicate a particular concern to justify inclusion of the developmental immunotoxicity cohorts. For example, there were no adverse findings relating to haematology, clinical chemistry, organ weights or histopathology that are associated with immunotoxicity.
- Route of administration: The test material will be administered orally by gavage.

Test material

Constituent 1
Chemical structure
Reference substance name:
Reaction mass of 4,4,15,15-tetraethoxy-3,16-dioxa-8,9,10,11-tetrathia-4,15-disilaoctadecane and 4,4,14,14-tetraethoxy-3,15-dioxa-8,9,10-trithia-4,14-disilaheptadecane and 4,4,13,13-tetraethoxy-3,14-dioxa-8,9-dithia-4,13-disilahexadecane
EC Number:
915-673-4
Cas Number:
211519-85-6
Molecular formula:
C18H42O6SxSi2
IUPAC Name:
Reaction mass of 4,4,15,15-tetraethoxy-3,16-dioxa-8,9,10,11-tetrathia-4,15-disilaoctadecane and 4,4,14,14-tetraethoxy-3,15-dioxa-8,9,10-trithia-4,14-disilaheptadecane and 4,4,13,13-tetraethoxy-3,14-dioxa-8,9-dithia-4,13-disilahexadecane

Test animals

Species:
rat

Administration / exposure

Route of administration:
oral: gavage

Results and discussion

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion