Registration Dossier

Administrative data

Endpoint:
extended one-generation reproductive toxicity - with developmental neurotoxicity (Cohorts 1A, 1B without extension, 2A and 2B)
Type of information:
experimental study planned
Study period:
To be determined.
Justification for type of information:
TESTING PROPOSAL ON VERTEBRATE ANIMALS
An Extended One-Generation Reproductive Toxicity Study including assessment for developmental neurotoxicity in the rat is proposed as a standard information requirement as laid down in Annex X, Section 8.7.3. of the REACH Regulation.

NON-CONFIDENTIAL NAME OF SUBSTANCE:
- Triallyl cyanurate

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: A 28-day and a 90-day oral Repeated Dose Toxicity Study are available, which were conducted in compliance with GLP according to OECD TG 407 or 408, respectively. Furthermore, a Prenatal Developmental Toxicity according to OECD TG 414 was conducted in the rat.
- Available non-GLP studies: none available for toxicity to reproduction endpoint
- Historical human data: no data available
- (Q)SAR: No data available. There are a large number of potential targets/mechanisms associated with reproductive toxicity which, on the basis of current knowledge, cannot normally be adequately covered by a battery of QSAR models. QSAR approaches are currently not well fitted-for-purpose for reproductive toxicity (according to Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.7a, Version 5.0, Dez 2016).
- In vitro methods: No accepted alternative in vitro methods to predict developmental toxicity for regulatory use are available (according to Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.7a, Version 5.0, Dez 2016).
- Weight of evidence: Insufficient data existing
- Grouping and read-across: No read-across data available.

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 adaptation posssiblities to address this specific endpoint.

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 study (OECD 443) with basic test design and developmental neurotoxicity (Cohorts 1A and 1B, without extension, 2A and 2B) will be conducted per oral administration with Triallyl cyanurate.







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: 10 weeks
- Basis for dose level selection: 90-day study (OECD408), developmental toxicity study in rats (OECD414), DRF to be conducted
- Inclusion/exclusion of extension of Cohort 1B: No trigger for the inclusion of cohort 1B were derived from previous studies.
- Termination time for F2: not applicable
- Inclusion/exclusion of developmental neurotoxicity Cohorts 2A and 2B: Obvious functional effects (slight waddling gait, a lack of normal response to toe or tail pinch, an impaired ability for wire maneuver, increased positional passivity, and a lowered resistance on limb rotation) were observed in the 90-day study in absence of histopathological effects in brain, sciatic nerve and spinal cord. Therefore, cohorts 2A and 2B are proposed in order to assess developmental neurotoxicity.
- Inclusion/exclusion of developmental immunotoxicity Cohort 3: No trigger for the inclusion of cohort 3 were derived from previous studies.
- Route of administration: oral (tbd if administration will be via gavage, diet or drinking water)
- Other considerations, e.g. on choice of species, strain, vehicle and number of animals: no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline

Test animals

Species:
rat

Administration / exposure

Route of administration:
oral: unspecified

Results and discussion

Applicant's summary and conclusion