Registration Dossier

Toxicological information

Toxicity to reproduction

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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:
See comments in section "Principles of method if other than guideline"
Justification for type of information:
TESTING PROPOSAL ON VERTEBRATE ANIMALS

CONSIDERATIONS THAT THE GENERAL ADAPTATION POSSIBILITIES OF ANNEX XI OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION
• available GLP studies: none.
• available non-GLP studies: none.
• historical human data: none.
• (Q)SAR: according to ECHA guidance, QSAR approaches are currently not well fitted-for-purpose for reproductive toxicity and not all necessary aspects can be covered by a QSAR prediction. (ECHA guidance R.7a, October 2015, page 382).
• in vitro methods: in vitro studies are not available on the test substance. Some in vitro test methods have been developed, however, according to Chapter R 7a Version 4.1, the regulatory acceptance of these in vitro methods has not been achieved as they do not provide equivalent information (ECHA guidance R.7a, October 2015, page 381).
• weight of evidence: no data is available which allow a weight of evidence approach.
• grouping and read-across: not appropriate.
• substance-tailored exposure driven testing [if applicable]: not applicable
• [approaches in addition to above [if applicable]: not applicable
• other reasons [if applicable]: none
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:
- Test proposal is fully compliant with ECHA guidance (R 7.a-Octobre 2015, page 373). No specific adaptation possibilities of Annexes VI to X (and column 2 thereof) are applicable.

Data source

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 443 (Extended One-Generation Reproductive Toxicity Study)
Principles of method if other than guideline:
Considering the actual workload of the contract research organizations (CRO) due to the next REACH registration deadline in May 2018 and also due to the test plans on the substances registered in 2013, the limited capacity of CROs to perform the OECD 443 studies and which are booked by the testing of the substances registered in 2010 and also to allow a sequential assessment of the reproductive end-points of the registered substance (OECD 414 study in rabbits and OECD 443 study in rats including a range-finding study), the registrant is requesting a delay of 48 months to update its dossier with the proposed studies.
GLP compliance:
yes
Limit test:
no
Justification for study design:
Based on the results of the OECD 413 study, there is no specific concern for neurotoxicity and immunotoxicity. Therefore, the registrant does not propose the inclusion of the developmental immunotoxicity (DIT) and developmental neurotoxicity (DNT) cohorts.

SPECIFICATION OF STUDY DESIGN FOR EXTENDED ONE-GENERATION REPRODUCTION TOXICITY STUDY WITH JUSTIFICATIONS [please address all points below]:

- Premating exposure duration for parental (P0) animals : 4 weeks
- Basis for dose level selection: according to a range-finding oral toxicity study (OECD 421 or 422) to be performed
- Exclusion of extension of Cohort 1B
- Termination time for F2: not relevant
- Exclusion of developmental neurotoxicity Cohorts 2A and 2B
- Exclusion of developmental immunotoxicity Cohort 3
- Route of administration: oral
- Other considerations, e.g. on choice of species, strain, vehicle and number of animals [if applicable]

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat

Administration / exposure

Route of administration:
oral: gavage

Results and discussion

Applicant's summary and conclusion