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:
The study period is to be confirmed following confirmation of the testing proposal by ECHA
Justification for type of information:
TESTING PROPOSAL ON VERTEBRATE ANIMALS
- Name of the substance on which testing is proposed to be carried out: Tetrahydro-2-methylfuran (MeTHF)

CONSIDERATIONS THAT THE GENERAL ADAPTATION POSSIBILITIES OF ANNEX XI OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION:
- Available GLP studies:
No GLP data are available to address this endpoint (reproductive toxicity. Repeated dose toxicity studies performed to GLP are not sufficient to address this endpoint, but do not indicate any specific concerns of relevance to reproductive toxicity.

- Available non-GLP studies:
No non-GLP studies are available to adequately address the reproductive toxicity endpoint for MeTHF.

- Historical human data:
No historical human data are available for MeTHF.

- (Q)SAR:
(Q)SAR models for the reproductive toxicity endpoint are not sufficiently validated for regulatory acceptance

- In vitro methods
No validated in vitro methods are available for the reproductive toxicity endpoint; models are not sufficiently reliable for regulatory acceptance.

- Weight of evidence
Insufficient reliable data are available to complete the data requirements as a weight of evidence approach.

- Grouping and read-across:
No substances with data suitable for grouping and read-across are identified.

- Substance-tailored exposure driven testing
Not applicable

- Approaches in addition to above
Not applicable

- Other reasons
Not applicable

FURTHER INFORMATION ON TESTING PROPOSAL IN ADDITION TO INFORMATION PROVIDED IN THE MATERIALS AND METHODS SECTION:
- It is proposed to conduct an EOGRTS in the rat using the registered substamce according to OECD TG 443 and using the (preferred) oral route of exposure.

The proposed study will include extension of the F0 pre-mating exposure period to 10 weeks.

In the absence of specific triggers or concerns, extension of cohort 1B to include the F2 generation is not proposed. The substance does not display genotoxic effects in somatic cell mutagenicity tests in vivo which could lead to classification as Mutagen Category 2 There is no indication that the internal dose for the substance and/or any of its metabolites will reach steady state only after extended exposure. Furthermore, there are no indications of relevant modes of action related to endocrine disruption.

It is not proposed to include Cohorts 2A or 2B in the absence of any specific triggers or concerns. There is no evidence from the existing dataset, from a MoA or from any analogous substance that MeTHF has any (developmental) neurotoxicity potential.

It is not proposed to include Cohort 3 in the absence of any specific triggers or concerns. There is no evidence from the existing dataset, from a MoA or from any analogous substance that MeTHF has any (developmental) immunotoxicity potential.









Data source

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 443 (Extended One-Generation Reproductive Toxicity Study)
Version / remarks:
2018
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, to cover a complete spermatogenic cycle

- Basis for dose level selection: dose levels will be selected based on existing toxicity data, taking into account the MTD and recommendations of the study guideline

- Inclusion/exclusion of extension of Cohort 1B: In the absence of specific triggers or concerns, extension of Cohort 1B to include the F2 generation is not proposed. The substance does not display genotoxic effects in somatic cell mutagenicity tests in vivo which could lead to classification as Mutagen Category 2 There is no indication that the internal dose for the substance and/or any of its metabolites will reach steady state only after extended exposure. Furthermore, there are no indications of relevant modes of action related to endocrine disruption.

- Termination time for F2: not applicable (extension of Cohort 1B to include the F2 generation is not proposed)

- Inclusion/exclusion of developmental neurotoxicity Cohorts 2A and 2B: It is not proposed to include Cohorts 2A or 2B in the absence of any specific triggers or concerns. There is no evidence from the existing dataset, from a MoA or from any analogous substance that MeTHF has any (developmental) neurotoxicity potential.

- Inclusion/exclusion of developmental immunotoxicity Cohort 3: It is not proposed to include Cohort 3 in the absence of any specific triggers or concerns. There is no evidence from the existing dataset, from a MoA or from any analogous substance that MeTHF has any (developmental) immunotoxicity potential.

- Route of administration: oral

- Other considerations, e.g. on choice of species, strain, vehicle and number of animals: not applicable

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 2-methyltetrahydrofuran; MeTHF CAS 96-47-9
- Substance type: Monoconstituent substance
- Physical state: no information
- Analytical purity: no information

Test animals

Species:
rat

Administration / exposure

Route of administration:
oral: unspecified
Details on exposure:
details to be provided

Results and discussion

Applicant's summary and conclusion