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
Justification for type of information:
TESTING PROPOSAL ON VERTEBRATE ANIMALS for Extended one generation reproductive toxicity study (EOGRTS).

Substance name: 2,2'-[OXYBIS(METHYLENE)]BIS[2-ETHYLPROPANE-1,3-DIOL]

CONSIDERATIONS THAT THE GENERAL ADAPTATION POSSIBILITIES OF ANNEX XI OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION:
- No existing GLP studies study available for this endpoint.
- No existing non-GLP studies study available for this endpoint.
- No historical human data available for this endpoint.
- No existing (Q)SAR information can properly assess this endpoint.
- No existing in vitro method could address this endpoint.
- No sufficient information available that could fulfill the standard information requirement through the weight of evidence approach.
- No information from structurally similar substance can be used to fulfill the standard information requirement through grouping and 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:
- Extended one generation reproductive toxicity studies (EOGRTS) basic test design is the standard information requirement for substance registered for 1000 tonnes or more per year (Annex X, Section 8.7.3., column 1, of the REACH Regulation).


FURTHER INFORMATION ON TESTING PROPOSAL IN ADDITION TO INFORMATION PROVIDED IN THE MATERIALS AND METHODS SECTION:

No evidence of effect on the reproductive organs was seen in a 28-day and a 90-day repeated dose toxicity study at dose levels up to 1000 mg/kg bw/d. An extended one generation reproductive toxicity study according to OECD 443 guideline, basic test design (cohorts 1A and 1B without extension to include a F2 generation) is proposed at the present time. The detailed study design of EOGRTS will be further assessed to ensure its adequate assessment of possible effects and avoid unnecessary vertebrate animal use.

Data source

Materials and methods

Test guideline
Qualifier:
according to
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: 10 weeks.
- Basis for dose level selection: to be confirmed.
- Exclusion of extension of Cohort 1B: No information indicate the genotoxicity, endocrine disruption related effect of this substance. No information indicate the substance leads to significant exposure or specific metabolism pattern that would require extended exposure. Therefore, extension of cohort 1B to include the F2 generation is not proposed.
- Exclusion of developmental neurotoxicity Cohorts 2A/2B and Cohort 3: No indication of the developmental neurotoxicity or immunotoxicity of this substance was seen from existing information. Cohort 2A/2B and cohort 3 are considered not needed at this moment.
- Route of administration: Oral
- Other considerations: A prenatal developmental toxicity study in rabbits in ongoing. The detail study design of EOGRTS will be further assessed once the results from the prenatal study are available to ensure its adequate assessment of possible effects and avoid unnecessary vertebrate animal use.

Based on above considerations, an extended one generation reproductive toxicity study according to OECD 443 guideline, basic test design (cohorts 1A and 1B without extension to include a F2 generation) is proposed at the present time. Further study design details will be provided when the ongoing OECD 414 study results are available.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): DI-TMP

Test animals

Species:
rat
Strain:
Sprague-Dawley
Details on species / strain selection:
The Sprague Dawley SD rad is the species and strain of choice because there is ample experience and background data on this species and strain. It is also the species and strain used in other toxicity studies of this substance (ex. 90 days repeated dose study) which provide better results-comparison between studies.
Sex:
male/female

Administration / exposure

Route of administration:
oral: unspecified

Results and discussion

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion