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:
to be determined by ECHA - see attached document - increase time needed
Justification for type of information:
The substance is handled in the EU at volumes of greater than 1000 tons per annum and therefore, data requirements of Annex X of EC regulation 1907/2006 need to be met.
Since no adaptations to the standard testing requirement can be applied, the registrant proposes to perform an extended one-generation study (OECD 443) with the basic design. For details it is referred to the attached document.


NON-CONFIDENTIAL NAME OF SUBSTANCE:
- Name of the substance on which testing is proposed to be carried out: Isononanoic acid, C16-18 (even numbered)-alkyl esters CAS 111937-03-2

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: No GLP study fulfilling the requirements of OECD 443 is known to the registrant
- Available non-GLP studies: No non-GLP study fulfilling the requirements of OECD 443 is known to the registrant
- Historical human data: No human historical data is known to the registrant
- (Q)SAR: No reliable and adequate (Q)SAR model for this endpoint is known to the registrant.
- In vitro methods: No reliable and adequate in-vitro methods for this endpoint are known to the registrant.
- Weight of evidence: In the absence of the above data, a weight of evidence assessment is not possible.
- Grouping and read-across: recheck of further read across possiblilities is currently ongoing
- Substance-tailored exposure driven testing: not applicable
- Approaches in addition to above: not applicable
- Other reasons:not applicable

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:
The substance does not meet the criteria of specific adaptation possibilities of Annex VI to X and coloumn 2 thereof.

FURTHER INFORMATION ON TESTING PROPOSAL IN ADDITION TO INFORMATION PROVIDED IN THE MATERIALS AND METHODS SECTION:
- Details on study design / methodology proposed [if relevant]: see justification for study design below and attached pdf documents

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:
There is already some basic information available indicating that a basic module OECD 443 is sufficient to achieve the missing information. Based on the available 90d study with extended reproduction parameter (BASF SE, 2018) investigation weekly physical examinations including detailed clinical signs did not show any signs of neurotoxicity which could be correlated to the treatment with the test item. Concluding no DNT module is necessary. Further no toxicologically significant changes in hematology occurred in this study nor histopathological changes in immune correlated tissues are reportet. Hence, no further investigation of immuntoxicity is suggested. Concluding no DIT module is proposed. Additional no effects on fertility/development were only observed in a 90d study with extended reproduction (BASF SE, 2018) or in a teratogenicity study (BASF SE, 1997), concluding no additional cohort is proposed.


SPECIFICATION OF STUDY DESIGN FOR EXTENDED ONE-GENERATION REPRODUCTION TOXICITY STUDY WITH JUSTIFICATIONS:

- Premating exposure duration for parental (P0) animals: according to guideline (2 weeks)
- Basis for dose level selection: available 90d with extended reproduction (BASF SE, 2018)
- Exclusion of extension of Cohort 1B: see above
- Exclusion of developmental neurotoxicity Cohorts 2A and 2B: see above
- Exclusion of developmental immunotoxicity Cohort 3: see above
- Route of administration: Oral route is suggested as common route.
- Other considerations, e.g. on choice of species, strain, vehicle and number of animals: Rat is choose as prefered species.

Test material

Constituent 1
Chemical structure
Reference substance name:
Isononanoic acid, C16-18 (even numbered)-alkyl esters
EC Number:
601-141-6
Cas Number:
111937-03-2
Molecular formula:
Unspecified
IUPAC Name:
Isononanoic acid, C16-18 (even numbered)-alkyl esters
Details on test material:
- Name of test material: Isononanoic acid, C16-18-alkyl esters
- Analytical purity: no data
Specific details on test material used for the study:
details will be given when test is performed

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