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

NON-CONFIDENTIAL NAME OF SUBSTANCE:
- Name of the substance on which testing is proposed to be carried out : Amides, C16-C18 (even) , N,N'-ethylenebis
- EC / List no.: 931-299-4

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 studies addressing reproductive toxicity are available, neither with the registered substance nor with any adequate analogue substance.
- Available non-GLP studies : No non-GLP studies addressing reproductive toxicity are available, neither with the registered substance nor with any adequate analogue substance.
- Historical human data: No historicaal human data addressing reproductive toxicity are available, neither with the registered substance nor with any adequate analogue substance.
- (Q)SAR: The reliable estimation of the reproductive toxicity by (Q)SAR calculations is not possible.
- In vitro methods: No in vitro methods reliably addressing reproductive toxicity are available.
- Weight of evidence: No studies to be accounted for by means of a Weight-of-Evidence approach are available.
- Grouping and read-across: Grouping and read-across are not possible as there are no adequate analogue substances. These approaches are further complicated due to the UVCB nature of the registered substance.

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:
An Extended One-Generation Reproductive Toxicity Study (EOGRTS, B.56 of the Commission Regulation on test methods as specified in Article 13(3) or OECD 443), basic test design (cohorts 1A and 1B without extension to include a F2 generation), one species, most appropriate route of administration, having regard to the likely route of human exposure, is a standard information requirement according to Annex X, Item 8.7.3., of the REACH Regulation (EC) No. 1907/2006. No specific adaptation possibilities are laid down in the Annexes VII to X, including Column 2 thereof. Moreover, the general adaptation options of Annex XI are not applicable to the registered substance as detailed above. In conclusion, since there are no data available addressing toxicity to reproduction of the registered substance, an EOGRTS, basic test design (cohorts 1A and 1B without extension to include a F2 generation), in rats, using the oral route of administration is proposed to comply with the information requirement relevant for the registered tonnage.

Data source

Materials and methods

Test guideline
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:

Since non of the conditions and triggers set out in Annex X, Item 8.7.3., Column 2, of REACH are met, the study design set out in Annex X, Item 8.7.3., Column 1 (basic test design (cohorts 1A and 1B without extension to include a F2 generation)) is considered appropriate to address the standard information requirement of toxicity to reproduction of the registered substance.

- Basis for dose level selection : Doses levels will be based on the results of the Repeated Dose 90-Day Oral Toxicity study in rats.
- Inclusion/exclusion of extension of Cohort 1B: The basic test design (cohorts 1A and 1B without extension to include a F2 generation) is required according to Annex X, Item 8.7.3., Column 1.
- Termination time for F2 : Only the basic test design is required according to Annex X, Item 8.7.3., Column 1.
- Inclusion/exclusion of developmental neurotoxicity Cohorts 2A and 2B : No effects indicative of neurotoxicity were observed in the subchronic (90-day) repeated dose toxicity study (OECD 408) and in the prenatal developmental toxicity study (OECD 414) performed with the registered substance. Moreover, only the basic test design is required according to Annex X, Item 8.7.3., Column 1.
- Inclusion/exclusion of developmental immunotoxicity Cohort 3 : No effects indicative of immunotoxicity were observed in the subchronic (90-day) repeated dose toxicity study (OECD 408) and in the prenatal developmental toxicity study (OECD 414) performed with the registered substance. Moreover, only the basic test design is required according to Annex X, Item 8.7.3., Column 1.
- Route of administration : Oral

Test material

Constituent 1
Reference substance name:
Amides, C16-18 (even), N,N'-ethylenebis
IUPAC Name:
Amides, C16-18 (even), N,N'-ethylenebis
Test material form:
solid: particulate/powder

Test animals

Species:
rat

Results and discussion

Applicant's summary and conclusion