Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study planned
Justification for type of information:
The attached document provides evidence generated for a testing proposal for developmental toxicity (OECD 414) using weight of evidence from structurally similar substances, identified using validated QSAR models.

The substance 1,2-Ethanediamine, N-(2-aminoethyl)-, reaction products with glycidyl tolyl ether is a multiconstituent substance which predominantly consists of secondary aliphatic amines, with the exception of one CGE dimer.
Various QSAR models were run on the identified constituents of the substance. Predictions with the CAESAR model revealed some positive predictions for developmental toxicity. The DART model profiler showed positive results of the unspecific category Known precedent reproductive and developmental toxic potential; Toluene and small alkyl toluene derivatives (8a) for all structures of the substance. And in the CAT-SAR system, for Human Developmental Toxicity the CGE-DIMER revealed equivocal results for developmental toxicity.
On the basis of positive indication for developmental effects from the various QSAR models it is proposed to conduct an OECD 414 Prenatal Developmental Toxicity Study (Annex IX 8.7.2) in order to clarify specifically this concern.
Thus, an OECD 421 Reproductive and Developmental Toxicity Screening Test would provide less information and is therefore waived in accordance with column 2 of REACH Annex VIII 8.7.1.

Alternative approaches are excluded based on the following considerations:
• Available GLP studies There is no experimental GLP- study regarding toxicity on reproduction or teratogenicity available
• Available non-GLP studies There is no experimental study regarding toxicity on reproduction or teratogenicity available
• Grouping and read-across Due to the concern from the QSAR calculations and the complexity of an multiconstituent read across is not further considered
• Historical human data Not available
• (Q)SAR Data provided, see above, in attached document and endpoint entries
• In vitro methods Due to the concern from the QSAR calculations and the complexity of an multiconstituent in in vitro systems, in vitro testing is not further considered
• Weight of evidence Data generated using QSAR raise a concern for developmental toxicity, which should be clarified by the proposed OECD 414 study, there is no further data available for a weight of evidence approach
• Substance-tailored exposure
driven testing [if applicable] Not applicable. In order to clarify the concern, the OECD study 414 is considered appropriate

Data source

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Version / remarks:
rats

Test material

Constituent 1
Chemical structure
Reference substance name:
1,2-Ethanediamine, N-(2-aminoethyl)-, reaction products with glycidyl tolyl ether
EC Number:
282-199-6
EC Name:
1,2-Ethanediamine, N-(2-aminoethyl)-, reaction products with glycidyl tolyl ether
Cas Number:
84144-79-6
Molecular formula:
C14H26N3O2
IUPAC Name:
1,2-Ethanediamine, N-(2-aminoethyl)-, reaction products with glycidyl tolyl ether
Details on test material:
1,2-Ethanediamine, N-(2-aminoethyl)-, reaction products with glycidyl tolyl ether as generic entry for a waiver or QSAR

Test animals

Species:
rat

Results and discussion

Applicant's summary and conclusion