Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

In vitro:
Gene mutation (Bacterial reverse mutation assay / Ames test, RA from CAS 3069-33-8): S. typhimurium TA 1535, TA 1537, TA 98, TA 100, and TA 102: negative with and without metabolic activation (OECD TG 471)
Mammalian Mutagenicity (HPRT Test, RA from CAS 1760-24-3): negative with and without metabolic activation (similar to OECD TG 476)


Link to relevant study records

Referenceopen allclose all

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
see attached document for justification of read-across
Reason / purpose:
read-across source
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
1000 ug/plate
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 98
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
100 - 1000 ug/plate
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
1000 ug/plate
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 102
Metabolic activation:
with
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
316 - 1000 ug/plate
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 102
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
100 - 1000 ug/plate
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
316 - 1000 ug/plate
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
100 - 1000 ug/plate
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1537
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
316 - 1000 ug/plate
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Conclusions:
Interpretation of results: negative

Endpoint:
in vitro gene mutation study in mammalian cells
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
see attached document for justification of read-across
Reason / purpose:
read-across source
Species / strain:
Chinese hamster Ovary (CHO)
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
4.0 mg/ml with metabolic activation
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Conclusions:
Interpretation of results: negative with and without metabolic activation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

In vivo:
Mouse Micronucleus Test (RA from CAS 1760-24-3): negative ( similar to OECD 474)

Link to relevant study records
Reference
Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
see attached document for justification of read-across
Reason / purpose:
read-across source
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Remarks:
LD50 354 mg/kg bw and above. PCE/NCE ratio was reduced at highest concentration, 48 h exposure and at all doses, 72 h exposure.
Vehicle controls validity:
valid
Negative controls validity:
not applicable
Positive controls validity:
valid
Conclusions:
Interpretation of results: negative
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

There are no data available on genetic toxicity of N-[3 -(dimethoxymethylsilyl)-2 -methylpropyl]ethylenediamine. In order to fulfil the standard information requirements set out in Annex VII, 8.3., in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from structurally related substances was conducted. In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across). Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006 whereby substances may be predicted as similar provided that their physicochemical and toxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity. Therefore, read across from the structural analogue substances N-[3-(methoxydimethylsilyl)propyl]ethylenediamine (CAS 3069-33-8) and N-(3 -(trimethoxysilyl)propyl)ethylenediamine (CAS 1760 -24 -3) were applied.

 

In vitro genotoxicity

In the available key study (LPT, 2002b) N-[3-(methoxydimethylsilyl)propyl]ethylenediamine (CAS 3069-33-8) was tested for bacterial mutagenicity according to the OECD TG 471, and in compliance with GLP. No test-substance related increase in the number of revertants was observed when tested in two independent experiments with and without metabolic activation up to the top concentration of 5000 µg/plate in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100, and TA 102 in the plate incorporation and preincubation assay. Appropriate solvent and positive controls were included and gave the expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.

 

In the available key study (Bushy Run Research Center, 1988a) N-(3-(trimethoxysilyl)propyl)ethylenediamine (CAS 1760-24-3) was tested for mammalian mutagenicity (HPRT Test) similar to the OECD TG 476, and in compliance with GLP. No increase in mutant frequency was observed at any concentration up to cytotoxicity with and without metabolic activation at 5 hours treatment. Expected results were obtained with positive, solvent, and negative controls. It is concluded that N-(3 -(trimethoxysilyl)propyl)ethylendiamine (CAS 1760 -24 -3) is negative for the induction of mutations in Chinese hamster Ovary cells (CHO) under the conditions of the test.

 

In vivo Genotoxicty

In the available key study (Bushy Run Research Center, 1988b) N-(3-(trimethoxysilyl)propyl)ethylenediamine (CAS 1760-24-3) was evaluated for genotoxicity to mammals in the in vivo mouse micronucleus assay in a study conducted according to the EPA Health Effect T G, EPA Report 560/6-83-001 (similar to the OECD TG 474), and in compliance with GLP. The test item was administered by a single intraperitoneal injection to both male and female Swiss Webster mice at doses of 87.5, 175 and 280 mg/kg bw (equivalent to approximately 25, 50, and 80% of the LD50 value determined in the range finding study). Samples from peripheral blood were taken 30, 48, and 72 h after test material injection. Appropriate vehicle and positive controls were included into the study and gave the expected results. No sex-related differences in the response were observed. No statistically significant (p ≤ 0.01) or treatment related increases in the numbers of micronuclei were observed at any dose or treatment interval. The PCE/NCE ratio was reduced at the highest concentration, 48 h exposure and at all doses, 72 h exposure, indicating exposure of the target tissue to the test substance.

Based on the outcome of this study, N-(3-(trimethoxysilyl)propyl)ethylenediamine (CAS 1760-24-3) is considered to be negative for the induction of micronuclei under the conditions of this test.

Based on the above results with the structural analogue substances sufficient evidence is given that the registration substance is considered to be not mutagenic.


Justification for classification or non-classification

The available in vitro and in vivo genotoxicity data are reliable and suitable for classification. Based on these data, classification for mutagenicity according to Regulation (EC)1272/2008 is not warranted.