1,2-Ethanediamine, N-{3-(trimethoxysilyl)propyl}-,N-{(ethenylphenyl)methyl}derivate,hydrochlorides

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Gene mutation (Bacterial reverse mutation assay / Ames test): negative with and without metabolic activation in Salmonella typhimurium strains TA98, TA100, TA1535, TA1537, and TA1538 (similar to OECD 471)

Gene mutation (Bacterial reverse mutation assay / Ames test): negative with and without metabolic activation in Salmonella typhimurium strains TA98, TA100, TA1535, TA1537 and Escherichia coli WP2 CM 881 and CM891 (EPA OPPTS 870.5100, similar to OECD 471) (RA from CAS 1760-24-3)

Cytogenicity in mammalian cells: testing not required as a reliable in vivo micronucleus is available.

Mutagenicity in mammalian cells: negative with and without metabolic activation in CHO cells (EPA Health Effects Test Guidelines HG-Gene Muta-Somatic Cells, similar to OECD TG 476) (RA from CAS 1760-24-3)

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Remarks:

Summary of available data used for the endpoint assessment of the target substance

Adequacy of study:

key study

Justification for type of information:

Please refer to the attached justification below and the overall justification for grouping of substances attached in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Species / strain:

E. coli WP2 uvr A pKM 101

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Species / strain:

E. coli, other: E. coli WP2 pKM101 (CM881)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not valid

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

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:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

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:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Remarks on result:

other: DCC, 1999

Three further reliable bacterial mutagenicity studies were performed with CAS 1760 -24 -3 which all showed solely negative results in test similar or according to OECD 471. The test substance was always test with and without metabolic activation and the vehicle and solvent controls were all valid.

Conclusions:

The source substance N-(3-(trimethoxysilyl)propyl)ethylenediamine (CAS 1760-24-3) has been tested for mutagenicity to bacteria, in a studies that were conducted similar or according to the OECD TG 471 and in compliance with GLP. No evidence of test substance related increase in the number of revertants was observed with or without activation in any of those tests. It is concluded that the source substance is negative for mutagenicity to bacteria under the conditions of the tests. As explained in the analogue justification, it is considered that the target and the source substances are unlikely to lead to differences in genetic toxicity potential.

Reference 2

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:

Please refer to the attached justification below and the overall justification for grouping of substances attached in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across source

GLP compliance:

yes

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:

The source substance N-(3-trimethoxysilyl)propyl)ethylenediamine has been tested in a reliable study according to an appropriate US EPA test guideline that is equivalent to OECD 476 and under GLP. An increase in mutant frequency was observed in one of two duplicate cultures with metabolic activation at one concentration in the initial experiment. No other increase in mutant frequency was observed at any concentration with and without activation (5 hours treatment). The experiment was repeated (with metabolic activation): no increase in mutant frequency was observed. The appropriate solvent and positive controls were included and gave expected results. It is concluded that the test substance is negative for the induction of mutations in CHO cells under the conditions of the test. As explained in the analogue justification, it is considered that the target and the source substances are unlikely to lead to differences in genetic toxicity potential.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

Micronucleus assay in mouse (ip administration): negative (EPA 560/6-83-001, similar to OECD 474) (RA from CAS 1760 -24-3). 

Micronucleus assay in mouse (ip administration): 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:

Please refer to the attached justification below and the overall justification for grouping of substances attached in IUCLID Section 13.

Reason / purpose for cross-reference:

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:

The source substance N-(3-(trimethoxysilyl)propyl)ethylenediamine (CAS 1760-24-3) has been tested in a reliable study according to EPA Health Effect T G, Report 560/6-83-001, which is similar to OECD 474, and under GLP conditions. No treatment related increases in numbers of micronuclei in PCE's of Swiss-Webster mice were observed. Relatively high dose levels of the test compound were tested up to 80% of the LD50 with no indication of significant induction of micronuclei. 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. The source substance is considered to be negative for the induction of micronuclei under the conditions of this test. As explained in the analogue justification, it is considered that the target and the source substances are unlikely to lead to differences in genetic toxicity potential.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Only limited genotoxicity data is available for 1,2-ethanediamine, N-{3-(trimethoxysilyl)propyl}-,N-{(ethenylphenyl)methyl}derivs,hydrochlorides (CAS 171869-89-9). Therefore, the risk assessment was performed based on the available data from the source substance, N-(3-(trimethoxysilyl)propyl)ethylenediamine (CAS 1760-24-3). In accordance with Regulation (EC) No. 1907/2006 Annex XI, 1.5 “Grouping of substances and read across” and following the Read across assessment framework (RAAF, ECHA 2017) read across from an analogue substance has been applied to support the human health hazard assessment of 1,2-ethanediamine, N-{3-(trimethoxysilyl)propyl}-,N-{(ethenylphenyl)methyl}derivs,hydrochlorides (CAS 171869-89-9). Details on read across justifications can be found in the attached justification in the respective target entry and in the overall justification for grouping of substances attached in IUCLID Section 13.

 

Bacterial Mutagenicity

A bacterial mutagenicity study that was conducted similarly to OECD TG 471 is available for 1,2-ethanediamine, N-{3-(trimethoxysilyl)propyl}-,N-{(ethenylphenyl)methyl}derivs,hydrochlorides (CAS 171869-89-9) (Dow Corning, 1977). Because this study was conducted prior to GLP standards and limited information on the test material, as well as study methods, were provided, it is considered a supporting study. In this study, there were no treatment-related increases in the number of revertants with or without metabolic activation for the overlay plate test for Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538. Appropriate positive and negative controls were evaluated concurrently.

The source substance N-(3-(trimethoxysilyl)propyl)ethylenediamine (CAS 1760-24-3) has been tested for mutagenicity to bacteria, in a study that was conducted similar to the OECD TG 471 and in compliance with GLP (DCC (1999)). No evidence of test substance related increase in the number of revertants was observed with or without activation in the initial or the repeat experiments using the plate incorporation method in Salmonella typhimurium strains TA 98, TA 100, TA 153, TA 1537, E coli WP2 trp uvrA pKM101 (CM891) and E coli WP2 trp pKM101 (CM881). The solvent used was water, and hydrolysis was likely to have occurred under test conditions, so it is assumed that exposure was to the hydrolysis product as well as the parent substance. It is not considered to invalidate the study, as it is considered that hydrolysis may occur in vivo. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test. The result of this study is supported by three older studies, where non-aqueous solvents were used: the results of all the studies on bacterial mutagenicity are in agreement. The most reliable study was selected as key.

Mammalian Mutagenicity

No data on mammalian mutagenicity is available for the registration substance (CAS 171869-89-9). However, the source substance N-(3-trimethoxysilyl)propyl)ethylenediamine (1760-24-3) has been tested in a reliable study according to an appropriate US EPA test guideline that is equivalent to OECD 476 and under GLP (Slesinski and Guzzie (1988)). An increase in mutant frequency was observed in one of two duplicate cultures with metabolic activation at one concentration in the initial experiment. No other increase in mutant frequency was observed at any concentration with and without activation (5 hours treatment). The experiment was repeated (with metabolic activation): no increase in mutant frequency was observed. The appropriate solvent and positive controls were included and gave expected results. It is concluded that the source substance is negative for the induction of mutations in CHO cells under the conditions of the test.

Cytogenicity

No in vitro cytogenicity study is available; testing is not required as a reliable in vivo micronucleus assay is available.

An in vivo micronucleus study conducted similarly to OECD 474 is available for 1,2-ethanediamine, N-{3-(trimethoxysilyl)propyl}-,N-{(ethenylphenyl)methyl}derivs,hydrochlorides (CAS 171869-89-9) (Dow Corning, 1992). This study is considered supporting because there is limited information regarding the test material. No treatment-related increases in the numbers of micronuclei in PCE's of CD-1 mice were observed after intraperitoneal administration. Animals in this study received three dose levels and the high-dose level of the test compound was tested up to the 60% of the LD50 with no indication of significant induction of micronuclei. Positive controls were evaluated concurrently and demonstrated an appropriate response. The test compound was considered to be negative for the induction of micronuclei under the conditions of this test.

The source substance N-(3-(trimethoxysilyl)propyl)ethylenediamine (CAS 1760-24-3) has been tested in a reliable in vivo micronucleus study according to EPA Health Effect T G, Report 560/6-83-001, which is similar to OECD 474, and under GLP conditions (BRRC (1988)). No treatment related increases in numbers of micronuclei in PCE's of Swiss-Webster mice were observed after intraperitoneal administration. Relatively high dose levels of the test compound were tested up to 80% of the LD50 with no indication of significant induction of micronuclei. 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. The test compound is considered to be negative for the induction of micronuclei under the conditions of this test.

 

In conclusion: No evidence of mutagenicity or clastogenicity was observed in any of the available in vitro and in vivo studies with the source and the target substance.

Justification for classification or non-classification

The available data on genetic toxicity do not meet the criteria for classification according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.