N-methyl-3-(trimethoxysilyl)propylamine

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Genetic toxicity in vitro:

Bacterial mutagenicity (Ames test, OECD 471, WoE): S. typhimurium TA 98, TA 100, TA 1535, TA 1537, TA 102 and E. coli WP2: negative with and without metabolic activation (RA from CAS 1760-24-3 and CAS 227085-51-0)

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

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

Adequacy of study:

weight of evidence

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

Key result

Species / strain:

S. typhimurium, other: TA 1535, TA 1537, TA 98 and 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

Key result

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

Key result

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

Key result

Species / strain:

other: S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

Exp. I: at 5000 µg/plate without S9-mix (TA 98, TA 102, TA 1535, TA 1537); Exp. II: ≥2500 µg/plate without S9-mix (TA 98, TA 100, TA 102)

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: CAS 1760-24-3

Remarks:

Huntingdon Life Sciences 1999

Conclusions:

CAS 1760-24-3 and CAS 227085-51-0 were not mutagenic in an Ames test. As explained in the analogue justification, the differences in molecular structure between the target and the source are unlikely to lead to differences in genetic toxicity. Thus, N-Methylaminopropyltrimethoxysilane is considered to be non-mutagenic in bacteria.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (positive)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

No data on genetic toxicity in vitro is available with N-methyl-3-(trimethoxysilyl)propylamine (CAS 3069-25-8). Therefore, read across from the structurally similar source substances N-(3-(trimethoxysilyl)propyl)ethylenediamine (CAS 1760-24-3) and N-ethyl-3-trimethoxysilyl-2-methylpropanamine (CAS 227085-51-0) was applied. In accordance with Regulation (EC) No. 1907/2006 Annex XI, 1.5 “Grouping of substances and read across” and in accordance with the Read across assessment framework (RAAF, ECHA 2017) read across from analogue substances has been applied to support the human health hazard assessment of N-methyl-3-(trimethoxysilyl)propylamine (CAS 3069-25-8).

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.

 

No measured data are available to assess the genotoxic potential in vitro of N-methyl-3-(trimethoxysilyl)propylamine (CAS 3069-25-8). However, reliable data are available for the source substances, N-(3-(trimethoxysilyl)propyl)ethylenediamine (CAS 1760-24-3) and N-ethyl-3-trimethoxysilyl-2-methylpropanamine (CAS 227085-51-0). Both structural analogues were found to be not mutagenic to bacteria. The substances are all structural analogues and have similar silicon containing hydrolysis products and therefore read-across to the target substance is appropriate. The other hydrolysis product methanol is not genotoxic.

 

 

Genetic toxicity (mutagenicity) in bacteria in vitro

A reliable bacterial gene mutation study (Ames test) performed according to an appropriate US EPA test guideline that is equivalent to OECD 471 and in compliance with GLP with N-(3-(trimethoxysilyl)propyl)ethylenediamine (CAS 1760-24-3) is available (Huntingdon Life Science, 1999). The strains Salmonella typhimurium TA 1535, TA 1537, TA 98 and TA 100 as well as the E. coli strains E. coli WP2 uvrA and E. coli WP2 were tested according to the plate incorporation (experiment I) and pre-incubation (experiment II) procedure in the absence and presence of a metabolic activation system (Aroclor 1254-induced rat liver S9-mix). Two independent experiments were conducted in three repetitions at each concentration from 50 to 5000 µg/plate. No cytotoxicity was observed with the test item up to 5000 µg/plate in the absence and presence of metabolic activation. Appropriate solvent (water) and positive controls were included and gave the expected results. No significant increase in the number of revertants was observed in any of the tester strains with and without metabolic activation. Therefore, the test material was considered to be non-mutagenic under the conditions of the test.

 

A further reliable bacterial gene mutation study (Ames test) performed according to OECD 471 and in compliance with GLP with N-ethyl-3-trimethoxysilyl-2-methylpropanamine (CAS 227085-51-0) is available (RCC, 2001a). The strains Salmonella typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102 were tested according to the plate incorporation (experiment I) and pre-incubation (experiment II) procedure in the absence and presence of a metabolic activation system (phenobarbital and β-naphtholflavone-induced rat liver S9-mix). Two independent experiments were conducted in three repetitions at each concentration from 33 to 5000 µg/plate. Relevant toxic effects occurred in all strains except TA 100 in the first experiment at 5000 µg/plate without metabolic activation. In the second experiment substantial toxic effects were observed in strains TA 98, TA 100 and TA 102 at 2500 and 5000 µg/plate without metabolic activation. Appropriate solvent (DMSO) and positive controls were included and gave the expected results. No significant increase in the number of revertants was observed in any of the tester strains with and without metabolic activation. Therefore, the test material was considered to be non-mutagenic under the conditions of the test.

 

Justification for classification or non-classification

Based on the available data on genetic toxicity the registered substance is not considered to induce genetic toxicity in bacteria. However, no final decision on classification for genetic toxicity according to Regulation (EC) 1272/2008 can be made, as no information on chromosomal aberration and mutagenicity in mammalian cells/in vivo is available.