N-{3-[dimethoxy(methyl)silyl]propyl}butan-1-amine

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Ames test according to OECD TG 471: negative

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

15th January to 18th January 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

21st July, 1997

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

Version / remarks:

May 30, 2008

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.5100 - Bacterial Reverse Mutation Test (August 1998)

GLP compliance:

yes (incl. QA statement)

Remarks:

Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit

Type of assay:

bacterial reverse mutation assay

Target gene:

His operon

Species / strain / cell type:

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

Metabolic activation:

with and without

Metabolic activation system:

cofactor supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of rats treated with phenobarbital and β-naphthoflavone

Test concentrations with justification for top dose:

Experiment I (plate incorporation test): 0.0100, 0.0316, 0.100, 0.316, 1.0, 2.5 and 5.0 µL/plate
Experiment II (pre-incubation test): 0.00316, 0.0100, 0.0316, 0.100, 0.316, 1.0, 2.5 and 5.0 µL/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: The solvent was compatible with the survival of the bacteria and the S9 activity.

Untreated negative controls:

yes

Remarks:

A. dest.

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

sodium azide

methylmethanesulfonate

other: 2-aminoanthracene

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar
- Cell density at seeding (if applicable): approx. 10E9 cells/mL

DURATION
- Preincubation period: 60 min for pre-incubation method
- Exposure duration: at least 48 h

NUMBER OF REPLICATIONS: 3

DETERMINATION OF CYTOTOXICITY
- Method: Cytotoxicity was detected by a clearing or rather diminution of the background lawn or a reduction in the number of revertants down to a mutation factor of approximately ≤ 0.5 in relation to the solvent control.

Evaluation criteria:

A test item was considered as mutagenic if:
- a clear and dose-related increase in the number of revertants occurs and/or
- a biologically relevant positive response for at least one of the dose groups occurs in at least one tester strain with or without metabolic activation.

A biologically relevant increase was described as follows:
- if in tester strains TA98, TA100 and TA102 the number of reversions was at least twice as high
- if in tester strains TA 1535 and TA 1537 the number of reversions was at least three times higher than the reversion rate of the solvent control.

Statistics:

Not reported

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

cytotoxic effects at 2.5 µL/plate and higher, ±S9

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

cytotoxic effects at 1.0 µL/plate and higher, ±S9

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

cytotoxic effects at 2.5 µL/plate and higher, ±S9

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

cytotoxic effects at 2.5 µL/plate and higher, ±S9

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

cytotoxic effects at 5.0 µL/plate, ±S9

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation:
No precipitation of the test item was observed in any tester strain used in experiment I and II (with and without metabolic activation).

RANGE-FINDING/SCREENING STUDIES:
Cytotoxicity was observed in both strains (TA98 and TA100) of the preliminary experiment at 5000 µg/plate, ±S9, as evidenced by a reduction in background lawn. Reduced background lawn also was observed at 2500 µg/plate, -S9, for strain TA100.

ADDITIONAL INFORMATION ON CYTOTOXICITY:
- Measurement of cytotoxicity used: Toxicity was detected by a clearing or rather diminution of the background lawn or a reduction in the number of revertants down to a mutation factor of approximately ≤ 0.5 in relation to the solvent control. Toxic effects of the test item were noted in all tester strains evaluated in experiment I and II.

Conclusions:

In conclusion, it can be stated that during the described mutagenicity test and under the experimental conditions reported, N-{3-[dimethoxy(methyl)silyl]propyl}butan-1-amine did not cause gene mutations by base pair changes or frameshifts in the genome of the tester strains used. Therefore, N-{3-[dimethoxy(methyl)silyl]propyl}butan-1-amine is considered to be non-mutagenic in this bacterial reverse mutation assay.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In the Ames assay conducted according to OECD 471 and GLP compliant, the plate incorporation test (Experiment I) and the pre-incubation test (Experiment II) were performed with N-{3-[dimethoxy(methyl)silyl]propyl}butan-1-amine using Salmonella typhimuriumstrains TA98, TA100, TA1535, TA1537 and TA102 with and without metabolic activation (Eurofins, 2018). The following concentrations of the test item were used in the experiments: 0.0100, 0.0316, 0.100, 0.316, 1.0, 2.5 and 5.0 µL/plate for Experiment I; and 0.00316, 0.0100, 0.0316, 0.100, 0.316, 1.0, 2.5 and 5.0 µL/plate for Experiment II.

No precipitation of the test item was observed in any tester strain used in experiment I and II (with and without metabolic activation). Cytotoxicity was observed in both experiments. In Experiment I, toxic effects of the test item were observed at concentrations of 2.5 µL/plate and higher, -S9, and at a concentration of 5.0 µl/plate, +S9, depending on the particular tester strain. In Experiment II toxic effects of the test item were noted at concentrations of 1.0 µL/plate and higher, -S9, and at concentrations of 2.5 µL/plate and higher, +S9, depending on the particular tester strain.

No biologically relevant increases in revertant colony numbers of any of the five tester strains were observed following treatment with N-{3-[dimethoxy(methyl)silyl]propyl}butan-1-amine at any concentration level, neither in the presence nor absence of metabolic activation in experiment I and II. In conclusion, it can be stated that during the described mutagenicity test and under the experimental conditions reported, N-{3-[dimethoxy(methyl)silyl]propyl}butan-1-amine did not cause gene mutations by base pair changes or frameshifts in the genome of the tester strains used. Therefore, N-{3-[dimethoxy(methyl)silyl]propyl}butan-1-amine is considered to be non-mutagenic in this bacterial reverse mutation assay.

Justification for classification or non-classification

Based on the available data on genetic toxicity, there is no indication that N-{3-[dimethoxy(methyl)silyl]propyl}butan-1-amine induces genetic toxicity in bacteria. However, no final decision on classification for genetic toxicity according to Regulation (EC) No. 1272/2008 can be made, as no information on chromosomal aberration and mutagenicity in mammalian cells/in vivo is available.