N-(5-chloro-2-isopropylbenzyl)cyclopropanamine

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

1997

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

N-{[5-chloro-2-(propan-2-yl)phenyl]methyl}cyclopropanamine

EC Number:

941-682-8

Cas Number:

1476113-93-5

Molecular formula:

C13 H18 Cl N

IUPAC Name:

N-{[5-chloro-2-(propan-2-yl)phenyl]methyl}cyclopropanamine

Method

Species / strain

Species / strain 1

Species / strain / cell type:

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

Species / strain 2

Species / strain / cell type:

E. coli WP2 uvr A

Metabolic activation:

with and without

Metabolic activation system:

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

Test concentrations with justification for top dose:

Initial Mutation Test (Exp.1) and Confirmatory Mutation Test (Exp.2):
- 0.5, 1.581, 5, 15.81, 50, 158.1, 500, 1581 μg/plate (with and without metabolic activation, all Salmonella strains)
- 5, 15.81, 50, 158.1, 500, 1581 and 5000 μg/plate (with and without metabolic activation, E. coli WP2 uvrA)

Complementary Confirmatory Mutation Test (Exp.3):
- 0.05, 0.1581, 0.5, 1.581, 5, 15.81, 50, 158.1 μg/plate (without metabolic activation, all Salmonella strains)
- 0.1581, 0.5, 1.581, 5, 15.81, 50, 158.1 and 500 μg/plate (with and without metabolic activation, E. coli WP2 uvrA)

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

sodium azide

methylmethanesulfonate

other: 4-nitro-1,2-phenylenediamine (-S9-mix: TA98), 2-aminoanthracene (+ S9-mix: all tester strains)

Results and discussion

Test results

Test results 1

Key result

Species / strain:

other: S. typhimurium TA98, TA100, TA1535 and TA1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

In Exp.1 cytotoxicity was observed in all 4 Salmonella strains starting at 500 μg/plate with and without S9-mix. In addition, in TA1537 the number of revertants decreased to less than half at 50 µg/plate without and at 158.1 μg/plate with S9-mix.

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 2

Key result

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

In Exp. 1 cytotoxicity was observed starting at 1581 μg/plate with S9-mix and starting at 500 μg/plate without S9-mix. In Exp.2 excessive cytotoxicity was observed starting at 158.1 μg/plate with and without S9-mix.

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Remarks on result:

other: In the Exp.2 excessive cytotoxicity was observed in TA98, TA100 and TA1537 starting at 50 μg/plate without S9-mix and starting at 158.1 μg/plate with S9-mix.

Remarks:

In TA1535 excessive cytotoxicity was observed in Exp.2 at 158.1 μg/plate without S9-mix and starting at 158.1 μg/plate with S9-mix. In Exp. 3 the number of revertants decreased to less than half in TA98 and TA100 at 158.1 μg/plate and in TA98 additionally at 50 μg/plate without S9-mix.

Applicant's summary and conclusion

Conclusions:

The potential of the test substance to induce gene mutations was examined in 4 Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537 and in the Escherichia coli WP2 uvrA strain in two independent experiments, which were carried out without and with metabolic activation. Due to excessive cytotoxicity in one of the other experiments a third, additional experiment was carried out with and without metabolic activation in the E.coli strain, but only without metabolic activation in the four Salmonella strains. The first experiment was carried out as a plate incorporation test and the second and third experiment as a preincubation test. The test material was considered to be non-mutagenic either in the presence or absence of metabolic activation in the plate incorporation as well as in the preincubation test.