3,4-dimethoxyphenethylamine

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Data is from publication.

Data source

Reference

Reference Type:

publication

Title:

Assay of 855 Test Chemicals in Ten Tester Strains Using a New Modification of the Ames Test for Bacterial Mutagens

Author:

Robert E. McMahon,' John C. Cline and Christina Z. Thompson

Year:

1979

Bibliographic source:

CANCER RESEARCH 39, 682-693, March 1979

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: As mention below

Principles of method if other than guideline:

To evaluate the mutagenic potential for Homoveratrylamine in 10 tester strain of Salmonella Typhimurium and E.coli by Bacterial Mutagen Screen on Gradient Plates with Metabolic Activation.

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

4-methoxyphenylacetone

EC Number:

204-578-7

EC Name:

4-methoxyphenylacetone

Cas Number:

122-84-9

Molecular formula:

C10H12O2

IUPAC Name:

1-(4-methoxyphenyl)propan-2-one

Details on test material:

- Name of test material (IUPAC name): 1-(4-methoxyphenyl)propan-2-one
- Common name: 4-Methoxyphenylacetone
- Molecular formula: C10H12O2
- Molecular weight: 164.203 g/mol
- Smiles notation: c1(ccc(OC)cc1)CC(C)=O
- InChl: 1S/C10H12O2/c1-8(11)7-9-3-5-10(12-2)6-4-9/h3-6H,7H2,1-2H3
- Substance type: Organic

Specific details on test material used for the study:

- Name: 2-(3,4-dimethoxyphenyl)ethan-1-amine
- InChI:1S/C10H15NO2/c1-12-9-4-3-8(5-6-11)7-10(9)13-2/h3-4,7H,5-6,11H2,1-2H3
- Smiles:COc1ccc(CCN)cc1OC
- Name of test material: Homoveratrylamine
- Molecular formula :C10H15NO2
- Molecular weight :181.2335 g/mol
- Substance type:organic

Method

Target gene:

Histidine for Salmonella Typhimurium and Tryptophan for E.coli

Species / strain

Species / strain / cell type:

bacteria, other: Salmonella Typhimurium strain D3052, TA1538, TA98, C3076,TA1537, G46, TA1535, and TA100. E.coli WP2, and WP2 uVrA

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

other: R-factor plasmids

Cytokinesis block (if used):

Not specified

Metabolic activation:

with and without

Metabolic activation system:

Adult male Fischer rats live induced with Aroclor 1254 were used to prepare S9 metabolic activation.

Test concentrations with justification for top dose:

1-1000-µg/ml

Vehicle / solvent:

DMSO

Controls

Untreated negative controls:

yes

Remarks:

Plates containing no compound are also prepared to serve as negative controls.

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: -S9;streptozotocin +S9;2- acetylaminofluorene

Details on test system and experimental conditions:

Details on test system and conditions
METHOD OF APPLICATION: in agar ( plate incorporation Method)
DURATION
- Exposure duration: 48 hour
NUMBER OF CELLS EVALUATED:

DETERMINATION OF CYTOTOXICITY
- Method: relative total growth

NUMBER OF REPLICATIONS:2 plates /concentration

Rationale for test conditions:

Preliminary work on sup plemental tests using additional tester strains has been done. One important objective was to find a Salmonella tester strain more sensitive than either strains.

Evaluation criteria:

Mutagenic concentration range and minimal inhibitory concentration was observed per plates.

Statistics:

Yes

Results and discussion

Test results

Species / strain:

bacteria, other: Salmonella Typhimurium strain D3052, TA1538, TA98, C3076,TA1537, G46, TA1535, and TA100. E.coli WP2, and WP2 uVrA

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: No mutagenic effect were observed

Applicant's summary and conclusion

Conclusions:

Homoveratrylamine (120-20-7) was tested for its mutagenic potential in 10 tester strain of Salmonella Typhimurium and E.coli by Bacterial Mutagen Screen on Gradient Plates with Metabolic Activation. The test result was considered to be negative both in the presence and absence of metabolic activation.

Executive summary:

Genetic toxicity in vitro study of Homoveratrylamine was assessed for its possible mutagenic potential . For this purpose was Bacterial Mutagen Screen on Gradient Plates method was performed. The advantage of the gradient method is its high capacity. For example, one compound can be evaluated in 10 tester strains over a 10,000-fold concentration range both with and without metabolic activation using only 8 agar plates. The test substance was exposed to S. typhimurium LT-2: G46 (histidine, missense), TA1535 (G46 with gal-bio-uVrB deletion and LPS deletion), TA100 (G46 with gal-bio-uvrB deletion and LPS deletion with the addition of R-factor pKM1O1), C3076 [histidine, (+) frame-shift],TA1537(C3076with gal-bio-uvrB deletion and LPS deletion), D3052 [histidine , (-F) frame-shift], TA1538 (D3052 with gal-bio-uVrB deletion and LPS deletion), and TA98 (D3052 with gal-bio-uvrB deletion and LPS deletion with the addition of A-factor pKM1O1).E.coli : WP2 (E.coli tryptophan) and WP2 uvrA (E. coli tryptophan with uvrA deletion).4 additional strains are used for supple mental testing. These strains are TA92 (G46 with the addition of A-factor pKM1O1), TA94 (D3052 with the addition of R-factor pKM1O1), CM881 (WP2 with the addition of R factor pKM1O1), and CM891 (WP2 with uVrA deletion and with the addition of A-factor pKM1O1) at the concentration of 1-1000-µg/ml. The test substance was exposed in the presence and absence of metabolic activation. No mutagenic effects were observed. Therefore Homoveratrylamine was considered to be non mutagenic in Salmonella Typhimurium strainD3052, TA1538, TA98, C3076,TA1537, G46, TA1535,TA100 and E.coli WP2, WP2 uVrA in thepresence and absence of metabolic activation. Hence the substance cannot be classified as gene mutant in vitro.