p-tert-butylcinnamaldehyde

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

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

Adequacy of study:

key study

Study period:

November 1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

A valid study is available for the analogue substance 3-(4-tert-butylphenyl)propionaldehyde. The study was performed in line with good scientific principles in basic compliance with agreed protocols, with no or minor deviations from standard testing guidelines. The read-across is considered to be suitable based on the structural and “mechanistic action” similarities between the target substance (3-(4-tert-butylphenyl)acrylaldehyde) and source substance (3-(4-tert-butylphenyl)propionaldehyde) and their similar physico-chemical properties.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

A strain capable of detecting cross-linking mutagens was not included.

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

3-(4-tert-butylphenyl)propionaldehyde

EC Number:

242-016-2

EC Name:

3-(4-tert-butylphenyl)propionaldehyde

Cas Number:

18127-01-0

IUPAC Name:

3-(4-tert-butylphenyl)propanal

Test material form:

other: liquid

Details on test material:

- Molecular formula (if other than submission substance): C13H18O
- Molecular weight (if other than submission substance): 190.2814
- Smiles notation (if other than submission substance): CC(C)(C)c1ccc(CCC=O)cc1
- InChl (if other than submission substance): InChI=1/C13H18O/c1-13(2,3)12-8-6-11(7-9-12)5-4-10-14/h6-10H,4-5H2,1-3H3
- Structural formula attached as image file (if other than submission substance): see Fig. 1

Method

Target gene:

Histidine for Salmonella.

Species / strain

Species / strain / cell type:

S. typhimurium, other: TA 1535, TA 1537, TA 1538, TA 98 and TA 100

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

Rat liver microsomes, S9

Test concentrations with justification for top dose:

main test: 0, 1.2, 3.7, 11.1, 33.3 and 100 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: Not reported

Controls

Controls 1

Untreated negative controls:

yes

Remarks:

Spontaneous mutation rates

Negative solvent / vehicle controls:

yes

Remarks:

DSMO

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-Aminoanthracene

Remarks:

With S9 mix

Controls 2

Untreated negative controls:

yes

Remarks:

Spontaneous mutation rates

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-Aminoanthracene

Remarks:

Without S9 mix

Controls 3

Untreated negative controls:

yes

Remarks:

Spontaneous mutation rates

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 4-Aminobiphenyl

Remarks:

with S9 mix

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: 72 hrs

NUMBER OF REPLICATIONS: Triplicate plating.

DETERMINATION OF CYTOTOXICITY
- Method: plates were assessed for numbers of revertant colonies and examined for effects on the growth of the bacterial background lawn.

Evaluation criteria:

Evaluation criteria:
Not stated

Statistics:

Not reported

Results and discussion

Test results

Species / strain:

S. typhimurium, other: TA 1535, TA 1537, TA 1538, TA 98 and TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

Incorporation of the test material up to non-inhibitory levels did not increase the numbers of his+ reveratnts with any of the five tester strains, either in the presence or in the absence of S-9 mix. At the lower dose levels tested, there were no signs that chemical toxicity interfered with the mutagenicity testing: the background lawn of bacterial growth in control and test plates was comparable. At the higher dose levels (i.e. 33-100 µg/plate) the test material was toxic to the bacteria as revealed by a less dense background lawn of bacterial growth.

From the present results it can be concluded that the test material did not reveal any mutagenic activity in the plate incorporation assay with S. typhimurium TA 1535, TA 1537, TA 1538, TA 98 or TA 100 in the presence or absence of the liver microsome activation system under the test conditions employed in this evaluation.

ANALOGUE APPROACH JUSTIFICATION:
- See attached “Justification for read-across” document for full details.
- In summary, important considerations for the use of read-across for genetic toxicity are: : i) 3-(4-tert-butylphenyl)acrylaldehyde (the target chemical) has similar predicted physico-chemical properties to those predicted and experimentally determined for 3-(4-tert-butylphenyl)propionaldehyde (the source substance), ii) there are structural similarities between the two chemicals and iii) the OECD QSAR Toolbox indicates that the two substances are expected to have similar interactions with biological receptors.
The information reported in this summary is included to demonstrate comparability between the source (3-(4-tert-butylphenyl)propionaldehyde) and target (3-(4-tert-butylphenyl)acrylaldehyde) substance.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'. Remarks: S. typhimurium (TA 1535, TA 1537, TA 1538, TA 98 and TA 100)

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative with and without metabolic activation

The test material was considered to be non-mutagenic under the conditions of this test.

Executive summary:

A mutagenicity test was performed with the test material according to a method of Ames et al. (1975) (equivalent to OECD 471).

1) The mutagenic activity of the test material was examined in the Salmonella/microsome mutagenicity test, using a set of five histidine requiring mutants of S. typhimurium (TA 1535, TA 1537, TA 1538, TA 98 and TA 100) and liver homogenate of Aroclor-induced rats.

2) Incorporation of the test material up to non-inhibitory levels did not increase the number of his⁺ revertants in any of the five tester strains, either in the presence or in the absence of the liver microsome activation system.

3) From the present results it can be concluded that the test material did not reveal any mutagenic activity in the plate incorporation assay with S. typhimurium TA 1535, TA 1537, TA 1538, TA 98 or TA 100 in the presence or absence of the liver microsome activation system under the test conditions employed in this evaluation.

It was concluded that the present results did not reveal any mutagenic activity of the test material in the Salmonella/microsome mutagenicity test.