(1α,2β,4β,6α)-2,2,7-trimethyl-3-oxatricyclo[4.1.1.02,4]octane

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:

supporting study

Study period:

No data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well-reported publication, similar to guideline, on the unspecified isomer.

Data source

Reference

Reference Type:

publication

Title:

Epoxides: comparison of the induction of SOS repair in Escherichia coli PQ37 and the bacterial mutagenicity in the Ames test

Author:

von der Hude W, Seelbach A, Basler A

Year:

1990

Bibliographic source:

Mutation Research 231, 205-218

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

at least 5 strains recommended (including Salmonella TA102 or E. coli WP2 uvrA) and a 5-30% S9-mix usually used

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

alpha pinene epoxide (unspecified isomer)

IUPAC Name:

alpha pinene epoxide (unspecified isomer)

Constituent 2

Reference substance name:

2,7,7-trimethyl-3-oxatricyclo[4.1.1.02,4]octane

EC Number:

216-869-6

EC Name:

2,7,7-trimethyl-3-oxatricyclo[4.1.1.02,4]octane

Cas Number:

1686-14-2

IUPAC Name:

2,7,7-trimethyl-3-oxatricyclo[4.1.1.0~2,4~]octane

Test material form:

not specified

Details on test material:

- Name of test material (as cited in study report): α-pinane oxide
- Molecular formula (if other than submission substance): C10-H16-O
- Molecular weight (if other than submission substance): 152.235
- Smiles notation (if other than submission substance): C1([C@@H]2[C@@]3(O[C@@H]3C[C@@H]1C2)C)(C)C
- InChl (if other than submission substance): 1S/C10H16O/c1-9(2)6-4-7(9)10(3)8(5-6)11-10/h6-8H,4-5H2,1-3H3
- Structural formula attached as image file (if other than submission substance): see Fig. 1
- Substance type: no data
- Physical state: no data
- Analytical purity: 98%
- Impurities (identity and concentrations): no data
- Composition of test material, percentage of components: no data
- Isomers composition: no data
- Purity test date: no data
- Lot/batch No.: no data
- Expiration date of the lot/batch: no data
- Stability under test conditions: no data
- Storage condition of test material: no data

Method

Target gene:

Histidine operon

Species / strain

Species / strain / cell type:

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

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

4% S9 fraction from Aroclor 1254-pretreated male Wistar rats [OECD guidelines state that a 5-10% v/v S9-mix is ususally used]

Test concentrations with justification for top dose:

0, 0.1, 0.3, 1.0, 3.3 or 10.0 μmole/plate [about 15, 45, 150, 500 or 1520 μg/plate]

Controls

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: without S9: 2-nitrofluorene (TA 98), methyl methanesulfonate (TA 100), sodium azide (TA 1535), 9-aminoacridine hydrochloride (TA 1537); with S9: aminoanthracene

Results and discussion

Test results

Species / strain:

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

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at about 1520 μg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

No convincing evidence of mutagenic activity was seen in a good-quality Ames test in which alpha pinene epoxide (unspecified isomer) was incubated with Salmonella typhimurium strains TA 98, TA 100, TA 1535 and TA 1537 at up to about 500 μg/plate (significant cytotoxicity was seen at about 1520 μg/plate) with and without S9.

Executive summary:

The mutagenic potential of alpha pinene epoxide (unspecified isomer) has been assessed in a good-quality Ames test similar to that described by OECD Guideline 471.

In two independent tests (using the plate incorporation method), triplicate cultures of Salmonella typhimurium strains TA 98, TA 100, TA 1535 and TA 1537 were incubated with alpha pinene epoxide (in DMSO) at 0, 0.1, 0.3, 1.0, 3.3 or 10.0 μmole/plate [about 15, 45, 150, 500 or 1520 μg/plate], in the absence or presence of metabolic activation with rat liver S9. Appropriate positive controls were also tested. The number of revertant colonies was then determined.

No convincing evidence of mutagenic activity was seen for alpha piene epoxide (unspecified isomer). Although there appeared to be a slight treatment-related increase in the number of revertant Salmonella TA 100 colonies without S9, this was less than double the controls. Significant cytotoxicity was seen in cultures treated with the highest concentration.

Based on these study findings, and according to the EU CLP and DSD regulations, there is no requirement to classify this substance as mutagenic.