3-methylbut-3-en-1-ol

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in mammalian cells

Type of information:

experimental study

Adequacy of study:

key study

Study period:

02.03.2010 - 17.05.2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)

GLP compliance:

yes (incl. QA statement)

Type of assay:

in vitro mammalian cell gene mutation test using the Hprt and xprt genes

Test material

Test material information

Constituent 1

Reference substance name:

3-methylbut-3-en-1-ol

EC Number:

212-110-8

EC Name:

3-methylbut-3-en-1-ol

Cas Number:

763-32-6

Molecular formula:

C5H10O

IUPAC Name:

3-methylbut-3-en-1-ol

Details on test material:

- Name of test material (as cited in study report): 3-Methylbuten-3-ol-1
- Analytical purity: 99%
- Lot/batch No.: 31-0342

Method

Target gene:

HPRT

Species / strain

Species / strain / cell type:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

with and without

Metabolic activation system:

Mammalian liver microsome preparations (S9 mix)

Test concentrations with justification for top dose:

concentrations in μg/mL
Experiment I
without S9 mix: 55.0 110 220 440 880
with S9 mix: 55.0 110 220 440 880

Experiment II
without S9 mix: 55.0 110 220 330 440
with S9 mix: 55.0 110 220 440 880

Vehicle / solvent:

Culture medium

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

7,12-dimethylbenzanthracene

ethylmethanesulphonate

Remarks:

As solvent/vehicle is culture medium, untreated negative controls and negative solvent/vehicle controls are the same.

Evaluation criteria:

A test item is classified as positive if it induces either a concentration-related increase of the mutant frequency or a reproducible and positive response at one of the test points.

Statistics:

A linear regression (least squares) was performed to assess a possible dose dependent
increase of mutant frequencies using SYSTAT􀂣11 (SYSTAT Software, Inc., 501, Canal
Boulevard, Suite C, Richmond, CA 94804, USA) statistics software. The number of mutant colonies obtained for the groups treated with the test item were compared to the solvent control groups. A trend is judged as significant whenever the p-value (probability value) is below 0.05. However, both, biological and statistical significance were considered together.

Results and discussion

Test results

Key result

Species / strain:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

In conclusion it can be stated that under the experimental conditions reported the test item did not induce gene mutations at the HPRT locus in V79 cells.
Therefore, Isoprenol is considered to be non-mutagenic in this HPRT assay.

Executive summary:

The study was performed to investigate the potential of Isoprenol to induce gene mutations at the HPRT locus in V79 cells of the Chinese hamster.

The assay was performed in two independent experiments, using two parallel cultures each. The first main experiment was performed with and without liver microsomal activation and a

treatment period of 4 hours. The second experiment was performed with a treatment time of 4 hours with and 24 hours without metabolic activation.

The highest concentration of the test item (880 μg/mL) was equal to a molar concentration of about 10 mM.

The tested concentrations are described in Table 2 (page 19). The evaluated experimental points and the results are summarised in Table 1 (page 13).

No substantial and reproducible dose dependent increase of the mutation frequency was observed in both main experiments.

Appropriate reference mutagens, used as positive controls, induced a distinct increase in mutant colonies and thus, showed the sensitivity of the test item and the activity of the metabolic activation system.