2-methyl-4-phenylpentanol

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

between 30 June 1987 and 12 July 1987

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in accordance with OECD guidelines and in compliance with GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals

Deviations:

no

Test guideline 4

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPPTS 870.5100 - Bacterial Reverse Mutation Test (August 1998)

Version / remarks:

Meets the requirements of the Japanese Regulatory Authorities including METI, MHLW and MAFF, OECD Guidelines for Testing of Chemicals No. 471 "and the USA, EPA (TSCA) OPPTS harmonised guidelines.

Deviations:

no

GLP compliance:

yes

Remarks:

no certificate included

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Pamplefleur

IUPAC Name:

Pamplefleur

Test material form:

other: Colourless viscous liquid

Details on test material:

Compound name: Pamplefleur.
Alternative name: 1-pentanol, 2-mathyl-4-phenyl.
Batch number: 18.6.87/3.
Purity: >99%.
Molecular weight: 178.13.
Appearance: Colourless viscous liquid.
Solvent: Dimethyl sulphoxide.
Storage: Stored at room temperature.

Method

Target gene:

Histidine for Salmonella.
Tryptophan for E.Coli

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium TA 1538

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

not applicable

Species / strain 2

Species / strain / cell type:

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

Details on mammalian cell type (if applicable):

Not applicable.

Additional strain / cell type characteristics:

not applicable

Species / strain 3

Species / strain / cell type:

E. coli WP2 uvr A

Details on mammalian cell type (if applicable):

Not applicable.

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

Aroclor-1254 induced rat liver, S9

Test concentrations with justification for top dose:

Test Concentrations:
Preliminary Toxicity Test: 5, 50, 500, 5000 µg/plate
Expt 1: 0, 10, 50, 100, 500, 1000, 5000 µg/plate.
Expt 2: 0, 10, 50, 100, 500, 1000, 5000 µg/plate

Vehicle / solvent:

Vehicle: Dimethyl sulphoxide

- Justification for choice of solvent/vehicle: No justification for solvent choice.

Controls

Controls 1

Untreated negative controls:

yes

Remarks:

Spontaneous mutation rates of TA100

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-Aminoanthracene: 0.5 µg/plate

Remarks:

With S9 mix

Controls 2

Untreated negative controls:

yes

Remarks:

Spontaneous mutation rates of TA1535

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-Aminoanthracene: 2 µg/plate

Remarks:

With S9 mix

Controls 3

Untreated negative controls:

yes

Remarks:

Spontaneous mutation rates of TA1537

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-Aminoanthracene: 2 µg/plate

Remarks:

With S9 mix

Controls 4

Untreated negative controls:

yes

Remarks:

Spontaneous mutation rates of WP2uvrA

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-Aminoanthracene: 80 µg/plate

Remarks:

With S9 mix

Controls 5

Untreated negative controls:

yes

Remarks:

Spontaneous mutation rates of TA98 and TA1538

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-Aminoanthracene: 0.5 µg/plate

Remarks:

With S9 mix

Controls 6

Untreated negative controls:

yes

Remarks:

Spontaneous mutation rates of TA98 and TA1538

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

2-nitrofluorene

other: 2-NF at 1 µg/plate TA98, 2 µg/plate TA1538

Remarks:

without S9 mix

Controls 7

Untreated negative controls:

yes

Remarks:

Spontaneous mutation rates of TA1537

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

without S9 mix

Migrated to IUCLID6: 9-Aminoacridine: 80 µg/plate

Controls 8

Untreated negative controls:

yes

Remarks:

Spontaneous mutation rates of TA100

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

N-ethyl-N-nitro-N-nitrosoguanidine

Remarks:

without S9 mix

Migrated to IUCLID6: N-ethyl-N'-nitro-N-nitrosoguanidine: 3 µg/plate

Controls 9

Untreated negative controls:

yes

Remarks:

Spontaneous mutation rates of TA1535

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

N-ethyl-N-nitro-N-nitrosoguanidine

Remarks:

Without S9 mix

Migrated to IUCLID6: N-ethyl-N'-nitro-N-nitrosoguanidine: 5 µg/plate

Controls 10

Untreated negative controls:

yes

Remarks:

Spontaneous mutation rates of WP2uvrA

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

N-ethyl-N-nitro-N-nitrosoguanidine

Remarks:

Without S9 mix

Migrated to IUCLID6: N-ethyl-N'-nitro-N-nitrosoguanidine: 2 µg/plate

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation both Expts 1 and 2)

DURATION
- Preincubation period for bacterial strains: 10h
- Exposure duration: 48 - 72 hrs
- Expression time (cells in growth medium): Not applicable
- Selection time (if incubation with a selection agent): Not applicable

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:
ASSESSMENT OF RESULTS

The mean number of revertant colonies for all treatment groups is compared with those obtained for negative and positive control groups. The effect of metabolic activation is assessed by comparing the results obtained both in the presence and absence of the liver microsomal fraction for each treatment group.
A compound is deemed to provide evidence of mutagenic potential if (1) a statistically significant dose-related increase in the number of revertant colonies is obtained in two separate experiments and (2) the increase in the number of revertant co.1onies is at least twice the concurrent solvent control value.

Statistics:

Standard deviation

Results and discussion

Test results

Test results 1

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

Cytotoxic but up to maximum recommended dose of 5000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 2

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:

Cytotoxic but up to maximum recommended dose of 5000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

TEST RESULTS

Materials sterility test:

Test solution: No contamination.

S-9 mix: No contamination.

 

(1) Test method

The compound was tested using the poured plate method.

 

(ii) Test conditions

Bacterial suspension: 0.1 ml

Test solution: 0.1 ml

Sodium phosphate buffer or S-9 mix: 0.5 ml

Top agar: 2.0 ml

Incubation: 72 hours at 37°C.

 

(iii) Test results

Mean revertant colony counts for the six tester strains were recorded. Individual plate counts were also reported.

 

 

REFERENCES:

1. Ames, B.N., Durston, W.E., Yamasaki, E. and Lee, F.D., Proc. Nat. Acad. Sci. USA (1973)70, 2281.

2. Ames, B.N., McCann, J. and Yamasaki, E., Mutation Res. (1975)31, 347.

3. McCann, J., Choi, E., Yamasaki, E. and Ames, B.N., froe. Nat. Acad. Sci. USA (1975)75, 5i35.

4. Garner, R.C., Miller, E.C. and Miller, J.A., Cancer Res. (1972)33, 2058.

5. de Serras, F.J. and Shelby, M.D., Mutation Res. (1979)61, 159.

6. Green, M.H.L., Muriel, W.J., Mutation Res. (1976)38, 3.

7. "Urgent Office Memo" dated June 13, 1979 from Director, Safety and Hygiene Department of Labour Standard Bureau, Ministry of Labour entitled "On Concrete Techniques for the Mutagenicity Test using Micro-organisms".

8. "Kihatsu No. 107" dated March 8, 1979 from Director, The Labour Standard Bureau, Ministry of Labour entitled “On the Standards of the Mutagenicity Test using Micro-organisms".

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

It is concluded that Pamplefleur shows no evidence of mutagenic activity when tested in this bacterial system.

Executive summary:

An Ames test was performed according to OECD TG 471, using S. typhimurium strains TA 1535, TA 1537, TA 98 and TA 100 as well as E.coli strains WP2, up to 5000 ug/pl. No mutagenicity was observed.