Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1983
Report date:
1983

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
no
Remarks:
pre-dates GLP standard
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
2-phenylpropan-1-ol
EC Number:
214-379-7
EC Name:
2-phenylpropan-1-ol
Cas Number:
1123-85-9
Molecular formula:
C9H12O
IUPAC Name:
2-phenylpropan-1-ol
Test material form:
liquid

Method

Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Species / strain / cell type:
S. typhimurium TA 1538
Metabolic activation:
with and without
Metabolic activation system:
S-9 liver fractions were prepared from Aroclor-pretreated rats (Aroclor 1254, 500 mg/kg ip) and adjusted to 25 mg protein/mL; 0.5 mL S-9 mix, equivalent to 50 µL S-9, was incorporated into the plates.
Test concentrations with justification for top dose:
Five doses of each substance were tested (for non-toxic compounds, up to 3.6 mg/plate) in all five tester strains with and without S-9 mix.
Vehicle / solvent:
Dimethylsulphoxide was used as solvent for test chemicals that were poorly soluble in water.
Details on test system and experimental conditions:
Vogel-Bonner medium (Vogel & Bonner, 1956) was used throughout; plates were incubated for 48 hr. Positive controls were run in each experiment with the reference mutagens sodium azide and benzo[a]pyrene. Over a period of 2 yr, the numbers of revertants/plate in positive controls were in the following ranges: with sodium azide, at 0.5 µg/plate, 430-760 in TA1535, 400-700 in TA100; with benzo[a]pyrene, at 5 µg/plate, 865-1210 in TA100, 235-350 in TA1537, 410-590 in TA1538, 660-1000 in TA98. All chemicals were tested at least twice.
Evaluation criteria:
Statistical significance was determined according to the methods of Kastenbaum & Bowman (1970). With regard to the Ames tests, results that met the following additional criteria were regarded as positive ( ' + " in Table 1): a reproducible, dose-related and at least two-fold elevation of the spontaneous revertant frequency. Agents producing reproducible, dose-related and significant (P ≤0.01) but less than two-fold elevations were classified as marginally mutagenic under the experimental conditions ('m' in Table 1).

Results and discussion

Test resultsopen allclose all
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
True negative controls validity:
not specified
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
True negative controls validity:
not specified
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
True negative controls validity:
not specified
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1537
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
True negative controls validity:
not specified
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
True negative controls validity:
not specified
Positive controls validity:
valid

Applicant's summary and conclusion

Conclusions:
Wild et al. have investigate flavouring agents for mutagenicity by Ames tests;, using salmonelly typhimurium strains TA98, TA100, TA1535, TA1537, and TA1538, with and without metabolic activation. No mutagenic potential of hydratropic alcohol was seen in this assay.
Executive summary:

Wild et al. have investigate 76 different flavouring agents for mutagenicity through Ames tests, but also Basc tests on Drosophila melanogaster and micronucleus tests. Hydratropic alcohol in this study was only investigated by an Ames-test, using salmonella typhimurium strains TA98, TA100, TA1535, TA1537, and TA1538, with and without metabolic activation. No mutagenic potential of hydratropic alcohol was seen in this assay. 89% of all substances tested were found negative, but 11% were found ambiguous or positive, supporting the validity of the test system applied.