Benzenemethanol, 3-hydroxy-.alpha.-[[methyl(phenylmethyl)amino]methyl]-, (.alpha.S)-

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:

2000

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.5265 (The Salmonella typhimurium Bacterial Reverse Mutation Test)

Test guideline 3

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

3-[(1S)-2-[benzyl(methyl)amino]-1-hydroxyethyl]phenol

Cas Number:

286426-31-1

Molecular formula:

C17 H20 O2

IUPAC Name:

3-[(1S)-2-[benzyl(methyl)amino]-1-hydroxyethyl]phenol

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Physical state: solid
- Analytical purity: 99.7 %
- Storage condition of test material: room temperature

Method

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Metabolic activation:

with and without

Test concentrations with justification for top dose:

Without metabolic activation : TA 1535 10 µg/plate
TA 100 10 µg/plate
TA 98 10 µg/plate
TA 1537 40µg/plate
TA 102 1µl/plate

With metabolic activation : for all strains except TA 102 2.5µg/plate
TA 102 10µg/plate

Vehicle / solvent:

Without metabolic activation: aqua dest or DMSO

With metabolic activation : DMSO

Solvent controls, consisting of the extraction vehicle alone and treadted in the same way as the treatment groups were included.
In additiona, untreated controls were used unless there are historical control data demonstrating that no deleterious or mutagenic
effects are induced by the chosen solvent.

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar

Evaluation criteria:

A test item is considered as mutagenic if : - a dose related increase in the number of revertants occurs and / or
- a reproductible biologically relevant positive response for at least one of the test points occurs
in at least one strain with or without metabolic activation.

A biologically relevant increase is described as follows : - if in strains TA 100 and TA102 the number of reversions is at least twice as high
- if in strains TA 1535,TA 1537 and TA 98 the number of reversions is at least three times higher
as comparedto the spontaneous reversion rate.

Results and discussion

Test results

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

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

In conclusion, it can be stated that during the decribed mutagenicity test and under the experimental conditions reported, the test item did not cause
gene mutations by base pair changes or frameshifts in the genome of the test strains used. Therefore, L_benzyladrianol Base is considered to be
non-mutagenic in this bacterial reverse mutation assay.

Executive summary:

In order to investigate the pontential of L-Benzyladrianol Base for its ability to induce gene mutations the plate incorporation test

( experiment I ) and the percubation test ( experiment II ) were performed with the Salmonella typhiurium strains TA 1535, TA 1537,

TA 98, TA 100 and TA 102.

The test item was tested in two independent experiments at serveral concentrations. Each assay was conducted with and without activation ( S9 mix ).The concentration, including the controls, were tested in triplicate. The following concentrations of the test item

were prepared and used in the experiment : 31.6,100.0,316.2,1000.0,2500.0 and 5000.0 µg/plate.

due to toxicity: exp. II ; TA 1535,TA 102 and TA 100 : 10.0,31.6,100.0,316.2,1000.0 and 2500.0 µg/plate.

Toxic effects of the test item ( indicated by reduction of the background lawn or by distinct reduction of the spontaneous rate ) were

observed in both experiments at the higher investigated doses in all strains used.

No substantial increase in the revertant colony number of any of the five test starins were detected at any dose level of the test item either with or without metabolic actiavtion in both independent performed experiments.

As positive controls reference mutagens were tested in paralell to the test item. They showed distinct of induced revertant colonies.