(2R)-4-hydroxybutan-2-aminium (2S)-hydroxy(phenyl)acetate

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:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP Guidelines Study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

L-2-hydroxy-2-phenylacetic acid

EC Number:

210-276-6

EC Name:

L-2-hydroxy-2-phenylacetic acid

Cas Number:

611-71-2

IUPAC Name:

hydroxy(phenyl)acetic acid

Constituent 2

Reference substance name:

Mandelic acid

EC Number:

202-007-6

EC Name:

Mandelic acid

Cas Number:

90-64-2

IUPAC Name:

hydroxy(phenyl)acetic acid

Details on test material:

- Name of test material (as cited in study report): ChiPros (R) - Mandelsäure
- Physical state: solid
- Analytical purity: 100 %
- Lot/batch No.: 29393/189
- Stability under test conditions: the stability of the test substance under storage conditions is guaranteed as indicated by the sponsor
- Storage condition of test material: room temperature

Method

Species / strain

Species / strain 1

Species / strain / cell type:

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

Species / strain 2

Species / strain / cell type:

E. coli WP2 uvr A

Metabolic activation:

with and without

Metabolic activation system:

S-9 mix

Test concentrations with justification for top dose:

20 µg - 5000 µg/plate (SPT)
4 µg - 2500 µg/plate (PIT)

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: [water]
- Justification for choice of solvent/vehicle: Due to the good solubility of the test substance in water, water was selected as the vehicle.

Controls

Controls 1

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene

Remarks:

with S-9 mix for strains TA 1535, TA 100, TA 1537, TA 98 and E.coli WP2 uvrA

Controls 2

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)

Remarks:

without S-9 mix for strains TA1535, TA 100

Controls 3

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: 4-nitro-o-phenylendiamine

Remarks:

without S-9 mix for strain TA 98

Controls 4

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

without S-9 mix for strain TA 1537

Controls 5

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

Remarks:

without S-9 mix for strain E.coli WP2 uvrA

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation); preincubation

DURATION
- Preincubation period: 20 min
- Exposure duration: 48-72 hours


DETERMINATION OF CYTOTOXICITY
- Method: relative total growth

Evaluation criteria:

The test chemical is considered positive in this assay if the following criteria are met:
- A dose-related and reproducible increase in the number of revertant colonies, i.e. about doubling of the spontaneous mutation rate in at least one
tester strain either without S-9 mix or after adding a metabolizing system.
A test substance is generally considered nonmutagenic in this test if:
- The number of revertants for all tester strains were within the historical negative control range under all experimental conditions in two experiments carried out independently of each other.

Statistics:

not applicable

Results and discussion

Test results

Test results 1

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

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 2

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

ADDITIONAL INFORMATION ON CYTOTOXICITY:
A bacteriotoxic effect (reduced background growth, decrease in the number of revertants, reduction in the titer) was observed in the standard plate
test depending on the strain and test conditions from about 2500 µg/plate onward.
In the preincubation assay bacteriotoxicity was observed depending on the strain and test conditions at 2500 µg/plate (without S-9 mix) or from about 100 µg - 500 µg/pIate onward (with S-9 mix).

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

A maximum increase in the number of revertants of 1.2 was observed. This increase was not dose dependent and well below 2.0. The test substance is therefore not mutagenic in the Ames test.