L-Tyrosine, N-(aminocarbonyl)-3-methoxy-O,.alpha.-dimethyl-

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:

1990-1991

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Principles of method if other than guideline:

T102 Salmonella, and E.Coli study was not performed.

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Tyrosine, N-(aminocarbonyl)-3-methoxy-O,α-dimethyl-

EC Number:

608-271-2

Cas Number:

28861-00-9

Molecular formula:

C13H18N2O5

IUPAC Name:

Tyrosine, N-(aminocarbonyl)-3-methoxy-O,α-dimethyl-

Method

Target gene:

Histidine

Species / strain

Species / strain / cell type:

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

Metabolic activation:

with and without

Metabolic activation system:

Arochlor induced / rat liver S9

Test concentrations with justification for top dose:

2.4-10000.0 g/plate (preliminary study)
156.3-1000.0 microgram/plate (main study)
312.5-10000.0 microgram/plate (confirmation study)

Arochlor induced rat S9 mix concentration: 4, 10 or 30 % S9 fraction.
- sodium-phosphate (pH=7.4): 100,
- magnesium-chloride 8 mM;
- Potassium-chloride 33 mM;
- glucose-6-phosphate 5mM;
- NADP 4mM

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: the tested substance is soluble up to 100 mg/l in DMSO.

Controls

Controls 1

Untreated negative controls:

yes

Remarks:

deionized two times distillated water

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

sodium azide

Controls 2

Untreated negative controls:

yes

Remarks:

deionized two times distillated water

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

methylmethanesulfonate

Controls 3

Untreated negative controls:

yes

Remarks:

deionized two times distillated water

Negative solvent / vehicle controls:

no

Remarks:

DMSO

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

9-aminoacridine

Controls 4

Untreated negative controls:

yes

Remarks:

deionized two times distillated water

Negative solvent / vehicle controls:

no

Remarks:

DMSO

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: 4-nitro-o-phenylenediamine

Details on test system and experimental conditions:

Plate incorporation technique.

Controls: see details in tables at Any other information on materials and methods incl. tables.

Experimental steps:
1. Solution probe- the tested substance is soluble in DMSO up to 100 mg/ml.
2. Preliminary experiment - dose finding test on TA100 with and without S9 (4%).
tested substance 2.4-9.8-39.1-156.3-625.0-2500.0-10000.0 microgram/plate.
3. Main study with TA1535, TA100, TA1537, TA98 with and without S9 (10%)
tested substance 156.3-312.5-625.0-1250-2500.0-10000.0 microgram/plate.
4. Validation study TA1535, TA100, TA1537, TA98 with and without S9 (30%)
tested substance 312.5-625.0-1250-2500.0-5000-10000.0 microgram/plate.

Evaluation criteria:

Well established, according to Guideline.

Results and discussion

Test results

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:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

Preliminary experiment: effect of mutagenitity or toxicity was not observed.
Main Study: effect of mutagenitity or toxicity was not observed.
Validation study: S9 concentration increase in S9 mix has not resulted as mutagenic effect.

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 the above experimental conditions, even if the highest dose was extremely high ( 10 mg/plate), the substance was not mutagenic in Salmonella.