Registration Dossier

Toxicological information

Genetic toxicity: in vitro

Currently viewing:

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:
20 January 1989 - 30 January 1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was performed according to OECD guidelines and GLP. Devation from the current guideline: With this test it is not possible to identify certain oxidising mutagens, cross-linking agents and hydrazines.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Name: M-3175; 1,3-propylenediamine-N,N,N',N'-tetra acetic acid, ammonium iron (+3) salt (mentioned in 28-day study report)
Appearance: yellow powder
Batch No.: VG-01
Purity: 99% (mentioned in 28-day study report)

Method

Target gene:
Histidine operon
Species / strain
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Additional strain / cell type characteristics:
other: see below
Metabolic activation:
with and without
Metabolic activation system:
S9-mix
Test concentrations with justification for top dose:
50, 158, 500, 1580, 5000 µg/plate
Vehicle / solvent:
Distilled water
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Remarks:
distilled water
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: see below
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: 2 days
- Expression time (cells in growth medium): 2 days

SELECTION AGENT (mutation assays): histidine

NUMBER OF REPLICATIONS: triplicate, two independent assays

NUMBER OF CELLS EVALUATED: numbers of revertant colonies were counted, either manually or with a Biotran II automatic colony counter.

DETERMINATION OF CYTOTOXICITY
- Method: absence of growth

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:
not examined
Positive controls validity:
valid
Additional information on results:
No increases in revertant colony numbers over control counts were obtained with any of the tester strains following exposure to M-3175 at levels from 50 to 5000 ug/per plate.
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

It was concluded that M-3175 was devoid of mutagenic activity under the conditions of the test.
Executive summary:

The compound M-3175 was examined for mutagenic activity in four histidine-dependent auxotrophs of Salmonella typhymurium, strains TA 98, TA 100, TA 1535 and TA 1537, using pour-plate assays. Each test, in each strain, was conducted on two separate occasions. The studies, which were conducted in the absence and presence of an activating system derived from rat liver (S-9 mix), employed a range of levels of M-3175 from 50 to 5000 ug per plate, selected following a preliminary toxicity test in strain TA 98, and included solvent (distilled water) controls with and without S-9 mix.

No increases in reversion to prototrophy were obtained-with any of the four bacterial strains at the compound levels tested, either in the presence or absence of S-9 mix. Marked increases in the number of revertant colonies were induced by the known mutagens benzo[a]pyrene, 2-nitrofluorene, .

2-aminoanthracene, 9-aminoacridine and sodium azide when examined under similar conditions.

It was concluded that M-3175 was devoid of mutagenic activity under the conditions of the test.