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Toxicological information

Genetic toxicity: in vitro

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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Data from peer review publication

Data source

Reference
Reference Type:
publication
Title:
The Induction of Bacterial Mutation and Hepatocyte Unscheduled DNA Synthesis by Mono-substituted Anilines
Author:
Christina Z. Thompson, Leo E. Hill, Janet K. Epp, and Gregory S. Probst
Year:
1983
Bibliographic source:
Environmental Mutagenesis 5:803-811 (1983)

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: as mentioned below
Principles of method if other than guideline:
Gradient Plate Test for Bacterial Mutation
GLP compliance:
no
Type of assay:
bacterial forward mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Name of test material (as cited in study report): m-aminoacetophenone
Substance type: Organic
Physical state: Liquid
Purchased from: Aldrich Chemical Company,
Inc. (Milwaukee, WI) or from Eastman Chemical Company (Rochester, NY).

Method

Target gene:
Plate Incorporation
S typhimurium (G46, TA 1535, TA 100, C3076,
TA1537, D3052, TA1538, and TA98) and two tryptophan auxotrophs of E coli (WP2
and WF2uvrA-).
Species / strain
Species / strain / cell type:
other: S typhimurium (G46, TA 1535, TA 100, C3076, TA1537, D3052, TA1538, and TA98) and two tryptophan auxotrophs of E coli (WP2 and WF2uvrA-).
Details on mammalian cell type (if applicable):
Not applicable
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Test concentrations with justification for top dose:
0-1000 µg/plate
Vehicle / solvent:
Vehicle used: DMSO
Controls
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: Streptozotocin (STZ) (Sigma Chemical Company, St. Louis, MO) and 2-acetylaminofluorene (2-AAF) (Aldrich Chemical Company, Milwaukee, WI) served as positive controls for the bacterial mutation assay.
Details on test system and experimental conditions:
METHOD OF APPLICATION :
in agar (plate incorporation)
DURATION
No data
SELECTION AGENT (mutation assays):No data
SPINDLE INHIBITOR (cytogenetic assays):No data
STAIN (for cytogenetic assays):No data
NUMBER OF REPLICATIONS: No data
NUMBER OF CELLS EVALUATED:
No data
Evaluation criteria:
The results indicate the number of strains
showing chemically induced revertant colonies as well as the concentration range
over which mutation was observed in the most sensitive strain.

Results and discussion

Test results
Species / strain:
other: S typhimurium (G46, TA 1535, TA 100, C3076, TA1537, D3052, TA1538, and TA98) and two tryptophan auxotrophs of E coli (WP2 and WF2uvrA-).
Metabolic activation:
with and without
Genotoxicity:
positive
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not valid
Positive controls validity:
valid
Additional information on results:
No data
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):
positive Positive with and without metabolic activation in S typhimurium TA100, TA98,TA1538

Mono- substituted aniline derivatives were tested for the induction of bacterial mutation using eight S typhimurium and two E coli strains. The gradient plate test for bacterial mutation was conducted with and without metabolic activation.
m-amino acetophenone exhibited mutagenic activity with and without metabolic activation in S typhimurium TA100, TA98,TA1538 strains
The Mutagenic concentration rang (MCR) in µg/ml of agar for the positive strains is 10-1000.
Executive summary:

Mono- substituted aniline derivatives were tested for the induction of bacterial mutation using eight S typhimurium and two E coli strains. The gradient plate test for bacterial mutation was conducted with and without metabolic activation.All compounds were tested as supplied without further purification or attempt to identify impurities. Streptozotocin (STZ) (Sigma Chemical Company,St.Louis, MO) and 2-acetylaminofluorene (2-AAF) (Aldrich Chemical Company, Milwaukee, WI) served as positive controls for the bacterial mutation assay.

This test employed ten bacterial strains: eight histidine auxotrophs of S typhimurium (G46, TA 1535, TA100,C3076, TA1537, D3052, TA1538, and TA98) and two tryptophan auxotrophs of E coli (WP2 and WF2uvrA-). Each compound was incorporated into the top wedge of agar on each of four square plates to give a 10-fold concentration gradient per plate and thus provide a 10,000-fold concentration range for the compound. All tests were conducted with and without Aroclor 1254-induced rat liver S-9 and a maximum compound concentration of 1000 µg/ml of agar.

The results indicate the number of strains showing chemically induced revertant colonies as well as the concentration range over which mutation was observed in the most sensitive strain.

m-amino acetophenone exhibited mutagenic activity with and without metabolic activation in S typhimurium TA100, TA98,TA1538 strains

The Mutagenic concentration rang (MCR) in µg/ml of agar for the positive strains is 10-1000