Registration Dossier

Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Well perfored study similar to OECD guideline using a deviating set of tester strains as compared to actual guidelines. However reliability is restricted because the unknown purity of the test sample allows no final conlusion regarding the mutagenic potential of the substance which is subject to registration.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1992

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: authors guideline similar to OECD 471
Deviations:
no
Principles of method if other than guideline:
TA 100, 1535, 1537, 97, 98 with and without metabolic activation, metabolic activation with Aroclor 1254-induced hamster liver S-9 (10%), or with Aroclor 1254-induced rat liver S-9 (10%), preincubation method, Concentrations tested: 0.0 - 1000.0 µg/plate
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 4-Methoxy-3-nitro-N-phenylbenzamide
- Analytical purity: not stated

Method

Species / strainopen allclose all
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Metabolic activation system:
Aroclor 1254-induced hamster or rat liver S-9 (10%)
Species / strain:
S. typhimurium TA 97
Metabolic activation:
with and without
Metabolic activation system:
Aroclor 1254-induced hamster or rat liver S-9 (10%)
Test concentrations with justification for top dose:
0.0, 1.0, 3.0, 10.0, 16.0, 33.0, 100.0, 333.0, 1000.0 µg/plate
Vehicle:
DMSO
Controls
Negative controls:
no
Solvent controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
sodium azide
other: 4-nitro-o-phenylenediamine, 2-aminoanthracene
Evaluation criteria:
A chemical was judged mutagenic (+) or weakly mutagenic (+W) if it produced a reproducible, dose-related response over the solvent control, under a single metabolic activation condition, in replicate trials. A chemical was judged questionable (?) if the results of individual trials were not reproducible, if increases in his revertants did not meet the criteria for a "+W" response, or if only single doses produced increases in his revertants in repeat trials. Chemicals were judged nonmutagenic ( —) if they did not meet the criteria for a mutagenic or questionable response.

Results and discussion

Test resultsopen allclose all
Species / strain:
S. typhimurium TA 97
Metabolic activation:
with and without
Genotoxicity:
other: TA100 pos. without MA, with MA rat, and with MA hamster / TA1535 neg. without MA, with MA rat, and with MA hamster / TA1537: neg. without MA, and pos. with MA rat, and with MA hamster / TA98: neg. without MA, and pos. with MA rat, and with MA hamster
Cytotoxicity:
not specified
Vehicle controls valid:
yes
Negative controls valid:
not examined
Positive controls valid:
yes
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
other: TA97: weakly pos. without MA, and pos. with MA rat, and with MA hamster
Cytotoxicity:
not specified
Vehicle controls valid:
yes
Negative controls valid:
not examined
Positive controls valid:
yes

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
positive

The test item exerts mutagenic activity in the reverse bacterial mutation assay with and without metabolic activation.
Executive summary:

Mutagenic activity of the test item was investigated in Salmonella typhimurium strains TA 100, 1535, 1537, 97, and 98 with and without metabolic activation (induced rat or hamster liver S-9 (10%)) at concentrations of 0.0, 1.0, 3.0, 10.0, 16.0, 33.0, 100.0, 333.0, 1000.0 µg/plate using the preincubation method. Mutagenic response in terms of a relevant increases in his revertants was determined as follows:

 

Without metabolic

activation

With metabolic

activation (rat)

With metabolic

activation (hamster)

TA 100

positive

positive

positive

TA1535

negative

negative

negative

TA1537

negative

positive

positive

TA98

negative

positive

positive

TA 97

weakly positive

positive

positive

The appropriate reference mutagenes showed distinct positive mutagenic effects.