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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well reported GLP study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report date:
2007

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Qualifier:
according to guideline
Guideline:
EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.5100 - Bacterial Reverse Mutation Test (August 1998)
GLP compliance:
yes (incl. QA statement)
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
4-(4-nitrophenyl)morpholin-3-one
EC Number:
610-199-1
Cas Number:
446292-04-2
Molecular formula:
C10 H10 N2 O4
IUPAC Name:
4-(4-nitrophenyl)morpholin-3-one
Details on test material:
4-(4-Nitrophenyl)-3-morpholinone, batch number BXR2LPC, 97.5% content

Method

Target gene:
histidin gene locus
Species / strain
Species / strain / cell type:
S. typhimurium, other: TA 1535, TA 100, TA 1537, TA 98, TA 102
Metabolic activation:
with and without
Metabolic activation system:
S9-mix
Test concentrations with justification for top dose:
4-(4-Nitrophenyl)-3-morpholinon: 50-5000 µg/plate
Sodium-azide: 10 µg/plate (TA 1535)
Nitrofurantoin: 0.2 µg/plate (TA 100)
4-Nitro-1,2-phenylene diamine: 10 µg/plate (TA 1537), 0.5 µg/plate (TA 98)
Mitomycin C: 0.2 µg/plate (TA 102)
2-Aminoanthracene: 3 µg/plate
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
no
Remarks:
No solvent control was used since sufficient evidence was available in the literature and from testing laboratory experience, indicating that the solvents used had no influence on the spontaneous mutant counts of the used strains.
Positive controls:
yes
Positive control substance:
other: Sodium-azide, Nitrofurantoin, 4-Nitro-1,2-phenylene diamine, Mitomycin C, 2-Aminoanthracene

Results and discussion

Test results
Species / strain:
S. typhimurium, other: TA 1535, TA 100, TA 1537, TA 98, TA 102
Metabolic activation:
with and without
Genotoxicity:
positive
Cytotoxicity / choice of top concentrations:
other: There was no indication of a bacteriotoxic effect at doses of up to and including 158 µg/plate. Higher doses had a strain-specific bacteriotoxic effect, therefore, they could only partly be used for assessment purposes up to and including 5000 µg/plate.
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: strain/cell type: TA 100, TA 98 and TA 102
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

Three of the five strains (TA 100, TA 98 and TA 102) concerned revealed dose-related increase in mutant counts to well over double those of negative controls with and without S9 mix. The lowest dose at which this finding was reproducible was 50 µg/plate for Salmonella typhimurium TA 100 and TA 98, and 158 µg/plate for Salmonella typhimurium TA 102.

Due to a clear mutagenic effect no independent repeat was needed.

Applicant's summary and conclusion

Executive summary:

4 -(4 -Nitrophenyl)-3-morpholinon was investigated using the Salmonella/microsome plate incorporation test for point-mutagenic effects in doses up to and including 5000 µg/plate on the five histidine-auxotrophic Salmonella typhimurium LT2 strains TA 1535, TA 100, TA 1537, TA 98 and TA 102.

Doses up to and including 158 µg/plate did not cause any bacteriotoxic effects. At higher doses, the substance had a strain-specific bacteriotoxic effect, so that this range could be used to a limited extent up to and including 5000 µg/plate for assessment purposes. Evidence of mutagenic activity of 4 -(4 -Nitrophenyl)-3 -morpholinon was seen comparably without and with S9 mix. On Salmonella typhimurium TA 100, TA 98 and TA 102, a biologically relevant increase was found in the mutant count compared to the corresponding negative control. The lowest reproducible effective was 50 µg/plate for Salmonella typhimurium TA 100 and TA 98, and 158 µg/plate for Salmonella typhimurium TA 102.

The Salmonella/microsome test thus showed 4 -(4 -Nitrophenyl)-3 -morpholinon to have a mutagenic effect.