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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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Salmonella mutagenicity tests: II. Results from the testing of 270 chemicals
Author:
Mortelmans K, Haworth S, Lawlor T, Speck W, Tainer B and Zeiger E
Year:
1986
Bibliographic source:
Environ. Mutagen. 8, 1-119.
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Version / remarks:
and OECD Guideline 472 (Genetic Toxicology: Escherichia coli, Reverse Mutation Assay)
Deviations:
no
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Analytical purity: 98 %

Method

Target gene:
histidine operon
Species / strain
Species / strain / cell type:
other: Salmonella typhimurium TA97, TA98, TA100, TA1535, TA1537
Metabolic activation:
with and without
Test concentrations with justification for top dose:
0, 33, 10, 333, 1000, 3333, 10000 µg/plate
Vehicle / solvent:
- Vehicle/solvent used: water
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
other: For strains tested in the absence of S9 TA98, 2-nitrofluorene or alternatively, TA98 and TA1538, 4-nitro-ophenylenediamine TA100 and TA1535, sodium azide TA97 and TA1537, 9-aminoacridine TA102, mitomycin C TA104, methyl methanesulfonate E.coli WP2 uvrA pK
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation); preincubation


DURATION
- Preincubation period: 20 minutes
- Exposure duration: 48 hours
- Expression time (cells in growth medium): 48 hours


SELECTION AGENT (mutation assays): histidine


NUMBER OF REPLICATIONS: 3


DETERMINATION OF CYTOTOXICITY
- Method: relative total growth


Evaluation criteria:
In this assay, a positive response is defined as a reproducible, dose-related increase in histidine-independent (revertant) colonies in any one strain/activation combination.
An equivocal response is defined as an increase in revertants that is not dose related, is not reproducible, or is not of sufficient magnitude to support a determination of mutagenicity.
A negative response is obtained when no increase in revertant colonies is observed following chemical treatment. There is no minimum percentage or fold increase required for a chemical to be judged positive or weakly positive.

Results and discussion

Test resultsopen allclose all
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:
other: >= 10000 µg/plate
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 97
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
other: >= 10000 µg/plate
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
other: >= 10000 µg/plate
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

Attached document: Appendix E of the NTP report TR 541; contains detail results.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative
Executive summary:

Conclusion:

Formamide was tested for its genotoxic potential in three independent bacterial test systems using S. typhimurium and E.coli.

Formamide was negative in two valid Ames Tests using S. typhimurium strains TA97, TA 98, TA1535, and TA1537, both with and without metabolic activation. The doses ranged from 0 to 10,000 µg/plate. Bacteriotoxicity was not observed. The test was conducted by the NTP, and the test conditions were closely related to OECD TG 471. Positive and negative controls were included and performed as expected (Mortelmans et al., 1986).

Formamide was also negative in a test using E. coli WP uvrA pK101, with and without metabolic activation. The doses ranged from 0 to 10,000 µg/plate. Bacteriotoxicity was not observed. The test was conducted by the NTP, and the test conditions were closely related to OECD TG 472. Positive and negative controls were includedand performed as expected (NTP, 2008).