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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: see 'Remark'
Remarks:
The study is comparable to OECD Guideline 471 with acceptable restrictions (no details about the test substance; no data on pH or osmolality [but negative results]; no data about historical controls [but vehicle control within values published elsewhere]).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report date:
1998

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Reference substance name:
monomethylformamide
IUPAC Name:
monomethylformamide
Constituent 2
Chemical structure
Reference substance name:
N-methylformamide
EC Number:
204-624-6
EC Name:
N-methylformamide
Cas Number:
123-39-7
Molecular formula:
C2H5NO
IUPAC Name:
N-methylformamide
Details on test material:
clourless liquid
stability of the test substance has been shown by analytical control (reanalysis)
no further data

Method

Target gene:
His- (S. typhimurium)
Try- (E.coli)
Species / strain
Species / strain / cell type:
other: Salmonella typhimurium TA 100, 98, 1535, 1537, E. coli WP2uvrA
Metabolic activation:
with and without
Metabolic activation system:
Liver S9-fraction prepared from livers of at least 5 male Sprague-Dawley rats i.p. injected with 500 mg/kg bw Aroclor1254 5 days prior to sacrifice.
Test concentrations with justification for top dose:
2 independent experiments with and without metabolic activation
1) standard plate test: 0, 40, 200, 1000, 5000, and 10000 µg/plate
2) preincubation assay: 0, 40, 200, 1000, 5000, and 10000 µg/plate
Vehicle / solvent:
water
Controls
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
other: see below
Details on test system and experimental conditions:
S9-mix prepared freshly prior to experiment.
3 plates per dose level.

Positive control with S-9 mix:
2.5 µg/plate 2-aminoanthracene (2-AA) dissolved in DMSO for the strains TA 100, TA 98, TA 1537 and TA 1535
and 60 µg/plate 2-aminoanthracene dissolved in DMSO for the strain E. coli WP2 uvrA

Positive control without S-9 mix:
5 µg/plate N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) dissolved in DMSO for the strains TA 100 and TA 1535
10 µg/plate 4-nitro-o-phenylendiamine (NOPD) dissolved in DMSO for the strain TA 98
100 µg/plate 9-aminoacridine chioride monohydrate (AAC) dissolved in DMSO for the strain TA 1537
10 µg/plate N-ethyl-N'-nitro-N-nitrosoguanidin (ENNG) dissolved in DMSO for the strain E. coli WP2 uvrA
Evaluation criteria:
- doubling of the spontaneous mutation rate (control)
- dose-response relationship
- reproducibility of the results
Statistics:
Mean +- SD (standard deviation) was calculated.

Results and discussion

Test results
Species / strain:
bacteria, other: Salmonella typhimurium TA 100, 98, 1535, 1537, E. coli WP2uvrA
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Remarks:
(10 mg/plate, no precipitates)
Vehicle controls validity:
valid
Positive controls validity:
valid
Additional information on results:
No test substance precipitation was found.
No data about historical controls but vehicle controls within values published elsewhere.

TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: no data
- Effects of osmolality: no data
Remarks on result:
other: other: standard plate test
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

Mutagenicity in the Ames test with and without metabolic activation

Mean number of revertants +- standard deviation

Dose in µg per plate

TA98

TA100

TA1535

TA1537

E. coli WP2uvrA

-MA

+MA

-MA

+MA

-MA

+MA

-MA

+MA

-MA

+MA

-

Standard plate test

Water

32+-2

40+-2

139+-3

157+-3

19+-3

19+-1

10+-2

10+-1

30+-4

39+-2

40

31+-4

38+-8

145+-14

161+-3

18+-1

18+-2

9+-1

10+-3

32+-0

37+-2

200

27+-5

36+-2

147+-7

155+-14

14+-2

18+-1

8+-1

10+-2

31+-1

31+-1

1000

26+-4

36+-1

143+-11

129+-21

13+-2

20+-2

8+-1

8+-2

33+-6

31+-2

5000

24+-5

37+-2

170+-9

151+-20

14+-1

13+-2

9+-1

9+-3

27+-5

32+-4

10000

23+-5

36+-5

159+-9

125+-19

12+-4

16+-2

8+-2

7+-1

25+-3

30+-3

Positive control

1004+-5

1151+-156

1264+-175

1227+-113

1821+-388

175+-43

734+-22

132+-18

501+-10

241+-19

-

Preincubation assay

Water

32+-3

47+-5

134+-12

149+-11

20+-3

21+-3

10+-3

12+-3

33+-2

43+-4

40

33+-2

41+-1

136+-11

141+-9

21+-4

19+-4

10+-1

11+-2

35+-3

42+-3

200

33+-3

41+-5

140+-16

148+-11

20+-4

19+-2

9+-2

12+-2

31+-2

43+-3

1000

30+-4

42+-3

121+-19

160+-6

20+-3

17+-1

11+-2

11+-1

31+-3

42+-5

5000

34+-4

39+-3

138+-11

156+-6

20+-3

16+-3

9+-1

11+-2

32+-4

45+-6

10000

32+-4

43+-2

126+-3

143+-4

20+-4

15+-3

7+-2

11+-3

33+-3

36+-3

Positive control

1144+-73

975+-39

1194+-51

866+-24

1027+-26

111+-16

833+-73

121+-3

507+-17

210+-12

MA: metabolic activation

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

No mutagenic and cytotoxic activity was detected with and without metabolic activation even at concentrations of 10 mg/plate in the Ames test using S. typhimurium TA98, 100, 1535, 1537 and E. coli WP2uvrA.
Executive summary:

The study is comparable to OECD Guideline 471 with acceptable restrictions (no details about the test substance solution; no data on pH or osmolality [but negative results]; no data about historical controls [but vehicle control within values published elsewhere]).

In the Ames test with S.typhimurium TA98, 100, 1535, 1537 and E. coli WP2uvrA the test substance was studied using two different protocols with and without addition of a metabolic activation system: the standard plate test and the preincubation test (dose levels: 0; 40; 200; 1000; 5000 and 10000 µg/plate). Negative and positive controls were valid. In each test system cytotoxic concentrations were not reached but dose levels were >= 5 mg/plate. There was no increase in revertants in any strain.

Conclusion: No mutagenic and cytotoxic activity was detected with and without metabolic activation even at concentrations of 10 mg/plate in the Ames test using S. typhimurium TA98, 100, 1535, 1537 and E. coli WP2uvrA.

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