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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report Date:
1999

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
Test substance: Carbamide peroxide, i.e hydrogen peroxide - urea (1:1)
CAS number: 124.43-6
Purity: not staterd

Method

Target gene:
his operon
Species / strainopen allclose all
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Metabolic activation system:
30% S9 from induced both rat and hamster liver
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Metabolic activation system:
30% S9 from induced both rat and hamster liver
Species / strain:
S. typhimurium TA 102
Metabolic activation:
with and without
Metabolic activation system:
30% S9 from induced both rat and hamster liver
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
without
Species / strain:
S. typhimurium TA 1538
Metabolic activation:
without
Test concentrations with justification for top dose:
according to guideline
Vehicle:
water
Controls
Negative controls:
yes
Positive controls:
yes
Positive control substance:
not specified

Results and discussion

Test resultsopen allclose all
Key result
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Genotoxicity:
positive
Cytotoxicity:
yes
Vehicle controls valid:
not specified
Negative controls valid:
yes
Positive controls valid:
yes
Remarks on result:
other: positive without metabolic activation
Key result
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity:
yes
Vehicle controls valid:
not specified
Negative controls valid:
yes
Positive controls valid:
yes
Key result
Species / strain:
S. typhimurium TA 102
Metabolic activation:
with and without
Genotoxicity:
positive
Cytotoxicity:
no, but tested up to limit concentrations
Vehicle controls valid:
not specified
Negative controls valid:
yes
Positive controls valid:
yes
Remarks on result:
other: positive without metabolic activation
Key result
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity:
yes
Vehicle controls valid:
not specified
Negative controls valid:
yes
Positive controls valid:
yes
Key result
Species / strain:
S. typhimurium TA 1538
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity:
yes
Vehicle controls valid:
not specified
Negative controls valid:
yes
Positive controls valid:
yes

Any other information on results incl. tables

Strain: TA100

 

Dose

No Activation
(Negative)

No Activation
(Negative)

No Activation
(Weakly Positive)

30% RLI
(Negative)

30% HLI
(Negative)

 

Protocol

Preincubation

Preincubation

Preincubation

Preincubation

Preincubation

 

ug/Plate

Mean

±SEM

Mean

±SEM

Mean

±SEM

Mean

±SEM

Mean

±SEM

 0         

131

3.8

177

7.8

164

.9

137

8.4

134

.6

10         

166

6.1

217

17.6

172

11.3

33         

145

8.7

181

4.5

211

5

100         

162

9

149 s

8.5

267

3.2

138

9.5

144

7

150         

105 s

19.8

248

10.4

200         

100 s

21.9

165 s

11.1

333         

66 s

5.8

149

3.5

141

5.7

1000         

t

141

2

152

4.9

3333         

147

6.1

162

6.3

10000         

142

3.2

165

3.7

Positive Control

433

12.1

554

2.1

383

9

796

10.4

393

9.8

 

Strain: TA102

 

Dose

No Activation
(Positive)

No Activation
(Weakly Positive)

30% RLI
(Negative)

30% HLI
(Negative)

 

Protocol

Preincubation

Preincubation

Preincubation

Preincubation

 

ug/Plate

Mean

±SEM

Mean

±SEM

Mean

±SEM

Mean

±SEM

 0         

283

11.7

239

11.1

389

5.6

391

7.9

10         

281

12.4

33         

357

13.4

282

7.7

100         

409

3.5

408

18.7

379

6.4

393

9.5

150         

424

11.9

200         

522

9.4

433

9.3

333         

635

7.5

429

25.2

348

34.2

1000         

789

15.7

430

14.8

396

9.5

3333         

435

4.7

389

12.4

10000         

441

8.6

424

7.7

Positive Control

1008

168.7

546

2.3

1254

215.7

2412

36.5

 


 

 

Strain: TA1535

 

Dose

No Activation
(Negative)

 

Protocol

Preincubation

 

ug/Plate

Mean

±SEM

 0         

11

3.4

10         

14

1.5

33         

15

.7

100         

15

2.6

150         

11 s

3

200         

9 s

.6

Positive Control

263

4

 

Strain: TA1538

 

Dose

No Activation
(Negative)

 

Protocol

Preincubation

 

ug/Plate

Mean

±SEM

 0         

5

.3

10         

3

.9

33         

6

.9

100         

6

1.5

150         

6

1.5

200         

3 s

0

Positive Control

292

9.9

 

Strain: TA98

 

Dose

No Activation
(Equivocal)

No Activation
(Equivocal)

No Activation
(Positive)

No Activation
(Weakly Positive)

30% RLI
(Negative)

30% HLI
(Negative)

 

Protocol

Preincubation

Preincubation

Preincubation

Preincubation

Preincubation

Preincubation

 

ug/Plate

Mean

±SEM

Mean

±SEM

Mean

±SEM

Mean

±SEM

Mean

±SEM

Mean

±SEM

 0         

15

2.3

13

.3

17

2.2

25

3.8

23

1.2

19

1.5

10         

18

.9

23

.9

20

3.4

30

4.5

33         

17

3.8

20

3.5

24

0

38

3.5

100         

26

1.2

42

4.4

35

2.6

50

6.7

20

1.5

23

1.5

150         

25

3

52

2.6

27

7.3

200         

13 s

1.2

37

6.7

4 s

1.2

333         

6 s

1.9

27

3.3

25

1.8

1000         

t

27

1.5

27

4

3333         

19

1.5

25

1.8

10000         

25

1.2

28

1.5

Positive Control

229

11

297

9.3

268

6.7

246

2

335

22.7

410

16

 

Abbreviations:
RLI = induced male Sprague Dawley rat liver S9
HLI = induced male Syrian hamster liver S9
s = Slight Toxicity; p = Precipitate; x = Slight Toxicity and Precipitate; t = Toxic;

 

Applicant's summary and conclusion

Conclusions:
Positive results were obtained in TA98 and TA102 in the absence of metabolic activation.
Executive summary:

Hydrogen peroxide-urea (1:1) (name in test report: carbamide peroxide) was tested in the AMES test using S. typhimurium strains TA98, TA100, TA102, TA1535, and TA1538 according to the OECD 471 test guideline both without and with metabolic activation (30% S9 supernatant from induced rat and hamster liver, respectively). Positive results were obtained in TA98 and TA102 in the absence of metabolic activation.

The study is considered to be fully reliable and suitable for assessment.