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EC number: 204-701-4 | CAS number: 124-43-6
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
In an Ames test with Hydrogen peroxide-urea (1:1) positive results were obtained in TA98 and TA102 in the absence of metabolic activation. As Hydrogen peroxide-urea (1:1) breaks down to hydrogen peroxide and urea, data from these can be used as source data in a read-across approach. Hydrogen peroxide was a weak mutagen in bacterial and mammalian cell in vitro assays. Urea was not mutagenic in bacterial test systems. Mixed results were obtained with mammalian cells. Positive results were only obtained at high dose levels.
Link to relevant study records
- 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
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- GLP compliance:
- not specified
- Type of assay:
- bacterial reverse mutation assay
- 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 - Target gene:
- his operon
- Species / strain / cell type:
- S. typhimurium TA 98
- Species / strain / cell type:
- S. typhimurium TA 100
- Species / strain / cell type:
- S. typhimurium TA 102
- Species / strain / cell type:
- S. typhimurium TA 1535
- Species / strain / cell type:
- S. typhimurium TA 1538
- Metabolic activation:
- with and without
- Metabolic activation system:
- 30% S9 from induced both rat and hamster liver
- Test concentrations with justification for top dose:
- according to guideline
- Vehicle / solvent:
- water
- Untreated negative controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- not specified
- Key result
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 102
- Metabolic activation:
- with and without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1538
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: positive without metabolic activation
- 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.
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- ANALOGUE APPROACH JUSTIFICATION
Please refer to the attached read across justification in section 13. - Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Key result
- Species / strain:
- S. typhimurium TA 97
- Metabolic activation:
- without
- Genotoxicity:
- positive
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- without
- Genotoxicity:
- positive
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 102
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1537
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1538
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: positive in standard plate assay: the result is adopted for the target substance
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- ANALOGUE APPROACH JUSTIFICATION
Please refer to the attached read across justification in section 13. - Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Key result
- Species / strain:
- other: CHO cells; CH DON-6 cells, CH lung V79 cells, BALB/c mouse back-skin cells, Syrian hamster lung cells, human fibroblasts, human lymphocytes, mouse ascites tumour cells
- Metabolic activation:
- without
- Genotoxicity:
- positive
- Remarks:
- in 10 of 14
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Key result
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- without
- Genotoxicity:
- ambiguous
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Key result
- Species / strain:
- other: human lymphocytes, rat bone-marrow cells
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Key result
- Species / strain:
- other: Syrian hamster
- Remarks:
- V79 and CHC cells
- Metabolic activation:
- without
- Genotoxicity:
- positive
- Remarks:
- 1 study; micronuclei
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Key result
- Species / strain:
- other: mouse
- Remarks:
- splenocytes
- Metabolic activation:
- without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Key result
- Species / strain:
- other: variant of HeLa cells, and embryonic fibroplasts
- Metabolic activation:
- without
- Genotoxicity:
- positive
- Remarks:
- 2 studies; chomosome aberration
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Remarks on result:
- other: results are for the source substance; may be adopted for the target substance
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- ANALOGUE APPROACH JUSTIFICATION
Please refer to the attached read across justification in section 13. - Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Key result
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- without
- Genotoxicity:
- positive
- Remarks:
- in 1 of 6 studies
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Key result
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Remarks:
- in 5 of 6 studies
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Key result
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- without
- Genotoxicity:
- positive
- Remarks:
- 2 studies
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Key result
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- without
- Genotoxicity:
- positive
- Remarks:
- 6 studies
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Key result
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- without
- Genotoxicity:
- positive
- Remarks:
- 3 studies
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Key result
- Species / strain:
- other: African Green monkey
- Remarks:
- kideney cells
- Metabolic activation:
- without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Remarks on result:
- other: HPRT mutation seen with the source substance; can be adopted for the target substance
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- ANALOGUE APPROACH JUSTIFICATION
Please refer to the attached read across justification in section 13. - Reason / purpose for cross-reference:
- read-across source
- Key result
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- valid
- Remarks on result:
- other: result for the source substance; can be adopted for the target substanceresult for the source substance; can be adopted for the target substance
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- ANALOGUE APPROACH JUSTIFICATION
Please refer to the attached read across justification in section 13. - Reason / purpose for cross-reference:
- read-across source
- Key result
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Remarks on result:
- other: result for the source substance; can be adopted for the target substance
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- ANALOGUE APPROACH JUSTIFICATION
Please refer to the attached read across justification in section 13. - Reason / purpose for cross-reference:
- read-across source
- Key result
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Remarks:
- several limitations of the study lead to this conclusion, differs from tthe authors' interpretation
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- valid
- Remarks on result:
- other: mutation frequency was 2.4-fold increased at only 530 mmol/l (31.7 mg/ml). Result for the source substance; can be adopted for the target substance
Referenceopen allclose all
Strain: TA100 |
||||||||||
Dose |
No Activation |
No Activation |
No Activation |
30% RLI |
30% HLI |
|||||
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 |
No Activation |
30% RLI |
30% HLI |
||||
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 |
|
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 |
|
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 |
No Activation |
No Activation |
No Activation |
30% RLI |
30% HLI |
||||||
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;
Urea Concentration [mol/l] |
Total growth [suspension growth x cloning efficiency] |
Mutation frequency [mutations per |
Mutation index [mutation frequency of treated culture / mutation frequency of control cultures] |
0 |
|
80 |
|
0 |
|
99 |
|
1.320 x 10 E-01 |
107 |
102 |
1.1 |
2.640 x 10 E-01 |
73 |
150** |
1..7 |
3.970 x 10 E-01 |
56 |
135 |
1.5 |
5.300 x 10 E-01 |
24 |
214*** |
2.4 |
6.620 x 10 E-01 |
8 |
256*** |
2.9 |
** p ≤0.01; *** p ≤0.001
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (positive)
Genetic toxicity in vivo
Description of key information
Hydrogen peroxide – urea (1:1) readily breaks down to hydrogen and urea in aqueous solution. On this basis data on hydrogen peroxide and urea, respectively, may be used for read across. Neither hydrogen peroxide nor urea was determined to be genotoxic in vivo. This result is adopted for hydrogen peroxide – urea (1:1).
Link to relevant study records
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- ANALOGUE APPROACH JUSTIFICATION
Please refer to the attached read across justification in section 13. - Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Key result
- Sex:
- not specified
- Genotoxicity:
- positive
- Remarks:
- the only study with positive results
- Toxicity:
- not specified
- Vehicle controls validity:
- not specified
- Negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Remarks on result:
- other: Mouse; increased chromatid aberrations (local) following i.p. injection. Local effect; response presumed to depend on the presence or absence of RBCs.
- Key result
- Sex:
- not specified
- Genotoxicity:
- negative
- Remarks:
- in 8 studies
- Toxicity:
- not specified
- Vehicle controls validity:
- not specified
- Negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Remarks on result:
- other: species tested: rat, mouse, Drosophila
- Key result
- Sex:
- not specified
- Genotoxicity:
- negative
- Toxicity:
- not specified
- Vehicle controls validity:
- not specified
- Negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Remarks on result:
- other: micronuclei in bone marrow polychromatic RBCs
- Key result
- Sex:
- not specified
- Genotoxicity:
- negative
- Remarks:
- rat; 1 study
- Toxicity:
- not specified
- Vehicle controls validity:
- not specified
- Negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Remarks on result:
- other: hepatocyte UDS assay
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- ANALOGUE APPROACH JUSTIFICATION
Please refer to the attached read across justification in section 13. - Reason / purpose for cross-reference:
- read-across source
- Key result
- Sex:
- male
- Genotoxicity:
- positive
- Toxicity:
- not specified
- Vehicle controls validity:
- not specified
- Negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Remarks on result:
- other: result for the source substance; can be adopted for the target substance
- Endpoint:
- in vivo mammalian cell study: DNA damage and/or repair
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- abstract
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- - Principle of test:
The induction of DNA damage (SCE) following long-term exposure to hydrogen peroxide -urea (1:1) was examined in-vivo using Chinese hamsters.
- Short description of test conditions:
20 Chines hamsters per dose group received 0 or 70 mg hydrogen peroxide -urea (1:1) /kg bw for 15 weeks (5 days/week) by oral gavage. The positive control group received cyclophosphamide. Another two animal groups received Rembrandt tooth whitener at doses of 500 and 2000 mg/kg bw (content of hydrogen peroxide -urea (1:1) not specified).
- Parameters analysed / observed:
The SCE frequency of bone marrow cells was determined. Further, gastroduodenal tissues were examined for histopathological changes. - GLP compliance:
- not specified
- Type of assay:
- sister chromatid exchange assay
- Specific details on test material used for the study:
- CAS: 124-43-6
Purity: not specified - Species:
- hamster, Chinese
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- route: oral gavage
exposure duration: 15 weeks
frequency: 5 per week - Duration of treatment / exposure:
- 15 weeks
- Frequency of treatment:
- 5/week
- Dose / conc.:
- 0 mg/kg bw/day (actual dose received)
- Remarks:
- vehicle (water)
- Dose / conc.:
- 70 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 20
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- cyclophosphamide
- Tissues and cell types examined:
- SCE frequency of bone marrow cells .
Histopathology of gastro duodenal tissue - Genotoxicity:
- negative
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Conclusions:
- No genotoxicity seen in vivo following long-term adminsitration to Chinese hamsters.
- Executive summary:
Reportedly, no DNA damage (SCE) was seen in Chinese hamsters dosed with 70 mg hydrogen-peroxide - urea (1:1)/kg bw and day for 15 weeks. Further, no changes were seen in in the gastro-duodenal tissue (Li et al., 1993).
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
Genetic toxicity in vitro
Only few studies on hydrogen peroxide – urea (1:1) itself (other name: Carbamide peroxide) were located. However, as Carbamide peroxide breaks down to one molecule of each hydrogen peroxide and urea, data from these can be used as source data in a read-across approach.
Hydrogen peroxide-urea (1:1) itself 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 (NTP, 1999).
Hydrogen peroxide (H2O2) was a mutagen in a variety of in vitro bacterial test systems, but a high percentage of ambiguous or negative results were also obtained which is attributable to modifying factors and also indicates that hydrogen peroxide is a weak mutagen (SCCP, 2007). Hydrogen peroxide induced chromosome aberration in vitro in mammalian cells from several species (rat, mouse, Chinese and Syrian hamster, human cells). Positive results were obtained in 10 of 14 studies, 2 studies each gave ambiguous or negative results. The lowest effective dose in the various test systems ranged from 0.34 to 510 µg/mL (SCCP, 2007; ECB, 2003). Regarding mutations in mammalian cells in vitro, SCCP evaluated six mutagenicity studies with mammalian cells (Chinese hamster V79 lung fibroblasts). HPRT mutation was seen in only one study (lowest effective dose 17 µg/mL) whereas no mutation at this locus was seen in the other five studies (highest ineffective doses ranged from 3.4 to 20 µg/mL). Thus it appears that the responses depend on whether hydrogen peroxide does reach the DNA and on cellular repair abilities (SCCP, 2007). The percentage of positive results was higher in ECB’s evaluation. Of the 12 mammalian cell gene mutation assays (in vitro) that ECB evaluated, hydrogen peroxide caused mutations of the HGPRT or TK locus or resistance in 9 of 12 studies without metabolic activation (with metabolic activation not tested). The species from which cells lines were derived included Chinese hamster, mouse, and the African Green monkey (ECB, 2003).
Urea was not genotoxic in bacterial cell assays in vitro (Mortelmans,et al., 1986). This is also evidenced in EPA’s Toxicological Review of Urea (2011). Mixed results were obtained in assay with mammalian cells (EPA, 2011). Positive results were most often weak and only seen at high urea test concentrations. For example, Ishidate (1981, 1997) reported only a weak induction of chromosome aberration in Chinese hamster lung fibroblasts at urea concentrations up to 13 mg/mL. Likewise, urea reportedly caused mutations at the TK locus were tested using mouse lymphoma L5178Y cells in vitro. However, the test concentrations of 0, 8, 16, 24, 32, and 40 mg/mL exceeded the maximal recommended test concentration of 5 mg/ml (OECD guideline 476) by far. Excessive cytotoxicity was seen at the highest dose level; a significant increase of CA formation was only seen at 32 mg/mL. As this this 6.4-fold above the recommended dose, and because there was no dose-related effect at lower dose levels, it is considered that a false-positive effect was reported (Wangenheim and Bolcfoldi, 1988).
Overall conclusions regarding genotoxicity in vitro:
- Hydrogen peroxide was a weak mutagen in bacterial and mammalian cell in vitro assays.
- Urea was not mutagenic in bacterial test systems. Mixed results were obtained with mammalian cells. Positive results were obtained at high dose levels, and effects were either false-positive or marginal.
- These result can be adopted for hydrogen peroxide – urea (1:1).
Genetic toxicity in vivo
As already stated earlier, hydrogen peroxide – urea (1:1) readily breaks down to hydrogen and urea in aqueous solution. The molar ratio is 1:1, i.e. hydrogen peroxide accounts for approx. 36% of the initial mass, and urea for 64%. On this basis data on hydrogen peroxide and urea, respectively, may be used for read across in instances where no or insufficient data are available for hydrogen peroxide – urea (1:1).
Hydrogen peroxide was a weak mutagen in vitro but was negative in vivo. ECB evaluated 9 in vivo mutagenicity studies conducted in the mouse, rat, and Drosophila melanogaster. The measured endpoints included cytogenicity (micronuclei and chromosome aberrations), DNA repair (UDS), DNA damage (quantity of 8-OH-2’- deoxyguanosine) and mutations (codon 61 of c-Ha-ras gene), and epidermal hyperplasia and dermal cellularity changes (as a pre-screen for carcinogenicity) in mammals, and the SLRL test in Drosophila melanogaster. Negative results were obtained in all studies. It was therefore concluded that hydrogen peroxide lacks genotoxicity in vivo (ECB, 2003).
SCCP endorsed in their opinion on tooth whiteners (2007) the conclusions of the European Chemicals Bureau (2003) which are cited below (quoted references contained in the EU RAR on Hydrogen Peroxide, 2003).
"Hydrogen peroxide is a mutagen and genotoxicant in a variety of in vitro test systems. The responses observed were modified by the presence of degrading enzymes (catalase), the extent of formation of hydroxyl radicals by Fenton reaction, and the cells repair abilities.
Hydrogen peroxide has been studied for possible in vivo genotoxicity. Studies employing modern methodologies have explored DNA repair in liver cells of rats administered hydrogen peroxide by intravenous infusion for 30 minutes (CEFIC, 1997), as well as micronucleus formation in mice in the context of a 2-week drinking water exposure (Du Pont, 1995), or after a single intraperitoneal injection (CEFIC, 1995), all with a negative outcome. Intravenous administration of hydrogen peroxide in the in vivo-in vitro unscheduled DNA synthesis study ensured that the substance had a fair chance to reach the target (liver) cells, although the duration of exposure was limited (CEFIC, 1997). In the micronucleus study by oral drinking water exposure (Du Pont, 1995), the systemic fate of hydrogen peroxide was uncertain, and there was no decrease in the ratio of polychromatic/normochromatic erythrocytes in the bone marrow. In the other micronucleus study (CEFIC, 1995), a single intraperitoneal injection of a large dose of hydrogen peroxide somehow affected the bone marrow (because the PE/NE decreased), but the absence of micronucleus formation must be viewed with caution because of the presumably very short lifetime of hydrogen peroxide. With a view to exploring target tissue in vivo genotoxicity and mutagenicity as a pre-screen for carcinogenicity, hydrogen peroxide 0.2-3.2% solutions in ethanol were applied to the skin of Sencar mice twice weekly for 4 weeks (Society for Plastic Industry, 1997). There was no indication of induced DNA damage (increased 8-OH- dG), c-Ha-ras mutations, epidermal hyperplasia and dermal cellularity changes. Thus, at low concentrations, and with a low application frequency, hydrogen peroxide did not induce local mutagenicity in this tissue model.
In conclusion, the available studies are not in support of a significant genotoxicity/mutagenicity for hydrogen peroxide under in vivo conditions."
Regarding urea, mixed results were obtained with mammalian cells in vitro at high dose levels, and also in vivo. EPA could not rule out genetic toxicity in vivo, especially since carcinogenicity studies were too short and provided only “inadequate information to assess the carcinogenetic potential of urea” (EPA, 2011). Urea is generated in appreciable amounts in vivo in the course of protein and amino acid metabolism, and the available information is not considered to provide sufficient evidence that urea is genotoxic in vivo or has a carcinogenic potential.
As to hydrogen peroxide – urea (1:1) itself, only abstracts are available that provide additional information that no DNA damage (SCE) was seen in Chinese hamsters dosed with 70 mg hydrogen-peroxide - urea (1:1)/kg bw and day for 15 weeks. Further, no changes were seen in in the gastro-duodenal tissue (Li et al., 1993).
Overall, it is concluded that neither hydrogen peroxide nor urea are genotoxic in vivo. This result is adopted for hydrogen peroxide – urea (1:1).
Justification for classification or non-classification
Classification, Labeling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on these data the substance is not considered to be classified for genetic toxicity under Regulation (EC) No. 1272/2008, as amended for the tenth time in Regulation (EC) No 2017/776.
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