Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information
There are conclusive but not suffcient data for the classification of substance Potassium oxide /Dipotassium oxide with regard to mutagenicity/genetic toxicity. Based on QSAR examination of the constituents of the substance and the potential of its constituents to induce structural chromosomal aberration in mammalian cells, it is concluded that Dipotassium oxide is not expected to induce structural chromosomal aberration in mammalian cells. Based on QSAR examination of the constituents of the substance and the potential of its constituents to induce gene mutation in mammalian cells, it is concluded that Dipotassium oxide is not expected to induce gene mutation in mammalian cells It is concluded that the substance Potassium oxide /Dipotassium oxide does not meet the criteria to be classified for human health hazards for Mutagenicity-Genetic Toxicity.
Link to relevant study records

Referenceopen allclose all

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
other: Published data
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Study was given Klimish 2 in OECD SIDS (Guideline study with acceptable restrictions). When Potassium oxide is hydrated is produced Potassium hydroxide. Therefore, the health effects of Potassium hydroxide need to be considered in the assessment of Potassium oxide
Qualifier:
no guideline followed
Principles of method if other than guideline:
Ames test
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Species / strain / cell type:
S. typhimurium TA 97
Species / strain / cell type:
S. typhimurium TA 102
Metabolic activation:
with and without
Metabolic activation system:
Species and cell type: S9 mix prepared from the liver homogenate of male SD rats (Jcl:SD). Quantity: S9 mix containing 10% S9 fraction, 50μl/plate. Induced: Aroclor 1254 induced rats.
Test concentrations with justification for top dose:
0.01, 0.05, 0.1, 0.5, 1mg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: distilled water
Untreated negative controls:
yes
Positive controls:
yes
Positive control substance:
9-aminoacridine
Positive controls:
yes
Positive control substance:
mitomycin C
Positive controls:
yes
Positive control substance:
other: 2-aminoanthracene
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)


NUMBER OF REPLICATIONS:3


DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; cloning efficiency; relative total growth; other:

OTHER:number of metaphases analysed: no data
Evaluation criteria:
Number of revertants/plate
Species / strain:
other: TA97 and TA102
Metabolic activation:
with and 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
Additional information on results:
No. revertants/plate in function of dose mg/plate:
mg/TA97-S9/TA97+S9/TA102-S9/TA102+S9
0/162/211/227/378
0.01/148/215/250/350
0.05/141/193/248/359
0.1/153/201/239/351
0.5/122/200/256/390
1/159/200/232/354
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.
Conclusions:
Interpretation of results :negative

Potassium hydroxide is not genotoxic based on the Ames test (with and without metabolic activation).
When Potassium oxide is hydrated is produced Potassium hydroxide. Therefore, the health effects of Potassium hydroxide need to be considered in the assessment of Potassium oxide
Endpoint:
in vitro gene mutation study in mammalian cells
Type of information:
(Q)SAR
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
QSAR prediction: Regulatory accepted QSAR method for chemicals properties assessment. An assessment was conducted based on an examination of the composition of the substance and the potential of its constituents to induce gene mutation in mammalian cells. This assessment was supported by data from a QSAR prediction on the registered substance and its components.
Qualifier:
according to
Guideline:
other: QSAR Toolbox Version 3.3.5.17
Principles of method if other than guideline:
This method is based on the Mutagenicity/Carcinogenicity module of the software Toxtree. It works as a decision tree for estimating in vitro (Ames test) mutagenicity, based on a list of 30 structural alerts (SAs). The SAs for mutagenicity are molecular functional groups or substructures known to be linked to the mutagenic activity of chemicals. As one or more SAs embedded in a molecular structure are recognised, the system flags the potential mutagenicity of the chemical. The present list of SAs is a subset of the original Toxtree list, obtained by eliminating the SAs for nongenotoxic carcinogenicity.
GLP compliance:
no
Remarks:
not applicable. QSAR model,
Type of assay:
other: Assessment based on an examination of the composition of the substance and the potential of its constituents to induce gene mutation in mammalian cells, supported by predictions using the QSAR toolbox.
Target gene:
QSAR model
Species / strain / cell type:
other: predictions using the QSAR toolbox
Details on mammalian cell type (if applicable):
Assessment based on an examination of the composition of the substance and the potential of its constituents to induce gene mutation in mammalian cells, supported by predictions using the QSAR toolbox
Metabolic activation:
with and without
Test concentrations with justification for top dose:
QSAR model
Vehicle / solvent:
QSAR model
Untreated negative controls:
other: QSAR model
Negative solvent / vehicle controls:
other: QSAR model
True negative controls:
other: QSAR model
Remarks:
This method is based on the Mutagenicity/Carcinogenicity module of the software Toxtree. It works as a decision tree for estimating in vitro (Ames test) mutagenicity, based on a list of 30 structural alerts (SAs).
Species / strain:
other: An assessment was conducted based on an examination of the composition of the substance and the potential of its constituents to induce gene mutation in mammalian cells.
Metabolic activation:
with and without
Genotoxicity:
negative
Additional information on results:
See attached assessment report for full details of the assessment methodology and results.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

An assessment was conducted based on an examination of the composition of the substance and the potential of its constituents to induce gene mutation in mammalian cells. This assessment used data from a QSAR prediction on the registered substance and its constituents, which was found to be negative in all cases. The results of the QSAR prediction for Dipotassium oxide and its constituents show that Dipotassium oxide is not expected to induce gene mutation in mammalian cells. On the basis of these results an experimental study on the potential of Dipotassium oxide to induce gene mutation in mammalian cells is not considered necessary since it is unlikely to provide additional relevant data about the in vivo mutagenicity potential of Dipotassium oxide in accordance with ECHA’s Endpoint Specific Guidance on Genotoxicity (ECHA, 2015), which states that the potential of a substance to induce gene mutation in mammalian cells does not need to be evaluated, if it can be demonstrated that it will not provide any further useful information about the potential in vivo mutagenicity of a substance

Conclusions:
Interpretation of results :negative

Based on an examination of the constituents of the substance and the potential of its constituents to induce gene mutation in mammalian cells, it is concluded that Dipotassium oxide is not expected to induce gene mutation in mammalian cells.
Executive summary:

An assessment was conducted based on an examination of the composition of the substance and the potential of its constituents to induce gene mutation in mammalian cells. This assessment used data from a QSAR prediction on the registered substance and its constituents, which was found to be negative in all cases. The results of the QSAR prediction for Dipotassium oxide and its constituents show thatDipotassium oxideis not expected to induce gene mutation in mammalian cells. On the basis of these results an experimental study on the potential of Dipotassium oxide to induce gene mutation in mammalian cells is not considered necessary since it is unlikely to provide additional relevant data about the in vivo mutagenicity potential ofDipotassium oxidein accordance with ECHA’s Endpoint Specific Guidance on Genotoxicity (ECHA, 2015), which states that the potential of a substance to induce gene mutation in mammalian cells does not need to be evaluated, if it can be demonstrated that it will not provide any further useful information about the potential in vivo mutagenicity of a substance

Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
(Q)SAR
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
QSAR prediction: Regulatory accepted QSAR method for chemicals properties assessment. An assessment was conducted based on an examination of the composition of the substance and the potential of its constituents to induce gene mutation in mammalian cells. This assessment was supported by data from a QSAR prediction on the registered substance and its components.
Qualifier:
according to
Guideline:
other: QSAR Toolbox Version 3.3.5.17
Principles of method if other than guideline:
The method is based on 28 structural alerts accounting for interactions of chemicals with specific proteins, such as topoisomerases, cellular protein adducts, etc. Associated with clear mechanistic justification, these alerts are included as a second reactivity component (complementing DNA reactivity) in the in vitro Chromosomal aberrations OASIS TIMES mutagenicity model. The scope of this profiler is to investigate the ability of target molecules to elicit clastogenicity and aneugenicity. Functionalities which bring about steric (or electronic) hindrance in molecules and thus impede interactions with proteins are explicitly defined and associated with some of the alerts as “inhibition” masks.
GLP compliance:
no
Remarks:
not applicable. QSAR model,
Type of assay:
other: An assessment was conducted based on an examination of the composition of the substance and the potential of its constituents to induce chromosomal aberration in mammalian cells.
Target gene:
QSAR model
Species / strain / cell type:
other: predictions using the QSAR toolbox
Details on mammalian cell type (if applicable):
An assessment was conducted based on an examination of the composition of the substance and the potential of its constituents to induce chromosomal aberration in mammalian cells, supported by data from a QSAR prediction.
Metabolic activation:
with and without
Test concentrations with justification for top dose:
QSAR model
Vehicle / solvent:
QSAR model
Untreated negative controls:
other: QSAR model
Negative solvent / vehicle controls:
other: QSAR model
True negative controls:
other: QSAR model
Remarks:
The method is based on 28 structural alerts accounting for interactions of chemicals with specific proteins, such as topoisomerases, cellular protein adducts, etc.
Statistics:
.
Species / strain:
other: An assessment was conducted based on an examination of the composition of the substance and the potential of its constituents to induce chromosomal aberration in mammalian cells. .
Metabolic activation:
with and without
Genotoxicity:
negative
Additional information on results:
See attached assessment report for full details of the assessment methodology and results.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

An assessment was conducted based on an examination of the composition of the substance and the potential of its constituents to induce chromosomal aberration in mammalian cells. This assessment was supported by data from a QSAR prediction on the registered substance and its components. An assessment of the available literature information on Dipotassium oxide, predicted to be the most abundant of the species Dipotassium oxide will dissociate into in the known pH range of mammalian cells, as well as a QSAR predictions of each substance, demonstrates that Dipotassium oxideis not expected to cause chromosomal aberrations in mammalian cells.

Conclusions:
Interpretation of results:negative

Based on an examination of the constituents of the substance and the potential of its constituents to induce structural chromosomal aberration in mammalian cells, it is concluded that Dipotassium oxide is not expected to induce structural chromosomal aberration in mammalian cells.
Executive summary:

An assessment was conducted based on an examination of the composition of the substance and the potential of its constituents to induce chromosomal aberration in mammalian cells. This assessment was supported by data from a QSAR prediction on the registered substance and its components. An assessment of the available literature information on Dipotassium oxide, predicted to be the most abundant of the species Dipotassium oxide will dissociate into in the known pH range of mammalian cells, as well as a QSAR predictions of each substance, demonstrates thatDipotassium oxideis not expected to cause chromosomal aberrations in mammalian cells

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
other: Published data
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
only 4 strains were used instead of 5
Principles of method if other than guideline:
Preincubation assay as described by Haworth et al (1983): Environ Mutagen 5[Suppl 1], 3-142
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Target gene:
not mentioned in the publication
Species / strain / cell type:
other: Salmonella typhimurium TA 98, TA100, TA1535, TA1537
Additional strain / cell type characteristics:
other: no details described
Metabolic activation:
with and without
Metabolic activation system:
S9-liver fractions of male Sprague-Dawley rats and male Syrian hamsters induced with Aroclor 1254
Test concentrations with justification for top dose:
0.000, 100.000, 333.000, 1000.000, 3333.000, 10000.000 µg/plate
Vehicle / solvent:
distilled water
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: 1342 sodium azide, 4-nitro-o-phenylene diamine, 9-aminoacridine, 2-aminoanthracene
Details on test system and experimental conditions:
Type: Ames test
Evaluation criteria:
positive response: dose-related reproducible increase in the number of revertants over background even if the increase was less than twofold
questionable response: absense of a clear-cut dose-reated increase of revertants or when the response was not reproducible
negative response: when no increase in the number of revertants was elicited by the chemical
Statistics:
no data
Species / strain:
other: S. typhimurium TA 98, TA 100, TA 1535, TA 1537
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
In a Salmonella Test using TA100, TA1538, TA1537 and TA98 , doses of KCl betwen 0 and 10000 mg/plate were tested with and without metabolic activation. No significant increases in mutation frequencies were noted .
Remarks on result:
other:
Remarks:
Migrated from field 'Test system'.
Conclusions:
Interpretation of results: negative without metabolic activation

In a Salmonella Test using TA100, TA1538, TA1537 and TA98 , doses of KCl betwen 0 and 10000 mg/plate were tested with and without metabolic activation. No significant increases in mutation frequencies were noted .
Executive summary:

In a Salmonella Test using TA100, TA1538, TA1537 and TA98 , doses of KCl betwen 0 and 10000 mg/plate were tested with and without metabolic activation. No significant increases in mutation frequencies were noted .

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
other: Published data
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
according to
Guideline:
other: SOS Chromotest
Principles of method if other than guideline:
E coli PQ37 strains were incubated for 2 hours with 1-100000 nM/ml potassium chloride without a metabolic activation system. ?-galyctosidate activivity was studyie by kinetic measurements as an induction assay
GLP compliance:
not specified
Type of assay:
other: SOS Chromotest
Target gene:
E coli PQ37
Species / strain / cell type:
other: E coli PQ37
Additional strain / cell type characteristics:
other: no details described
Metabolic activation:
with and without
Test concentrations with justification for top dose:
1-100000 nM/ml
Vehicle / solvent:
no data specified
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
not specified
True negative controls:
not specified
Positive controls:
not specified
Details on test system and experimental conditions:
E coli PQ37 strains were incubated for 2 hours with 1-100000 nM/ml potassium chloride without a metabolic activation system. ?-galyctosidate activivity was studyie by kinetic measurements as an induction assay
Evaluation criteria:
no data specified
Statistics:
no data
Species / strain:
other: E coli PQ37
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
100000 nM/ml
Vehicle controls validity:
not specified
Untreated negative controls validity:
not specified
Positive controls validity:
not specified
Additional information on results:
The genotoxic potentioal of potassiumchloride was studied using the bacterial colorimetirc assa: the SOS Chromotest. Potassium chloride revealed no mutagenic activity in this test.
Remarks on result:
other:
Remarks:
Migrated from field 'Test system'.
Conclusions:
Interpretation of results :negative

The genotoxic potentioal of potassiumchloride was studied using the bacterial colorimetirc assa: the SOS Chromotest. Potassium chloride revealed no mutagenic activity in this test.
Executive summary:

The genotoxic potentioal of potassium chloride was studied using the bacterial colorimetirc assa: the SOS Chromotest. Potassium chloride revealed no mutagenic activity in this test.

Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
other: Published data
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Alternatively and more conveniently Potassium oxide is synthesized by heating potassium nitrate with metallic potassium: 2 KNO3 + 10 K → 6 K2O + N2 Therefore, the health effects of potassium nitrate need to be considered in the assessment of Potassium oxide
Qualifier:
no guideline followed
Principles of method if other than guideline:
According to Ishidate & Odashima (1977).
TEST SYSTEM
- Species/cell type: Chinese hamster fibroblast cell line

ADMINISTRATION
- Dosing: three different doses (0 – 1.0 mg/ml)
- Number of replicates: 2
- Exposure time: 24 and 48 hours. Colcemid was added 2 h prior to cell harvesting.
- Positive and negative control groups and treatment: positive: not indicated; negative: untreated or solvent (physiological saline) treated cells
- Duration of incubation: 24 and 48 hours.

CRITERIA FOR EVALUATING RESULTS
- Statistical method: not indicated
- method of calculation: The result was considered to be negative if the incidence of aberrations was less than 4.9%, equivocal if it was between 5.0 and 9.9% and positive if it was more than 10%.
GLP compliance:
not specified
Type of assay:
in vitro mammalian chromosome aberration test
Species / strain / cell type:
other: Chinese hamster fibroblast cell line (CHL)
Details on mammalian cell type (if applicable):
fibroblast cell line
Metabolic activation:
without
Test concentrations with justification for top dose:
Potassium nitrate: 0-1.0 mg/ml
Vehicle / solvent:
physiological saline
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
yes
Positive controls:
yes
Details on test system and experimental conditions:
- Exposure duration: 24 and 48 hr
- Colcemid was added 2 h prior to cell harvesting
- cells fized with acetic-acid methanol
- stained with Giemsa
- 100 metaphases observed
Species / strain:
other: Chinese Hamster Fibroblast cell line
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Additional information on results:
GENOTOXIC EFFECTS

Potassium nitrate was not clastogenic.


Incidence of cells with structural aberrations

Without S9-mix


potassium nitrate
24 hr Not presented
48 hr 3.0%

CYTOTOXIC CONCENTRATION
Maximum dose tested = non cytotoxic dose
Polyploid cells 2.0%
Conclusions:
Interpretation of results :negative

Does not cause structural chromosomal aberrations.
Alternatively and more conveniently Potassium oxide is synthesized by heating potassium nitrate with metallic potassium:
2 KNO3 + 10 K → 6 K2O + N2
Therefore, the health effects of potassium nitrate need to be considered in the assessment of Potassium oxide
Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
other: Published data
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
The strains used are no standard strains as recommended by the OECD, not all necessary substitutions are added. Alternatively and more conveniently Potassium oxide is synthesized by heating potassium nitrate with metallic potassium: 2 KNO3 + 10 K → 6 K2O + N2 Therefore, the health effects of potassium nitrate need to be considered in the assessment of Potassium oxide
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Target gene:
TEST SYSTEM
- Species/cell type: bacteria strains
- Deficiency/Proficiency: histidine
- Metabolic activation system: Rat liver S9-mix (polychlorinated biphenyls induced, KC-400)

ADMINISTRATION
- Dosing: pre-incubation assay, 6 different concentrations (not given).
- Number of replicates: 2
- Application: cells were pre-incubated with test sample and S9-mix for 20 minutes before plating.
- Positive and negative control groups and treatment: positive: not indicated; negative: untreated or solvent (phosphate buffer) treated cells
- Pre-incubation time: 20 minutes
- Duration of incubation: 2 days.

CRITERIA FOR EVALUATING RESULTS
- Statistical method: not indicated
- method of calculation: The result was considered positive if the number of revertant colonies found was twice or more that of the control. If no dose response was detected, additional experiments using different doses were performed.
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Species / strain / cell type:
other: TA92
Metabolic activation:
with and without
Test concentrations with justification for top dose:
20 mg/plate (highest dose tested), 6 different concentrations
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
yes
Positive controls:
yes
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:
not specified
Species / strain:
other: TA 92
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Conclusions:
Interpretation of results :negative

GENOTOXIC EFFECTS: Negative in all tested strains.
Alternatively and more conveniently Potassium oxide is synthesized by heating potassium nitrate with metallic potassium:
2 KNO3 + 10 K → 6 K2O + N2
Therefore, the health effects of potassium nitrate need to be considered in the assessment of Potassium oxide
Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
other: Published data
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Well described study. Alternatively and more conveniently Potassium oxide is synthesized by heating potassium nitrate with metallic potassium: 2 KNO3 + 10 K → 6 K2O + N2 Therefore, the health effects of potassium nitrate need to be considered in the assessment of Potassium oxide
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
no
Type of assay:
bacterial reverse mutation assay
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Species / strain / cell type:
S. typhimurium TA 1538
Metabolic activation:
with and without
Test concentrations with justification for top dose:
0.0033 to 10 mg per plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: potassium or sodium phosphate buffer 0.067M, pH 7.0
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
yes
Positive controls:
yes
Details on test system and experimental conditions:
- test performed according to Ames et al (1975)
- no details given on Materials and Methods

OTHER:
- positive controls used in the absence of S9 were 2-nitrofluorene, sodium azide, 9-aminoacridine for S. typhimurium strains, and AF-2 or N-methyl-N'-nitro-N-nitrosoguanidine for E coli strain.
- positive controls used in the presence of S9 was 2-anthramine for all bacterial strains.
Evaluation criteria:
no data
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:
not specified
Species / strain:
S. typhimurium TA 1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Conclusions:
Interpretation of results :negative

non-mutagenic
Genotoxic effects:
With metabolic activation: negative
Without metabolic activation: negative
Alternatively and more conveniently Potassium oxide is synthesized by heating potassium nitrate with metallic potassium:
2 KNO3 + 10 K → 6 K2O + N2
Therefore, the health effects of potassium nitrate need to be considered in the assessment of Potassium oxide
Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
other: Published data
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
Deviations:
yes
Remarks:
measurement of osmotic pressure of the medium
GLP compliance:
not specified
Type of assay:
in vitro mammalian chromosome aberration test
Target gene:
Chromosome aberration in V79 cells of Chinese Hamster
Species / strain / cell type:
Chinese hamster lung fibroblasts (V79)
Details on mammalian cell type (if applicable):
Chinese hamster lung fibroblasts (V79)
Additional strain / cell type characteristics:
other: Chinese hamster lung fibroblasts (V79)
Metabolic activation:
without
Test concentrations with justification for top dose:
0, 27, 107, 161 mM = 0, 2000, 8000, 12000 µg/ml
Vehicle / solvent:
no data specified
Untreated negative controls:
yes
Negative solvent / vehicle controls:
not specified
True negative controls:
yes
Remarks:
ethanol
Positive controls:
yes
Positive control substance:
other: 1342 N-methyl-N'-nitro-N-nitrosoguanine
Details on test system and experimental conditions:
according to guideline and additional measurement of the osmotic pressure of the medium
Evaluation criteria:
A compound was defined mutagenic when the mutation frequency in its presence was at least three times the sponaneous frequency and showed a dose-dependent increase
Statistics:
no data specified
Species / strain:
Chinese hamster lung fibroblasts (V79)
Metabolic activation:
without
Genotoxicity:
positive
Remarks:
only at the highest test dose
Cytotoxicity / choice of top concentrations:
other: 12000 µg/ml, osmotic pressure 530 mOsmol/kg versus 253 mOsmol/kg in untreated control
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
osmotic pressiure of the medium increased with the concentration of KCl in the medium:
27, 107, 161mM: 292, 436, 530 mOsmol/ kg versus 253 mOsmol/kg in normal medium
Remarks on result:
other: strain/cell type: Chinese hamster lung fibroblasts (V79)
Remarks:
Migrated from field 'Test system'.
Conclusions:
Interpretation of results :positive only at the highest test dose

In a test similar or equivalent to OECD TG 476 potassium chloride induced a significant increase
in Chinese Hamster lung fibroblasts (V79) cells with chromosme Aberrations only at the highest test dose (12000 µg/ml) in the absence of a metabolic activation system. Measurements of the osmotic pressure of the medium revealed a twofold increase at this test compound concentration when compared to the normal medium (530 mOsmol/ kg versus 253 mOsmol/kg.
Executive summary:

In a test similar or equivalent to OECD TG 476 potassium chloride induced a significant increase in Chinese Hamster lung fibroblasts (V79) cells with chromosme Aberrations only at the highest test dose (12000 µg/ml) in the absence of a metabolic activation system. Measurements of the osmotic pressure of the medium revealed a twofold increase at this test compound concentration when compared to the normal medium (530 mOsmol/ kg versus 253 mOsmol/kg

Endpoint:
in vitro gene mutation study in mammalian cells
Remarks:
Type of genotoxicity: gene mutation
Type of information:
other: Published data
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
according to
Guideline:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
GLP compliance:
not specified
Type of assay:
mammalian cell gene mutation assay
Target gene:
Chromosome aberration in V79 cells of Chinese Hamster
Species / strain / cell type:
mouse lymphoma L5178Y cells
Details on mammalian cell type (if applicable):
mouse lymphoma L5178Y cells
Additional strain / cell type characteristics:
other: mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Metabolic activation system:
S9 prepared fromöovers pf Aroclor 1254-treated Fisdher 344 male rats
Test concentrations with justification for top dose:
with and without S9: 0 (solvent control), 156, 313, 625, 1250, 2500, 5000 µg/ml
with and without S9: 0 (solvent control): 500, 1000, 2000, 4000, 5000 µg/ml
with without S9: 0 (solvent control); 4000, 5000, 7000, 8000, 9000 µg/ml
Vehicle / solvent:
distilled water
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: 1342 ethylmetansulfonate. 3-methylcholantrene
Details on test system and experimental conditions:
as requested by the guideline
Evaluation criteria:
no details given
Statistics:
no details given
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
>=7000 µg/ml
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
with
Genotoxicity:
positive
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
>= 7000 µg/ml
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
With metabolic activation KCl yielded positive results at 4000 and 5000 µg/ml; without activation it was negative up to 5000 µg/ml. However higher concentrations appeared to be toxic and mutagenic
Remarks on result:
other:
Remarks:
Migrated from field 'Test system'.
Conclusions:
Interpretation of results :negative without metabolic activation

A Mouse Lymphoma assay was performed according to OECD TG 476 with KCl in the presence and in the absence of a metabolic activation system.With metabolic activation KCl yielded positive results at 4000 and 5000 µg/ml; without activation it was negative up to 5000 µg/ml. However higher concentrations appeared to be toxic and mutagenic.
Executive summary:

A Mouse Lymphoma assay was performed according to OECD TG 476 with KCl in the presence and in the absence of a metabolic activation system.With metabolic activation KCl yielded positive results at 4000 and 5000 µg/ml; without activation it was negative up to 5000 µg/ml. However higher concentrations appeared to be toxic and mutagenic.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Link to relevant study records

Referenceopen allclose all

Endpoint:
in vivo mammalian germ cell study: cytogenicity / chromosome aberration
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
other: Published data
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Justification for type of information:
Alternatively and more conveniently Potassium oxide is synthesized by heating potassium nitrate with metallic potassium: 2 KNO3 + 10 K → 6 K2O + N2 Therefore, the health effects of potassium nitrate need to be considered in the assessment of Potassium oxide
Qualifier:
no guideline followed
GLP compliance:
not specified
Type of assay:
rodent dominant lethal assay
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Route of administration:
oral: feed
Duration of treatment / exposure:
10-weeks
Frequency of treatment:
not stated
Post exposure period:
not stated
Remarks:
Doses / Concentrations:
not stated
Basis:

No. of animals per sex per dose:
not stated
Control animals:
not specified
Sex:
male/female
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls validity:
valid
Negative controls validity:
valid
Additional information on results:
Body weight gains did not show a clear dose-response effect. The weight gains ranged from 3 to 13% above control values. The dominant lethal test produced no consistent responses to suggest that potassium nitrate is mutagenic to rats.
Conclusions:
Interpretation of results : negative
Potassium nitrate tested negative in a dormant lethal assay.
Alternatively and more conveniently Potassium oxide is synthesized by heating potassium nitrate with metallic potassium:
2 KNO3 + 10 K → 6 K2O + N2
Therefore, the health effects of potassium nitrate need to be considered in the assessment of Potassium oxide
Executive summary:

The dominant lethal test produced no consistent responses to suggest that potassium nitrate is mutagenic to rats.

Endpoint:
in vivo mammalian germ cell study: cytogenicity / chromosome aberration
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
(Q)SAR
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
QSAR prediction:Regulatory accepted QSAR method for chemicals properties assessment.
Qualifier:
according to
Guideline:
other: QSAR Toolbox Version 3.3.5.17
Principles of method if other than guideline:
This method is based on the ToxMic rulebase of the software Toxtree. This rulebase provides a list of 35 structural alerts (SAs) for a preliminary screening of potentially in vivo mutagens. These SAs are molecular functional groups or substructures that are known to be linked to the induction of effects in the in vivo micronucleus assay. The compilation of SAs for the in vivo micronucleus assay in rodents provided here, is based on both the existing knowledge on the mechanisms of toxic action and on a structural analysis of the chemicals tested in the assay.
GLP compliance:
no
Remarks:
not applicable. QSAR model
Type of assay:
other: An assessment was conducted based on an examination of the composition of the substance and the potential of its constituents to induce chromosomal aberration in mammalian cells.
Species:
other: QSAR model
Strain:
other: QSAR model
Sex:
male/female
Route of administration:
other: QSAR model
Details on exposure:
This method is based on the ToxMic rulebase of the software Toxtree. This rulebase provides a list of 35 structural alerts (SAs) for a preliminary screening of potentially in vivo mutagens. These SAs are molecular functional groups or substructures that are known to be linked to the induction of effects in the in vivo micronucleus assay. The compilation of SAs for the in vivo micronucleus assay in rodents provided here, is based on both the existing knowledge on the mechanisms of toxic action and on a structural analysis of the chemicals tested in the assay.
Duration of treatment / exposure:
QSAR model
Frequency of treatment:
QSAR model
Post exposure period:
QSAR model
Remarks:
Doses / Concentrations:

Basis:
other: QSAR model
No. of animals per sex per dose:
QSAR model
Control animals:
other: QSAR model
Tissues and cell types examined:
This profiler is based on the ToxMic rulebase of the software Toxtree. This rulebase provides a list of 35 structural alerts (SAs) for a preliminary screening of potentially in vivo mutagens. These SAs are molecular functional groups or substructures that are known to be linked to the induction of effects in the in vivo micronucleus assay. The compilation of SAs for the in vivo micronucleus assay in rodents provided here, is based on both the existing knowledge on the mechanisms of toxic action and on a structural analysis of the chemicals tested in the assay.
Evaluation criteria:
An assessment was conducted based on an examination of the composition of the substance and the potential of its constituents to induce chromosomal aberration in mammalian cells, supported by data from a QSAR prediction.
Sex:
male/female
Genotoxicity:
negative
Toxicity:
not specified
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
not specified
Additional information on results:
Available QSAR methods does not identify Dipotassium oxide as genotoxic/non-genotoxic mutagen.

See attached background material and QSAR study report

Conclusions:
Interpretation of results (migrated information): negative
Available QSAR methods does not identify Dipotassium oxide as genotoxic/non-genotoxic mutagen.
Executive summary:

Based on QSAR in vivo mutagenicity (Micronucleus) examination of the constituents of the substance and the potential of its constituents to induce structural chromosomal aberration in mammalian cells, it is concluded that Dipotassium oxide is not expected to induce structural chromosomal aberration in mammalian cells.

Additional information

Additional information from genetic toxicity in vitro:

Mutagenicity

 

Studies in Animals

 

In vitro Studies

The results of an Ames assay study with Salmonella typhimurium TA 97 and TA 102, with and without metabolic activation and up to 1 mg KOH/plate, were negative (Fujita et al., 1992).

 

KCl has been classified as non-genotoxic in a bacterial reverse mutation assay withS. typhimuriumTA 100, TA 1535, TA 1537 and TA 9, at 0, 100, 333, 1000, 3333 and 10000 μg/plate, with andwithout metabolic activation (Mortelmans et al., 1986). In a DNA damage and repair assay (SOSChromotest Institut Pasteur) withE. coliPQ 37, at 1-100000 nM/ml, without metabolic activation,KCl was negative (Olivier and Marzin, 1987).

 

Two publications (Myhr and Caspary, 1988; Mitchell et al., 1988) report the genotoxic effect of KCl in a mammalian cell gene mutation assay with mouse lymphoma cell L5178Y, TK+/-

heterozygote, at 0-5000 μg/ml, with and without metabolic activation (OECD guideline 476). The result was positive only at high KCl concentration with metabolic activation. This has been attributed by the authors to the changed physical environment of the cells (increased osmotic pressure; K+ effects on sequestering of Mg2+ ions required for chromatin integrity), rather than to a direct genotoxic effect. Several authors confirm this type of non-specific genotoxic effect (Brusick, 1986; Seeberg, 1988).

 

Potassium nitrate has been classified has non-genotoxic in an Ames test withSalmonella typhimuriumstrains TA 1535, TA 1537, TA 98 and TA 100 and TA92, at up to 20 mg/plate, with and without metabolic activation (liver S-9 mix of Fischer rats) (Ishidate et al., 1984).

Potassium nitrate has been classified has non-genotoxic in a cytogenetic assay with Chinese hamster fibroblasts (CHL cells) at up to 1 mg/ml, without metabolic activation (Ishidate et al., 1984).

 

Based on QSAR examination of the constituents of the substance and the potential of its constituents to induce structural chromosomal aberration in mammalian cells, it is concluded that Dipotassium oxide is not expected to induce structural chromosomal aberration in mammalian cells.

Based on QSAR examination of the constituents of the substance and the potential of its constituents to induce gene mutation in mammalian cells, it is concluded that Dipotassium oxide is not expected to induce gene mutation in mammalian cells.

In vivo Studies

No studies were identified regarding the “in vivo” genotoxicity.

Potassium nitrate tested negative in a dormant lethal assay.

The dominant lethal test produced no consistent responses to suggest that potassium nitrate is mutagenic to rats.

Based on QSAR in vivo mutagenicity (Micronucleus) examination of the constituents of the substance and the potential of its constituents to induce structural chromosomal aberration in mammalian cells, it is concluded that Dipotassium oxide is not expected to induce structural chromosomal aberration in mammalian cells.

Conclusion

Based on the data with other potassium compounds, it could be concluded that potassium has no or a negligible contribution to the Mutagenicity of Potassium oxide.

Alternatively and more conveniently Potassium oxide is synthesized by heating potassium nitrate with metallic potassium:

2 KNO3 + 10 K → 6 K2O + N2

Therefore, the health effects of potassium nitrate need to be considered in the assessment of Potassium oxide

When Potassium oxide is hydrated is produced Potassium hydroxide. Therefore, the health effects of Potassium hydroxide need to be considered in the assessment of Potassium oxide.

Potassium chloride (KCl)is the most common sourceof Potassium oxide (K2O).

Therefore, the health effects ofpotassiumchlorideneed to be considered in the assessment of Potassium oxide

With the sum of information of the studies on Potassium hydroxide, Potassium chloride and Potassium nitrate, apart from the artefacts due to high pH with KOH and high osmotic pressure with KCl, there is no evidence for a mutagenic activity.Is not expected to be systemically available in the body over the normal limits, under non-irritating conditions. A genotoxic effect is also not very likely because both the K+ and OH- ions are naturally present in the human body, K+ is present in the cells at much higher concentration than outside (30 – 40x) and an high concentration of OH- is incompatible with cell life.

Justification for classification or non-classification

Based on the hazard assessment of Potassium oxide/Dipotassium oxide in section 2.1 and 2.2. in IUCLID 5.4., available data for the substance and following the “Guidance on Information Requirement and Chemical Safety Assessment R.8. Characterisation of dose [concentration]- response for human health” andaccording to the criteria described in Directive 67/548 and in the CLP Regulation:

 

 

 

Mutagenicity-Genetic Toxicity

Muta. Cat. 1; R46 May cause heritable genetic damage.

Muta. Cat. 2; R46 May cause heritable genetic damage.

Muta. Cat. 3; R68 Possible risk of irreversible effects.

CLP

Germ cell mutagenicity

Muta. 1A

Muta. 1B

Muta. 2

H340: May cause genetic defects <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>.

H341: Suspected of causing genetic defects <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>.

 

 

It is concluded that the substance Potassium oxide/Dipotassium oxide does not meet the criteria to be classified for human health hazards for Mutagenicity-Genetic Toxicity