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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:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Cross-referenceopen allclose all
Reason / purpose:
read-across source
Reference
Endpoint:
in vitro DNA damage and/or repair study
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Justification for type of information:
Read across approach adequate to support 7.6.1 according to "Guidance on information requirements and chemical safety assessment Chapter R.6: QSARs and grouping of chemicals" (ECHA 2008) and Read-Across Assessment
Framework (RAAF) (ECHA 2017)
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
other: Galloway et al. 1985 NTP Protocol
GLP compliance:
yes
Type of assay:
sister chromatid exchange assay in mammalian cells
Specific details on test material used for the study:
Name of test material: Boric acid
- Analytical purity: 99.7%
- Stability: Stable
Species / strain / cell type:
Chinese hamster Ovary (CHO)
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
Aroclor 1254 induced rat (Sprague-Dawley) liver S9 fraction
Test concentrations with justification for top dose:
With S-9; 200,300,400,and 500 µg/mL
Without S-9; 250, 500, 1600, 2000 µg/mL
Vehicle / solvent:
Water
Positive controls:
yes
Positive control substance:
other: Mitomycin
Positive controls:
yes
Positive control substance:
cyclophosphamide
Details on test system and experimental conditions:
Induction of SCEs in Chinese Hamster Ovary Cells
Evaluation criteria:
Induction of SCEs in Chinese Hamster Ovary Cells
Statistics:
No data
Species / strain:
Chinese hamster Ovary (CHO)
Metabolic activation:
with and without
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Remarks on result:
other: all strains/cell types tested
Conclusions:
Interpretation of results (migrated information):
negative

This method generally complies with OECD 482 (DNA damage and repair, unscheduled DNA synthesis in mammalian cells in vitro). Negative result obtained for induction of sister chromatid exchange.
Reason / purpose:
read-across source
Reference
Endpoint:
in vitro gene mutation study in bacteria
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Justification for type of information:
Read across approach adequate to support 7.6.1 according to "Guidance on information requirements and chemical safety assessment Chapter R.6: QSARs and grouping of chemicals" (ECHA 2008) and Read-Across Assessment
Framework (RAAF) (ECHA 2017)
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
other: Ames test with preincubation Yagahi et el 1975
Deviations:
not specified
GLP compliance:
no
Remarks:
Study predate GLP
Type of assay:
bacterial reverse mutation assay
Target gene:
Histidine
Species / strain / cell type:
S. typhimurium TA 98
Details on mammalian cell type (if applicable):
NA
Additional strain / cell type characteristics:
not applicable
Species / strain / cell type:
S. typhimurium TA 100
Details on mammalian cell type (if applicable):
NA
Additional strain / cell type characteristics:
not applicable
Species / strain / cell type:
S. typhimurium TA 1535
Details on mammalian cell type (if applicable):
NA
Additional strain / cell type characteristics:
not applicable
Species / strain / cell type:
S. typhimurium TA 1537
Details on mammalian cell type (if applicable):
NA
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with and without
Test concentrations with justification for top dose:
10-2000 µg/plate
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
not specified
True negative controls:
not specified
Positive controls:
not specified
Positive control substance:
not specified
Details on test system and experimental conditions:
Preincubation: Yes
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Species / strain:
S. typhimurium TA 1537
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Remarks on result:
other: all strains/cell types tested
Conclusions:
interpretation of results (migrated information):
negative with metabolic activation

Negative with metabolic activation.
Reason / purpose:
read-across source
Reference
Endpoint:
in vitro cytogenicity / micronucleus study
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Justification for type of information:
Read across approach adequate to support 7.6.1 according to "Guidance on information requirements and chemical safety assessment Chapter R.6: QSARs and grouping of chemicals" (ECHA 2008) and Read-Across Assessment
Framework (RAAF) (ECHA 2017)
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
other: no data
Deviations:
not specified
Principles of method if other than guideline:
Whole heparinised blood from 10 healthy male non-smoking donors between the ages of 24 and 30 with no history of exposure to toxic agents were used. Boric acid and borax were tested at concentrations in blood of 0, 5, 10, 20, 40, 50, 80, 100, 150, 200, 300, 400 and 500 mg/L on the peripheral blood lymphocyte cultures.
GLP compliance:
not specified
Type of assay:
in vitro mammalian cell micronucleus test
Target gene:
No data
Species / strain / cell type:
lymphocytes: Human peripheral cell lymphocytes
Details on mammalian cell type (if applicable):
Whole heparinised blood from 10 healthy male non-smoking donors between the ages of 24 and 30 with no history of exposure to toxic agents were used.
Additional strain / cell type characteristics:
not specified
Metabolic activation:
not specified
Test concentrations with justification for top dose:
0, 5, 10, 20, 40, 50, 80, 100, 150, 200, 300, 400 and 500 mg/L
Untreated negative controls:
yes
Negative solvent / vehicle controls:
not specified
True negative controls:
not specified
Positive controls:
not specified
Positive control substance:
not specified
Species / strain:
lymphocytes: Peripheral human lymphocytes
Metabolic activation:
not specified
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
Remarks on result:
other: ll strains/cell types tested
Conclusions:
Interpretation of results (migrated information):
negative

Peripheral blood cultures were exposed to various doses (5 to 500 mg/L) of boric acid and borax. Sister chromatid exchange, micronucleus and chromosomal aberration tests were applied to estimate the amound of DNA damage and biochemical parameters were examined to determine oxidative stress. At low doses the boron compunds were useful in supporting antioxidant enzyme activities in human blood cultures. It was found that the boron compounds do not have genotoxic effects even in the highest concentrations, although in increasing doses they constitute oxidative stress.
Reason / purpose:
read-across source
Reference
Endpoint:
in vitro cytogenicity / micronucleus study
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Read across approach adequate to support 7.6.1 according to "Guidance on information requirements and chemical safety assessment Chapter R.6: QSARs and grouping of chemicals" (ECHA 2008) and Read-Across Assessment
Framework (RAAF) (ECHA 2017)
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Qualifier:
no guideline available
GLP compliance:
not specified
Species / strain / cell type:
Chinese hamster Ovary (CHO)
Metabolic activation:
with and without
Test concentrations with justification for top dose:
10-50 mg/L
Species / strain:
Chinese hamster Ovary (CHO)
Metabolic activation:
with and without
Genotoxicity:
not determined
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Conclusions:
Negative

Data source

Reference
Reference Type:
publication
Title:
Salmonella mutagenicity tests: III. Results from the testing of 255 chemicals.
Author:
[Zeiger E et al; Environ Mutagen 9:1-110 (1987)
Year:
1987
Bibliographic source:
Environ Mutagen 9:1-110 (1987

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: [Zeiger E et al; Environ Mutagen 9:1-110 (1987)
Deviations:
not specified
Principles of method if other than guideline:
The substance was tested under code using a preincubation modification of the Salmonella/microsome test in the absence of exogenous metabolic activation and in the presence of liver S-9 from Aroclor-induced male Sprague-Dawley rats and Syrian hamsters.
Standard protocol approved by the National Toxicology Program
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Target gene:
Histidine
Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 98
Details on mammalian cell type (if applicable):
NA
Additional strain / cell type characteristics:
not applicable
Species / strain / cell type:
S. typhimurium TA 100
Details on mammalian cell type (if applicable):
NA
Additional strain / cell type characteristics:
not applicable
Species / strain / cell type:
S. typhimurium TA 1535
Details on mammalian cell type (if applicable):
NA
Additional strain / cell type characteristics:
not applicable
Species / strain / cell type:
S. typhimurium TA 1537
Details on mammalian cell type (if applicable):
NA
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with and without
Test concentrations with justification for top dose:
µg/plate, 100, 333, 1000, 3333, and 10,000
Controls
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
not specified
True negative controls:
not specified
Positive controls:
not specified
Positive control substance:
not specified
Details on test system and experimental conditions:
Preincubation: Yes

Results and discussion

Test resultsopen allclose all
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Species / strain:
S. typhimurium TA 1537
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity

Applicant's summary and conclusion

Conclusions:
interpretation of results (migrated information):
negative with metabolic activation

Negative with metabolic activation.