Potassium fluoroborates and potassium fluorohydroxyborates, exothermic reaction products of boron and potassium hydroxides and fluorohydroxides

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro DNA damage and/or repair study

Remarks:

Type of genotoxicity: DNA damage and/or repair

Type of information:

experimental study

Adequacy of study:

key study

Study period:

No data

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

GLP guideline study. This study is conducted on an analogue substance. Read-across is justified on the following basis: In aqueous solutions at physiological and acidic pH, low concentrations of simple inorganic borates such as boric acid, disodium tetraborate decahydrate, disodium tetraborate pentahydrate, boric oxide and disodium octaborate tetrahydrate will predominantly exist as undissociated boric acid. At about pH 10 the metaborate anion (B(OH)4-) becomes the main species in solution (WHO, 1998). This leads to the conclusion that the main species in the plasma of mammals and in the environment is un-dissociated boric acid. Since other borates dissociate to form boric acid in aqueous solutions, they too can be considered to exist as un-dissociated boric acid under the same conditions. For comparative purposes, exposures to borates are often expressed in terms of boron (B) equivalents based on the fraction of boron in the source substance on a molecular weight basis. Some studies express dose in terms of B, whereas other studies express the dose in units of boric acid. Since the systemic effects and some of the local effects can be traced back to boric acid, results from one substance can be transferred to also evaluate the another substance on the basis of boron equivalents. Therefore data obtained from studies with these borates can be read across in the human health assessment for each individual substance. Conversion factors are given in the table below. Conversion factor for equivalent dose of B Boric acid H3BO3 0.175 Boric Oxide B2O3 0.311 Disodium tetraborate anhydrous Na2B4O7 0.215 Disodium tetraborate pentahydrate Na2B4O7•5H2O 0.148 Disodium tetraborate decahydrate Na2B4O7•10H2O 0.113 Disodium octaborate tetrahydrate Na2B8O13•4H2O 0.210 Sodium metaborate (anhydrous) NaBO2 0.1643 Sodium metaborate (dihydrate) NaBO2•2H2O 0.1062 Sodium metaborate (tetrahydrate) NaBO2•4H2O 0.0784 Sodium pentaborate (anhydrous) NaB5O8 0.2636 Sodium pentaborate (pentahydrate) NaB5O8∙5H2O 0.1832 References: WHO. Guidelines for drinking-water quality, Addendum to Volume 1, 1998.

Qualifier:

according to guideline

Guideline:

other: Galloway et.al., 1985; NTP protocol

Deviations:

no

GLP compliance:

yes

Type of assay:

sister chromatid exchange assay in mammalian cells

Target gene:

No data

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

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Additional information on results:

No data

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

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.
Read-across is justified on the basis detailed in the rationale for reliability above. This study is therefore considered to be of sufficient adequacy and reliability to be used as a supporting study and no further testing is justified.

Reference 2

Endpoint:

in vitro gene mutation study in mammalian cells

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

No data

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

GLP guideline study. This study is conducted on an analogue substance. Read-across is justified on the following basis: In aqueous solutions at physiological and acidic pH, low concentrations of simple inorganic borates such as boric acid, disodium tetraborate decahydrate, disodium tetraborate pentahydrate, boric oxide and disodium octaborate tetrahydrate will predominantly exist as undissociated boric acid. At about pH 10 the metaborate anion (B(OH)4-) becomes the main species in solution (WHO, 1998). This leads to the conclusion that the main species in the plasma of mammals and in the environment is un-dissociated boric acid. Since other borates dissociate to form boric acid in aqueous solutions, they too can be considered to exist as un-dissociated boric acid under the same conditions. For comparative purposes, exposures to borates are often expressed in terms of boron (B) equivalents based on the fraction of boron in the source substance on a molecular weight basis. Some studies express dose in terms of B, whereas other studies express the dose in units of boric acid. Since the systemic effects and some of the local effects can be traced back to boric acid, results from one substance can be transferred to also evaluate the another substance on the basis of boron equivalents. Therefore data obtained from studies with these borates can be read across in the human health assessment for each individual substance. Conversion factors are given in the table below. Conversion factor for equivalent dose of B Boric acid H3BO3 0.175 Boric Oxide B2O3 0.311 Disodium tetraborate anhydrous Na2B4O7 0.215 Disodium tetraborate pentahydrate Na2B4O7•5H2O 0.148 Disodium tetraborate decahydrate Na2B4O7•10H2O 0.113 Disodium octaborate tetrahydrate Na2B8O13•4H2O 0.210 Sodium metaborate (anhydrous) NaBO2 0.1643 Sodium metaborate (dihydrate) NaBO2•2H2O 0.1062 Sodium metaborate (tetrahydrate) NaBO2•4H2O 0.0784 Sodium pentaborate (anhydrous) NaB5O8 0.2636 Sodium pentaborate (pentahydrate) NaB5O8∙5H2O 0.1832 References: WHO. Guidelines for drinking-water quality, Addendum to Volume 1, 1998.

Qualifier:

according to guideline

Guideline:

other: 40 CFR Part 158 US-EPA-FIFRA, Section 156.340

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)

Deviations:

not specified

GLP compliance:

yes

Type of assay:

mammalian cell gene mutation assay

Target gene:

Thymidine kinase, TK locus of the L5178Y mouse lymphoma cell line

Species / strain / cell type:

mouse lymphoma L5178Y cells

Details on mammalian cell type (if applicable):

No data

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

S9 mix or other (Aroclor 1254 induced rat (Fischer 344) liver S9 fraction used at 1 %).

Test concentrations with justification for top dose:

0, 1.2, 1.7, 2.45, 3.5 and 5.0 mg/mL boric acid.

Vehicle / solvent:

No data

Positive controls:

yes

Positive control substance:

3-methylcholanthrene

Positive controls:

yes

Positive control substance:

other: Hycanthone methylsulphonate

Details on test system and experimental conditions:

METHOD OF APPLICATION: ROP plus 5 % heat treated horse serum

NUMBER OF CELLS EVALUATED: Approximately 600/dose

Evaluation criteria:

Mutations at the TK locus

Statistics:

No data

Species / strain:

mouse lymphoma L5178Y cells

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

Concentration related cytoxicity (60 % reduction over controls at 5 mg/mL)

Additional information on results:

Concentration related cytotoxicity (60 % reduction over controls at 5 mg/mL).
Increase in ouabain resistance seen (not significant).

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Gene mutation assay results:

Concentration mg/mL	Number of mutant cells per 10^6cells ± SD				Comments give information on cytotoxicity or other
	Exp 1	Exp 2	Exp 1	Exp 2
	-S9	-S9	+S9	+S9
0	54 ± 10	42 ± 1	29 ± 10	36 ± 7
1.2	46 ± 28	38 ± 15	34 ± 0	36 ± 7
1.7	39 ± 17	31 ± 9	41 ± 7	49 ± 4
2.45	27 ± 3	32 ± 9	40 ± 16	36 ± 6	Minor cytotoxicity seen
3.5	31 ± 18	46 ± 1	41 ± 13	41 ± 6	Cytotoxicity seen
5	50 ± 22	41 ± 5	53 ± 2	47 ± 3	Cytotoxicity seen. Increase in + S9 in first study not reproduced.

Conclusions:

Interpretation of results (migrated information):
negative

The test substance was not mutagenic but cytotoxicity observed at 5 mg/mL (maximum dose level).
Read-across is justified on the basis detailed in the rationale for reliability above. This study is therefore considered to be of sufficient adequacy and reliability to be used as a supporting study and no further testing is justified.

Reference 3

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

14-05-91 to 12-08-91

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study conducted to GLP and in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not effect the quality of the relevent results. This study is conducted on an analogue substance. Read-across is justified on the following basis: In aqueous solutions at physiological and acidic pH, low concentrations of simple inorganic borates such as boric acid, disodium tetraborate decahydrate, disodium tetraborate pentahydrate, boric oxide and disodium octaborate tetrahydrate will predominantly exist as undissociated boric acid. At about pH 10 the metaborate anion (B(OH)4-) becomes the main species in solution (WHO, 1998). This leads to the conclusion that the main species in the plasma of mammals and in the environment is un-dissociated boric acid. Since other borates dissociate to form boric acid in aqueous solutions, they too can be considered to exist as un-dissociated boric acid under the same conditions. For comparative purposes, exposures to borates are often expressed in terms of boron (B) equivalents based on the fraction of boron in the source substance on a molecular weight basis. Some studies express dose in terms of B, whereas other studies express the dose in units of boric acid. Since the systemic effects and some of the local effects can be traced back to boric acid, results from one substance can be transferred to also evaluate the another substance on the basis of boron equivalents. Therefore data obtained from studies with these borates can be read across in the human health assessment for each individual substance. Conversion factors are given in the table below. Conversion factor for equivalent dose of B Boric acid H3BO3 0.175 Boric Oxide B2O3 0.311 Disodium tetraborate anhydrous Na2B4O7 0.215 Disodium tetraborate pentahydrate Na2B4O7•5H2O 0.148 Disodium tetraborate decahydrate Na2B4O7•10H2O 0.113 Disodium octaborate tetrahydrate Na2B8O13•4H2O 0.210 Sodium metaborate (anhydrous) NaBO2 0.1643 Sodium metaborate (dihydrate) NaBO2•2H2O 0.1062 Sodium metaborate (tetrahydrate) NaBO2•4H2O 0.0784 Sodium pentaborate (anhydrous) NaB5O8 0.2636 Sodium pentaborate (pentahydrate) NaB5O8∙5H2O 0.1832 References: WHO. Guidelines for drinking-water quality, Addendum to Volume 1, 1998.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

There is a failure to justify the maximum concentration of 2500 ug/plate

Qualifier:

according to guideline

Guideline:

other: US EPA 40 CFR Part 158; FIFRA, Section 158.340

Deviations:

not specified

Qualifier:

according to guideline

Guideline:

EPA OPP 84-2

Deviations:

not specified

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Target gene:

Histidine

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

not specified

Species / strain / cell type:

S. typhimurium TA 1538

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254 induced rat liver S9 at 4 % and 10 %

Test concentrations with justification for top dose:

10; 50; 100; 1000; 2500 μg/plate

Vehicle / solvent:

Water

Positive controls:

yes

Positive control substance:

sodium azide

Positive controls:

yes

Positive control substance:

9-aminoacridine

Positive controls:

yes

Positive control substance:

2-nitrofluorene

Positive controls:

yes

Positive control substance:

other: 2-Anthramine

Details on test system and experimental conditions:

METHOD OF APPLICATION: In water

DURATION
- Preincubation period: None

Evaluation criteria:

No data

Statistics:

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

Additional information on results:

No data

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Conclusions:

Interpretation of results (migrated information):
negative

The study was performed according to Guideline 84-2 and is comparable to OECD 471. The test substance was not mutagenic in any of the strains tested with or without metabolic activation.
Read-across is justified on the basis detailed in the rationale for reliability above. This study is therefore considered to be of sufficient adequacy and reliability to be used as a supporting study and no further testing is justified.

Genetic toxicity in vivo

Link to relevant study records

Reference

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Study period:

No data

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study conducted to GLP and in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not effect the quality of the relevant results. This study is conducted on an analogue substance. Read-across is justified on the following basis: In aqueous solutions at physiological and acidic pH, low concentrations of simple inorganic borates such as boric acid, disodium tetraborate decahydrate, disodium tetraborate pentahydrate, boric oxide and disodium octaborate tetrahydrate will predominantly exist as undissociated boric acid. At about pH 10 the metaborate anion (B(OH)4-) becomes the main species in solution (WHO, 1998). This leads to the conclusion that the main species in the plasma of mammals and in the environment is un-dissociated boric acid. Since other borates dissociate to form boric acid in aqueous solutions, they too can be considered to exist as un-dissociated boric acid under the same conditions. For comparative purposes, exposures to borates are often expressed in terms of boron (B) equivalents based on the fraction of boron in the source substance on a molecular weight basis. Some studies express dose in terms of B, whereas other studies express the dose in units of boric acid. Since the systemic effects and some of the local effects can be traced back to boric acid, results from one substance can be transferred to also evaluate the another substance on the basis of boron equivalents. Therefore data obtained from studies with these borates can be read across in the human health assessment for each individual substance. Conversion factors are given in the table below. Conversion factor for equivalent dose of B Boric acid H3BO3 0.175 Boric Oxide B2O3 0.311 Disodium tetraborate anhydrous Na2B4O7 0.215 Disodium tetraborate pentahydrate Na2B4O7•5H2O 0.148 Disodium tetraborate decahydrate Na2B4O7•10H2O 0.113 Disodium octaborate tetrahydrate Na2B8O13•4H2O 0.210 Sodium metaborate (anhydrous) NaBO2 0.1643 Sodium metaborate (dihydrate) NaBO2•2H2O 0.1062 Sodium metaborate (tetrahydrate) NaBO2•4H2O 0.0784 Sodium pentaborate (anhydrous) NaB5O8 0.2636 Sodium pentaborate (pentahydrate) NaB5O8∙5H2O 0.1832 References: WHO. Guidelines for drinking-water quality, Addendum to Volume 1, 1998.

Qualifier:

according to guideline

Guideline:

other: US-EPA-FIFRA section 158.340 Guideline 84-2

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

not specified

GLP compliance:

yes

Type of assay:

micronucleus assay

Species:

mouse

Strain:

Swiss Webster

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

Distilled water.

Details on exposure:

Mice given two doses (in 10 mL distilled water) by gavage.

Duration of treatment / exposure:

2 days.

Frequency of treatment:

Animals dosed once per day.

Post exposure period:

No data

Remarks:

Doses / Concentrations:
0, 225, 450, 900, 1800, 3500 mg/kg bw/day
Basis:
actual ingested

No. of animals per sex per dose:

No data

Control animals:

not specified

Tissues and cell types examined:

No data

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

not specified

Negative controls validity:

not specified

Positive controls validity:

not specified

Additional information on results:

Clinical signs included rough fur and haunched position.

Conclusions:

Interpretation of results (migrated information): negative
The test substance was not genotoxic.
Read-across is justified on the basis detailed in the rationale for reliability above. This study is therefore considered to be of sufficient adequacy and reliability to be used as a supporting study and no further testing is justified.

Additional information

Assessment entity approach

"Brazing fluxes" are mixtures of boron-containing constituents (potassium(fluoro)borates), which undergo chemical exchanges (anion exchange) and condensation reactions (e.g. formation of oligoborates, polyborates) upon mixing and further manufacturing. This results in a complex mixture of potassium borates, which cannot be fully chemically characterised for substance identity. Thus, according to the definition under REACH, such brazing fluxes must be described as a UVCB substance.

 

Data specifically on the UVCB substance to be registered ("reaction product of mixed inorganic base and acid resulting in complex boron, potassium and fluoride constituents") are not available. An assessment entity approach is followed based on the transformation products of this UVCB uppon dissolution in aqueous media. The substance is highly soluble and forms complex boron, potassium and fluoride constituents. The quantitatively predominant transformation product of this UVCB is represented by boric acid, which is assumed to be the determinant of human health effects because of its classification and its toxicity. For this reason, the assessment is based on information for “borates” (including potassium borate, boric acid and other borate substances).

 

Based on the information provided below, it may safely be assumed that under physiological conditions the chemical speciation of most of the unknown potassium boron compounds corresponds to boric acid. Thus, from a chemical point of view, there is no reason to assume that brazing fluxes would behave differently than boric acid and/or borates under physiological conditions.

 

The basis of this assessment entity approach is further justified by the following reasoning:

In aqueous solutions at physiological and acidic pH, low concentrations of simple inorganic borates such as boric acid B(OH)₃, potassium pentaborate (K₂B₁₀O₁₆*8H₂O), potassium tetraborate (K₂B₄O₇*4H₂O), disodium tetraborate decahydrate (Na₂B₄O₇.10H₂O; borax), disodium tetraborate pentahydrate (Na₂B₄O₇*5H₂O; borax pentahydrate), boric oxide (B₂O₃) and disodium octaborate tetrahydrate (Na₂B₈O₁₃*4H₂O) will predominantly exist as undissociated boric acid. Above pH 9 the metaborate anion (B(OH)₄^-) becomes the main species in solution (WHO, 1998). This leads to the conclusion that the main species in the plasma of mammals and in the environment is undissociated boric acid. Since other borates dissociate to form boric acid in aqueous solutions, they too can be considered to exist as undissociated boric acid under the same conditions.

For comparative purposes, exposures to borates are often expressed in terms of boron (B) equivalents based on the fraction of boron in the source substance on a molecular weight basis. Some studies express dose in terms of B, whereas other studies express the dose in units of boric acid. Since the systemic effects and some of the local effects can be traced back to boric acid, results from one substance can be transferred to also evaluate the another substance on the basis of boron equivalents. Therefore data obtained from studies with these borates can be read across in the human health assessment for each individual substance. Conversion factors are given in the table below.

 

Substance		Formula		Conversion factor for equivalent dose of B (multiply by)
Boric acid		H3BO3		0.1748
Boric Oxide		B2O3		0.311
Disodium tetraborate anhydrous		Na2B4O7		0.2149
Disodium tetraborate pentahydrate		Na2B4O7•5H2O		0.1484
Disodium tetraborate decahydrate		Na2B4O7•10H2O		0.1134
Disodium octaborate tetrahydrate		Na2B8O13·4H2O		0.2096
Sodium metaborate (anhydrous)		NaBO2		0.1643
Sodium metaborate (dihydrate)		NaBO2·2H2O		0.1062
Sodium metaborate (tetrahydrate)		NaBO2·4H2O		0.0784
Sodium pentaborate (anhydrous)		NaB5O8		0.2636
Sodium pentaborate (pentahydrate)		NaB5O8∙5H2O		0.1832
Dipotassium tetraborate (anhydrous)		K2B4O7		0.185
Dipotassium tetraborate (tetrahydrate)		K2B4O7^.4H2O		0.1415
Potassium pentaborate (anhydrous)		B5KO8		0.244
Potassium pentaborate (tetrahydrate)		B5KO8^.4H2O		0.1843

 

Reference: WHO. Guidelines for drinking-water quality, Addendum to Volume 1, 1998

 

 

Conclusions on genetic toxicity of brazing flux:

In the absence of substance-specific information on genetic toxicity for the test item brazing fluxes, and because borates are considered the transformation product driving the human health effects for brazing fluxes, the results for borates are also applicable for brazing fluxes.

A number of in vitro mutagenicity studies, including bacterial mutation assays in Salmonella typhimurium and Escherichia coli, gene mutation in mammalian cells (L5178Y mouse lymphoma, V79 Chinese hamster cells, C3H/10T1/2 cells), bacterial DNA-damage assay, unscheduled DNA synthesis (hepatocytes), chromosomal aberration and sister chromatid exchange in mammalian cells (Chinese hamster ovary, CHO cells) have been carried out on boric acid and one study on disodium tetraborate decahydrate.

In conclusion, no evidence of mutagenic activity whatsoever was observed in vitro. In addition, one in vivo study on boric acid also indicated no mutagenic activity.

Short description of key information:
No substance specific information on genetic toxicity of the test item brazing fluxes is available. In vitro gene mutation studies in bacteria (Stewart, 1991) in vitro gene mutation studies in mammalian cells (Rudd, 1991) and in vitro cytogenicity studies (NTP, 1987) concluded that boric acid is not genotoxic under the conditions of the studies. In addition the results of an in vivo bone marrow cytogenetic assay (chromosome aberration assay, O’Loughlin 1991) also showed boric acid to be non genotoxic.

Because borates are considered the transformation product driving the human health effects for brazing fluxes (see 'discussion`), this result is also applicable to the brazing fluxes.

Cytotoxicity observed at 5 mg/mL in the in vitro gene mutation studies in mammalian cells (Rudd, 1991).

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Justification for classification or non-classification:

Genetic toxicity

None of the in vitro and in vivo studies for boric acid and disodium tetraborate decahydrate (all rated as reliable) showed any indications of genotoxicity whatsoever, rendering the group of borates void of genotoxicity. The classification criteria according to Regulation (EC) 1272/2008 as germ cell mutagen are also not met.

The above described results are considered to apply to the brazing fluxes substances without restriction because borates are considered the transformation product driving the human health effects for brazing fluxes (see 'discussion`).