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Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
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: GLP guideline study.
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
not reported
Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Davidson’s Mill Farms, South Brunswick, NJ.
- Age at study initiation: Young adult
- Weight at study initiation: Males: 314 -411 g; females: 256-441 g
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
0.4 g 95 % w/w substance.
Route:
other: Not specified
Vehicle:
water
Concentration / amount:
0.4 g 95 % w/w substance.
No. of animals per dose:
Test group: 20 animals
Naive control: 10 animals
Positive control: 20 animals
Positive naive control: 10 animals
Details on study design:
A. INDUCTION EXPOSURE
- No. of exposures: Three
- Exposure period: Day 0, Day 7 and Day 21
- Test groups: 0.4 g 95 % w/w substance moistened with distilled water to enhance skin contact.
- Frequency of applications: Day 0, Day 7 and Day 21


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: Day 28
- Exposure period: After 6 hours test substance wiped off with water
- Concentrations: 95 % w/w substance moistened with distilled water to enhance skin contact
- Evaluation: 24h & 48 h
Challenge controls:
No data
Positive control substance(s):
yes
Remarks:
Dinitrochlorobenzene
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.4 g 95 % w/w
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None specified
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.4 g 95 % w/w. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: None specified.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.4 g 95 % w/w
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None specified
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.4 g 95 % w/w. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: None specified.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Not applicable
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None specified
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: Not applicable. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None specified.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
Not applicable
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None specified
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: Not applicable. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None specified.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
Not specified
No. with + reactions:
10
Total no. in group:
20
Clinical observations:
Not specified
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: Not specified. No with. + reactions: 10.0. Total no. in groups: 20.0. Clinical observations: Not specified.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
Not specified
No. with + reactions:
7
Total no. in group:
20
Clinical observations:
Not specified
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: Not specified. No with. + reactions: 7.0. Total no. in groups: 20.0. Clinical observations: Not specified.
Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
A study was performed according to OECD Guideline 406 "Skin Sensitisation" method (Buehler test ) using 95 % w/w disodium tetraborate pentahydrate moistened with distilled water to enhance skin contact. No irritation was observed.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
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 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

Na2B8O13·4H2

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 skin sensitisation:

Skin sensitisation studies specifically with brazing fluxes are not available. However, data on borate substances indicate that these are not skin sensitisers: disodium tetraborate decahydrate and disodium tetraborate pentahydrate were tested in a Buehler method skin sensitisation test (Wnorowski, 1994) applied at a concentration of 95% (powder moistened with water) during both the induction and challenge phase of the test.


Migrated from Short description of key information:
No skin sensitization studies with the brazing fluxes or dipotassium tetraborates were available however the data indicate that these borates are not sensitizers. Skin sensitisation tests on disodium tetraborate decahydrate and disodium tetraborate pentahydrate were performed according to OECD Guideline 406 (Buehler method).

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Migrated from Short description of key information:
There is no evidence on specific respiratory hypersensitivity in test animals following acute inhalation exposure with borates.

Justification for classification or non-classification

Skin Sensitisation:

 

In studies performed with the substances disodium tetraborate decahydrate and disodium tetraborate pentahydrate according to OECD Guideline 406 "Skin Sensitisation" method (Buehler test), no skin sensitisation was observed.

 

According to the criteria specified by Directive 67/548/EEC borates are correspondingly considered not to require classification for skin sensitisation; the same conclusion is derived also according to the criteria set forth by EC Regulation No. 1272/2008 and subsequent regulations, 

 

 Respiratory sensitisation:

 

There is no evidence on specific respiratory hypersensitivity in test animals following acute inhalationexposure with borates.