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Exposure related observations in humans: other data

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Endpoint:
exposure-related observations in humans: other data
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Comparable to guideline study. Read-across is justified on the following basis: The family of zinc borates that include Zinc Borate 500, Zinc Borate 2335 and Zinc Borate 415 (also known as Zinc Borate 411). Zinc borate 500 is anhydrous Zinc Borate 2335 and Zinc Borate 415 has different zinc to boron ratio. Zinc borate 2335 (in common with other zinc borates such as Zinc borate 415 and 500) breaks down to Zinc Hydroxide (via Zinc oxide) and Boric Acid, therefore the family of zinc borates shares the same toxicological properties. Zinc borates are sparingly soluble salts. Hydrolysis under high dilution conditions leads to zinc hydroxide via zinc oxide and boric acid formation. Zinc hydroxide and zinc oxide solubility is low under neutral and basic conditions. This leads to a situation where zinc borate hydrolyses to zinc hydroxide, zinc oxide and boric acid at neutral pH quicker than it solubilises. Therefore, it can be assumed that at physiological conditions and neutral and lower pH zinc borate will be hydrolysed to boric acid, zinc oxide and zinc hydroxide. Hydrolysis and the rate of hydrolysis depend on the initial loading and time. At a loading of 5% (5g/100ml) zinc borate hydrolysis equilibrium may take 1-2 months, while at 1 g/l hydrolysis is complete after 5 days. At 50 mg/l hydrolysis and solubility is complete (Schubert et al., 2003). At pH 4 hydrolysis is complete. Zinc Borate 2335 breaks down as follows: 2ZnO • 3B2O3 •3.5H2O + 3.5H2O + 4H+ ↔ 6H3BO3 + 2Zn2+ 2Zn2+ + 4OH- ↔ 2Zn(OH)2 ____________________________________________________________ Overall equation 2ZnO • 3B2O3 •3.5H2O + 7.5H2O ↔ 2Zn(OH)2 + 6H3BO3 The relative zinc oxide and boric oxide % are as follows: Zinc borate 2335:zinc oxide = 37.45% (30.09% Zn) B2O3 = 48.05% (14.94% B) Water 14.5% Zinc borate 415: zinc oxide = 78.79%; (63.31% Zn) B2O3 = 16.85% (5.23% B) Water 4.36% Zinc borate, anhydrous: Zinc oxide = 45 % B2O3= 55% (17.1 % B)

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1997
Report date:
1997
Reference Type:
publication
Title:
In vivo percutaneous absorption of boric acid, borax and disodium octaborate tetrahydrate in humans compared to in vitro absorption in human skin from infinite to finite doses.
Author:
Wester RC, Hui X, Hartway T, Maibach HI, Bell K, Schell MJ, Northington DJ, Strong P & Culver BD.
Year:
1998
Bibliographic source:
Toxicol. Sciences. 45: 42 - 51.
Reference Type:
publication
Title:
In vitro percutaneous absorption of boron as boric acid, borax and disodium octaborate tetrahydrate in human skin.
Author:
Wester RC, Hartway T, Maibach HI, Schell MJ, Northington DJ, Culver BD & Strong P.
Year:
1998
Bibliographic source:
Biological Trace Element Research 66: 111 - 120.

Materials and methods

Type of study / information:
Percutaneous absorption through human skin in vitro.
Endpoint addressed:
basic toxicokinetics
dermal absorption
Test guideline
Qualifier:
according to guideline
Guideline:
other: No data
Deviations:
not specified
Principles of method if other than guideline:
In vitro diffusion from aqueous solution was determined in receptor fluid accumulation over a 24 h period. Human cadaver skin (dermatomed) was clamped onto an AMIE Systems in-line cell in a flow-through apparatus, with 1 cm2 surface area of skin exposed. Receptor fluid was pumped at a rate of 3 mL/hr and collected every 4 h to 24 h. After 24 h the skin surface was washed. Boric acid (enriched ) was applied at 0.05 %, 0.5 % and 5 % and either an infinite dose of 1000 mL/ cm2 or a finite dose of 2 mL/ cm2. Changes in boron isotope ratios by ICPMS (Inductively Coupled Plasma-Mass Spectrometry) was used to measure absorption.
GLP compliance:
yes

Test material

Constituent 1
Reference substance name:
Boric acid, borax and disodium octaborate tetrahydrate.
IUPAC Name:
Boric acid, borax and disodium octaborate tetrahydrate.
Details on test material:
- Name of test material: Enriched boric acid; Enriched borax; Disodium octaborate tetrahydrate.
- Lot/batch No.: Boric acid BL-EV-94-36(BA); Enriched borax 1797-16; Disodium octaborate tetrahydrate 1797-17.
- Analytical purity: Boric acid 99.6 ± 0.78 %; Enriched borax 100.5 ± 1.9 %; Disodium octaborate tetrahydrate 99.8 % calculated from its constituents, boric acid and borax.
- Specific activity: B-10

Method

Ethical approval:
not specified
Details on study design:
In vitro diffusion from aqueous solution was determined in receptor fluid accumulation over a 24 h period. Human cadaver skin (dermatomed) was clamped onto an AMIE Systems in-line cell in a flow-through apparatus, with 1 cm2 surface area of skin exposed. Receptor fluid was pumped at a rate of 3 mL/hr and collected every 4 h to 24 h. After 24 h the skin surface was washed. Boric acid (enriched ) was applied at 0.05 %, 0.5 % and 5 % and either an infinite dose of 1000 mL/ cm2 or a finite dose of 2 mL/ cm2. Changes in boron isotope ratios by IPCMS (Inductively Coupled Plasma-Mass Spectrometry) was used to measure absorption.
Exposure assessment:
not specified
Details on exposure:
TYPE OF EXPOSURE MEASUREMENT: Percutaneous absorption was determined by receptor fluid accumulation and by skin content as determined by ICPMS.

EXPOSURE LEVELS:
Boric acid was applied as a 5 % solution (w/v) at 2 μL/cm2 and 1000 μL/cm2; as a 0.5 % solution at 1000 μL/cm2 and as a 0.05 % solution at 1000 μL/cm2.
Borax was applied as a 5 % solution (w/v) at 1000 μL/cm2.
DOT was applied as a 10 % solution (w/v) at 1000 μL/cm2.

EXPOSURE PERIOD: 24 h

Results and discussion

Results:
Percent doses absorbed for boric acid were 1.2 for 0.05 % solution, 0.28 for 0.5 % solution and 0.70 % for 5 % solution. Skin surface and soap washed removed 72.4 ± 9.1, 86.0 ± 5.9 and 81.9 ± 2.9 % doses after the 24 h dosing interval. The final wash removed 1.2 ± 2.0 % dose, thus the washing procedure was essentially complete. These absorption amounts translated into flux values of 0.25, 0.58 and 14.58 mg/cm²/h and permeability constants (Kp) of 5.0 x 10-4, 1.2 x 10-4 and 2.9 x 10-4 /cm²/hr. The above doses were at a standard 1000 μL/cm² dosing solutions. When the 5 % solution was applied at 2 μL/cm² (in vivo dosing volume), flux decreased some 200-fold to 0.07 mg/cm²/hr and Kp of 1.4 x 10 –6 cm/hr. Borax dosed at 5 %/1000 μL/cm² had 0.41 % dose absorbed. Skin surface wash recovery was 87.7 ± 5.9 % dose. Flux was 8.5 ±g/cm²/h, and Kp was 1.7 x 10-4 cm/h. Disodium octaborate tetrahydrate dosed at 10 % /1000 μL/cm² was 0.19 % dose absorbed. Skin surface wash recovery was 91.3 ± 25.2 % dose. Flux was 0.8 x 10-4 cm/h. These in vitro results from infinite dose (1000 μL) were several magnitudes higher than those obtained in vivo. The results from the finite dose ( 2 μL) were closer to in vivo results (also 2 μL).

Any other information on results incl. tables

In vitro percutaneous absorption of boron administered as boric acid, borax and disodium octaborate tetrahydrate (DOT) in human skin:

Dosing solution

Dose

μg B10

Percent dose absorbed

Geometric mean

(95 % C.I.)

Flux

(μg/cm2/h)

Kp

(cm/h)

Boric acid (w/v)

5 % at 2 μL/cm2

16.33

1.75 (0.18 – 17)

0.07

1.4 X 10-4

Boric acid (w/v)

5 % at 1000 μL/cm2

81.65

0.70 (0.072 – 6.81)

14.58

2.9 X 10-4

Boric acid (w/v)

0.5 % at 1000 μL/cm2

81.65

0.28 (0.029 – 2.72)

0.58

1.2 X 10-4

Boric acid (w/v)

0.05 % at 1000 μL/cm2

 

81.65

1.20 )0.012 – 11.7)

0.25

5.0 X 10-4

Borax (w/v)

5 % at 1000 μL/cm2

5270

0.41 (0.042 – 3.99)

8.5

1.7 X 10-4

DOT (w/v)

10 % at 1000 μL/cm2

19620

0.19 (0.018 – 1.81)

7.9

0.8 X 10-4

Applicant's summary and conclusion

Conclusions:
Larger amounts of boron could be absorbed in in vitro study that in in vivo study.
Executive summary:

In the in vitro study, where the amount of borate available to the skin surface was not limited to the amount that could be kept in contact with the surface, larger amounts of boron could be absorbed.

Percent doses absorbed for boric acid were 1.2 for 0.05 % solution, 0.28 for 0.5 % solution and 0.70 % for 5 % solution. Skin surface and soap washed removed 72.4 ± 9.1, 86.0 ± 5.9 and 81.9 ± 2.9 % doses after the 24 h dosing interval. The final wash removed 1.2 ± 2.0 % dose, thus the washing procedure was essentially complete. These absorption amounts translated into flux values of 0.25, 0.58 and 14.58 mg/cm²/h and permeability constants (Kp) of 5.0 x 10-4, 1.2 x 10-4 and 2.9 x 10-4 /cm²/hr. The above doses were at a standard 1000 μL/cm² dosing solutions. When the 5 % solution was applied at 2 μL/cm² (in vivo dosing volume), flux decreased some 200-fold to 0.07 mg/cm²/hr and Kp of 1.4 x 10 –6 cm/hr. Borax dosed at 5 %/1000 μL/cm² had 0.41 % dose absorbed. Skin surface wash recovery was 87.7 ± 5.9 % dose. Flux was 8.5 ±g/cm²/h, and Kp was 1.7 x 10-4 cm/h. Disodium octaborate tetrahydrate dosed at 10 % /1000 μL/cm² was 0.19 % dose absorbed. Skin surface wash recovery was 91.3 ± 25.2 % dose. Flux was 0.8 x 10-4 cm/h. These in vitro results from infinite dose (1000 μL) were several magnitudes higher than those obtained in vivo. The results from the finite dose ( 2 μL) were closer to in vivo results (also 2 μL).

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