Reaction product of mixed inorganic base and acid resulting in dipotassium hydroxytetrafluoro triborontrioxide, dipotassium tetrahydroxy tetraboronpentaoxide dehydrate, potassium fluoride, potassium tetrafluroborate, water in paste form

Exposure related observations in humans: other data

Administrative data

Endpoint:

exposure-related observations in humans: other data

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: Comparable to guideline study.

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Reference 2

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 3

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

Test material information

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 0.005 % dose, 0.28 for 0.5 % dose and 0.70 % for 5 % dose. 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 /cm/hr. The above doses were at a standard 1000 μL/cm2 dosing solutions. When the 5 % dose 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 μg/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 B^10	Percent dose absorbed Geometric mean (95 % C.I.)	Flux (μg/cm^2/h)	Kp (cm/h)
Boric acid (w/v) 5 % at 2 μL/cm^2	16.33	1.75 (0.18 – 17)	0.07	1.4 X 10^-4
Boric acid (w/v) 5 % at 1000 μL/cm^2	81.65	0.70 (0.072 – 6.81)	14.58	2.9 X 10^-4
Boric acid (w/v) 0.5 % at 1000 μL/cm^2	81.65	0.28 (0.029 – 2.72)	0.58	1.2 X 10^-4
Boric acid (w/v) 0.05 % at 1000 μL/cm^2	81.65	1.20 )0.012 – 11.7)	0.25	5.0 X 10^-4
Borax (w/v) 5 % at 1000 μL/cm^2	5270	0.41 (0.042 – 3.99)	8.5	1.7 X 10^-4
DOT (w/v) 10 % at 1000 μL/cm^2	19620	0.19 (0.018 – 1.81)	7.9	0.8 X 10^-4

Applicant's summary and conclusion

Conclusions:

Percent doses absorbed for boric acid were 1.2 for 0.005 % dose, 0.28 for 0.5 % dose and 0.70 % for 5 % dose. 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 /cm/hr. The above doses were at a standard 1000 μL/cm2 dosing solutions. When the 5 % dose 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).