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Exposure related observations in humans: other data

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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

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:
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

Reference
Name:
Unnamed
Type:
Constituent
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 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:
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).