Registration Dossier

Toxicological information

Exposure related observations in humans: other data

Currently viewing:

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: see 'Remark'
Remarks:
Comparable to a 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.

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1996
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.

Materials and methods

Type of study / information:
In vivo percutaneous absorption study in humans.
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:
Human study specifically designed and therefore no specific guidelines available, but designed to comply with US 40 CFR, 160.
After 5 days during which urine samples were collected the test substance was applied topically; air-dried and a commercial white T-shirt worn for 24 hours during which time urine was collected. At 24 hours the T-shirt was removed and analysed. The exposed areas were analysed for transepidermal water loss (TEWL) and then washed carefully with soap and distilled deionised water and all washing analysed. On day 11 the TEWL was measured and the treatment site dosed with 1.8 mL of 2 % SDS (sodium lauryl sulphate) to cause irritation. On day 12 the TEWL was measured and the test substance was applied again topically; air-dried and a commercial white T-shirt worn for 24 hours during which time urine was collected. At 24 hours the T-shirt was removed and analysed. The exposed areas were analysed for transepidermal water loss (TEWL) and then washed carefully with soap and distilled deionised water and all washing analysed.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material: Boric Acid, sodium tetraborate decahydrate (Borax) and DOT
- Physical state: White powder
- Analytical purity: > 99 %
- Specific activity: 10B
- Stability: Stable

Method

Ethical approval:
not specified
Details on study design:
Males and females aged 22 - 50 with 8 people per group were exposed to the test substance. Urine was sampled as well as T-shirts worn and skin washings sampled.
Exposure assessment:
not specified
Details on exposure:
TYPE OF EXPOSURE: Dermal both intact and abraded skin; skin was washed and a 30 cm x 30 cm area marked on back.


EXPOSURE LEVELS: 5 % Boric acid ; 5 % Borax or 10 % DOT in distilled water.


EXPOSURE PERIOD: After 5 days during which urine samples were collected the test substance was applied topically; air-dried and a commercial white T-shirt worn for 24 hours during which time urine was collected. At 24 hours the T-shirt was removed and analysed. The exposed areas were analysed for transepidermal water loss (TEWL) and then washed carefully with soap and distilled deionised water and all washing analysed. On day 11 the TEWL was measured and the treatment site dosed with 1.8 ml of 2% SDS (sodium lauryl sulphate) to cause irritation. On day 12 the TEWL was measured and the test substance was applied again topically; air-dried and a commercial white T-shirt worn for 24 hours during which time urine was collected. At 24 hours the T-shirt was removed and analysed. The exposed areas were analysed for transepidermal water loss (TEWL) and then washed carefully with soap and distilled deionised water and all washing analysed.

Results and discussion

Results:
No adverse toxic or clinical signs were observed. There was no skin irritation.

Recovery of labelled compound: Boric acid 76.5 %; Borax 72 %; DOT 78.5 %. Since the skin was washed 10 times and less 1 % was found in the last wash, it is assumed that most of the substance unaccounted for was in lost to outside clothing (over the T-shirt) and bedding during the 24 hour dosing period.
Boric acid percent dose absorbed was 0.226 ± 0.125, with flux and permeability constant calculated at 0.0094 μg/cm2/hr and 1.9 x 10-7 cm/hr, respectively. Borax percent dose absorbed was 0.210 ± 0.194, with flux and permeability constant calculated at 0.00875 μg/cm2/hr and 1.8 x 10-7 cm/hr, respectively. DOT percent dose absorbed was 0.122 ± 0.108, with flux and permeability constant calculated at 0.010 μg/cm2/hr and 1.0 x 10-7 cm/hr, respectively.

Any other information on results incl. tables

Percutaneous absorption:

Substance

% Dose Absorbed (95% CI)

Flux

mg/cm2/hr

Permeability

Kp cm/hr.

5 % Boric Acid

0.226 ± 0.125

0.009

1.8 x 10-7

5 % Borax1

0.210 ± 0.194

0.009

1.8 x 10-7

10% DOT2

0.122 ± 0.10

0.010

1.0 x 10-7

1Disodium tetraborate decahydrate 

2Disodium octaborate tetrahydrate

Applicant's summary and conclusion

Conclusions:
Low skin absorption. For risk assessment where an absorbed dose is used the mean plus the standard deviation is used as a conservative absorption figure: Boric acid = 0.351 % absorption; Borax = 0.404 % absorption; DOT = 0.132 % absorption.
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.