Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
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:
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. 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

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: FIFRA (40 CFR 163)
Deviations:
no
GLP compliance:
no
Remarks:
Study pre-dates GLP
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material: Boric acid
- Molecular formula: H3BO3
- Molecular weight: 61.8
- Smiles notation: B(OH)3
- Substance type: Inorganic
- Physical state: Solid
- Analytical purity: > 99.9 % w/w
- Stability under test conditions: Stable
- Lot/batch No.: OA 107-3
- Other: White and odourless

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan F. Plummer
- Weight at study initiation: 1623 - 2922 g

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
physiological saline
Details on dermal exposure:
TEST SITE
- Area of exposure: The skin of all animals was abraded longitudinally every 2 - 3 cm, deep enough to penetrate the stratum corneum, but not cause bleeding.
- % coverage: > 10 % of body surface implied
- Type of wrap if used: Semi occlusive


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Moist towel
- Time after start of exposure: 24 h


TEST MATERIAL
- For solids, paste formed: Yes


VEHICLE
- Amount applied: Substance moistened with 1.5 mL saline
Duration of exposure:
24 h
Doses:
Dosage to 2 g/kg
No. of animals per sex per dose:
5/sex/group
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs, histopathology
Statistics:
Not applicable - limit test.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred
Clinical signs:
Clinical changes were limited to transient diarrhoea in 2 rabbits and some incidences of erythema (9), and oedema (30), atonia (2), desquamation (4), necrosis, and other evidence of irritation at 23 and ~70.5 h after treatment.
Body weight:
No data
Gross pathology:
No gross necrospy findings were observed. Observations included one animal with gas filled intestine, one animal with pale yellow-coloured kidneys and 5 animals with enlarged or swollen fallopian tubes.
Other findings:
No data

Any other information on results incl. tables

Gross necropsy findings in male and female rabbits at the end of the observation period:

Gross Necropsy Findings

Dosage at 2 g/kg

Number of animals necropsied

10

No gross necropsy findings

5

Intestine

Gas-filled

1

Kidneys

Pale yellow coloured

1

Fallopian tubes

Enlarged or swollen

4

Pale

1

External

Diarrhoea stains

1

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The study was performed according to FIFRA (40 CFR 163). The LD50 > 2000 mg/kg bw indicating no acute dermal toxicity. No deaths occurred. Clinical changes were limited to erythema, oedema, atonia, desquamation, necrosis and some incidences of skin irritation at more than 24 h of treatment.
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.