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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
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:
GLP 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

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not specified
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
not specified
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material: Diboron trioxide (anhydrous boric acid)
- Physical state: White powder
- Analytical purity: > 99 %
- Lot/batch No.: 5C183709
- Other: CHE dispensary No. 0604/95-1341

Test animals

Species:
rat
Strain:
other: Crl:CD.BR
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd., Margate
- Age at study initiation: 5 - 8 weeks of age
- Weight at study initiation: 142 - 217 g
- Housing: Up to 5 rats were accommodated in suspended stainless steel mesh cages (dimensions 55 x 34 x 20 cm). The cages were suspended over carboard lined trays for collection of excreta. The liners were replaced at least twice weekly.
- Diet: Ad libitum except during fasting period
- Water: Ad libitum
- Fasting period before study: 18 h prior to dosing until 3 h after dosing
- Acclimation period: 6 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25 C
- Humidity (%): 40 - 70 % relative humidity
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12 dark/light; typically 0600 to 1800 h.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Amount of vehicle: 10 mL/kg
- Lot/batch no.: 1132


MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg


DOSAGE PREPARATION: All formulations were used on the day of preparation.
Doses:
1540 and 2600 mg/kg
No. of animals per sex per dose:
5 males per dose
Control animals:
no
Details on study design:
No data
Statistics:
No data

Results and discussion

Effect levels
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 600 mg/kg bw
Based on:
test mat.
Remarks on result:
other: There were no deaths at this dose level.
Mortality:
No animal died following administration.
Clinical signs:
No clinical signs were observed for animals dosed at 1540 mg/kg.
Piloerection was apparent from approximately 15 min after dosing and for the remainder of Day 1, for all 5 males dosed at 2600 mg/kg. Two rats were lethargic three hours after dosing and one of these rats displayed an increased breathing rate at the same time. Recovery, as judged by external appearance and behaviour was complete by Day 2.
Body weight:
All rats acheived satisfactory gains on Day 8 and 15.
Gross pathology:
No macroscopic changes were observed during necropsy of Day 15 for animals at 2600 mg/kg.
Isolated changes seen in two rats dosed at 1540 mg/kg included a few red foci on the thymus (animals no 677) and pale lungs and distension of the jejunum (animal No. 678).
Other findings:
No data

Any other information on results incl. tables

Clinical signs following treatment at dose level 2600 mg/kg:

Clinical sign

Animal No.

Time of

first observation

Time

of recovery

675

M

658

M

659

M

660

M

661

M

Pilo-erection

+

+

+

+

+

0.25 h

Day 2

Lethargy

-

+

-

+

-

3 h

Day 2

Tachypnoea

-

+

-

-

-

3 h

Day 2

+/- = sign present or absent

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: Classification and Labelling Requirements for Dangerous Substances and Preparations, as stated in Annex IV to Commission Directive 93/21/EC
Conclusions:
A single oral administration of anhydrous boric acid to groups of five fasted rats at dose levels of 1540 or 2600 mg/kg resulted in no deaths. The acute median lethal oral dose was therefore considered to be greater than 2000 mg/kg bw.
Based on the results of this study, the general Classification and Labelling Requirements for Dangerous Substances and Preparations, as stated in Annex IV to Commission Directive 93/21/EC, indicate that no risk phrase is required for anhydrous boric acid in respect of its acute oral toxicity.
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.