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Toxicological information

Acute Toxicity: other routes

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Administrative data

Endpoint:
acute toxicity: other routes
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Meets generally accepted scientific standards with acceptable restrictions. 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:
publication
Title:
Acute intravenous and intraperitoneal toxicity studies on sodium pentaborate decahydrate and sodium tetraborate decahydrate.
Author:
Easterday OD & Hamel H
Year:
1963
Bibliographic source:
Arch. Int. Pharmacodyn. 143 (1-2)144 – 164.

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: No data
Deviations:
not specified
Principles of method if other than guideline:
The toxicity observations in mice of varying borate-glucose molar ratios and relative potencies was reported following intravenous and intraperitoneal administration. Also presented were data showing the effect of age on tetraborate toxicity. Swiss mice were administered with reagent grade sodium tetraborate decahydrate and intravenous 50 % d-glucose dissolved in sterile water or saline. The doses were injected as mg of the parent drug/g body weight per 0.01 or 0.02 mL. By maintaining a constant borate dose and varying the amount of d-glucose in the injected preparation the effect of different borate-glucose molar ratios on toxicity was determined. The observation period was 24 h after intravenous administration and after intraperitoneal administration 5 to 12 days. The acute toxicity data were statistically analysed by probit transformation, maximum likelihood solution and relative potency techniques.
GLP compliance:
no
Remarks:
Studypre-dates GLP
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material: Sodium pentaborate decahydrate; Sodium tetraborate decahydrate

Test animals

Species:
mouse
Strain:
Swiss
Sex:
male/female

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
other: Water or saline
Doses:
Sodium pentaborate decahydrate: 2175 and 2300 mg/kg
Sodium tetraborate decahydrate: 2700, 2750, 2800 and 2884 mg/kg
No. of animals per sex per dose:
Sodium pentaborate decahydrate: Between 14 and 42 males; and between 1 and 26 females
Sodium tetraborate decahydrate: Between 7 and 30 males; and between 9 and 34 females
Control animals:
yes

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 737 mg/kg bw
Based on:
other: Borate
Remarks on result:
other: Tetraborate : distilled water; 2737 ± 479
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 792 mg/kg bw
Based on:
other: Borate
Remarks on result:
other: Tetraborate : saline; 2792 ± 420
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 037 mg/kg bw
Based on:
other: Borate
Remarks on result:
other: Tetraborate : d-glucose; 3037 ± 620.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 817 mg/kg bw
Based on:
other: Borate
Remarks on result:
other: Tetraborate : d-glucose; 2817 ± 243.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 375 mg/kg bw
Based on:
other: Borate
Remarks on result:
other: Pentaborate : d-glucose; 2375 ± 118.

Applicant's summary and conclusion

Conclusions:
Toxic responses of intraperitoneally administered sodium pentaborate decahydrate and sodium tetraborate decahydrate were convulsions which generally occurred during the first 3 h. Trunk muscular contractions and opisthotonic responses occassionally occurred. General motor activity and the respiration rate were markedly depressed and usually existed for several hours. Frequently observable motor activity depression continuing through the second day after administration was observed. Most of the deaths occurred during the first 3 days.
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.