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Endpoint:
additional toxicological information
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:
The ototoxic effect of boric acid solutions applied into the middle ear of guinea pigs.
Author:
Öztürkcan S, Dündar R, Katilmiş H, İlknur AE, Aktaş S & Haciömeroğlu S.
Year:
2009
Bibliographic source:
Eur. Arch. Otorhinolaryngol. 266: 663 - 667.

Materials and methods

Type of study / information:
The study analysed the ototoxic effects of boric acid solutions on 22 young guinea pigs.
Test guideline
Qualifier:
according to
Guideline:
other: No data
Deviations:
not specified
Principles of method if other than guideline:
The study analysed the ototoxic effects of boric acid solutions on 22 young guinea pigs. Auditory Brainstem Response (ABR) test was applied prior to adminsitration. A perforation was created on the tympanic membrane of the right ear and small gelfoam pieces were inserted into the perforation. Test solutions were administered for 10 days by means of a transcanal route. 15 days after insertion of the gelfoams they were removed and the ABR repeated.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

Any other information on results incl. tables

When the saline control group and the 4 % boric acid solution prepared with distilled water group were compared against the initial condition of both groups, a borderline significance was detected (P = 0.046; P = 0.046, respectively). When the ototoxic control (Gentamicine) and 4 % boric acid solution prepared with 70 % alcohol groups were compared against their initial conditions, statistically signifcant changes in the ABRs threshold was found (P = 0.026; P = 0.011, repectively). When the ototoxic control group was compared with the 4 % boric acid solution prepared with distilled water and with the saline group, a statistically significant toxic effect was found in the ototoxic control group ( P = 0.003; P = 0.001, respectively). When the Gentamicine group was compared with 4 % boric acid solution prepared with 70 % alcohol group, no significant difference in ototoxic effect was detected between the two groups (p = 0.128).

As a result of the comparison of the 4 % boric acid solution prepared with 70 % alcohol group with the saline group and the 4 % boric acid prepared with distilled water groups statistically significant effect in the 4 % boric acid solution prepared with 70 % alcohol was detected (P = 0.002 ; P = 0.000). No statistically significance was found in comparison of the saline and 4 % boric acid solution prepared with distilled water groups (P: 0.653). In the group where 4 % boric acid solutions prepared with 70 % alcohol statistically significant alterations in the test thresholds were detected.

Applicant's summary and conclusion

Conclusions:
The study analysed the ototoxic effects of boric acid solutions on 22 young guinea pigs. Prior to application of the boric acid solution under general anaesthesia an Auditory Brainstem Response (ABR) test was applied to the right ear of the guinea pigs. Following the test a performation was created on the tympanic membrane of the right ear of each guinea pig and small gelfoam pieces inserted into the perforated area. Test soluitons were administered to the middle ear for 10 days by means of a transcanal route. 15 days after inserting the gelfoams they were removed and the ABR test performed again. The ABRs were within the normal range before applications after hte application no singificant changes were deteced in the ABRs threshold in the saline group or the group administered boric acid and dstilled water solution. However, significant changes were detected in the ototoxic control group (Gentamicine) and boric acid and alcohol solution groups.
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.