Potassium metaborate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Remarks:

publication / peer-reviewed report

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

peer-reviewed

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
see target record

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Remarks:

publication / peer-reviewed report

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

peer-reviewed

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
see target record

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

read-across source

Remarks:

target record

Qualifier:

no guideline required

Principles of method if other than guideline:

Review of literature data

GLP compliance:

no

Species:

other: mostly rabbits, also guinea pigs, rats, dogs

Strain:

not specified

Type of coverage:

other: various

Preparation of test site:

other: various

Vehicle:

other: various

Details on study design:

a) The procedure for testing and evaluating the primary skin irritation of borax, Na2B4O7.10H2O, (10 ml, 5% in water (w/v)) or boric acid (5ml, 10% in water (w/v)) on rabbit skin was identical to that described in the U.S. Regulations (21 CFR 191.11), except that the rabbits were not immobilised, and the 1-inch square cellulose pads were used instead of surgical gauze. The substance was applied to 6 rabbits with intact and 6 with abraded skin. A similar test procedure in the guinea pig included application of the aqueous solutions of the materials on cellulose pads held in contact with the skin under an appropriate sleeve. Six guinea pigs with clipped, depilated, intact abdomens and 6 with clipped, depilated, abraded backs were used with each material.
b) The primary dermal irritation of disodium tetraborate pentahydrate, Na2O4O7 * 5H2O, was determined by applying 0.5 g moistened with saline on two clipped sites on the backs of 6 rabbits. The contact time was 4 hours under an occlusive dressing, with observation for up to 76 hours.
c) The detailed toxicological properties of boric oxide (B2O3) in rats, rabbits and dogs have been published. boric oxide dust (1g/25cm2) was topically applied to the clipped wetted backs of four rabbits.
d) Sodium perborate tetrahydrate was tested for skin irritation on six male rabbits. An area on the right flank of each animal was clipped and about 500 mg perborate, moistened to a paste with water, was applied to the test site (25x25 mm) under an occlusive dressing for 4 hours. The Draize scale was used to assess the degree of erythema and oedema at the site 1 hour and 1, 2 and 3 days after the removal of the dressing.
e) Sodium perborate tetrahydrate was applied as a paste in oil, for a 4 hour exposure.
f) A study investigating the irritant effects of repeated exposures of sodium perborate tetrahydrate to rat skin was performed over a course of 12 consecutive daily applications.

Time point:

other: 24&72h

Remarks on result:

other: Mild irritant after 24 and 72 h in primary irritation test

Remarks:

H3BO3, rabbit, 5ml, 10% in water (w/v), intact and abraded skin

Time point:

other: 24&72h

Remarks on result:

other: Moderate irritant after 24 and 72 h in primary irritation test

Remarks:

H3BO3, guinea pig, 5ml, 10% in water (w/v), intact and abraded skin

Time point:

other: 24&72h

Remarks on result:

other: Mild irritant after 24 and 72 h in primary irritation test

Remarks:

Na2B4O7.10H2O, rabbit, 10ml, 5% in water (w/v), intact and abraded skin

Time point:

other: 24&72h

Remarks on result:

other: Mild irritant after 24 and 72 h in primary irritation test

Remarks:

Na2B4O7.10H2O, guinea pig, 10ml, 5% in water (w/v), intact and abraded skin

Remarks on result:

no indication of irritation

Remarks:

Na2B4O7.5H2O, rabbit, 0.5 g, clipped back, 4h, Non-irritant

Remarks on result:

no indication of irritation

Remarks:

NaBO3.4H2O, rabbit, 500 mg, paste with 0.2 ml water, on intact skin, 4h, Classified as non-irritant

Remarks on result:

no indication of irritation

Remarks:

NaBO3.4H2O, guinea pig, in vegetable oil ointment, 4h, Non-irritant

Remarks on result:

other: Moderately to severely irritant, but 1% solution non-irritating after 12d

Remarks:

NaBO3.4H2O, rat, solid applied to skin, 12 daily

Remarks on result:

other: Slightly irritating

Remarks:

NaBO3.H2O, rabbit, 0.5 g on skin, 4h

Remarks on result:

no indication of irritation

Remarks:

NaBO3.H2O, rabbit, 500 mg, paste with 0.2 ml water, on intact skin, 4h, Non-irritant

Remarks on result:

other: Produced erythema, that persisted for 2-3 d

Remarks:

B2O3, rabbit, 1 g/25cm2 dust applied to clipped wetted back

Irritation parameter:

erythema score

Time point:

24/48/72 h

Remarks on result:

other: not available

Irritation parameter:

edema score

Time point:

24/48/72 h

Remarks on result:

other: not available

Interpretation of results:

study cannot be used for classification

Conclusions:

The present information was based on a literature review (peer-reviewed) of borate studies, which gave inconsistent results ranging from not irritating to irritating. Edema and erythema scores as indicated in Regulation 1272/2008, which are required for classification, are not given. Further, due to inconsistent results, no conclusion based on expert judgement can be drawn.

Executive summary:

A literature review of borate studies showed that these borates induced none to irritating responses, no conclusion on classification can be drawn.

Cross-reference 2

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Remarks:

publication / peer-reviewed report

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

peer-reviewed

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

no guideline required

Principles of method if other than guideline:

Review of literature data

GLP compliance:

no

Type of study:

other: "skin sensitization test"

Justification for non-LLNA method:

The present review was published in 1995 and takes into account all information available at that time. The LLNA method was not adopted as guideline at that time yet.

Species:

guinea pig

Strain:

Hartley

Sex:

male/female

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

0.5ml of the solid

Adequacy of induction:

not specified

Vehicle:

water

Concentration / amount:

5% dilution in distilled water

Day(s)/duration:

after 14 days

Adequacy of challenge:

not specified

No. of animals per dose:

5

Details on study design:

A skin sensitization test on sodium perborate monohydrate was carried out on 5 male and 5 female Hartley albino guinea pigs. Another similar group served as controls. Twenty four hours prior to each induction, an area of 5 x 5 cm on the left flank of each animal was clipped free of hair, 0.5 ml of the solid was applied to the depilated area and covered with an occlusive dressing. The challenge (5% dilution in distilled water) was applied to the depilated right flank 14 days after the induction.

Positive control substance(s):

not specified

Key result

Remarks on result:

no indication of skin sensitisation

Interpretation of results:

GHS criteria not met

Cross-reference 3

Reason / purpose for cross-reference:

read-across source

Remarks:

target record

Reference

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Remarks:

publication / peer-reviewed report

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

peer-reviewed, read-across

Justification for type of information:

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
Borates in general dissociate immediately upon contact with water and are converted rapidly into i.a. boric acid. This includes salts of boric acid (borates), metaboric acid (metaborates), hydrated borates (hydroborates) or borax. Boron compounds are highly soluble in water, and upon dissolving form essentially two species, undissociated boric acid (H3BO3) and borate anion (B(OH)4- [Soucek, Environmental Toxicology and Chemistry, Vol. 30, No. 8, pp. 1906–1914, 2011]. Orthoboric acid (Short: Boric acid, H3BO3) is a weak monobasic acid, which does not act as a proton donator but OH- acceptor (Lewis base) according to the following equilibrium:
B(OH)3 + 2 H2O ↔ B(OH)4- + H3O+ pKs = 9.2
Metaboric acid ((HBO2)n is formed during heating >90°C via intermolecular condensation while releasing a water molecule. Upon solubilisation in water, orthoboric acid is formed again. In diluted solutions practically only the monomeric H3BO3 are present [Riedel, Anorganische Chemie, de Gruyter, 1999]. A study by Zhu et al. [Zhu FY, Journal of Molecular Structure, Volume 1070, 24 July 2014, Pages 80-85] shows that the main borate species in aqueous KB(OH)4 solutions is B(OH)4−. This ion is in an equilibrium with H3BO3.
So 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 [WHO, Environmental Health Criteria 204, boron, World Health Organization, Geneva, 1998]. Also borax readily dissolves in water to form undissociated boric acid (H3BO3) and borate anion (B(OH)4-) [Soucek, 2011]. Most of the simple inorganic borates exist predominantly as undissociated boric acid in dilute aqueous solution at physiological pH [Hubbard SA, Biological Trace Element Research Vol. 66, 1998]. In aqueous solution, the metaborate ion is rapidly converted to the borate anion and the weakly dissociated boric acid by the sequential reactions shown by the following equations [Antia NJ, 1975, J. Fish. Res. Board Can. 32: 2487-2494]:
BO2- + 2 H2O → B(OH)4-
B(OH)4- + H3O+ ↔ B(OH)3 + 2 H2O
So if metaboric acid (resp. borates) is dissolved in water, orthoboric acid is formed [Riedel, 1999].
So summarizing, upon contact with water, potassium metaborate dissociates immediately into potassium and metaborate ions, whereas the latter is converted rapidly into boric acid.
As stated above, in diluted solutions and biologically relevant pH values, only undissociated boric acid is present, irrespective of which borate was dissolved in water, which so also applies to potassium metaborate. This is applicable for both ecotoxicity tests (usual limit concentration: 100 mg/l) as well as toxicological studies. Borates are readily absorbed orally in humans and animals [Hubbard, 1998], so the expected plasma levels are maximally as high as the applied dose, which still indicates that the boron species dissolved in plasma is H3BO3.
In consequence, data from boric acid and also all types of borates mentioned above, may be used to cover data gaps for potassium metaborate via read-across.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Target: Potassium metaborate, CAS 13709-94-9, EC 237-262-2, BKO2, MW = 81.9081 g/mol, SMILES [K+].[O-]B=O
Source: Boric acid / Orthoboric acid, CAS 10043-35-3, EC 233-139-2, H3BO3, MW = 61.83 g/mol, SMILES OB(O)O
Source: Borax / di-Sodium tetraborate decahydrate / sodium borate, CAS 1303-96-4, EC 603-411-9, Na2B4O7 *10H2O, MW = 381.365, SMILES (anhydrous) [Na+].[Na+].[O-]B(OB=O)OB([O-])OB=O
Source: Sodium tetraborate pentahydrate / Boron sodium oxide, pentahydrate, CAS 12179-04-3, EC 601-808-1, B4-O7.2Na.5H2-O, MW = 291.291 g/mol, SMILES B(=O)OB([O-])OB([O-])OB=O.O.O.O.O.O.[Na+].[Na+]
Source: Disodium octaborate tetrahydrate / Boron sodium oxide, tetrahydrate, CAS ‎12280-03-4, EC 602-894-3, B8Na2O13
Source: Sodium metaborate tetrahydrate / Boric acid, sodium salt, tetrahydrate, CAS 10555-76-7, EC 600-663-1
Source: Dipotassium tetraborate / boron potassium oxide, CAS 1332-77-0, EC 215-575-5, B4K2O7, MW = 233.4358, SMILES [K+].[K+].[O-]B([O-])[O-].[O-]B([O-])[O-].[O-]B([O-])[O-].[O-]B([O-])[O-]
Source: Diammonium tetraborate tetrahydrate / azane;2-hydroxy-4-[(4-hydroxy-1,3,2,4-dioxadiboretan-2-yl)oxy]-1,3,2,4-dioxadiboretane;tetrahydrate, CAS 10135-84-9; 12228-87-4, B4H16N2O11, MW = 263.371, SMILES B1(OB(O1)OB2OB(O2)O)O.N.N.O.O.O.O
Source: Zinc borate, hydrate / dodecaboron tetrazinc docosaoxide heptahydrate / Boron zinc hydroxide oxide / hexaboron dizinc undecaoxide, CAS 138265-88-0, EC 235-804-2, B12Zn4(OH)14O15, MW = 425.7 g/mol

There are no impurities known in neither target nor source chemical(s) which may affect the feasibility of the read-across approach.

3. ANALOGUE APPROACH JUSTIFICATION
As obvious in detail from the available data matrix, all borates exhibit similar (eco-)toxicological properties.
With regard to ecotoxicity, all available studies on various borates on fish, invertebrates, and algae, both short and long term, consistently indicate that, recalculated from the molecular weight, Potassium metaborate does not need to be classified as aquatic toxic (acute and chronic) according to Regulation 1272/2008 and amendments.
Similarly, with regard to human-relevant endpoints, Potassium metaborate does not need to be classified as acutely toxic, as consistently indicated by various borates in also various species.
Both boric acid and borax do not trigger classification as skin sensitizing, no further study data is available, However, Sodium Borate and Boric Acid are used in cosmetics in various functions, and no sensitizing reactions induced by these cosmetic products have been reported.
Borax and Boric acid were similarly non-mutagenic in the Ames Test, and the non-genotoxic potential is further supported by a negative chromosome aberration test. Both Borax and Boric however gave in different species, although via partially species-specific mode of actions, indication that they interfere via a certain threshold with reproduction. Proof via human data is however not available.
Further, all borates chosen for read-across, incl. the registered substance itself, are highly soluble in water, and upon dissolving form essentially two species, undissociated boric acid (H3BO3) and borate anion (B(OH)4-. Hence, read-across is further based on common breakdown products.
So summarizing, read-across is justified via similar (eco-)toxicological effects and common breakdown products.

4. DATA MATRIX
See attachment

Reason / purpose for cross-reference:

read-across source

Qualifier:

no guideline required

Principles of method if other than guideline:

Review of literature data

GLP compliance:

no

Species:

rabbit

Strain:

not specified

Details on test animals or tissues and environmental conditions:

no data

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

various, see free-text field below

Duration of treatment / exposure:

various, see free-text field below

Observation period (in vivo):

various, see free-text field below

Duration of post- treatment incubation (in vitro):

various, see free-text field below

Number of animals or in vitro replicates:

various, see free-text field below

Details on study design:

a) Six young rabbits had 100 mg of boric acid applied to one eye of each rabbit. The eyes were rinsed after 24 hours and irritation scores in individual animals ranged from 0 to 18.
b) Six young rabbits had 77 mg of borax, Na2B4O7.10H2O, applied to one eye of each rabbit. The eyes were rinsed after 24 hours and irritation scores in individual animals ranged from 0 to 39.
c) Six young rabbits had 100 mg of disodium tetraborate pentahydrate, Na2B4O7.5H2O, applied to one eye of each rabbit. The eyes were not rinsed, and the ocular reaction was recorded after 1, 24, and 72 hours and up to 10 days after treatment.
d) About 50 mg of boric oxide was placed in the left eye of four rabbits.
e) Sodium perborate tetrahydrate was tested for eye irritation on two female rabbits and the Draize scale was used for assessment of irritation. The test substance (approximately 100 mg) was applied to the conjunctival sac of the left eye of each rabbit, the other eye was untreated. The eyes were examined after 1 to 2 hours, and up to 3 or 21 days after application for each of the animals, respectively.
f) 50 mg of sodium perborate tetrahydrate was introduced into the rabbit eye.
g) The irritation of a small volume of sodium perborate tetrahydrate was assessed in three rabbits. The methods used were similar to those described above except that the amount of test material used was less, in this case a volume of 0.01 ml was used (approximating to 6 mg).
h) A 1% solution of sodium perborate tetrahydrate was instilled to the rabbit eye.
i) A test in rabbits investigated the effect of an eye washing procedure on the irritant effect of sodium perborate tetrahydrate. After instilling 100 mg of the test material into the left eye, groups of 3 rabbits received either no further treatment or the eye was washed 4 or 30 seconds later.

Reversibility:

fully reversible within: 7 days

Remarks:

or less

Remarks on result:

other: irritating

Remarks:

100 mg H3BO3 in one eye

Reversibility:

fully reversible within: 8-21 days

Remarks on result:

other: corneal irritation

Remarks:

77 mg Borax in one eye

Reversibility:

not fully reversible within: 21 days

Remarks on result:

other: severe irritation

Remarks:

100 mg Na2B4O7 * 5H2O in one eye

Remarks on result:

other: Severe irritant to the rabbit eye

Remarks:

Observed up to 21d; 100 mg NaBO3 * 4H2O in one eye.

Remarks on result:

other: Serious damage to unwashed left eye, but slight damage when rinsed after 4 or 30 seconds

Remarks:

100 mg NaBO3 * 4H2O in one eye

Reversibility:

fully reversible within: 10 days

Remarks on result:

other: Acute conjunctivitis, corneal irritation at 48 hours

Remarks:

50 mg NaBO3 * 4H2O in one eye

Remarks on result:

other: moderate irritant

Remarks:

observed up to 21 d; 6 mg (0.01ml) NaBO3 * 4H2O in one eye

Remarks on result:

other: non-irritant

Remarks:

1% NaBO3 * 4H2O solution in one eye

Remarks on result:

other: severe irritant

Remarks:

Observed up to 21 days; 50 mg NaBO3 * H2O in one eye

Remarks on result:

other: corrosive to unwashed eye

Remarks:

Observed up to 21 days; 0.1 mg NaBO3 * H2O in one eye

Remarks on result:

other: Immediate conjunctivitis, caused by exothermic hydrolysis to boric acid

Remarks:

50 mg B2O3 in one eye

Irritation parameter:

cornea opacity score

Time point:

24/48/72 h

Remarks on result:

other: not available

Irritation parameter:

iris score

Time point:

24/48/72 h

Remarks on result:

other: not available

Irritation parameter:

conjunctivae score

Time point:

24/48/72 h

Remarks on result:

other: not available

Irritation parameter:

chemosis score

Time point:

24/48/72 h

Remarks on result:

other: not available

Interpretation of results:

study cannot be used for classification

Conclusions:

The present information was based on a literature review (peer-reviewed) of various borates studies, which gave inconsistent results ranging from not irritating to irritating. The scores as indicated in Regulation 1272/2008, which are required for classification, are not given. Further, due to inconsistent results, no conclusion based on expert judgement can be drawn.

Executive summary:

A literature review of borates showed that these borates induced none to irritating responses, no conclusion on classification can be drawn.

Data source

Reference

Reference Type:

review article or handbook

Title:

Technical Report No 63, Reproductive and General Toxicology of some Inorganic Borates and Risk Assessment for Human Beings

Author:

ECETOC

Year:

1995

Bibliographic source:

ISSN-0773-8072-63

Materials and methods

Test guideline

Qualifier:

no guideline required

Principles of method if other than guideline:

Review of literature data

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Boric acid

EC Number:

233-139-2

EC Name:

Boric acid

Cas Number:

10043-35-3

Molecular formula:

H3BO3

IUPAC Name:

Boric acid

Constituent 2

Reference substance name:

Diboron trioxide

EC Number:

215-125-8

EC Name:

Diboron trioxide

Cas Number:

1303-86-2

Molecular formula:

B2O3

IUPAC Name:

oxo(oxoboranyloxy)borane

Constituent 3

Reference substance name:

1303-96-4

EC Number:

603-411-9

Cas Number:

1303-96-4

IUPAC Name:

1303-96-4

Constituent 4

Reference substance name:

Reference substance 002

EC Number:

601-808-1

Cas Number:

12179-04-3

Molecular formula:

B4-O7.2Na.5H2-O

Constituent 5

Reference substance name:

Disodium tetraborate, anhydrous

EC Number:

215-540-4

EC Name:

Disodium tetraborate, anhydrous

Cas Number:

1330-43-4

Molecular formula:

B4Na2O7

IUPAC Name:

Disodium tetraborate

Constituent 6

Reference substance name:

Reference substance 001

EC Number:

602-894-3

Cas Number:

‎12280-03-4

Constituent 7

Reference substance name:

Sodium metaborate dihydrate

Cas Number:

16800-11-6

IUPAC Name:

Sodium metaborate dihydrate

Constituent 8

Reference substance name:

Sodium metaborate tetrahydrate

EC Number:

600-663-1

Cas Number:

10555-76-7

IUPAC Name:

Sodium metaborate tetrahydrate

Constituent 9

Reference substance name:

Sodium perborate

EC Number:

239-172-9

EC Name:

Sodium perborate

Cas Number:

10486-00-7

Molecular formula:

BH3O4.Na

Constituent 10

Reference substance name:

azane;2-hydroxy-4-[(4-hydroxy-1,3,2,4-dioxadiboretan-2-yl)oxy]-1,3,2,4-dioxadiboretane;tetrahydrate

Cas Number:

10135-84-9; 12228-87-4

Molecular formula:

B4H16N2O11

IUPAC Name:

azane;2-hydroxy-4-[(4-hydroxy-1,3,2,4-dioxadiboretan-2-yl)oxy]-1,3,2,4-dioxadiboretane;tetrahydrate

Constituent 11

Reference substance name:

12046-04-7

EC Number:

601-709-3

Cas Number:

12046-04-7

IUPAC Name:

12046-04-7

Constituent 12

Reference substance name:

Dipotassium tetraborate

EC Number:

215-575-5

EC Name:

Dipotassium tetraborate

Cas Number:

1332-77-0

Molecular formula:

B4K2O7

IUPAC Name:

dipotassium tetraborate

Constituent 13

Reference substance name:

Hexaboron dizinc undecaoxide

EC Number:

235-804-2

EC Name:

Hexaboron dizinc undecaoxide

Cas Number:

138265-88-0

Molecular formula:

2ZnO·3B2O3·3H2O [ZnB3O4(OH)3]

IUPAC Name:

dodecaboron tetrazinc docosaoxide heptahydrate

Test animals / tissue source

Species:

rabbit

Strain:

not specified

Details on test animals or tissues and environmental conditions:

no data

Test system

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

various, see free-text field below

Duration of treatment / exposure:

various, see free-text field below

Observation period (in vivo):

various, see free-text field below

Duration of post- treatment incubation (in vitro):

various, see free-text field below

Number of animals or in vitro replicates:

various, see free-text field below

Details on study design:

a) Six young rabbits had 100 mg of boric acid applied to one eye of each rabbit. The eyes were rinsed after 24 hours and irritation scores in individual animals ranged from 0 to 18.
b) Six young rabbits had 77 mg of borax, Na2B4O7.10H2O, applied to one eye of each rabbit. The eyes were rinsed after 24 hours and irritation scores in individual animals ranged from 0 to 39.
c) Six young rabbits had 100 mg of disodium tetraborate pentahydrate, Na2B4O7.5H2O, applied to one eye of each rabbit. The eyes were not rinsed, and the ocular reaction was recorded after 1, 24, and 72 hours and up to 10 days after treatment.
d) About 50 mg of boric oxide was placed in the left eye of four rabbits.
e) Sodium perborate tetrahydrate was tested for eye irritation on two female rabbits and the Draize scale was used for assessment of irritation. The test substance (approximately 100 mg) was applied to the conjunctival sac of the left eye of each rabbit, the other eye was untreated. The eyes were examined after 1 to 2 hours, and up to 3 or 21 days after application for each of the animals, respectively.
f) 50 mg of sodium perborate tetrahydrate was introduced into the rabbit eye.
g) The irritation of a small volume of sodium perborate tetrahydrate was assessed in three rabbits. The methods used were similar to those described above except that the amount of test material used was less, in this case a volume of 0.01 ml was used (approximating to 6 mg).
h) A 1% solution of sodium perborate tetrahydrate was instilled to the rabbit eye.
i) A test in rabbits investigated the effect of an eye washing procedure on the irritant effect of sodium perborate tetrahydrate. After instilling 100 mg of the test material into the left eye, groups of 3 rabbits received either no further treatment or the eye was washed 4 or 30 seconds later.

Results and discussion

In vivo

Results

Results 1

Reversibility:

fully reversible within: 7 days

Remarks:

or less

Remarks on result:

other: irritating

Remarks:

100 mg H3BO3 in one eye

Results 2

Reversibility:

fully reversible within: 8-21 days

Remarks on result:

other: corneal irritation

Remarks:

77 mg Borax in one eye

Results 3

Reversibility:

not fully reversible within: 21 days

Remarks on result:

other: severe irritation

Remarks:

100 mg Na2B4O7 * 5H2O in one eye

Results 4

Remarks on result:

other: Severe irritant to the rabbit eye

Remarks:

Observed up to 21d; 100 mg NaBO3 * 4H2O in one eye.

Results 5

Remarks on result:

other: Serious damage to unwashed left eye, but slight damage when rinsed after 4 or 30 seconds

Remarks:

100 mg NaBO3 * 4H2O in one eye

Results 6

Reversibility:

fully reversible within: 10 days

Remarks on result:

other: Acute conjunctivitis, corneal irritation at 48 hours

Remarks:

50 mg NaBO3 * 4H2O in one eye

Results 7

Remarks on result:

other: moderate irritant

Remarks:

observed up to 21 d; 6 mg (0.01ml) NaBO3 * 4H2O in one eye

Results 8

Remarks on result:

other: non-irritant

Remarks:

1% NaBO3 * 4H2O solution in one eye

Results 9

Remarks on result:

other: severe irritant

Remarks:

Observed up to 21 days; 50 mg NaBO3 * H2O in one eye

Results 10

Remarks on result:

other: corrosive to unwashed eye

Remarks:

Observed up to 21 days; 0.1 mg NaBO3 * H2O in one eye

Results 11

Remarks on result:

other: Immediate conjunctivitis, caused by exothermic hydrolysis to boric acid

Remarks:

50 mg B2O3 in one eye

Results 12

Irritation parameter:

cornea opacity score

Time point:

24/48/72 h

Remarks on result:

other: not available

Results 13

Irritation parameter:

iris score

Time point:

24/48/72 h

Remarks on result:

other: not available

Results 14

Irritation parameter:

conjunctivae score

Time point:

24/48/72 h

Remarks on result:

other: not available

Results 15

Irritation parameter:

chemosis score

Time point:

24/48/72 h

Remarks on result:

other: not available

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Conclusions:

The present information was based on a literature review (peer-reviewed) of various borates studies, which gave inconsistent results ranging from not irritating to irritating. The scores as indicated in Regulation 1272/2008, which are required for classification, are not given. Further, due to inconsistent results, no conclusion based on expert judgement can be drawn.

Executive summary:

A literature review of borates showed that these borates induced none to irritating responses, no conclusion on classification can be drawn.