Registration Dossier

Administrative data

Description of key information

In vivo irritation studies on skin and eye were performed on boric acid, which showed boric acid to be a non-irritant. 

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
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: GLP guideline study. Study conducted on the hydrolysis product of reference substance, boric acid.
Qualifier:
according to guideline
Guideline:
other: FIFRA (40 CFR 163)
Deviations:
no
GLP compliance:
no
Remarks:
Study pre-dates GLP
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan F Plummer
- Weight at study initiation: 1623 - 2922 g
Type of coverage:
occlusive
Preparation of test site:
abraded
Vehicle:
physiological saline
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 g
- Concentration: Moistened with physiological saline.
Duration of treatment / exposure:
24 h
Observation period:
72 h
Number of animals:
10
Details on study design:
TEST SITE
- Area of exposure: Saddle area
- Type of wrap if used: Occlusive


REMOVAL OF TEST SUBSTANCE
- Washing: Moistened towel
- Time after start of exposure: 24 h


SCORING SYSTEM: Draize
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 72 h
Score:
0.1
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritant / corrosive response data:
No irritancy was observed
Other effects:
No data

Results for skin irritation:

Site

Time

Erythema

Edema

Intact

24 h

0

0

72 h

0.25

0

Abraded

24 h

0

0

72 h

0.17

0

Average score

24 h, 72 h

0.105

0

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). No irritancy was observed and it is therefore not classifiable in the EU.
Further testing not warranted in the interests of animal welfare.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
No data
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study. Study conducted on the hydrolysis product of reference substance, boric acid.
Qualifier:
according to guideline
Guideline:
other: FIFRA (40 CFR 158, 162); TSCA (40 CFR 798). Although not carried out to an OECD protocol, the study has been carried out to a US EPA acceptable protocol and conducted in accordance with GLP standards (40CFR160).
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
not specified
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Approved USDA supplier
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 100 mg boric acid was applied to one eye of each of 6 rabbits.
- Concentration: Boric acid used at up to 5 % in eye washes
Duration of treatment / exposure:
24 h
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
6 animals
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: Rinsed with physiological saline
- Time after start of exposure: 24 h


SCORING SYSTEM: According to Draize, reported as according to EU 67/548/EEC
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: Average 24, 48, 72 h
Score:
13.6
Max. score:
110
Reversibility:
fully reversible
Remarks on result:
other: Average 60 min score was 0.17
Irritant / corrosive response data:
Slightly irritating
Changes in colouration and texture of the eye and blistered appearance to conjunctiva.
Chemosis and redness reversed by seven days.
Other effects:
No data

Results of the eye irritation study:

Score (average of animals investigated)

Cornea

Iris

Conjunctiva

Redness

Chemosis

0 to 4

0 to 2

0 to 3

0 to 4

60 min

0.17

0.83

1.00

1.67

24 h

0.00

0.33

1.00

0.83

48 h

0.00

0.00

1.00

0.50

72 h

0.00

0.00

0.83

0.33

Average 24 h, 48 h, 72 h

0.00

0.11

0.94

0.56

Reversibility*

 

c

c

c

Average time for reversion

 

By 48 h

By 7 d

By 7 d

*complete

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 158, 162); TSCA (40 CFR 7998). Minor effects on the iris and effects on the conjunctivae were reversed by Day 7. Not classifiable in the EU under directive 67/548/EEC.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The reference substance (BAGE) hydrolyses within less than an hour to its hydrolysis products: Boric acid and glycerol. Therefore, conducting irritation studies on the reference substance will give a result representative of the hydrolysis products mentioned above.

Boric acid is considered to be the hydrolysis product of main concern, due to its known reproductive/developmental effects. An assessment of the skin and eye irritancy of boric acid has therefore been made based on available study data on boric acid.

Boric acid

Skin irritation:

Weiner AS et al (1982):

The study was performed according to FIFRA (40 CFR 163). 10 rabbits were exposed to a single application (24 hour exposure) of test substance (boric acid) on intact and abraded test sites. For a period of 72 hours any clinical signs and dermal abrasions observed were recorded.

No significant irritancy was observed and the primary dermal irritation index was calculated to be 0.1.

Based on this data boric acid is not a skin irritant.

Eye irritation:

Doyle RL (1989):

The study was performed according to FIFRA (40 CFR 158, 162); TSCA (40 CFR 7998) (similar to OECD Guideline 405). 6 rabbit eyes were treated with the test substance (boric acid), with eyes being rinsed after 24 hours.Observations for irritation were made at 60 min, 24 h. 48 h, 72 h, 7 d and 21 d.

Boric acid induced mild conjunctivae redness and chemosis and minor effects on the iris. The effects were reversible within 7 days.Therefore, no classification is indicated.

Glycerol

Glycerol is the other hydrolysis product of BAGE. It is not classified for human health according to CLP or DSD and is essentially non-toxic. Further evaluation of the skin and eye irritancy of glycerol has not been assessed.

Refer to section 13, Toxicological expert report, for further details of the evalaution of the hydrolysis of BAGE and its consequences for toxicity testing.

Supporting data:

As skin irritation and eye irritation studies are not feasible to conduct on the reference substance itself, DEREK predictions were made to assess the potential irritation and ocular toxicity of the reference substance itself.

The test substance was predicted to be a non- irritant to the skin and eye as no alerts were triggered for irritation or ocular toxicity by the structure of the substance.


Justification for selection of skin irritation / corrosion endpoint:
Study conducted on boric acid, the hydrolysis product of the reference substance, which is of most concern to human health and is most applicable to evaluate.

Justification for selection of eye irritation endpoint:
Study conducted on boric acid, the hydrolysis product of the reference substance, which is of most concern to human health and is most applicable to evaluate.

Justification for classification or non-classification

Boric acid was not classified for skin or for eye irritation under criteria defined in directive 67/548/EEC (DSD) or CLP as no significant

irritating effects were observed on application to the skin or eyes of test animals and all effects were fully reversible.