Boric acid

Endpoint summary

Description of key information

In vivo irritation studies on skin (Weiner et al, 1982), eye (Doyle, 1999) and respiratory tract were performed.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

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

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:

72 h

Score:

0.1

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: intact skin

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: intact skin

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: intact skin

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: intact skin

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: intact skin

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: intact skin

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: intact skin

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: intact skin

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: intact skin

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: intact skin

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: intact skin

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: intact skin

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: intact skin

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: intact skin

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: intact skin

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: intact skin

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: intact skin

Irritation parameter:

edema score

Basis:

animal #6

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: intact skin

Irritation parameter:

edema score

Basis:

animal #1

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: intact skin

Irritation parameter:

edema score

Basis:

animal #2

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: intact skin

Irritation parameter:

edema score

Basis:

animal #3

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: intact skin

Irritation parameter:

edema score

Basis:

animal #4

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: intact skin

Irritation parameter:

edema score

Basis:

animal #5

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: intact skin

Irritation parameter:

edema score

Basis:

animal #6

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: intact skin

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

animal 1 - 6

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

animal 1 - 6

Time point:

48 h

Remarks on result:

not measured/tested

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:

other: Not classifiable in the EU

Remarks:

Classified in US Toxicity Category IV (slight or no irritation)

Conclusions:

The study was performed according to FIFRA (40 CFR 163). No irritancy was observed and it is therefore not classifiable in the EU.
Classified in US in Toxicity Category IV (slight or no irritation).
Data from other studies confirm the results. Further testing not warranted in the interests of animal welfare.

Reference 2

Endpoint:

skin irritation: in vivo

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: Meest generally accepted scientific standards with acceptable restrictions.

Qualifier:

according to guideline

Guideline:

other: 172.4 Title 49 Code of Federal Regs (Fed Reg Feb12, 1973)

Deviations:

no

Remarks:

Although the study was not carried out to OECD protocols, it was carried out to US Government Guidelines and other tests confirm the results. Further testing is therefore not justified in the interests of animal welfare.

GLP compliance:

no

Remarks:

Study pre-dates GLP

Species:

rabbit

Strain:

not specified

Type of coverage:

occlusive

Preparation of test site:

abraded

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Duration of treatment / exposure:

4 hours

Observation period:

No data

Number of animals:

6

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

48 h

Score:

0

Max. score:

8

Reversibility:

other: Not applicable, no irritation observed.

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Not irritating

Other effects:

No data

Interpretation of results:

GHS criteria not met

Conclusions:

Not irritating.

Reference 3

Endpoint:

skin irritation: in vivo

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: Meets generally accepted scientific standards with acceptable restrictions.

Qualifier:

according to guideline

Guideline:

other: 173.240 under title 49 of the Code of Federal Regulations, 1973

Deviations:

not specified

GLP compliance:

no

Remarks:

Study pre-dates GLP

Species:

rabbit

Strain:

not specified

Type of coverage:

occlusive

Preparation of test site:

abraded

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Duration of treatment / exposure:

Four h

Observation period:

48 h

Number of animals:

Six

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

48 h

Score:

0

Max. score:

8

Reversibility:

other: Not applicable

Other effects:

No corrosive effects were noted at any time during the study in any animal.

Primary irritation and corrosivity scores in rabbits following 4-h patch application of anhydrous boric acid - 100 mesh.

Rabbit No.	Skin	Erythema-Eschar Observation			Edema Observation
		4 h	24 h	48 h	4 h	24 h	48 h
7	Intact	0	0	0	0	0	0
	Abraded	0	1	1	0	0	0
8	Intact	0	0	0	0	0	0
	Abraded	0	0	0	0	0	0
9	Intact	0	0	0	0	0	0
	Abraded	0	0	0	0	0	0
10	Intact	0	0	0	0	0	0
	Abraded	0	0	0	0	0	0
11	Intact	0	0	0	0	0	0
	Abraded	0	0	0	0	0	0
12	Intact	0	0	0	0	0	0
	Abraded	0	0	0	0	0	0

Scoring key:

Evaluation of skin reaction	Value
Erythema and eschar formation
No erythema	0
Very slight erythema (barely perceptible)	1
Well-defined erythema	2
Moderate to severe erythema	3
Severe erythema (beet redness) to slight eschar formation (injuries in depth)	4
Edema formation
No edema	0
Very slight edema(barely perceptible)	1
Slight edema (edges of area well defined by definite raising)	2
Moderate edema (raised approximately1 mm)	3
Severe edema (raised more than 1 mm and extending beyond the area of exposure)	4

191.11 of Regulations under the Federal Hazardous Substances Labelling Act.

Interpretation of results:

GHS criteria not met

Conclusions:

The corrosive potential of anhydrous boric acid - 100 mesh was evaluated in accordance with the procedure described in section 173.240 (CFR 49). No corrosive effects were noted at any time during the study.
Based on the results the test material was not classified as corrosive.

Reference 4

Endpoint:

skin irritation: in vivo

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: Meets generally accepted scientific standards with acceptable restrictions.

Qualifier:

according to guideline

Guideline:

other: US Reg. (21 CFR 191.11)

Deviations:

no

GLP compliance:

no

Remarks:

Study pre-dates GLP

Species:

rabbit

Strain:

not specified

Type of coverage:

occlusive

Preparation of test site:

abraded

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount applied: Six rabbits with intact and 6 rabbits with abraded skin. 5 mL of boric acid was applied as a 10 % solution on a cellulose pad.

- Concentration: 10 % solution

Duration of treatment / exposure:

No data

Observation period:

No data

Number of animals:

12

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Score:

0.8

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: Intact skin

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Score:

2.5

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: Abraded skin

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Score:

1.7

Max. score:

8

Reversibility:

not specified

Remarks on result:

other: Intact plus abraded skin

Other effects:

No data

Interpretation of results:

GHS criteria not met

Conclusions:

Not irritating

Reference 5

Endpoint:

skin irritation: in vivo

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: Meets generally accepted scientific standards with acceptable restrictions.

Qualifier:

no guideline followed

Principles of method if other than guideline:

No data

GLP compliance:

no

Remarks:

Study pre-dates GLP

Species:

guinea pig

Strain:

Hartley

Type of coverage:

occlusive

Preparation of test site:

abraded

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Six guinea pigs with clipped depilated intact abdomens and 6 guinea pigs with clipped depilated, abraded backs. 5 mL of boric acid was applied as a 10% solution on a cellulose pad.
- Concentration: 10 %

Duration of treatment / exposure:

No data

Observation period:

No data

Number of animals:

12

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Score:

2.7

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: Intact skin

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Score:

1.4

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: Abraded skin

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Score:

2.1

Max. score:

8

Reversibility:

not specified

Remarks on result:

other: Intact plus abraded skin

Irritant / corrosive response data:

Not irritating

Other effects:

No data

Interpretation of results:

GHS criteria not met

Conclusions:

Not irritating

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye 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.

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:

24/48/72 h

Score:

13.6

Max. score:

110

Reversibility:

fully reversible

Remarks on result:

other: Average 60 min score was 0.17

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

cornea opacity score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

cornea opacity score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

cornea opacity score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 48 h

Irritation parameter:

iris score

Basis:

animal #1

Time point:

48 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

animal #1

Time point:

72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

animal #6

Time point:

24 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 48 h

Irritation parameter:

iris score

Basis:

animal #6

Time point:

72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7 d

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

48 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

72 h

Score:

0

Max. score:

3

Reversibility:

other: not applicable

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7 d

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7 d

Irritation parameter:

conjunctivae score

Basis:

animal #5

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7 d

Irritation parameter:

conjunctivae score

Basis:

animal #6

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 4 d

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

48 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

48 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 4 d

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 4 d

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

24 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

48 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

chemosis score

Basis:

animal #5

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 d

Irritation parameter:

chemosis score

Basis:

animal #6

Time point:

24 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal #6

Time point:

48 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

chemosis score

Basis:

animal #6

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

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:

GHS criteria not met

Remarks:

Toxicity Category III - corneal involvement or irritation clearing in 7 days or less.

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.
Classified in US category III (40 CFR 156) "corneal involvement or irritation clearing in 7 days or less".
Non irritant under US CPS (16 CFR 15000.42).

Reference 2

Endpoint:

eye irritation: in vivo

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: Meets generally accepted scientific standards with acceptable restrictions.

Qualifier:

no guideline followed

Principles of method if other than guideline:

No data

GLP compliance:

no

Remarks:

Study pre-dates GLP

Species:

rat

Strain:

not specified

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 100 mg

Duration of treatment / exposure:

No data

Observation period (in vivo):

No data

Number of animals or in vitro replicates:

12

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: One group had eyes irrigated immediately, the other group had no irrigation.

Irritation parameter:

other: No data

Basis:

mean

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

The non-irrigated group had mild or moderate erythema in 5/6 animals which subsided by 4th day after treatment. The irrigated group had mild erythema 6/6 and mild oedema 1/6 which subsided by 4th day after treament.

Other effects:

No data

Interpretation of results:

GHS criteria not met

Conclusions:

The non-irrigated group had mild or moderate erythema in 5/6 animals which subsided by 4th day after treatment. The irrigated group had mild erythema 6/6 and mild oedema 1/6 which subsided by 4th day after treament.

Classified as Not irritating.

Reference 3

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

No data

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

EPA OPP 81-4 (Acute Eye Irritation)

Deviations:

not specified

Qualifier:

according to guideline

Guideline:

other: FIFRA 40 CFR 158

Deviations:

not specified

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Irish Farms (Norco, CA)
- Weight at study initiation: 2.07 and 2.47

Vehicle:

unchanged (no vehicle)

Controls:

other: the left eye remained untreated to serve as a control.

Amount / concentration applied:

0.1 g

Duration of treatment / exposure:

72 h in unrinsed rabbits

Observation period (in vivo):

72 h

Number of animals or in vitro replicates:

Nine in total; 6 in Group A (unrinsed) and 3 in Group B (rinsing).

Details on study design:

One drop of proparacaine was applied to both eyes. Approximately 0.1 g of the test article was instilled into the lower conjunctival sac of the right eye of each test animal. The lids were held together for one second and released.
The three animals in Group B had the test article rinsed from the eye with normal saline immediately following instillation. The eyes were examined at 24, 48 and 72 h after instillation and the presence of irritation was recorded.

Irritation parameter:

other: No data

Basis:

other: No data

Reversibility:

fully reversible within: 72 h

Irritant / corrosive response data:

The test article was irritating when applied to the eyes of rabbits. The severity of the irritation was less irritating in those animals that were rinsed with saline immediately following test article application. The irritation was confined to redness and slight swelling of the conjunctival tissue. This irritation decreased over time with a return to normal in two of the three rabbits 72 h after exposure to the test article.
The rabbit that did not have the test article immediately rinsed from the eyes had a more severe reaction to the test article. In addition to the redness and swelling, there was slight corneal swelling and one animal developed iritis at 24 h. The eyes were improved in two animals at 48 h and in four animals at 72 h. The irritation in the remaining 2 group A animals was slight and not considered significant. Therefore the test was terminated at 72 h.

Other effects:

No data

Ocular irritation scores

Group	Rabbit No.	Eye	0 h	24 h	48 h	72 h
A	289	Right	0	IIIA2, IIIBI	0	0
		Left	0	0	0	0
	290	Right	0	I1, II1, IIIA2, IIIB2	IIIA1	IIIA1, IIIB1
		Left	0	0	0	0
	294	Right	0	IIIA1, IIIB1	0	0
		Left	0	0	0	0
	295	Right	0	IIIA2, IIIB2	0	0
		Left	0	0	0	0
	296	Right	0	I1, IIIA1, IIIB2	IIIA1, IIIB1	IIIA1, IIIB2
		Left	0	0	0	0
	297	Right	0	IIIA1, IIIB1	IIIA1, IIIB1	0
		Left	0	0	0	0
B	291	Right	0	IIIA2, IIIB1	IIIA1, IIIB2	IIIA1, IIIB1
		Left	0	0	0	0
	292	Right	0	IIIA1, IIIB1	IIIB1	0
		Left	0	0	0	0
	293	Right	0	IIIA1, IIIB2	IIIA1	0
		Left	0	0	0	0

I = cornea

II = iris

II = conjunctivae

A = redness

B = swelling

0 = normal

1 = slight

2 = moderate

3 = severe

Interpretation of results:

other: Toxicity Category IV

Remarks:

Criteria used for interpretation of results: 40 CFR 156

Conclusions:

The test article was an ocular irritant when applied directly to the eyes of rabbits. It is less irritating when flushed immediately from eyes. The irritation was reversible after 24 h with a return to near normal by 72 h after exposure to the test article. These results place the material in Toxicity category IV (40 CFR 156) by ocular administration.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Skin Irritation

Boric acid is not a skin irritant.

Eye Irritation

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.

Respiratory tract

Borates act as mild sensory irritants, indicated by the effects observed in humans (i.e.nose, eye and throat irritation; sneezing)and by the results of the Alarie-tests by Krystofiak & Schaper (1996) and Kirkpatrick (2010), which demonstrated a depression of the respiratory frequency in mice after exposure to sodium borate. This reflex can be triggered by agents that stimulate receptors in the respiratory tract e.g. on the trigeminal nerve (Wegman et al. 1991, Nielsen et al., 2007, Krystofiak & Schaper, 1996, Kirkpatrick, 2010). The actual mechanism, however, has not yet been elucidated. The Kirkpatrick (2010) study of boric acid using the Alarie ASTM mouse RD50 test was unable to reach an exposure concentration of boric that would cause a 50 % depression of respiration and thus did not meet the criteria specified by the test protocol for a respiratory irritant.

Wegman et al. (1991) and Woskie et al. (1998) proposed changes of osmolarity in the lining fluid of the mucous membrane as possible cause for receptor activation. Changes in osmolarity could also act indirectly by stimulating mast cells to secrete histamine or other immune modulators. Histamine is known to be able to mediate the sensory component of irritation. The importance of osmolarity in the case of borate dusts is further substantiated by Cain et al. (2008) where the changes of local osmolality from a desiccating dust may cause sensations of dryness. They also indicated that more acidic dusts, as compared to borate dusts, would lead to a change in nasal pH which might trigger the nasal receptors in a different way.

Acute irritant effects are extensively documented in human workers exposed to sodium borates (EPA, 2004; Wegman et al. 1991; Garabrant 1984, 1985; Woskie et al., 1994, 1998; Cain et al., 2004, 2008). The described symptoms are typical for those which would be produced in the exposed population rather than being an isolated reaction or response triggered only in individuals with hypersensitive airways. Symptoms include nasal and eye irritation, throat irritations, cough, and breathlessness. Boric acid exposure was only studied by Garabrant (1984) and Cain et al. (2008). The Garabrant (1984) study did not distiquish which of the two exposures (boron oxide or boric acid) was associated with reported symptoms. Boron oxide reacts exothermically with water to form boric acid suggesting a possible mechanism for boron oxide irritancy. It is believed that these irritant effects are caused by the exothermic hydration of boron oxide to boric acid. Cain et al. (2008) reported a NOAEL for irritation among human volunteers inhaling boric acid of 1.75 mg B/m3 (10 mg/m3 of boric acid), the highest exposure evaluated for boric acid. The exposures of 2, 5 and 10 mg/m3 evaluated in Cain et al. (2008) did not reach a level defined by the investigators as being irritating. Furthermore, for any given point in exposure time the dose-response curve had a very low slope, not characteristic of an irritant.

In the Transitional Annex XV Dossier, Poisson regression analysis of the results from Wegman et al. (1991) was used to estimate a NOEC (See Appendix A). For NOEC derivation 15-minute interval exposure data were plotted against the sum of “any symptom” (nose, eye, and throat irritation, sneezing breathlessness, coughing; Table 37, attached in appendix A; Wegman et al., 1991). The lower limits of the exposure ranges presented in Table 37 were used for the non-linear regression analysis (Poisson-model). Applying the equation derived from the regression analysis, resulted in a predicted rate for effects at background of 0.002, with lower and upper 95 % CI of 0.0002 and 0.016, respectively. The upper 95 % CI of this rate was considered equivalent to “no-observed-effect”. The boron concentration with a lower 95 % CI of the predicted rate of symptoms equal to this value (0.016) was used as the point of departure for DNEL derivation. The corresponding boron concentration equals 0.4 mg B/m³. A correction factor of 2 was then applied for the methodological underestimation of exposure measurements resulting in a NOEC of 0.8 mg B/m³. However, Wegman et al. did not study boric acid but instead an alkaline dust containing unspecified sodium borates. And sodium borate information can not be extrapolated to boric acid for irritant responses.

The Wegman data is based on subjective responses on a severity scale assigned to exposure ranges rather than a specific exposure level and contains no clear dose-response information. There is no way to identify where in this exposure spectrum symptoms occurred. Furthermore, symptoms were also reported in the group of workers not considered to be exposed (office workers), making any estimate of the NOEC unreliable. 

Benchmark dose analysis was conducted of the data presented in Table 37 of Wegman et al. (1991, attached in Appendix A). Table 37 presents the incidence of “Any Symptom” reported by a participant in the study that was confirmed by both the marker being pressed on the data logger worn by the worker and by a subsequent questionnaire administered by a study technician. The exposure doses used were the calculated mean concentration of each concentration range presented in the table. The identified dose-descriptor for acute irritant effects is the BMDL05 value of 0.94 mg B/m³ based on Wegman et al. (1991). The methods used for exposure measurements in this study were underestimates and a conversion factor of 2.5 was used to correct for the methodological underestimation of exposure measurements. This results in a final BMDL05of 2.35 mg B/m3 for exposure to sodium borate dusts.

An airway sensory irritation respiratory depression (RD50) study of boric acid and sodium tetraborate pentahydrate was conducted in male Swiss-Webster mice based on the ASTM E981-04 (2004) standard test method of estimating sensory irritancy of airborne chemicals. The ASTM E981-04 sensory iritancy test (Alarie assay) has been demonstrated to be a reliable test for estimating sensory irritancy of airborne irritants and RD50s are a basis, at least partially, for OELs by ACGIH (Kuwabara et al. 2007). ECHA guidelines (Chapter R.8) acknowledges the use of the Alarie assay in assessing respiratory irritation. 

It was not possible to achieve an aerosol concentration high enough to result in a 50 % respiratory depression in mice for boric acid based on the results in the mouse sensory irritation model. The highest concentration of boric acid that was achievable with acceptable control of the aerosol concentration was 1096 mg/m³ with a % RD of 19 %. Based on these results, the RD50 is > 1096 mg/m³ for boric acid. The ASTM standard uses the value of 0.03 x RD50 for estimation of threshold limit values (TLV). Alarie et al. (2001) has established that a value of 0.01 x RD50 as the concentration where no sensory irritation would be seen in humans. Therefore, although the highest achievable concentration was below the RD50 value for boric acid, based on the high aerosol concentrations achieved with % RD values below 50 %, it is clear that boric acid is not a respiratory irritant or at worst has extremely low potency as a sensory irritant. The practical side of these results is that occupational exposure limit of 10 mg/m3 total particulate will prevent any sensory irritation in workers.

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 as no irritating effects were observed on application to the skin or eyes of test animals. All scores were under the cut-off values triggering classification and labelling. Boric acid does not meet the criteria for a respiratory irritant. Therefore, boric acid does not meet criteria under Regulation (EC) No 1272/2008 for classification and labelling as an irritant.