Boronic acid, (4-ethylphenyl)-

Endpoint summary

Description of key information

No skin irritating potential of the test item could be detected in a primary skin irritation test in rabbits according to OECD guideline 404. In an in vivo eye irritation study according to OECD guideline 405, the test item showed eye irritating effects and is thus categorized as irritating to the eye “UN GHS Category 2” (reference 7.3.1-1 and 7.3.2-1).

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:

2007-03-16 to 2007-07-13

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Kifilegg
- Age at study initiation: approx. 15 weeks
- Weight at study initiation: The mean initial body weight at the start of the study was 2.88 kg
- Housing: Animals were kept separately in special rabbit cages in an air-conditioned room
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: More than 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-19
- Humidity (%): 45-50
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 g

VEHICLE
- Amount applied: 0.5 g of the test item was mixed with some drops of Aqua pro injectione before administration.

Duration of treatment / exposure:

4 hours

Observation period:

The rabbits were examined for skin alterations, behavior, and general condition 1 hour after removal of the patches, after 24, 48, 72 hours, and then daily up to experimental day 8.

Number of animals:

3 females

Details on study design:

TEST SITE
- Area of exposure: 6 cm^2
- Type of wrap: Fixomull® stretch, Beiersdorf

REMOVAL OF TEST SUBSTANCE
- Washing: Test material residues were wiped off
- Time after start of exposure: 4 hours after start of exposure

OBSERVATION TIME POINTS
The rabbits were examined for skin alterations, behavior, and general condition 1 hour after removal of the patches, after 24, 48, 72 hours, and then daily up to experimental day 8

SCORING SYSTEM:
- Method of calculation: Skin changes at the application sites were evaluated according to the DRAIZE-, OECD-and EEC recommendations (see table 1).

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Remarks on result:

no indication of irritation

Other effects:

- Other adverse systemic effects: No signs of clinical toxicity were observed.
- Mortality: All animals survived the observation period.
- Body weight: Body weight development of the treated rabbits was insonspicious.

Table 2: Individual local findings (scores)

     

Animal No.	Finding	Day
		1(1 h)	2 (24 h)	3 (48 h)	4 (72 h)	5	6	7	8
14	Erythema	0	0	0	0	0	0	0	0
	Edema	0	0	0	0	0	0	0	0
15	Erythema	0	0	0	0	0	0	0	0
	Edema	0	0	0	0	0	0	0	0
16	Erythema	0	0	0	0	0	0	0	0
	Edema	0	0	0	0	0	0	0	0

 

Interpretation of results:

GHS criteria not met

Conclusions:

No skin irritating potential of the test item could be detected in a primary skin irritation test in rabbits according to OECD guideline 404.

Executive summary:

The test material was mixed with some drops of Aqua pro injectione to ensure good contact with the skin. Afterwards, the test material was spread onto patches and applied to the intact skin of previously shaven rabbits for 4 hours under semi-occlusive conditions. The study was performed initially with one animal and followed by the confirmatory test with two further animals according to OECD guideline 404. The first examination of the treated skin followed 1 hour after patch removal. Thereafter, examinations were performed daily for a further 7 days. Under the conditions of the present study no signs of irritation were seen.

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:

experimental study

Adequacy of study:

key study

Study period:

2007-04-12 to 2008-02-14

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Kißlegg
- Age at study initiation: Approx. 17 and 47 weeks
- Weight at study initiation: 3.79 kg
- Housing: Separately in a special rabbit cage (manufacturer: Becker; type K.99/30 KU) placed on mobile racks.
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: More than 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15 to 18
- Humidity (%): 42 to 70
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: Day 0 To: Day 14

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 g of the test material

Duration of treatment / exposure:

14 days

Observation period (in vivo):

Day 0 to day 14

Number of animals or in vitro replicates:

2 females

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: The test substance remained in the eyes of the rabbits up to the end of the observation period.

SCORING SYSTEM: See table 1 in section "Any other information on materials and methods incl. tables".

Irritation parameter:

other: discharge

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.66

Max. score:

3

Reversibility:

fully reversible within: 5 days

Remarks on result:

positive indication of irritation

Irritation parameter:

other: discharge

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.33

Max. score:

3

Reversibility:

fully reversible within: 5 days

Remarks on result:

positive indication of irritation

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 6 days

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 8 days

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 5 days

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 5 days

Remarks on result:

positive indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 8 days

Remarks on result:

positive indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 6 days

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

The cornea developed diffuse areas of opacity (scores 1 and 2) from the first investigation up to day 5 and 7 of the experimental part. At the iris signs of irritation were observed (score 1) from day 2 up to day 5 in one animal. The conjunctivae showed redness (scores 1 and 2) from the first investigation up to day 6 and 7. Chemosis (score 1 and 2) was seen up to experimental day 4. Furthermore, discharge was observed 1 hour after instillation of the test material up to day 4 of the experimental part (scores 1 and 4). The untreated eye was unchanged.

Other effects:

- Lesions and clinical observations: No signs of pain were observed immediately after instillation.

Table 1: Body weights

 

Animal No.	Body weight in kg on experimental day					Body weight gain
	1	5	8	11	15	dayl to 15
18	3.40	3.36	3.42	3.46	3.48	+ 0.08
16	4.18	4.21	4.25	4.25	4.23	+ 0.05
Mean	3.79	3.79	3.84	3.86	3.86	+ 0.07

 

Table 2: Eye alterations, mean score 24, 48 and 72 hours oft wo rabbits

	Mean score (24, 48 and 72 hours)		Maximum value (24, 48 and 72 hours)
Animal No	1	2	1	2
Cornea	1.33	1	2	1
Iris	1	0	1	0
Conjunctivae	1	2	1	2
Chemosis	1	1.33	1	2

 

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

In this in vivo eye irritation study according to OECD guideline 405, the test item showed eye irritating effects and is thus categorized as irritating to the eye “UN GHS Category 2”.

Executive summary:

The test item was tested for its eye irritating properties. Prior to testing, the hen's egg test on the chorioallantoic membrane was performed and no irritating potential could be detected. The test for primary eye irritation was performed initially with one animal and followed by the confirmatory test with one further animal according to OECD guideline 405. For the test of primary eye irritation, the test material was applied into the conjunctival sac of rabbits. The first examination of the eyes followed 1 hour after instillation. The other examinations of the eyes were performed daily for a further 14 days. Two rabbits were used in this study. No signs of pain were observed immediately after instillation. Diffuse areas of opacity were seen at the cornea 1 hour after instillation up to day 5 and 7 of the experimental part. The iris showed signs of irritation from day 2 up to day 5 in one animal. The conjunctivae were reddened from the first investigation up to day 6 and 7. Chemosis was observed in both animals up to experimental day 4. The individual scores after 24/48/72 hours were 0 (animal 1) and 2 (animal 2) for iris irritation, 2 (animal 1) and 1 (animal 2) for reddening of the conjunctivae, 1.33 (animal 1) and 1 (animal 2) for chemosis and 1 (animal 1) and 1.33 (animal 2) for corneal opacity. The untreated eyes were unchanged. In conclusion, the test item was considered to be irritating to the eye.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation, key study

The test material was mixed with some drops of Aqua pro injectione to ensure good contact with the skin. Afterwards, the test material was spread onto patches and applied to the intact skin of previously shaven rabbits for 4 hours under semi-occlusive conditions. The study was performed initially with one animal and followed by the confirmatory test with two further animals according to OECD guideline 404. The first examination of the treated skin followed 1 hour after patch removal. Thereafter, examinations were performed daily for a further 7 days. Under the conditions of the present study no signs of irritation were seen.

 

Eye irritation, key study

The test item was tested for its eye irritating properties. Prior to testing, the hen's egg test on the chorioallantoic membrane was performed and no irritating potential could be detected. The test for primary eye irritation was performed initially with one animal and followed by the confirmatory test with one further animal according to OECD guideline 405. For the test of primary eye irritation, the test material was applied into the conjunctival sac of rabbits. The first examination of the eyes followed 1 hour after instillation. The other examinations of the eyes were performed daily for a further 14 days. Two rabbits were used in this study. No signs of pain were observed immediately after instillation. Diffuse areas of opacity were seen at the cornea 1 hour after instillation up to day 5 and 7 of the experimental part. The iris showed signs of irritation from day 2 up to day 5 in one animal. The conjunctivae were reddened from the first investigation up to day 6 and 7. Chemosis was observed in both animals up to experimental day 4. The individual scores after 24/48/72 hours were 0 (animal 1) and 2 (animal 2) for iris irritation, 2 (animal 1) and 1 (animal 2) for reddening of the conjunctivae, 1.33 (animal 1) and 1 (animal 2) for chemosis and 1 (animal 1) and 1.33 (animal 2) for corneal opacity. The untreated eyes were unchanged. In conclusion, the test item was considered to be irritating to the eye.

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No 1272/2008

The available data for skin and eye irritation are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. The test item is not considered to be classified for skin irritation/corrosion but for eye irritation (category 2) according to EU Regulation (EC) No 1272/2008 (CLP), as amended for fifteenth time in Regulation (EU) No 2020/217.