Sodium 2-biphenylate

Endpoint summary

Description of key information

Skin irritation / corrosion (OECD 404): corrosive

Eye irritation / corrosion (OECD 405): serious eye damage

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:

08 - 15 Mar 1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted May 1981

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Interfauna UK Ltd. (breeder)
- Weight at study initiation: 3.1, 3.2 and 3.3 kg, respectively
- Housing: The rabbits were individually housed in single cages (wire cages type III-high). Below the cages excrement trays with low-dust wood granulate type S 8/15 (Ssniff, Soest, Germany) were located.
- Diet: Standard diet "Ssniff K 4" (supplied by Versuchstierdiäten GmbH, Soest, Germany), approximately 100 - 120 g per animal and day
- Water: Tap water, ad libitum
- Acclimation period: at least 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 2
- Humidity (%): Approximately 50
- Air changes (per hr): Approximately 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 08 Mar 1988 To: 15 Mar 1988

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

yes, concurrent vehicle

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 g
- Concentration: The test substance was made into a paste with water.

Duration of treatment / exposure:

4 h

Observation period:

7 days
Reading time points: 1, 24, 48 and 72 h and 7 days

Number of animals:

3 males

Details on study design:

TEST SITE
- Area of exposure: Approximately 6 cm² on the dorsal area of the trunk
- Type of wrap: The treated skin was covered with Hansamed plaster and fixed with an elastic adhesive bandage (Fixomull-Strech adhesive non-woven material, Beiersdorf No. 1524).

REMOVAL OF TEST SUBSTANCE
- Washing: Residual test substance was removed with water.
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
1, 24, 48 and 72 h and 7 days

SCORING SYSTEM:
- Method of calculation: Draize scoring system

Irritation parameter:

erythema score

Basis:

mean

Remarks:

of all 3 animals

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks:

within 7 days

Irritation parameter:

edema score

Basis:

mean

Remarks:

of all 3 animals

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks:

within 7 days

Irritant / corrosive response data:

All 3 animals showed edema and erythema scores of 3 at the 1-h reading time point, which resulted in an edema and erythema score of 4 at the 24-, 48- and 72-h and at the 7-day reading time point. In addition, the skin of all 3 rabbits displayed necrotic changes after 24 h.

Table 1: Summary of results

Observation time	Rabbit no.
	1		2		3
	Erythema	Edema	Erythema	Edema	Erythema	Edema
1 h	3	3	3	3	3	3
24 h	4	4	4	4	4	4
48 h	4	4	4	4	4	4
72 h	4	4	4	4	4	4
Mean value 24 + 48 + 72 h	4,00	4,00	4,00	4,00	4,00	4,00

Interpretation of results:

other: Skin Corr 1A, H314 according to Regulation (EC) No. 1272/2008

Conclusions:

CLP: Skin Corr 1A, H314

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted May 1981

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Interfauna UK Ltd. (breeder)
- Weight at study initiation: 3.0, 3.1 and 3.6 kg, respectively
- Housing: The rabbits were individually housed in single cages (wire cages type III-high). Below the cages excrement trays with low-dust wood granulate type S 8/15 (Ssniff, Soest, Germany) were located.
- Diet: Standard diet "Ssniff K 4" (supplied by Versuchstierdiäten GmbH, Soest, Germany), approximately 100 - 120 g per animal and day
- Water: Tap water, ad libitum
- Acclimation period: at least 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 2
- Humidity (%): Approximately 50
- Air changes (per hr): Approximately 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 08 Mar 1988 To: 15 Mar 1988

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1 mL

Duration of treatment / exposure:

24 h

Observation period (in vivo):

7 days
Reading time points: 1, 24, 48 and 72 h and 7 days

Number of animals or in vitro replicates:

3 males

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: The treated eye was rinsed with pysiological sodium chloride solution.
- Time after start of exposure: 24 h

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: 1% fluorescein solution and ultraviolet light

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of all 3 rabbits

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

not reversible

Remarks:

within 7 days

Irritation parameter:

cornea opacity score

Basis:

animal: #1 and #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Remarks:

within 7 days

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not reversible

Remarks:

within 7 days

Irritation parameter:

iris score

Basis:

mean

Remarks:

of all 3 rabbits

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

not reversible

Remarks:

within 7 days

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

of all 3 rabbits

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

not reversible

Remarks:

within 7 days

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of all 3 rabbits

Time point:

24/48/72 h

Score:

1.78

Max. score:

4

Reversibility:

not reversible

Remarks:

within 7 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Remarks:

within 7 days

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.3

Max. score:

4

Reversibility:

not reversible

Remarks:

within 7 days

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not reversible

Remarks:

within 7 days

Irritant / corrosive response data:

Animal #1 and #2 showed a cornea opacity score of 2 at the 1-, 24-, 48- and 72-h reading time point, which increased at the 7-day reading time point (score of 3). Animal #3 showed a cornea opacity score of 1 at all reading time points. The iris score was 1 and the conjunctivae score was 2 for all 3 rabbits at all reading time points. A slight swelling (chemosis score of 1) was determined in rabbit #1 at the 1-h and 7-day reading time point, which enhanced to a distinct swelling (score of 2) at the 24-, 48- and 72-h reading time point. A slight swelling was also observed at the 1-h reading time point in rabbit #2, which resulted in a distinct swelling (score of 2) at the 24- and 48-h reading time point in a score of 3 at the 72-h reading time point. This effect was not reversible within 7 days (score 2). Rabbit #3 showed a chemosis score of 1 at all reading time points.
The mucous membrane of the third eyelid of the animals was necrotized from the first evaluation. At the 7-day reading time point, 1/3 rabbits had a corneal pannus and hair loss at the upper and lower margin of the eyelid, respectively.

Table 1: Summary of Results

Rabbit #	Time [h]	conjunctivae		iris	cornea
		redness	swelling
1	1	2	1	1	2
	24	2	2	1	2
	48	2	2	1	2
	72	2	2	1	2
	average	2,0	2,0	1,0	2,0
2	1	2	1	1	2
	24	2	2	1	2
	48	2	2	1	2
	72	2	3	1	2
	average	2,0	2,3	1,0	2,0
3	1	2	1	1	1
	24	2	1	1	1
	48	2	1	1	1
	72	2	1	1	1
	average	2,0	1,0	1,0	1,0
	Time [h]	conjunctivae		iris	cornea
		redness	swelling
average score	1	2,00	1,00	1,00	1,67
	24	2,00	1,67	1,00	1,67
	48	2,00	1,67	1,00	1,67
	72	2,00	2,00	1,00	1,67
	24+48+72	2,00	1,78	1,00	1,67

Interpretation of results:

other: Eye Dam. 1, H318 according to Regulation (EC) No. 1272/2008

Conclusions:

CLP: Eye Dam. 1, H318

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

There are in vivo data available regarding skin and eye irritation / corrosion for sodium 2-biphenylate (CAS 132-27-4) in order to fulfil the standard data requirements defined in Regulation (EC) No 1907/2006, Annex VIII, 8.1 and 8.2.

Skin

The skin irritation potential of the registered substance was examined in an in vivo skin irritation test with 3 male NZW rabbits performed according to OECD Guideline 404 and in compliance with GLP (Bayer AG, 1988). A dose of 0.5 g of the test substance was applied on the dorsal area of the trunk under semiocclusive conditions for 4 h. Thereafter the test substance was removed with water. Skin reactions were assessed 1, 24, 48 and 72 hours, and 7 days after exposure according to the Draize scoring system. All 3 animals showed edema and erythema scores of 3 at the 1-h reading time point, which respectively increased up to 4 at the 24-, 48- and 72-h and at the 7-day reading time point. In addition, the skin of all 3 rabbits displayed necrotic changes after 24 h. Based on these results the test substance is considered to be corrosive.

A non-GLP conform in vivo skin irritation test according to Draize with the test substance was used as supporting information (Bayer AG, 1983). In this study, 0.5 g of the test substance was applied on the inner surface of one ear each of 2 NZW rabbits for 24 h under occlusive dressings. The untreated ear served as control. Skin reactions were assessed 24 and 72 hours, and 7 days after exposure according to Draize scoring system. Reddening of the skin was observed at the 24-h and 72-h reading time point in both animals with a score of 4, which persisted up to the end of the observation period of 7 days. Swelling of the skin with a score of 3 was determined in both rabbits at the 24-h and 72-h reading time point, which slightly decreased to a score of 2 at the end of the observation period. Based on these results the test substance is considered to be corrosive.

Information on skin irritation was available from a further study (Bayer AG, 1978). Due to methodical limitations, e. g. individual scores at different reading time points were not given, the study was taken into account for the evaluation but not included as separate record. In this study, the inner surface of one ear each of 2 NZW rabbits was treated with 500 mg test substance for 24 h. The test substance was removed with water and soap/vegetable oil and thereafter the animals were observed for 7 days. The test substance was reported to be highly irritant.

Overall, sodium 2-biphenylate (CAS 132-27-4) is considered to exhibit corrosive properties towards the skin.

 

Eye

The eye irritation/corrosion potential of the registered substance was examined in an in vivo eye irritation test in 3 male NZW rabbits according to OECD Guideline 405 and in compliance with GLP (Bayer AG, 1988). An amount of 0.1 mL of the test substance was instilled into the conjunctival sac of each rabbit, the untreated eye served as control. Observations were made 1, 24, 48 and 72 h, and 7 days after instillation according to Draize scoring system. 2/3 animals showed a cornea opacity score of 2 at the 1-, 24-, 48- and 72-h reading time point, which increased at the 7-day reading time point (score of 3). The other animal showed a cornea opacity score of 1 at all reading time points. The iris score was 1 and the conjunctivae score was 2 for all 3 rabbits at all reading time points. A slight swelling (chemosis score of 1) was determined in rabbit #1 at the 1-h and 7-day reading time point, which enhanced to a distinct swelling (score of 2) at the 24-, 48- and 72-h reading time point. A slight swelling was also observed at the 1-h reading time point in rabbit #2, which resulted in a distinct swelling (score of 2) at the 24- and 48-h reading time point in a score of 3 at the 72-h reading time point. This effect was not reversible within 7 days (score 2). Rabbit #3 showed a chemosis score of 1 at all reading time points. Moreover, the mucous membrane of the third eyelid of the animals was necrotized from the first evaluation. At the 7-day reading time point, 1/3 rabbits had a corneal pannus and hair loss at the upper and lower margin of the eyelid, respectively. Based on these results, the test substance is considered to result in severe eye damage.

A non-GLP in vivo eye irritation test performed in 2 NZW rabbits and according to Draize was used as supporting information (Bayer AG, 1983). In this study, 0.1 g of the test substance was instilled into the conjunctival sac of each rabbit for 4 h. Observations were made 1, 24, 48 and 72 hours, and 7 days after instillation. In animal #1 a cornea opacity score and an iris score of 1 was noted at all reading time points, only the effects on the iris were fully reversible at the 7-day reading time point. In animal #2 opacity of the cornea and effects on the iris were observed at the 1-h reading time point (score 1), which increased to a score of 2 at the 24-, 48-, 72-h reading time point. Both effects were not fully reversible up to the end of the observation period. Redness (scores 3) and swelling (score 2) were noted in both animals at the 1-, 24-, 48-, 72-h reading time point without being fully reversible at the 7-day reading time point. Based on these results, the test substance is considered to result in severe eye damage.

Information on eye irritation was available and taken into account from a further study (Bayer AG, 1978). Due to methodical limitations, the study was taken into account for the evaluation but not included as separate record. In this study, 50 mg test substance was instilled into the conjunctival sac each of 2 NZW rabbits. The animals were observed for 7 days (not further details given). The test substance was reported to be highly irritant and corrosive.

Overall, sodium 2-biphenylate (CAS 132-27-4) causes severe damages to the eye due to its corrosive properties.

Justification for classification or non-classification

The available data on skin and eye irritation / corrosion meet the criteria for classification according to Regulation (EC) No. 1272/2008, and therefore sodium 2-biphenylate (CAS 132-27-4) is classified as Skin Corr. 1, H314 and Eye Dam. 1, H318.