Biphenyl-4-ol

Endpoint summary

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP study, pre-dates OECD guidelines, limitations in reporting but acceptable design.

Justification for data waiving:

other:

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Principles of method if other than guideline:

Rabbit patch test
Based on: Code of Federal Regulations, Title 16, Section 1500.41

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: laboratory animal breeder W. Ostrop / Meerbusch
- Housing: The animals were housed individually in cages
- Weight: average weight of 2.8 kg
- Diet (e.g. ad libitum): provided with “Mümmel Z” feed (ssniff / Soest) ad libitum
- Water (e.g. ad libitum): water ad libitum

ENVIRONMENTAL CONDITIONS (Rearing conditions)
- Temperature (°C): 16 -18
- Humidity (%): 40 (relative humidity)
- Photoperiod (hrs dark / hrs light): 12 - hour light/dark cycle

- Other:
- Male rabbits.
- Habituation period 7 - 14 d.

Type of coverage:

occlusive

Preparation of test site:

other: left and right rump clipped and right side abraded

Vehicle:

other: oil used to form a paste

Controls:

not required

Amount / concentration applied:

500 mg of the substance mixed with oil to form a paste

Duration of treatment / exposure:

24 hour

Observation period:

Findings were recorded immediately (approx. 30 min) after removal of the patches (24-hour reading), and then 48h and 72h after the start of the test (48h after the first reading). The 48h reading does not appear in the report sheet. The control findings after 8d are not taken into account in calculating the irritation index.

Number of animals:

6

Details on study design:

Test execution: 24 hours before the start of the test, an area of flank skin measuring approx. 8 x 8 cm on either side of the rump of 6 rabbits with an average weight of 2.8 kg was shaved using electric hair clippers. The skin on the right flank was additionally scratched with the aid of a scarificator in the area where the test patches were to be applied. 2.5 x 2.5 cm patches of double - layered surgical gauze were coated with/soaked in 500 mg of the substance mixed with oil to form a paste and covered with inert, impermeable PVC film (5 x 5 cm).

The film with the patches underneath it was attached to the two test areas with the aid of skin - friendly adhesives strips (Leukoflex). Then the animal’s entire rump was wrapped in elastic bandage (EloflexR) for the duration of the 24 - hour exposure time. The animals were immobilised.

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 72 hours

Score:

1.1

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 72 hours

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 8 days

- See attached report for Results - individual scores - total score - PRIMARY SKIN IRRITATION in rabbits

- Primary irritation index: 13.0 / 4 = 3.3

- Classification: moderate irritant

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

The product is thus classified as a moderate irritant to the skin.

Executive summary:

- The aforementioned product yielded a primary irritation index of 3.3 in the primary skin irritation study conducted in accordance with Code of Federal Regulations, Title 16, Section 1500.41.

- The product is thus classified as a moderate irritant to the skin.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP study, pre-dates OECD guielines and some limitations in reporting but otherwise adequate for assessment.

Justification for data waiving:

other:

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

Based on: Code of Federal Regulations, Title 16, Section 1500.42

Deviations:

no

Remarks:

6 rabbit study

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: W. Ostrop / Meerbusch (Breeder)
- Weight at study initiation: average weight of 2.8 kg
- Housing: The animals were housed individually in cages
- Diet (e.g. ad libitum): provided with “Mümmel Z” feed (ssniff / Soest) ad libitum
- Water (e.g. ad libitum): water ad libitum

ENVIRONMENTAL CONDITIONS (Rearing conditions)
- Temperature (°C): 16 - 18
- Humidity (%): 40 (relative humidity)
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

- Other:
- Male rabbits used
- Habituation period 7- 14 d.

Vehicle:

unchanged (no vehicle)

Controls:

other: The animal’s left eye remained untreated as a control.

Amount / concentration applied:

single application of 100 µl bulk volume

Duration of treatment / exposure:

8 d (the eye was not rinsed after the application)

Observation period (in vivo):

8 d

Number of animals or in vitro replicates:

6

Details on study design:

Test execution: The test was performed on 6 pre-screened rabbits with an average weight of 2.8 kg by a single application of 100 µl bulk volume of the polymorphous substance in the conjunctival sack of each animal’s lower right eyelid. The lids were then gently held together for 1 sec. The eye was not rinsed after the application. The animal’s left eye remained untreated as a control.

The eyes were then examined with the aid of an ophthalmoscope.

The corneal result was verified after 8 d by the fluorescein test. (Instillation of one drop of fluorescein ophthalmic solution directly onto the cornea. After rinsing with physiological saline solution, corneal damage appears as a yellow-green area. UV light and cobalt blue filter)

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

0.17

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

0

Max. score:

4

- Findings were recorded 24, 48 and 72 h and 8 days after the start of the test. The control findings after 8 d are not included in the appraisal for the irritation index.

- See the attached report for the results of mucous membrane irritation in rabbits.

- Primary irritation index: 12/18 = 0.7

- Classification: non-irritant

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The product is thus classified as a non irritant to the eye.

Executive summary:

The aforementioned product yielded a primary irritation index of 0.7 in the primary mucous membrane irritation study conducted in accordance with Code of Federal Regulations, Title 16, Section 1500.42.

 

The product is thus classified as a non-irritant to the eye.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Skin irritation:

- Primary irritation index of 3.3 in the primary skin irritation study

- The product is classified as a moderate irritant to the skin according to Code of Federal Regulations, Title 16, Section 1500.41.

Justification for selection of eye irritation endpoint:
The product is classified as a non irritant to the eye according to Code of Federal Regulations, Title 16, Section 1500.42.

Effects on skin irritation/corrosion: moderately irritating