1,1'-Biphenyl, 4-methyl-4'-(3E)-3-penten-1-yl-

Endpoint summary

Description of key information

Skin irritation in vivo, OECD TG 404: not irritating (reference 7.3.1 -1)
Eye irritation in vivo, OECD TG 405: not irritating (reference 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:

2003-07-16 to 2003-07-25

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 (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: about 15 weeks
- Weight at study initiation: 3.08 kg (3.05 - 3.13 kg)
- Housing: individually
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 21 - 23 °C
- Humidity: 35 - 60 %
- Air changes: not specified
- Photoperiod:12 / 12 hrs dark / hrs light

The room temperature and relative atmospheric humidity in the animal room was transiently outside the target range of 16 to 22 °C and > 40 %. This deviation did not influence the integrity of the study.

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

not required

Amount / concentration applied:

0.5 g

Duration of treatment / exposure:

4 hours

Observation period:

24, 48, 72 hours after removal of patches

Number of animals:

3 female rabbits

Details on study design:

TEST SITE
- Area of exposure: back
- Type of wrap: The patch was fastened to the left side of the animal's back and kept in place by a self-adhesive fabric.

REMOVAL OF TEST SUBSTANCE
- Washing: wiping off dry
- Time after start of exposure: 4 h

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. Body weight was recorded on experimental days 1 and on experimental days 5 and 8.

SCORING SYSTEM: According to Draize

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Clinical findings
After a single application to the intact dorsal skin of rabbits, for a 4 hours period of exposure under semiocclusive conditions, no signs of irritation were observed in the treated areas.
No signs of clinical toxicity were detected.

Other effects:

Mortality
All animals survived the observation period.

Body weight
Body weight development of the treated rabbits was inconspicuous.

Table 1 Individual local findings

Animal No.		Local findings on day
		1	2	3	4	5	6	7	8
1	Erythema	0	0	0	0	0	0	0	0
	Edema	0	0	0	0	0	0		0
2	Erythema	0	0	0	0	0	0	0	0
	Edema	0	0	0	0	0	0	0	0
3	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 could be detected, thus the test material is not considered to be a skin irritant.

Executive summary:

The purpose of this assay was to identify the skin irritation/corrosion potential of the test item when applied to the intact skin of previously shaven rabbits for a 4 hours period under semiocclusive conditions. This study should provide a rational basis for risk assessment to the irritating potential of the test item in man.

To test for primary skin irritation, 0.5 g of 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 6 cm2 patches and applied to the intact skin of previously shaven rabbits for a 4 hours period under semiocclusive conditions. The study was started as an initial test with one animal and followed by the confirmatory test with 2 further animals. The first examination of the treated skin sites followed 1 hour after removal of the patches. Thereafter, examinations were performed daily for a further 7 days.

Under the conditions of the present study no signs of irritation were seen. The evaluation of the mean scores yields zero at all time points investigated.

In conclusion, no skin irritating potential could be detected, thus the test material is not considered a skin irritant.

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:

2006-09-05 to 2006-11-20

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 (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: about 37 weeks
- Weight at study initiation: 5.62 kg
- Housing: individually
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18 - 20 °C
- Humidity: 47 - 75 %
- Air changes: not specified
- Photoperiod: 12 / 12 hrs dark / hrs light

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.1 g

Observation period (in vivo):

1 hour after treatment, after 24, 48, and 72 hours, then daily up to day 8 of the experimental part.

Number of animals or in vitro replicates:

3 female rabbits

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: not done

SCORING SYSTEM: according to Draize

- Preparation: Before the application, the test material was ground in a mortar using a pestle.

- Administration and dose level: To ensure that only rabbits with normal eyes were included in the study, approximately 24 hours before treatment ophthalmological examinations were performed after instillation of a 0.15 % fluorescein solution (Dr. Thilo & Co.) using an ophthalmoscope according to Eisenhut (Basel). Animals with eye defects, injury or irritation were excluded. 0.1 g test material was instilled into the conjunctival sac of the left eye of each animal by gently pulling the lower lid away from the eyeball to form a cup into which the test material was placed. The right eye remained untreated and served as control. After instillation, the eyelids were closed for about 30 seconds.


- Observation for clinical symptoms
The rabbits were examined for eye irritation and for changes in behavior and general condition 1 hour after treatment, after 24, 48, and 72 hours, then daily up to day 8 of the experimental part. Eye changes were evaluated according to the DRAIZE- , OECD- and EEC recommendations.

- Body weight
Body weight was recorded on days 1, 5, and 8, of the experimental part.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

No signs of irritation were observed at the cornea or iris. One hour after treatment the conjunctivae showed only discharge (score 1). Thereafter no signs of irritation were observed.
The confirmatory test with two further animals showed no signs of irritation at the cornea or iris. One hour and 24 hours after treatment the conjunctivae showed redness (score 1) in two animals. Furthermore discharge (score 1) was seen in both animals one hour after treatment. Thereafter, no signs of irritation were observed.

Other effects:

- Clinical signs
No signs of clinical toxicity were detected.

- Mortality
All animals survived the observation period.

- Body weight
Body weight development of the treated rabbits was inconspicuous.

Table 1 Individual findings

Animal	Day		1	2	3	4	5	6	7	8
No.	Hour(s)		(1)	(24)	(48)	(72)
1	Cornea A		0	0	0	0	0	0	0	0
	B		0	0	0	0	0	0	0	0
	Iris A		0	0	0	0	0	0	0	0
	Conjunctivae A		1	1	0	0	0	0	0	0
	B		0	0	0	0	0	0	0	0
	C		1	0	0	0	0	0	0	0
2	Cornea A		0	0	0	0	0	0	0	0
	B		0	0	0	0	0	0	0	0
	Iris A		0	0	0	0	0	0	0	0
	Conjunctivae A		1	1	0	0	0	0	0	0
	B		0	0	0	0	0	0	0	0
	C		1	0	0	0	0	0	0	0
3	Cornea A		0	0	0	0	0	0	0	0
	B		0	0	0	0	0	0	0	0
	Iris A		0	0	0	0	0	0	0	0
	Conjunctivae A		0	0	0	0	0	0	0	0
	B		0	0	0	0	0	0	0	0
	C		1	0	0	0	0	0	0	0

Interpretation of results:

GHS criteria not met

Conclusions:

No eye irritating potential could be detected, thus the test material is considered to be not an eye irritant.

Executive summary:

The purpose of this primary eye irritation assay was to provide information on possible health hazards in case of acute eye contact with a test material and serve as a a rational basis for risk assessment to the eye irritating potential of the test item in man. To test for eye irritation a test according to the OECD-Guidelines for Testing of Chemicals No. 405, the annex to Directive 92/69 EEC, and the recommendations of DRAIZE (1959) was performed. No signs of irritation were observed at the cornea or iris. One hour and 24 hours after treatment, the conjunctivae showed redness (score I) in two animals. Furthermore, discharge (score I) was seen one hour after treatment. Thereafter no signs of irritation were observed. The untreated eyes were unchanged. No eye irritating potential could be detected, thus the test material is considered to not be an eye irritant.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation in vivo (reference 7.3.1.-1)

In a primary dermal irritation study, young adult New Zealand White rabbits (3 females) were dermally exposed to 0.5 g of moistened test material for 4 hours under semiocclusive conditions. Animals then were observed 1, 24, 48 and 72 hours, as well as 7 days after treatment. No erythema and no edema irritation were observed within the course of the observation period. The cumulative irritation score was 0.00 based on the DRAIZE scheme indicating no irritant potential. In this study, the test material was not a dermal irritant.

Eye irritation in vivo (reference 7.3.2 -1)

In a primary eye irritation study 0.1 g of the test material was instilled into the conjunctival sac of the left eye of young adult New Zealand White rabbits (3 females). Animals then were observed 1, 24, 48 and 72 hours, as well as 7 days after treatment.

No signs of irritation were observed at the cornea or iris. One hour and 24 hours after treatment, the conjunctivae showed redness (score I) in two animals. Furthermore, discharge (score I) was seen one hour after treatment. Thereafter no signs of irritation were observed. The untreated eyes were unchanged. In this study, the test material was not an eye irritant.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data the test item does not require classifcation as skin or eye irritant according to Regulation (EC) No 1272/2008 (CLP), as amended for the twelfth time in Regulation (EU) 2019/521.