4-trans-Pentyl-[1,1-bicyclohexyl]-4-on

Endpoint summary

Description of key information

Skin irritation/corrosion: The test material produced corrosive effects on contaminated skin (reference 7.3.1-1).

Eye irritation: In the primary eye irritation test no irritation of the cornea and iris was observed. The test item is not considered to be irritative (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:

17-04-1991 to 09-07-1991

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:

OECD 1981

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Remarks:

Iva: NZW

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: SAVO-Ivanovas, Kisslegg
- Age at study initiation: 17 - 19 weeks
- Mean weight at study initiation: 3.33 (3.25 - 3.40) kg
- Housing: cages type KK 017 (floor area: 75 x 54.5 = 4087 cm2, height: 38 cm; manufacturer: Hulskamp) on metal grids
- Diet: Altromin Standard Diet TPFV 2113, pellets from an automatic drinking device ad libitum
- Water: acidified, fully demineralized water from an automatic drinking device ad libitum
- Acclimation period: more than 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 43 - 64
- Photoperiod (hrs dark / hrs light): daylight

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

water

Remarks:

the test material was moistened with aqua pro injectione

Controls:

no

Amount / concentration applied:

0.5 g test item

Duration of treatment / exposure:

4 hours

Observation period:

14 days

Number of animals:

3 animals - 1 male and 2 female

Details on study design:

TEST SITE
- Area of exposure: back side
- Type of wrap: polyethylene foil kept in place by a leather sleeve

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

OBSERVATION TIME POINTS
1 hour after removal of the patches and afterwards daily for 14 days

SCORING SYSTEM: Draize and OECD 404

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

left side

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

right side

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

left side

Time point:

24/48/72 h

Score:

2.33

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

right side

Time point:

24/48/72 h

Score:

2.67

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

left side

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

right side

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

left side

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

right side

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

left side

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

right side

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

left side

Time point:

24/48/72 h

Score:

2.33

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

right side

Time point:

24/48/72 h

Score:

2.67

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

1.9

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

1.97

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritant / corrosive response data:

Skin alterations:
Single application of 0.5 g test item to the intact dorsal skin of rabbits, after a 4 hour period of exposure under occlusive conditions, led to severe skin irritation. Erythema (score 1 or 2) from day 1 until day 6 of the study was seen. Edema (score 1 - 3) was observed from day 1 up to day 8 of the study. Erythema and edema were followed by necrosis, large scales (as indicated by score 4), and small scales, which are indicative of corrosivity of the test material.
The cumulative mean scores for erythema and edema were:
Day 1 : 1.9
Day 2 : 2.2
Day 3 : 1.8
Though the cumulative scores for erythema and edema for days 1, 2, and 3 were not indicative of serious effects attention must be given to the corrosive effects.

Other effects:

Signs of systemic toxicity, body weight, mortality:
No signs of systemic toxicity were detected. The body weight development corresponded to that of untreated rabbits of the same age. All rabbits survived the 15 day observation period.

Skin irritation results

Animal No.	Sex	back site		Local findings (study day)
				1	2	3	4	5	6	7	8	9	10	12	14	15
91012	male	left	Erythema	2	2	2	2	2	4	4	4	0	0	0	0	0
			Edema	2	3	2	2	2	0	0	0	0	0	0	0	0
			Others						G	G	0	S	S	S	S	S
		right	Erythema	2	2	2	2	2	4	4	4	4	4	4	0	0
			Edema	2	3	3	3	3	0	0	0	0	0	0	0	0
			Others						G	G	G	G	G	G	S	S
91023	female	left	Erythema	2	2	1	1	1	1	4	4	0	0	0	0	0
			Edema	2	1	1	1	1	1	0	0	0	0	0	0	0
			Others							G	G	S	S	S	S	S
		right	Erythema	2	2	1	1	1	1	4	4	0	0	0	0	0
			Edema	1	1	0	0	0	1	0	0	0	0	0	0	0
			Others							G	0	S	S	S	S	S
91015	female	left	Erythema	2	2	2	2	2	2	4	4	4	4	4	4	4
			Edema	2	3	2	2	2	2	2	2	0	0	0	0	0
			Others							N	N	N	N	N	GS	0G
		right	Erythema	2	2	2	4	4	4	4	4	4	4	4	4	4
			Edema	2	3	3	3	3	3	3	3	0	0	0	0	0
			Others				N	N	N	N	N	N	N	N	NGS	GS
Mean values			Erythema	2.0	2.0	1.7
			Edema	1.8	2.3	1.8
Cumulative mean values				1.9	2.2	1.8

Body weight development

Body weight development in kg
Administration	Animal No.	Sex		Study day					Difference day 1 to 8
				1	5	8	11	15
Skin	91012	m		3.40	3.45	3.55	3.55	3.66	+0.26
	91023	f		3.34	3.34	3.38	3.42	3.46	+0.12
	91015	f		3.25	3.23	3.24	3.24	3.23	-0.02
Mean values				3.33	3.34	3.39	3.40	3.45	+0.12

Interpretation of results:

Category 1 (corrosive) based on GHS criteria

Conclusions:

The test material produced corrosive effects on contaminated skin.

Executive summary:

The primary skin irritation potential of the test item was investigated by topical application of 0.5 g to skin of the back and sides of each of three young adult New Zealand White rabbits in a OECD 404 study. The duration of treatment was four hours. The scoring of skin reactions was performed 1 hour after removal of the dressing and afterwards daily for 14 days. The scores of each animal at the following reading times (24, 48, 72 hours) were used in calculating the respective mean values for each type of lesion. In the primary skin irritation test slight and well-defined erythema (score 1 or 2) and edema were observed on the first days after application, and were followed by necrosis, large scales, and small scales later on, indicating corrosivity of the test material. Though the cumulative mean scores for erythema and edema for days 1, 2, and 3 were not indicative of serious effects, the test material produced corrosive effects on skin contaminated under conditions comparable to those of this test.

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

Study period:

17-04-1991 to 09-07-1991

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:

OECD 1981, updated Guideline adopted February 24, 1987

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Remarks:

Iva: NZW

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: SAVO-Ivanovas, Kisslegg
- Age at study initiation: 17 - 19 weeks
- Mean weight at study initiation: 3.40 (3.25 - 3.49) kg
- Housing: cages type KK 017 (floor area: 75 x 54.5 = 4087 cm2, height: 38 cm; manufacturer: Hulskamp) on metal grids
- Diet: Altromin Standard Diet TPFV 2113, pellets from an automatic drinking device ad libitum
- Water: acidified, fully demineralized water from an automatic drinking device ad libitum
- Acclimation period: more than 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 43 - 64
- Photoperiod (hrs dark / hrs light): daylight

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1 g test item

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

3 animals - 1 male and 2 females

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: not performed

SCORING SYSTEM: OECD 405

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

24/48/72 h

Score:

0.22

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.11

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

other: discharge

Basis:

mean

Time point:

24/48/72 h

Score:

0.55

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no 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:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

other: discharge

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

not fully reversible within: 48 hours

Irritation parameter:

other: discharge

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

other: discharge

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritant / corrosive response data:

Ocular alterations:
After single instillation of 0.1 g test item into the conjunctival sac of the left eye, without rinsing, no irritation of the cornea and iris was observed. Examination of the conjunctivae revealed redness (score 1), chemosis in 1 animal (score 1), and discharge (score 1 - 2) at the first reading. Later on no irritation was seen. According to these results the test material is not regarded as an irritant.

Other effects:

Signs of systemic toxicity, body weight, mortality:
No signs of systemic toxicity were seen. The body weight development corresponded to that of untreated rabbits of the same age. All animals survived the 8 day observation period.

Eye irritation results

		Animal No.	Sex	Local findings (study day)
				1	2	3	4	5	6	7	8
I Cornea	A	91003	m	0	0	0	0	0	0	0	0
		91015	f	0	0	0	0	0	0	0	0
		91021	f	0	0	0	0	0	0	0	0
	B	91003	m	0	0	0	0	0	0	0	0
		91015	f	0	0	0	0	0	0	0	0
		91021	f	0	0	0	0	0	0	0	0
II Iris	A	91003	m	0	0	0	0	0	0	0	0
		91015	f	0	0	0	0	0	0	0	0
		91021	f	0	0	0	0	0	0	0	0
III Conjunctivae	A	91003	m	1	0	0	0	0	0	0	0
		91015	f	0	0	0	0	0	0	0	0
		91021	f	1	0	0	0	0	0	0	0
	B	91003	m	1	0	0	0	0	0	0	0
		91015	f	0	0	0	0	0	0	0	0
		91021	f	0	0	0	0	0	0	0	0
Discharge		91003	m	2	0	0	0	0	0	0	0
		91015	f	1	0	0	0	0	0	0	0
		91021	f	2	0	0	0	0	0	0	0

Cornea A: rating according to OECD 405, B: rating according to Draize method, Iris A: rating according to OECD 405, Conjunctivae A: redness rating according to OECD 405, B: chemosis rating according to OECD 405

Body weight development

Body weight development in kg
Administration	Animal No.	Sex	Study day			Difference day 1 to 8
			1	5	8
Eye	91003	m	3.45	3.51	3.49	+0.04
	91015	f	3.25	3.27	3.32	+0.07
	91021	f	3.49	3.58	3.61	+0.12
Mean values			3.40	3.45	3.47	+0.07

Interpretation of results:

GHS criteria not met

Conclusions:

In the primary eye irritation test no irritation of the cornea and iris was observed. The test item is not considered to be irritative.

Executive summary:

The primary irritation potential of the test item was investigated by instillation of 0.1 g into conjunctival sac of the left eye of each of three young adult New Zealand White rabbits in an OECD 405 study. The right eye remained untreated and served as control. After instillation the eyelids were closed for about 30 seconds. Rinsing of the eyes was not performed. Scoring of irritation effects was performed daily after application for 8 days. After single instillation of 0.1 g test item into the conjunctival sac of the left eye, without rinsing, no irritation of the cornea and iris was observed. Examination of the conjunctivae revealed redness (score 1), chemosis in 1 animal (score 1), and discharge (score 1 - 2) at the first reading. Later on no irritation was seen. According to these results the test material is not regarded as an irritant. No signs of systemic toxicity were seen. The body weight development corresponded to that of untreated rabbits of the same age. All animals survived the 8 day observation period. The average irritation values for conjunctival redness, conjunctival swelling, iritis and clouding of the cornea were 0 in each case. The test item was thus evaluated as not irritating to the eye. No staining of the cornea, sclera or conjunctivae of the treated eyes by the test item was observed. No corrosion was observed at any of the measuring intervals. Based upon the above results, the test item is considered to not be severely irritating to the eye.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

OECD 404

The primary skin irritation potential of the test item was investigated by topical application of 0.5 g to skin of the back and sides of each of three young adult New Zealand White rabbits in a OECD 404 study (reference 7.3.1-1). The duration of treatment was four hours. The scoring of skin reactions was performed 1 hour after removal of the dressing and afterwards daily for 14 days. The scores of each animal at the following reading times (24, 48, 72 hours) were used in calculating the respective mean values for each type of lesion. In the primary skin irritation test slight and well-defined erythema (score 1 or 2) and edema were observed on the first days after application, and were followed by necrosis, large scales, and small scales later on, indicating corrosivity of the test material. Though the cumulative mean scores for erythema and edema for days 1, 2, and 3 were not indicative of serious effects, the test material produced corrosive effects on skin contaminated under conditions comparable to those of this test.

OECD 405

The primary irritation potential of the test item was investigated by instillation of 0.1 g into conjunctival sac of the left eye of each of three young adult New Zealand White rabbits in an OECD 405 study (reference 7.3.2-1). The right eye remained untreated and served as control. After instillation the eyelids were closed for about 30 seconds. Rinsing of the eyes was not performed. Scoring of irritation effects was performed daily after application for 8 days. After single instillation of 0.1 g test item into the conjunctival sac of the left eye, without rinsing, no irritation of the cornea and iris was observed. Examination of the conjunctivae revealed redness (score 1), chemosis in 1 animal (score 1), and discharge (score 1 - 2) at the first reading. Later on no irritation was seen. According to these results the test material is not regarded as an irritant. No signs of systemic toxicity were seen. The body weight development corresponded to that of untreated rabbits of the same age. All animals survived the 8 day observation period. The average irritation values for conjunctival redness, conjunctival swelling, iritis and clouding of the cornea were 0 in each case. The test item was thus evaluated as not irritating to the eye. No staining of the cornea, sclera or conjunctivae of the treated eyes by the test item was observed. No corrosion was observed at any of the measuring intervals. Based upon the above results, the test item is considered to not be severely irritating to the eye.

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. As a result the substance is classified as corrosive to skin Cat 1 (H314) under Regulation (EC) No 1272/2008, as amended for the twelfth time in Regulation (EU) 2019/521. The substance is not considered to be classified for eye damage/irritation under Regulation (EC) No 1272/2008, as amended for the twelfth time in Regulation (EU) 2019/521.