cyclohexadecanone

Endpoint summary

Description of key information

Skin irritation/corrosion (OECD 404): not irritating

Eye irritation (OECD 405): not irritating

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:

12 - 16 Feb 2001

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:

(1992)

Deviations:

yes

Remarks:

occlusive instead of semi-occlusive dressing; 4 test substance concentrations were tested; 4 rabbits instead of 3 rabbits were used

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

(Commission Directive 92/69/EEC)

Deviations:

yes

Remarks:

4 substance concentrations were tested

GLP compliance:

yes (incl. QA statement)

Remarks:

MINISTERIUM FÜR RAUMORDNUNG UND UMWELT DES LANDES SACHSEN-ANHALT, Germany

Species:

rabbit

Strain:

New Zealand White

Remarks:

SPF Crl:NZW

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2465 - 2720 g
- Housing: in stainless steel cages (50 x 55 x 40 cm) with bottom grid of oval steel and with tub for faeces, granulated soft wood bedding
- Diet: ALTROMIN 2123 standard diet for rabbits (ALTROMIN, Lage/Lippe, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.5 - 22.5
- Humidity (%): 30 - 40
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

other: mixture of ethanol/diethylphthalate 1:1 (v/v)

Remarks:

(used for moistening of the test substance)

Controls:

yes, concurrent no treatment

yes, concurrent vehicle

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 g
- Concentrations: 10, 25, 50% [w/v], 100% (undiluted)

VEHICLE
- Amount applied: 0.5 mL
- Lot/batch no.: S31826035 (Diethylphthalate), 46047117 (Ethanol)

Duration of treatment / exposure:

4 h

Observation period:

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

Number of animals:

4 males

Details on study design:

TEST SITE
- Area of exposure: three pairs of areas of approx. 4 x 5 cm at the dorsal area of the trunk so that one of each pair lies on each side of the spine
- Type of wrap if used: one layer of gauze patch (two layers of gauze patch for test substance solutions and for the vehicle) covered with aluminium foil, which was held in contact with the skin by occlusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing: The application area was rinsed with a mixture of ethanol/diethylphthalate 1:1 (v/v) without altering the integrity of the epidermis.
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
1, 24, 48 and 72 h

SCORING SYSTEM:
- Method of calculation: Draize scoring system

Irritation parameter:

erythema score

Basis:

mean

Remarks:

of 4 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

mean

Remarks:

of 4 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritant / corrosive response data:

All skin areas, treated with the moistened original test item or with solutions of the test item in the vehicle (50, 25 and 10 % [w/v]) and also the control skin areas (untreated and treated with vehicle), did not show any alterations at any observation time.

No animal died during the course of investigation and no clinical signs were observed. Necropsy was not carried out, because no clinical signs were observed.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

Under the conditions of the Acute Dermal Irritation/Corrosion Test in rabbits the test substance does not possess any skin irritating potential.

Executive summary:

The skin irritation potential of the test substance was determined by an in vivo skin irritation test (2001) in albino rabbits according to OECD Guideline 404 and in compliance with GLP. 0.5 g of the crushed test substance moistened with ethanol/diethylphthalate 1:1 (v/v) and 0.5 mL of the test substance in dilutions of 10, 25 and 50% (w/v) in ethanol/diethylphthalate 1:1 (v/v) were applied to the skin of four rabbits under occlusive conditions for 4 hours. After the exposure period the patch was removed and the administration areas were rinsed with ethanol/diethylphthalate 1:1 (v/v) . Scores were taken 1, 24, 48 and 72 hours after patch removal using the Draize scoring system. All skin areas, treated with the undiluted or with one of the three solutions of the test substances, did not show any alterations at any observation time point. The overall mean score after 24, 48 and 72 hours for erythema and edema of all animals was 0. Based on the results, the undiluted test substance as well as the 10, 25 and 50% (w/v) solutions were not irritating to the skin under the conditions of the test.

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:

27 Feb - 03 Mar 2001

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:

(1987)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

(Commission Directive 92/69/EEC)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

MINISTERIUM FÜR RAUMORDNUNG UND UMWELT DES LANDES SACHSEN-ANHALT, Germany

Species:

rabbit

Strain:

New Zealand White

Remarks:

SPF Crl:NZW

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2955 - 3292 g
- Housing: in stainless steel cages (50 x 55 x 40 cm) with bottom grid of oval steel and with tub for faeces, granulated soft wood bedding
- Diet: ALTROMIN 2123 standard diet for rabbits (ALTROMIN, Lage/Lippe, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: 3 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 - 22.5
- Humidity (%): 30 - 40
- Photoperiod (hrs dark / hrs light): 12 / 12

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 g
The test substance was crushed with a pestle and mortar to a fine dust before application.

Duration of treatment / exposure:

24 hours
single application without washing

Observation period (in vivo):

72 hours
Reading time points: 1, 24, 48 and 72 hours

Number of animals or in vitro replicates:

4 males

Details on study design:

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: hand-slit lamp

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of 4 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

mean

Remarks:

of 4 animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritation parameter:

conjunctivae score

Basis:

animal: #1, #3, #4

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

Max. score:

3

Reversibility:

other: not applicable

Irritation parameter:

chemosis score

Basis:

animal: #1, #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal: #2, #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritant / corrosive response data:

A slight redness of the conjunctivae (score 1) of the treated eyes was observed in all four animals on the day of instillation and in three animals until 24 hours after exposure. A slight swelling of the conjunctivae (score 1) was observed in all four animals on the day of exposure and in two animals until 24 hours after exposure. The cornea and iris were not affected. 48 hours after exposure no signs of irritation were observed. The control eyes of the animals showed no alterations at any observation time.

Table 1. Results of the eye irritation study

Alteration	Animal No.	Time (h)
		1	24	48	72	mean 24/48/72	Overall mean (24/48/72)/ 4 animals
Cornea	1	0	0	0	0	0	0
	2	0	0	0	0	0
	3	0	0	0	0	0
	4	0	0	0	0	0
Iris	1	0	0	0	0	0	0
	2	0	0	0	0	0
	3	0	0	0	0	0
	4	0	0	0	0	0
Conjunctivae Redness	1	1	1	0	0	0.33	0.25
	2	1	0	0	0	0
	3	1	1	0	0	0.33
	4	1	1	0	0	0.33
Conjunctivae Chemosis	1	1	1	0	0	0.33	0.17
	2	1	0	0	0	0
	3	1	1	0	0	0.33
	4	1	0	0	0	0

No animal died during and no clinical signs were observed during the study.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

Under the conditions of this eye irritation study in rabbits the test substance was not irritating to the eye.

Executive summary:

The eye irritation potential of the test substance was investigated in four albino rabbits according to OECD Guideline 405 (1987) and in compliance with GLP. 0.1 g of the test substance, which was crushed to a fine dust, was placed in one eye of each animal. The other eye remained untreated and served as control. The eyes were examined and scored according to the Draize scoring system 1, 24, 48 and 72 hours after application. A slight redness of the conjunctivae (score 1) of the treated eyes was observed in all four animals on the day of instillation and in three animals until 24 hours alter instillation. A slight swelling of the conjunctivae (score 1) was observed in all four animals on the day of instillation and in two animals until 24 hours after instillation.The cornea and iris were not affected. The mean scores at 24/48/72 of all 4 animals for redness, chemosis, cornea and iris was 0.25, 0.17, 0 and 0, respectively. Based on the results of this study, the test substance was not irritating to the eyes under the conditions of the test.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin

The skin irritation potential of the test substance was determined by an in vivo skin irritation test (2001) in albino rabbits according to OECD Guideline 404 and in compliance with GLP. 0.5 g of the crushed test substance moistened with ethanol/diethylphthalate 1:1 (v/v) and 0.5 mL of the test substance in dilutions of 10, 25 and 50% (w/v) in ethanol/diethylphthalate 1:1 (v/v) were applied to the skin of four rabbits under occlusive conditions for 4 hours. After the exposure period the patch was removed and the administration areas were rinsed with ethanol/diethylphthalate 1:1 (v/v) . Scores were taken 1, 24, 48 and 72 hours after patch removal using the Draize scoring system. All skin areas, treated with the undiluted or with one of the three solutions of the test substances, did not show any alterations at any observation time point. The overall mean score after 24, 48 and 72 hours for erythema and edema of all animals was 0. Based on the results, the undiluted test substance as well as the 10, 25 and 50% (w/v) solutions were not irritating to the skin under the conditions of the test.

Eye

The eye irritation potential of the test substance was investigated in four albino rabbits according to OECD Guideline 405 (1987) and in compliance with GLP. 0.1 g of the test substance, which was crushed to a fine dust, was placed in one eye of each animal. The other eye remained untreated and served as control. The eyes were examined and scored according to the Draize scoring system 1, 24, 48 and 72 hours after application. A slight redness of the conjunctivae (score 1) of the treated eyes was observed in all four animals on the day of instillation and in three animals until 24 hours alter instillation. A slight swelling of the conjunctivae (score 1) was observed in all four animals on the day of instillation and in two animals until 24 hours after instillation.The cornea and iris were not affected. The mean scores at 24/48/72 of all 4 animals for redness, chemosis, cornea and iris was 0.25, 0.17, 0 and 0, respectively. Based on the results of this study, the test substance was not irritating to the eyes under the conditions of the test.

Justification for classification or non-classification

The available data on skin and eye irritation of the test substance do not meet the criteria for classification according to Regulation (EC) No 1272/2008, and are therefore conclusive but not sufficient for classification.