4-propylcyclohexanone

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1990-02-12 to 1990-03-05

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1990-02-12 to 1990-03-05

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1987

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: SAVO-Ivanovas, Kisslegg
- Age at study initiation: 15 - 16 weeks
- Weight at study initiation (mean): 2.75 (2.70 - 2.78) kg
- Housing: All rabbits were housed in an air-conditioned room of 39 m² in the rabbit experimental station with daylight. They were kept separately in cages type KK 017 (floor area: 75 x 54.5 = 4087 cm2, height: 38 cm; manufacturer: Hulskamp) on metal grids. The paper underneath the cages was changed three times a week. The cages were machine-cleaned before the start of the study.
- Diet: ad libitum, Altromin Standard Diet TPF 2113
- Water: ad libitum, acidified, fully demineralized water from an automatic drinking device
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 25 °C
- Humidity (%): 38 to 58%

To ensure that only rabbits without ocular abnormalities were included in the study, 24 hours before treatment ophthalmological examinations were performed after instillation of 0.15 % fluorescein solution (Dr. Thilo & Co.) using an ophthalmoscope after Eisenhut (Basel).

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 mL

Observation period (in vivo):

8 days

Number of animals or in vitro replicates:

3 rabbits (1 male and 2 females)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: no

OBSERVATION TIME POINTS:
The rabbits were investigated for eye irritation and for changes in behavior and general condition 1 hour after treatment and then daily for a period of further 7 days.
All rabbits were weighed before the start of the study and on days 5 and 8.

SCORING SYSTEM:
- Method of calculation: Local changes of the eye were evaluated according to the recommendations of the OECD

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

Remarks on result:

other: At one reading (day 4) congestion of the iris (value 1) was observed.

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

other: discharge

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.7

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

other: discharge

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

other: discharge

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.6

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.6

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.6

Max. score:

3

Reversibility:

fully reversible within: 4 days

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.6

Max. score:

3

Reversibility:

fully reversible within: 5 days

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Other effects:

- Ophthalmoscopic findings:
After single instillation of 0.1 mL test item, into the conjunctival sac of the left eye, without rinsing, no irritation of the cornea was observed. At one reading (animal No. 90010, day 4) congestion of the iris (value 1) was observed.
Examination of the conjunctivae revealed chemosis and discharge at the first reading followed by redness on day 2. All irritation symptoms had disappeared on day 5 without any residues.

- Other observations:
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.

Interpretation of results:

GHS criteria not met

Conclusions:

In this primary eye iritation test according to OECD TG 405, the test substance is not considered to be irritating to the eyes and does not requiring classification according to (EC) No 1272/2008

Executive summary:

A study was performed according to OECD 405 under GLP conditions. To test for primary eye irritation the test item was instilled into the conjunctival sac of rabbits (left eye). The right eye served as untreated control. The first examination of the eyes was performed 1 hour after instillation. Then examinations were performed daily for 7 days. In the primary eye irritation test no irritation of the cornea was observed (all animals, mean score (24/48/72 h) = 0). Congestion of the iris (score 1) was seen at one reading (day 4). The mean iris score (24/48/72 h) was 0 for all animals. The conjunctivae showed chemosis and discharge at the first reading followed by redness on day 2. The mean chemosis scores (24/48/72 h) for animal 1, 2 and 3 were 0.3, 0.6 and 0.3, respectively. The mean conjunctivae scores (24/48/72 h) for animal 1, 2 and 3 were 0.6, 0.6 and 0.3, respectively. All irritation symptoms had disappeared on day 5 without any residues. According to the results of this study, the test substance is not considered to be irritating to the eyes and does not requiring classification according to (EC) No 1272/2008 (reference 7.3.2-1).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1981

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4-propylcyclohexanone

EC Number:

406-810-4

EC Name:

4-propylcyclohexanone

Cas Number:

40649-36-3

Molecular formula:

C9H16O

IUPAC Name:

4-propylcyclohexan-1-one

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: SAVO-Ivanovas, Kisslegg
- Age at study initiation: 15 - 16 weeks
- Weight at study initiation (mean): 2.71 (2.56 - 2.87) kg
- Housing: All rabbits were housed in an air-conditioned room of 39 m² in the rabbit experimental station with daylight. They were kept separately in cages type KK 017 (floor area: 75 x 54.5 = 4087 cm2, height: 38 cm; manufacturer: Hulskamp) on metal grids. The paper underneath the cages was changed three times a week. The cages were machine-cleaned before the start of the study.
- Diet: ad libitum, Altromin Standard Diet TPF 2113
- Water: ad libitum, acidified, fully demineralized water from an automatic drinking device
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 25 °C
- Humidity (%): 38 to 58%

Test system

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

22 days

Number of animals:

3 rabbits (1 male and 2 females)

Details on study design:

TEST SITE
- Area of exposure: 24 hours before the start of the study the backs and flanks of the animals were cautiously shaved with an electric clipper (shear head: 1/10mm), so that the skin stayed intact.
- Type of wrap: The application sites were wrapped with polyethylene foil which was kept in place by leather sleeve.

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: After 4 hours of occlusive exposure the patches were removed and any test material left was wiped off.

OBSERVATION TIME POINTS
The rabbits were investigated for skin alterations, behavior, and general condition 1 hour after removal of the patches, and then daily for a period of further 21 days .
All rabbits were weighed before start of the study and on days 5, 8, 11, 15 and 22.

SCORING SYSTEM:
- Method of calculation: Skin changes at the application site were evaluated according to the DRAIZE and OECD recommendations.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.34

Max. score:

4

Reversibility:

not reversible

Remarks:

from day 5 onwards: formation of scabs, scales, necrosis

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.5

Max. score:

4

Reversibility:

not reversible

Remarks:

from day 5 onwards: scales, large scales, leathery skin

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

not reversible

Remarks:

from day 5 onwards: formation of scabs, scales, large scales, necrosis

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not reversible

Remarks:

from day 5 onwards: formation of scabs, scales, necrosis

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.5

Max. score:

4

Reversibility:

not reversible

Remarks:

from day 5 onwards: scales, large scales, leathery skin

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Remarks:

from day 5 onwards: formation of scabs, scales, large scales, necrosis

Irritant / corrosive response data:

- Other adverse local effects:
Single application of 0.5 mL of the test item, to the intact dorsal skin of rabbits, after a 4 hour period of exposure under occlusive conditions, led to severe irritation in the skin irritation test. Beginning at the first reading up to day 8 of the study, erythema and edema were observed. They were followed by other irritation symptoms such as formation of large scales, leathery skin, scabs, and necrosis from day 5 on According to the results of this study the test material has to be regarded as a severe irritant for the skin.

- Other adverse systemic effects:
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 22 day observation period.

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

Under the conditions of the present study, the test substances is considered to be irritating to the skin and has to be classified as a skin irritant, Cat. 2 (H315, 'causes skin irritation').

Executive summary:

A study was performed according to OECD 404 under GLP conditions. To test for primary skin irritation the test item was applied to intact skin (for a 4 hour period under occlusive conditions) of rabbits. The first examination of the treated skin sites followed 1 hour after removal of the patches. Then examinations were performed daily for a further 21 days. The skin irritation test revealed severe irritation. Beginning at the first reading, up to day 8 of the study, erythema and edema occurred. The mean erythema scores (24/48/72 h) for animal 1, 2 and 3 were 1.34, 0.5 and 0.67, respectively. The mean edema scores (24/48/72 h) for animal 1, 2 and 3 were 1, 1.5 and 2, respectively. Erythema and edema were from day 5 onwards followed by other irritation symptoms such as formation of large scales, leathery skin, scabs, and necrosis. According to the results of this study, the test substances is considered to be irritating to the skin and has to be classified as a skin irritant, Cat. 2 (H315, 'causes skin irritation').