Cyclohexane, 1-methyl-4-(1-methylethyl)-, tetradehydro deriv.

Endpoint summary

Description of key information

Key acute dermal irritation and eye irritation studies in rabbits were conducted with Depanol I, demonstrating  slight reactions both for skin and eye irritation, however below  threshold for classification. 

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:

14.12.1984-19.12.1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to GLP and valid methods, however few data were available on test substance composition. Nevertheless it is considered relevant, reliable and adequate for classification.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

other: Albino New Zealand, Hy / Cr

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River France (76410 Saint Aubin les Elbeuf, France)
- Weight at study initiation: 2410 g mean weight
- Housing: Individually in polystyrene cages (0.35 x 0.55 x 0.32 m); each cage was equipped with a food container and a water bottle.
- Diet (e.g. ad libitum): Ad libitum with a certified pelleted diet Rabbit Diet SQC (Special Diets Services Ltd, Witham, Essex England)
- Water (e.g. ad libitum): Tap water filtered with Millipore filters in water bottles ad libitum
- Acclimation period: At least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3 °C
- Humidity (%): 50% ± 30%
- Air changes (per hr): No data (The incoming, non-recycled air, was filtered by an absolute filter.)
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

4 days

Number of animals:

6 males

Details on study design:

TEST SITE
- Area of exposure: 6 cm2 of the back and flanks
- % coverage: Not provided
- Type of wrap if used: The treated area was covered with a hydrophilic gauze patch (Codex) to prevent loss of test material. The test material and the gauze patch were held in contact with the skin with a semi-occlusive patch adhesive tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No

SCORING SYSTEM: See under "Any other information on material and methods incl. tables"

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48, 72 hour

Score:

1.84

Max. score:

4

Reversibility:

fully reversible within: 4 days

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 24, 48, 72 hour

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 4 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 24, 48, 72 hour

Score:

2

Max. score:

4

Reversibility:

no data

Remarks on result:

other: animal found dead day 4

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 24, 48, 72 hour

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 4 days

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

other: 24, 48, 72 hour

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 4 days

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

other: 24, 48, 72 hour

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

other: 24, 48, 72 hour

Score:

2.67

Max. score:

4

Reversibility:

fully reversible within: 4 days

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48, 72 hour

Score:

0.39

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 24, 48, 72 hour

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 24, 48, 72 hour

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Remarks on result:

other: animal found dead day 4

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: 24, 48, 72 hour

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

edema score

Basis:

animal #4

Time point:

other: 24, 48, 72 hour

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #5

Time point:

other: 24, 48, 72 hour

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72

Irritation parameter:

edema score

Basis:

animal #6

Time point:

other: 24, 48, 72 hour

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 48 h

Evaluation of skin reactions

	Rabbit No.	D1 1hour	D2 24 hours	D3 48 hours	D4 72 hours	D5
Erythema	01	1	2	2	1	0
	02	1	2	2	-	-
	03	2	2	2	2	0
	04	2	1	1	1	0
	05	3	3	2	0	-
	06	2	3	3	2	0
Oedema	01	1	1	0	0	0
	02	1	1	0	-	-
	03	1	1	0	0	0
	04	1	0	0	0	0
	05	2	1	1	0	-
	06	1	1	1	0	0

The animal no. 02 was found dead on Day 4

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under these experimental conditions and according to the directive 83/467 EEC concerning classification, the packing and the labeling of the dangerous substances, the compound was considered as non-irritant.

Executive summary:

An acute dermal irritation study was performed with the compound Depanol I in six New-Zealand rabbits, according to the OECD Guideline No. 404 and the OECD Guideline for Good Laboratory Practice.
Erythema and oedema were observed in all animals one hour after instillation (very slight to moderate erythema and very slight to slight oedema). Oedema disappeared from Day 2 to Day 4 and erythema from Day 4 to Day 5.
Under these experimental conditions and according to the Directive 83/467 EEC concerning classification, the packing and the labeling of the dangerous substances, the compound was considered as non-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:

1985

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to GLP and valid methods, however few data were available on test substance composition. Nevertheless it is considered relevant, reliable and adequate for classification.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

other: Albino New Zealand, Hy / Cr

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River France (76410 Saint Aubin les Elbeuf, France)
- Age at study initiation: Not provided
- Weight at study initiation: 2390 g mean weight
- Fasting period before study: Not provided
- Housing: Individually in polystyrene cages (0.35 x 0.55 x 0.32 m); each cage was equipped with a food container and a water bottle.
- Diet (e.g. ad libitum): Ad libitum with a certified pelleted diet Rabbit Diet SQC (Special Diets Services Ltd, Witham, Essex England)
- Water (e.g. ad libitum): Tap water filtered with Millipore filters in water bottles ad libitum
- Acclimation period: At least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3 °C
- Humidity (%): 50% ± 30%
- Air changes (per hr): No data (The incoming, non recycled air, was filtered by an absolute filter.)
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

single treatment

Observation period (in vivo):

4 days

Number of animals or in vitro replicates:

6

Details on study design:

A dose of 0.1 mL of the test compound was instilled into the inferior conjunctival sac of the left eye of each rabbit with a plastic syringe. The upper and lower eye lids were held together for several seconds to avoid any loss of test substance. The right eye served as control.

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24, 48, 72 hour

Score:

0.73

Max. score:

3

Reversibility:

fully reversible within: 4 dyas

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 24, 48, 72 hour

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 4 days

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: 24, 48, 72 hour

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: 24, 48, 72 hour

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

other: 24, 48, 72 hour

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal #5

Time point:

other: 24, 48, 72 hour

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal #6

Time point:

other: 24, 48, 72 hour

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24, 48, 72 hour

Score:

0.73

Max. score:

4

Reversibility:

fully reversible within: 4 dyas

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 24, 48, 72 hour

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 4 days

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: 24, 48, 72 hour

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: 24, 48, 72 hour

Score:

0.67

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

other: 24, 48, 72 hour

Score:

0.67

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

animal #5

Time point:

other: 24, 48, 72 hour

Score:

0.67

Max. score:

4

Reversibility:

fully reversible

Remarks:

72 h

Irritation parameter:

chemosis score

Basis:

animal #6

Time point:

other: 24, 48, 72 hour

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48, 72 hour

Score:

0

Max. score:

2

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48, 72 hour

Score:

0

Max. score:

4

Eye irritation evaluation

	Scores	D1 (1 hour)						D2 (24 hours)
	Rabbit No.	01	02	03	04	05	06	01	02	03	04	05	06
Con-junctivae	Chemosis	3	3	3	3	3	3	1	1	1	1	1	1
	Discharge	0	0	0	0	0	0	0	0	0	0	0	0
	Redness	2	2	2	2	2	2	1	1	1	1	1	1
Iris	Degree of congestion	0	0	0	0	0	0	0	0	0	0	0	0
Cornea	Degree of opacity	0	0	0	0	0	0	0	0	0	0	0	0
	Area of opacity	0	0	0	0	0	0	0	0	0	0	0	0

 

 

	Scores	D3						D4						D5
	Rabbit No.	01	02	03	04	05	06	01	02	03	04	05	06	01
Con-junctivae	Chemosis	1	1	1	1	1	1	1	0	0	0	0	0	0
	Discharge	0	0	0	0	0	0	0	0	0	0	0	0	0
	Redness	1	1	1	1	1	1	1	0	0	0	0	0	0
Iris	Degree of congestion	0	0	0	0	0	0	0	0	0	0	0	0	0
Cornea	Degree of opacity	0	0	0	0	0	0	0	0	0	0	0	0	0
	Area of opacity	0	0	0	0	0	0	0	0	0	0	0	0	0

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under these experimental conditions and according to the directive 83/467 EEC concerning classification, the packing and the labeling of the dangerous substances, the compound was considered as non-irritant.

Executive summary:

An acute eye irritation study was performed with the compound Depanol I after instillation into the conjunctival sac of six New-Zealand rabbits, according to OECD Guideline 405 and the OECD Guideline for Good Laboratory Practice.
Chemosis, redness appeared in all animals on Day 1. These reactions disappeared between Day 4 and Day 5. No reactions were observed on the iris and cornea.
Under these experimental conditions and according to the Directive 83/467 EEC concerning classification, the packing and the labeling of the dangerous substances, the compound was considered as non-irritant.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

A key acute dermal irritation study was performed with the compound Depanol I in six New-Zealand rabbits, according to the OECD Guideline No. 404 and the OECD Guideline for Good Laboratory Practice (Hoechst AG, 1985). Erythema and edema were observed in all animals one hour after instillation (very slight to moderate erythema and very slight to slight edema). Edema disappeared from Day 2 to Day 4 and erythema from Day 4 to Day 5. Under these experimental conditions and according to the Directive 83/467 EEC or CLP regulation No. 1272/2008 concerning classification, the packing and the labeling of the dangerous substances, the compound was considered as non-irritant.

A key acute eye irritation study (Hoechst AG, 1985) was performed with the compound Depanol I after instillation into the conjunctival sac of six New-Zealand rabbits, according to OECD Guideline 405 and the OECD Guideline for Good Laboratory Practice. Chemosis, redness appeared in all animals on Day 1. These reactions disappeared between Day 4 and Day 5. No reactions were observed on the iris and cornea.
Under these experimental conditions and according to the directive 83/467 EEC or CLP regulation No. 1272/2008 concerning classification, the packing and the labeling of the dangerous substances, the compound was considered as non-irritant.

Justification for selection of skin irritation / corrosion endpoint:
Key study with Depanol I

Justification for selection of eye irritation endpoint:
Key study

Justification for classification or non-classification

Depanol I does not have to be classified for skin and eye irritation according the EU labelling regulations Commission Directive 93/21/EEC or CLP regulation No. 1272/2008 of 16 December 2008.