Reaction mass of 1-methyl-4-(4-methylpentyl)cyclohex-3-ene-1-carbaldehyde and 1-methyl-3-(4-methylpentyl)-3-cyclohexene-1-carboxaldehyde

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

November 08, 1988 - November 15, 1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study has been performed equivalent to OECD guidelines and according to GLP principles. Limited details on test material, the observation period was limited to 7 days.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1989

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

Limited details on test material, the observation period was limited to 7 days.

Principles of method if other than guideline:

The procedure were based on the test for skin irritation described on pages 106 to 108 of document L251, an EEC Commission Directive of 25th April 1984.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1-methyl-4-(4-methylpentyl)cyclohex-3-ene-1-carbaldehyde

EC Number:

266-314-7

EC Name:

1-methyl-4-(4-methylpentyl)cyclohex-3-ene-1-carbaldehyde

Cas Number:

66327-54-6

Molecular formula:

C14H24O

IUPAC Name:

1-methyl-4-(4-methylpentyl)cyclohex-3-ene-1-carbaldehyde

Constituent 2

Reference substance name:

1-methyl-3-(4-methylpentyl)-3-Cyclohexene-1-carboxaldehyde

Cas Number:

693252-50-5

Molecular formula:

C14H24O

IUPAC Name:

1-methyl-3-(4-methylpentyl)-3-Cyclohexene-1-carboxaldehyde

impurity 1

Reference substance name:

Cyclohexanecarboxaldehyde, 1-methyl-4-(4-methylpentyl)-, trans-

Cas Number:

76169-46-5

Molecular formula:

C14H26O

IUPAC Name:

Cyclohexanecarboxaldehyde, 1-methyl-4-(4-methylpentyl)-, trans-

impurity 2

Reference substance name:

Cyclohexanecarboxaldehyde, 1-methyl-4-(4-methylpentyl)-, cis-

Cas Number:

76169-45-4

Molecular formula:

C14H26O

IUPAC Name:

Cyclohexanecarboxaldehyde, 1-methyl-4-(4-methylpentyl)-, cis-

impurity 3

Reference substance name:

1-methyl-4-(4-methylpentylidene)cyclohexanecarbaldehyde

Molecular formula:

C14H24O

IUPAC Name:

1-methyl-4-(4-methylpentylidene)cyclohexanecarbaldehyde

impurity 4

Reference substance name:

1-methyl-4-(4-methyl-3-pentenyl)cyclohex-3-ene-1-carbaldehyde

EC Number:

257-942-2

EC Name:

1-methyl-4-(4-methyl-3-pentenyl)cyclohex-3-ene-1-carbaldehyde

Cas Number:

52475-86-2

Molecular formula:

C14H22O

IUPAC Name:

1-Methyl-4-(4-methylpent-3-en-1-yl)cyclohex-3-ene-1-carbaldehyde

impurity 5

Reference substance name:

1-methyl-3-(4-methylpentylidene)cyclohexanecarbaldehyde

Molecular formula:

C12H24O

IUPAC Name:

1-methyl-3-(4-methylpentylidene)cyclohexanecarbaldehyde

Specific details on test material used for the study:

- Test material label: 1018-88
- Material name: 1-Formyl-1-methyl-4(4-methyl-3-penten-1-yl)-3-cyclohexene
- CAS no.: 66327-54-6

Please note that although the substance is stated as a mono-constituent substance 1-Formyl-1-methyl-4(4-methyl-3-penten-1-yl)-3-cyclohexene in the report, recent analytical data had been determined the substance to be a multi-constituent (Reaction mass of 1-methyl-3-(4-methylpentyl)-3-cyclohexene-1-carboxaldehyde and 1-methyl-4-(4-methylpentyl)-3-cyclohexene-1-carboxaldehyde). As the chemical manufacturing process has not changed since the report was written, the recent analytical information is relevant to the batch which was tested.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

- Source: Gorseside Rabbits, Northchurch, Berkhamsted, Herfordshire
- Age at study initiation: 10-12 weeks
- Weight at study initiation: approx. 2.0 kg
- Housing: Animals were housed individually in grid bottomed cages.
- Diet: Free access to an antibiotic free rabbit diet (SQC standard rabbit pellets produced by Special Diets Services, Witham, Essex).
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 – 23
- Humidity (%): 37 - 68
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

The heating equipment failed during the acclimatisation period, resulting in the low temperatures recorded (5-24 °C). Temperature was typically greater than 14 °C during the study period.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: Adjacent areas of the untreated skin of each animal served as controls.

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

7 days.

Number of animals:

4 females

Details on study design:

TEST SITE
The day before dosing commenced rabbits were placed in restraining stocks and the dorsal surfaces of the trunk clipped free of hair using an Oster Model A2 clipper with Angra blade.
The test material was applied over an area of approx. 6 cm2 on the dorsal clipped skin on one flank of the animal.

REMOVAL OF TEST SUBSTANCE
After a period of 4 hours the adhesive tapes were removed and the treated sites cleaned by gentle swabbing with cotton wool soaked in warm water.

OBSERVATIONS
- Irritation:
The skin reactions were assessed at approximately 1, 24, 48 and 72 hours and 7 days after the removal of the dressings and test substance. Other signs of reaction to treatment were fully described.

SCORING SYSTEM:
The irritation was assessed according to the numerical scoring system according to OECD 404. Reaction to treatment considered to fall mid-way between the points described was scored as a fraction (i.e. 0.5, 1.5, 2.5, etc).

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal #1, #2, #3 and #4

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: Score after 7 days: 2x2, 1.5 and 1

Results 2

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

(mean)

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: Score after 7 days: 1

Results 3

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

(mean)

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 4

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

(mean)

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: Score after 7 days: 0.5

Results 5

Irritation parameter:

edema score

Basis:

animal #4

Remarks:

(mean)

Time point:

24/48/72 h

Score:

0.5

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: Score after 7 days: 0.5

Irritant / corrosive response data:

One hour after the dosing period very slight erythema of the treated skin was noted in one animal, very slight to well defined erythema was apparent in two animals and a score of 0.5 was given to erythematous reaction in the remaining animal. A score of 0.5 was given to oedematous reaction at the treated site of three animals. The irritation observed had increased within 24 hours, well defined erythema being observed in all animals. At this time very slight oedema was noted in one rabbit, slight oedema was apparent in one rabbit and slight to moderate oedema was apparent in one animal. Oedematous reaction in the remaining animal was scored at 0.5. Well defined erythematous reaction was maintained at the 48 and 72 hour examinations.Very slight oedema was noted in one rabbit, very slight to slight oedema was noted in one rabbit, slight oedema was apparent in one rabbit and oedema scored at 0.5 was noted in the remaining animal at the 48 hour examination. Slight decline in oedematous reaction was apparent in one animal after 72 hours. 7 days after dosing well defined erythema remained in two rabbits, very slight erythema was apparent in one rabbit and very slight to well defined erythema was observed in one rabbit. Very slight oedema was apparent at the tretaed site of one rabbit and oedematous reaction scored at 0.5 was apparent in two rabbits.

Other effects:

Desquamation from the surface of the treated skin was apparent in three rabbits at day 7.

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

In a skin irritation study with rabbits, performed equivalent to OECD 404 test guideline and GLP principles, irritation was observed, which was not reversible after 7 days.

Executive summary:

The test substance was tested in a skin irritation study with four rabbits, performed equivalent to OECD 404 test guideline and GLP principles. Well defined erythema was observed in all animals which was not fully reversible within 7 days. Very slight to slight oedema was observed which was not fully reversible within 7 days. Desquamation from the surface of the treated skin was apparent in three rabbits at day 7. As after 7 days still clear erythema was observed in all animals, the substance should be classified as Category 2 irritant and labelled as H315: Causes skin irritation.