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

Endpoint summary

Description of key information

Skin Irritation:

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.

Eye Irritation:

In an acute eye irritation/corrosion study with albino rabbits, performed equivalent to OECD 405 test guideline, no irritation was observed with the diluted substance.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin corrosion: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

March 30, 1964 - May 08, 1964

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Not a validated method for determining skin irritation or skin sensitisation, but provides reliable supporting information for “in-use” concentrations using a “standard practice” applied to ingredients for consumer formulations.

Qualifier:

no guideline followed

Principles of method if other than guideline:

The method followed in this study was that of the repeated insult method approved by the Food and Drug Administration.

GLP compliance:

no

Specific details on test material used for the study:

- Name of test material (as cited in study report): 7155, 1-Formyl-1-methyl-4-(4-methylpentyl)-3-cyclohexene

Please note that although the substance is stated as a mono-constituent substance 1-Formyl-1-methyl-4-(4-methylpentyl)-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.

Species:

human

Strain:

other: male and female volunteers

Details on test animals or test system and environmental conditions:

- ages varied from 16 to 67 years
- No person was accepeted who had active dermatologic conditions or other indicated illness

Type of coverage:

occlusive

Preparation of test site:

not specified

Vehicle:

other: dimethyl phthalate

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 mL
- Concentration (if solution): 2%

Duration of treatment / exposure:

10 occlusive applications for 48 hours, except for the weekends when the applications would remain for 72 hours

Number of animals:

- 21 males and 31 females

Details on study design:

PRE-TEST:
In a pilot group with 10 subjects, the test material was applied in closed patch test to the medial surfaces of the left deltoid areas. 48 hours later, the patch was removed and te reading was recorded. 72 hour readings for possible delayed reactions were taken on the next day. When all the results were negative, it was considered safe to initiate the main study.


MAIN STUDY:
The procedure consists in the repeated application of closed patch tests with 0.5 mL of test material being applied to individual absorbent patch. The patch was then applied to the area to be tested in a consecutive order. The patch was then secured by means of overlying strips of adhesive tape which was then further sealed completely with additional overlying strips of similarly impervious tape. The patch was allowed to remain in situ for 48 hours and then removed, at which readings were recorded.
The initial site of application of the patch was the inner surface of the right deltoid area. When it was removed 48 hours after application, the next application was made to the inner surface of the left deltoid area. In turn, the next application was made to the upper portion of the right forearm and the following application to the volar surface of the upper portion of the left forearm. Upon completion of this cycle, a return to the inner surface of the right deltoid area was made. Subsequently, the cycle of rotation was continued until 10 similar test applications had been made.
Followed by a two week rest period after which the challenge test series was applied.

Irritation parameter:

overall irritation score

Remarks on result:

other: There were no irritative reactions observed in any of the subjects during the sensitizing or challenge test phase.

Irritant / corrosive response data:

There were no irritative reactions observed in any of the subjects during any part of the test phase.

Other effects:

There were 6 subjects who responded at various times to the adhesive tape which was used to occlude the patches. Three of these subjects responded twice and one of these three responded an additional two times. In all instances the reponses were redness and small groups of pinpoint to pinhead size papules which disappeared by the time the rotation cycle required cycle required the re-application of the patch tests to the same site.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of a repeated occlusive patch test procedure, the 2% test material 7155, 1-Formyl-1-methyl-4-(4-methylpentyl)-3-cyclohexene produced no irritative reactions observed in any of the subjects during any part of the test phase. No conclusions can de drawn on the 100% test substance.

Reference 3

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.

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

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.

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.

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).

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

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

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

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

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.

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

March, 1964

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study meets the EC Standards (conducted equivalent to OECD 405). Non GLP. Deviations: lack of study design details in the report, no details on test material, no details on test animals and environmental conditions and the observation period was limited to 7 days. Only a very short description is reported. The main parameters, amount of substance, number of animals, scoring times and scoring system are reliable and thus the result is considered reliable with restrictions.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

(1981)

Deviations:

yes

Remarks:

lack of study design details in the report, no details on test material, no details on test animals and environmental conditions and the observation period was limited to 7 days

Principles of method if other than guideline:

The method of procedure is that suggested by Dr. Draize and described in 'Appraisal of the Saftey of Chemicals in Foods, Drugs and Cosmetics', published by the Association of Food and Drug Officials of the United States.

GLP compliance:

no

Specific details on test material used for the study:

Vernaldehyde
- Name of test material (as cited in study report): #7155

Species:

rabbit

Strain:

other: albino

Details on test animals or tissues and environmental conditions:

Three normal, healthy, albino rabbits were used in the experiment.

Vehicle:

other: alcoholic propylene glycol

Controls:

other: the left eye of each animal remained untreated and served as the reference control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): 2% in 80% alcoholic propylene glycol (by weight)

Duration of treatment / exposure:

Single instillation on Day 1.

Observation period (in vivo):

The eyes of each animal were examined approximately 24, 48, 72 and 96 hours and 7 days after instillation of the test substance

Number of animals or in vitro replicates:

3

Details on study design:

STUDY DESIGN
No data

TREATMENT
Each animal had 0.1 mL of the diluted test sample instilled into the right eye with no further treatemt.

REMOVAL OF TEST SUBSTANCE
Washing: No

OBSERVATIONS
The scorings recorded were made according to the Draize scale for scoring ocular lesions (according to OECD).

The scorings were made according to the Draize scale for scoring ocular lesions.

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

Max. score:

3

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

No irritation was observed in the treated eyes.

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute eye irritation/corrosion study with albino rabbits, performed equivalent to OECD 405 test guideline, no irritation was observed with the diluted substance.

Executive summary:

The diluted test substance (2% in 80% alcoholic propylene glycol) was tested in an acute eye irritation/corrosion study in 3 albino rabbits, performed equivalent to OECD 405 test guideline. No irritation was observed.

Based on the results, the diluted test substance does not have to be classified for eye irritation. No conclusions can be drawn on the 100% test substance.