3-methyl-2-pent-2-enylcyclopent-2-enone

Endpoint summary

Description of key information

Skin irritation (no guideline stated), rabbits and guinea pigs: irritating to skin

Eye irritation (no guideline stated), rabbits: irritating to eyes

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

April 1977

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: One page summary, no guideline included and study not GLP.

Qualifier:

no guideline available

Principles of method if other than guideline:

No guideline followed

GLP compliance:

no

Species:

rabbit

Strain:

not specified

Type of coverage:

not specified

Preparation of test site:

not specified

Vehicle:

not specified

Controls:

not specified

Duration of treatment / exposure:

No data

Observation period:

14 days

Number of animals:

10

Remarks on result:

other: substance is an irritant

Irritation parameter:

edema score

Basis:

other: all

Time point:

14 d

Reversibility:

not specified

Remarks on result:

other: moderate in 10

Irritation parameter:

other: redness

Basis:

other: all

Time point:

14 d

Reversibility:

not specified

Remarks on result:

other: moderate in 1, severe in 9

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Reversibility:

not specified

Remarks on result:

not measured/tested

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Reversibility:

not specified

Remarks on result:

not measured/tested

5 g/kg irritant effects.

Moderate redness in 1, severe redness in 9 and moderate edema in all 10.

Bleeding at exposure site in 1, slight eschar in 2, heavy eschar in 1 and severe escar in 1.

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Jasmone-Cis is irritating.

Executive summary:

Jasmone-Cis is irritating.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study has no guideline and not conducted to GLP standards.

Qualifier:

no guideline available

Principles of method if other than guideline:

No guideline described in the attached test report.

GLP compliance:

no

Species:

guinea pig

Strain:

not specified

Type of coverage:

open

Preparation of test site:

clipped

Vehicle:

water

Controls:

yes

Duration of treatment / exposure:

24 hours

Observation period:

21 days

Number of animals:

1-6 experimental groups

Remarks on result:

other: Substance is an irritant

Irritation parameter:

other: Irritation

Basis:

other: not specified

Time point:

other: 7d/14d/21d

Reversibility:

not specified

Remarks on result:

other: no score measured

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Irritant / corrosive response data:

100 % irritant effects , skin effects, slight irritation was observed at the 7 day reading. Moderate irritation was observed at the 14 day reading. Strong irritation was observed at the 21 day reading.
30 % irritant effects , skin effects, slight irritation was observed at the 7 and 14 day reading. Moderate irritation was observed at the 21 day reading.
10 % irritant effects , skin effects, very slight irritation was observed at the 7 and 14 day reading. Slight irritation was observed at the 21 day reading.
3 % irritant effects , skin effects, no skin irritation was observed at the 7 and 14 day reading. Very slight skin irritation was observed at the 21 day reading.

Substance is an irritant.

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Jasmone-Cis, as determined by the attached study report, is concluded to be a skin irritant.

Executive summary:

Jasmone-Cis, as determined by the attached study report, is concluded to be a skin irritant.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Report contains tabulated results only. The study was conducted prior to introduction of GLP and current test guidelines.

Qualifier:

no guideline available

Principles of method if other than guideline:

The study was conducted prior to development of current guidelines. Reporting of the methodology is poor; the study does not appear to conform to current guidelines but generally follows the method of Draize - irritation was assessed following a single application, and following 7 daily applications.

GLP compliance:

no

Remarks:

Conducted prior to development of GLP

Species:

rabbit

Strain:

not specified

Details on test animals or tissues and environmental conditions:

Rabbits were used, no further information is provided

Vehicle:

other: Neantime; diethyl benzene-1,2-dicarboxylate

Controls:

yes, concurrent vehicle

Amount / concentration applied:

Test concentrations for the single application were 100%, 30%, 10%, 3% and 1%
Test concentrations for the repeat applications were 10%, 3% and 1% (based on results obtained in the single application study).

The vehicle used was neantime.

Duration of treatment / exposure:

The irritation was assessed following a single application of the test substance initially and then proceeded to repeated application for 7 consecutive days.

Observation period (in vivo):

Observations were made for 7 days after the last application

Number of animals or in vitro replicates:

No information provided

Details on study design:

Irritation was scored according to the following system:
- = no reaction
(+) = slight redness
+ = moderate redness and secretion
++ = strong redness and strong secretion
+++ = strong redness and strong secretion and oedema

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24 h

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Remarks:

Based on the results provided on the irritation test on the rabbit eye, it is concluded that this substance does cause eye irritation at 3%.

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

48 h

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Remarks:

Based on the results provided on the irritation test on the rabbit eye, it is concluded that this substance does cause eye irritation at 100%.

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Remarks:

Based on the results provided on the irritation test on the rabbit eye, it is concluded that this substance does cause eye irritation at 100%.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Reversibility:

not specified

Remarks on result:

not measured/tested

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Reversibility:

not specified

Remarks on result:

not measured/tested

Remarks:

not specified

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Reversibility:

not specified

Remarks on result:

not measured/tested

Remarks:

not specified

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Reversibility:

not specified

Remarks on result:

not measured/tested

Remarks:

not specified

Irritant / corrosive response data:

Single application: no reactions were observed following treatment with the 1% concentration. Treatment with 3% caused slight redness 1 day after application that had completely resolved by day 2. Treatment with 30% caused moderate redness and secretion 1 day after application, which reduced to slight redness 2 days after application. Signs of irritation had resolved by Day 3. Treatment with the undiluted test substance caused strong redness, strong secretion and oedema 1 day after application; signs of irritation ameliorated from then on and eyes were completely free of irritation by Day 6.
Repeat applications: no reactions were observed following 7 days repeat exposure to the 1% concentration. 7 days repeat treatment with the 3% and 10% concentrations resulted in slight redness at each observation, which persisted to study termination on Day 7.
The vehicle (neantime) was reported to have a highest non-irritant concentration of 10% following single application, and 100% following repeat application.

Other effects:

No other effects reported.

A: Single application:

 

Substance	Lowest irritant concentration	Highest non-irritant concentration
Giv 1-0985 Ro 6-8198	3%	1%
Solvent	-	10%

 

Duration of the lesions:

Substance	Concentration %	Day 1	Day 2	Day 3	Day 4	Day 5	Day 6	Day 7
Giv 1-0985 Ro 6-8198	100	+++	++	+	(+)	(+)	-	-
	30	+	(+)	-	-	-	-	-
	10	(+)	-	-	-	-	-	-
	3	(+)	-	-	-	-	-	-
	1	-	-	-	-	-	-	-
Solvent	100	-	-	-	-	-	-	-

 

Evaluation:

- = No reaction

(+) = Slight redness

+ = Slight redness and secretion

++ = Moderate redness and strong secretion

+++ = Strong redness and strong secretion and oedema

 

B: Repeated application on 7 consecutive days-Score after last application:

Substance	Lowest irritant concentration	Highest non-irritant concentration
Giv 1-0985 Ro 6-8198	3%	1%
Solvent	-	10%

 

Substance	Concentration %	Day 1	Day 2	Day 3	Day 4	Day 5	Day 6	Day 7
Giv 1-0985 Ro 6-8198	100	Not done
	30	Not done
	10	(+)	(+)	(+)	(+)	(+)	(+)	(+)
	3	(+)	(+)	(+)	(+)	(+)	(+)	(+)
	1	-	-	-	-	-	-	-
Solvent	100	-	-	-	-	-	-	-

 

Evaluation:

- = No reaction

(+) = Slight redness

+ = Slight redness and secretion

++ = Moderate redness and strong secretion

+++ = Strong redness and strong secretion and oedema

Interpretation of results:

irritating

Remarks:

Migrated information at 3% concentration Criteria used for interpretation of results: EU

Conclusions:

Based on the results provided on the irritation test on the rabbit eye, it is concluded that this substance does cause eye irritation at 3%.

Executive summary:

The eye irritation potential of Jasmone was evaluated in rabbits. A single application was made to the rabbit eye at concentrations of 100%, 30%, 10%, 3% and 1% (in neantime). Signs of irritation were recorded daily for 7 days after application. In addition, concentrations of 10%, 3% and 1% were applied daily for 7 days and signs of irritation recorded daily for 7 days after the last application. A single application of 3, 10 or 30% test substance caused slight redness (erythema) which resolved by Day 2. No irritant reactions were observed following treatment with 1%. A single application of 100% test substance caused strong redness (erythema), secretion and oedema; symptoms reduced over the following days and eyes were free from irritation by Day 6. Repeated application with 1% test substance caused no adverse effects. Slight redness (erythema) was observed following 7 -days repeat application with 3% and 10% test substance; effects persisted to study termination (7 days after the last application). The vehicle (neantime) was reported to have a highest non-irritant concentration of 10% following single application, and 100% following repeat application.

It was concluded that the highest non-irritating concentration of the test substance was 1%, and the lowest irritant concentration was 3%.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation / corrosion

There are two investigations of the skin irritation / corrosion potential of the registered substance available. The first study is properly reported and is therefore considered reliable with restrictions (Klimisch score 2), while the second one is only a short summary and hence its reliability cannot be assigned (Klimisch score 4). However, the results obtained are consistent and confirm irritating properties. Both studies are therefore taken into account by means of a Weight-of-Evidence approach.

cis-Jasmone has been tested for its skin irritation potential in an open epicutaneous test (Giv, 1977; no guideline stated; no GLP). The test consisted of two experiments. While the purpose of the first experiment was to establish the lowest irritating and the highest non irritating concentration, the second experiment investigated effects on skin after repeated exposure to the test substance.

In the first experiment test material concentrations of 100%, 30%, 10%, 3% in acetone were applied to the clipped flanks of 6 to 8 guinea pigs per concentration under open conditions. A single application of 0.025 ml of each test concentration was performed and skin reactions were read 24 h after the application of the test material. The lowest irritating and the highest non irritating concentrations were determined by an all-or-none criterion. The lowest irritating concentration is defined as the lowest concentration causing skin irritation. The highest non irritating concentration is defined as the highest one not causing macroscopic skin reactions in any of the animals. The minimal irritant concentration was established at 10% and the highest non irritant concentration at 3% by visual inspections of all animals.

On day zero of the second experiment, 0.1 ml of the undiluted test material and its progressively diluted solutions (concentrations of 30%, 10% and 3%) was applied to an area measuring 8 cm2 on the clipped flank of 6 to 8 guinea pigs per concentration group. The applications were repeated daily for 3 weeks or were done 5 times/week during a period of 4 weeks, always using the same skin site. The application site was left uncovered and the reactions were read 24 h after each application or at the end of each week. After exposure to the test substance for 21 consecutive days, the following skin reactions were observed:

• Test item concentration 100 % (undiluted): slight irritation at the 7 day reading, moderate irritation at the 14 day reading and strong irritation at the 21 day reading.
• Test item concentration 30 %: slight irritation at the 7 and 14 day readings and moderate irritation at the 21 day reading.
• Test item concentration 10 %: very slight irritation at the 7 and 14 day readings and slight irritation at the 21 day reading.
• Test item concentration 3 %: no skin effects at the 7 and 14 day readings and very slight skin irritation at the 21 day reading.

The results of both experiments clearly indicate a skin irritating potential of the test substance.

Observations of skin reactions were also made in an acute dermal toxicity study (Givaudan, 1977; no GLP). A group of 10 rabbits (no further details given in study report) were exposed to 5000 mg/kg bw of the test item and observed for a period of 14 days. At the end of the test moderate redness was apparent in 1/10 and severe redness in 9/10 animals and moderate edema occurred in all 10 animals. In addition, bleeding at exposure site was observed in 1/10, slight eschar in 2/20, heavy eschar in 1/10 and severe eschar in 1/10 of the test animals. The test substance was therefore considered to be irritating to skin.

Eye irritation

The eye irritation potential of cis-Jasmone was evaluated in rabbits (Roche, 1971; no guideline stated; no GLP). A single application of the test substance was made to the rabbit eyes at concentrations of 100%, 30%, 10%, 3% and 1% (in Neantine as solvent). Signs of irritation were recorded daily for 7 days after application. In addition, concentrations of 10%, 3% and 1% were applied daily for 7 days and signs of irritation recorded daily for 7 days after the last application. A single application of 3, 10 or 30% test substance caused slight redness (erythema) which resolved by Day 2. No irritant reactions were observed following treatment with 1%. A single application of 100% test substance caused strong redness (erythema), secretion and oedema; symptoms reduced over the following days and eyes were free from irritation by Day 6. Repeated application with 1% test substance caused no adverse effects. Slight redness (erythema) was observed following 7 days repeat application with 3% and 10% test substance; effects persisted to study termination (7 days after the last application). The vehicle (Neantine) was reported to have a highest non-irritant concentration of 10% following single application, and 100% following repeat application. It was concluded that the highest non-irritating concentration of the test substance was 1%, and the lowest irritant concentration was 3%. Overall, the test substance was considered to be irritating to eyes.

Conclusion

In all available studies investigating the irritation potential of cis-Jasmone, skin and eye effects have not been scored according to a recognised scheme, e.g. the Draize scoring scheme, but only qualitative descriptions of skin and eye reactions are given. However, the qualitative descriptions are comparable to the parameters of current test guidelines and accepted classification criteria. The validity of the data is also underlined by the fact that all results are consistent, clearly reflecting an irritation potential for skin and eyes. Although individual study reports might not meet acceptance criteria, all studies taken together in a Weight-of-Evidence approach, result in a unanimous characterisation of the irritation properties of cis-Jasmone. Therefore, the data provided is deemed sufficient to establish a reliable classification with regard to skin irritation / corrosion and eye irritation.

Justification for classification or non-classification

The available data on skin and eye irritation are suitable to derive a classification and labelling. The available data meet the criteria for classification for Skin irrit. 2, H315, and Eye irrit. 2, H319, according to Regulation (EC) No. 1272/2008 (CLP) and are therefore conclusive but not sufficient for classification.