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

Endpoint summary

Description of key information

Skin sensitisation (various non-guideline tests), guinea pigs: not sensitising

Skin sensitisation (RIPT), humans: not sensitising

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

March 1972

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Study not conducted to guideline. Study not in compliance with GLP.

Qualifier:

no guideline available

Principles of method if other than guideline:

The technique employed in this study was that of the repeated insult method approved by the Food and Drug Administration and known as the Draize Technique,

GLP compliance:

no

Type of study:

Draize test

Justification for non-LLNA method:

Study carried out in 1972.

Species:

human

Strain:

not specified

Sex:

male/female

Route:

epicutaneous, occlusive

Vehicle:

not specified

Concentration / amount:

0.5cc.

Day(s)/duration:

48h

Adequacy of induction:

not specified

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

not specified

Concentration / amount:

not specified

Day(s)/duration:

48h

Adequacy of challenge:

not specified

Positive control substance(s):

not specified

Key result

Reading:

1st reading

Hours after challenge:

72

Group:

test chemical

Dose level:

0.5cc.

No. with + reactions:

11

Total no. in group:

54

Clinical observations:

reaction to tape

Remarks on result:

no indication of skin sensitisation

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: not specified

Conclusions:

It is therefore concluded that none of the eight preparations in the indicated concentrations, as studied in this investigation, manifested either primary irritation or sensitizing effects on the fifty-four subjects who completed this full study.

Reference 2

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study not GLP and no guideline stated.

Qualifier:

no guideline available

Principles of method if other than guideline:

No guideline is stated in the study report.

GLP compliance:

no

Type of study:

open epicutaneous test

Justification for non-LLNA method:

Alternative in vivo testing method available

Species:

guinea pig

Strain:

not specified

Sex:

not specified

Route:

intradermal

Vehicle:

other: FCA

Concentration / amount:

3%

Day(s)/duration:

2days

Adequacy of induction:

not specified

Route:

epicutaneous, occlusive

Vehicle:

other: petrolatum

Concentration / amount:

25%

Day(s)/duration:

2days

Adequacy of induction:

not specified

No.:

#1

Route:

intradermal

Vehicle:

other: petrolatum

Concentration / amount:

3%

Day(s)/duration:

2 and 3 weeks

Adequacy of challenge:

not specified

No. of animals per dose:

4

Positive control substance(s):

not specified

Key result

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

3%

No. with + reactions:

0

Total no. in group:

6

Clinical observations:

none

Remarks on result:

no indication of skin sensitisation

Remarks:

The highest non irritant concentration of Jasmone Cis after one and after repeated applications is 3%. The preparation does not sensitise the guinea pig in the OET.

Reading:

1st reading

Hours after challenge:

48

Group:

negative control

Remarks on result:

not measured/tested

Reading:

1st reading

Hours after challenge:

48

Group:

positive control

Remarks on result:

not measured/tested

The highest non irritant concentration of Jasmone Cis after one and after repeated applications is 3%. The preparation does not sensitise the guinea pig in the OET.

From a dermatological point of view, one may gather the following from the results for the dermatological tests in man:

1) The preparation may well be tolerated in man up to a concentration of 10%

2) Therefore an allergic sensitisation in man is most unlikely up to this concentration.

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: not specified

Conclusions:

The highest non irritant concentration of Jasmone Cis after one and after repeated applications is 3%. The preparation does not sensitise the guinea pig in the OET.

Executive summary:

The highest non irritant concentration of Jasmone Cis after one and after repeated applications is 3%. The preparation does not sensitise the guinea pig in the OET.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

The potential of cis-Jasmone to induce skin sensitisation in guinea pigs has been investigated using a battery of 4 tests, all summarised in the same study report (Givaudan, 1977). For each individual study only a short summary is provided and hence their reliability cannot be assessed (Klimisch score 4). Although individual summaries might not meet acceptance criteria, all studies yield the same result, identifying cis-Jasmone as not being a skin sensitiser. Therefore, all studies reported in Givaudan (1979) are accounted for in a Weight-of-Evidence approach.

In the first test, cis-Jasmone was investigated for its skin sensitisation potential in an open epicutaneous test in guinea pigs (no guideline stated). On day zero of the experiment, 0.1 ml of the undiluted test material and its progressively diluted solutions (concentrations of 30%, 10% and 3% in acetone) 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 skin was observed for reactions 24 h after each application or at the end of each week. To determine whether contact sensitisation was induced, all the groups of guinea pigs previously treated for 21 days as well as 6 to 8 untreated or only with the vehicle pretreated controls (not further specified in study report, presumably acetone) were tested on days 21 and 35 on the contralateral flank with the test material at the lowest irritating concentration of 3% and some lower concentrations. The lowest irritating concentration of each material was used in order to confirm the biological activity and  to exclude false results based  on instability of the test material. The tests were performed by applying with a pipette 0.025 ml of each concentration to skin areas measuring 2 cm2. The reactions were read after 24, 48 and/or 72 h. No sensitisation reaction was observed in any animal at any observation time point with any test concentration. Hence, cis-Jasmone was demonstrated not to induce skin sensitisation in guinea pigs.

The second experiment was performed according to the Draize method. On day 0, groups of 8 animals were injected intradermally with 0.05 ml of a 0.1% solution of the test substance in saline and with 0.1 ml on nine further alternate days resulting in 10 individual induction injections (total dose = 0.95 mg). Experimental and control animals were challenged intradermally with 0.05 ml of a 0.1% solution of the test substance in saline on days 35 and 49, the mean diameter of the papular reactions being evaluated. No sensitisation reactions occurred in any of the test animals. cis-Jasmone does therefore not induce skin sensitisation in guinea pigs in the Draize test.

Additionally, a guinea pig maximisation test was performed with cis-Jasmone. On day zero, the animals were injected intradermally with (a) 0.1 ml of a 5% solution of the test substance, (b) 0.1 ml of a 5% emulsion of the test substance in FCA and (c) 0.1 ml of FCA alone, each injection was given twice. In addition, on day 8 the test substance dissolved in petrolatum up to 25%, was applied to a clipped skin area of the neck and kept under occlusive bandage for 2 days (total dose 20 mg intradermally plus 250  mg epicutaneously). On day 21, an occlusive patch test with the test substance in petrolatum was applied to the flank for 24 h and the reactions were read 24 and 48 h after removing the patch. No positive patch tests were seen in the guinea pig challenged with the test substance. Additionally performed epicutaneous tests with non irritant alcoholic solutions of the test substance 2 and 3 weeks after the challenge patch test were also negative. In consequence, cis-Jasmone did not sensitise guinea pigs.

In another experiment, the potential of cis-Jasmone to induce skin sensitisation was tested using the intradermal test with Freund's Complete Adjuvants (FCA). 0.05 ml of cis-Jasmone (undiluted, diluted or suspended) mixed with the same volume of FCA were injected intradermally into the neck on days 0, 2, 4, 7 and 9 (total dose approx. 250 mg). The experimental animals and controls, treated with 0.05 ml of FCA only, were tested epicutaneously on days 21 and 35. These tests were performed by applying 0.025 ml of each test concentration to skin areas measuring 2 cm2, The reactions were read after 24, 48 and 72 h. No allergic sensitisation was found with the test substance, challenged with the highest non irritant solution of cis-Jasmone 3 and 5 weeks after the first intradermal injection for sensitisation.

The findings of the experiments on guinea pigs are supported by those of a human repeated insult patch test performed according to the Draize technique (Givaudan, 1972). The site of application of the patch tests containing the test material was the inner surface of the right deltoid area. Patches were removed after 24 h and then another application was made to the inner surface of the left deltoid area. A third application was made to the original site of the first application followed by a fourth application to the site of the second application. Following these applications was a rest period, during which the development of sensitisation was permitted to occur. Fifty-four subjects, 40 female and 14 male, of representative age groups concluded the full sensitisation and challenge test study. There were no reactions in response to the test material in the patch tests. The only reactions which did occur were in response to the adhesive tape materials, thereby indicating the presence of a potentiality to react had the test material been adequately stimulating to the fifty-four subjects. It is therefore concluded that cis-Jasmone did not induce either primary irritation or sensitising effects.

Conclusion on skin sensitisation

All available studies indicate the absence of a skin sensitisation potential of cis-Jasmone. Although individual studies might not be sufficient to derive this conclusion and might not meet the current acceptance and validity criteria, all results draw a coherent and consistent picture and are therefore well suited to be used for hazard and risk assessment when taken together in the Weight-of-Evidence approach. Based on all available data, cis-Jasmone is considered not to induce skin sensitisation.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The available data on skin sensitisation are suitable to derive a classification and labelling. The available data do not meet the criteria for classification according to Regulation (EC) No. 1272/2008 (CLP) and are therefore conclusive but not sufficient for classification.