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

Endpoint summary

Description of key information

Oral (no guideline stated), male/female rats: LD50 = 4300 mg/kg bw

Dermal (no guideline stated), rabbits: LD50 > 5000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

June 1971

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: 2 page summary available, but study not done to guideline and not GLP.

Qualifier:

no guideline available

Principles of method if other than guideline:

The limits of confidence were determined by the method of Litchfield and Wilcoxon.

GLP compliance:

not specified

Test type:

fixed dose procedure

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

3500 mg/kg, 4000 mg/kg, 4500 mg/kg

No. of animals per sex per dose:

3500 mg/kg = 9
4000 mg/kg = 9
4500 mg/kg = 10

Control animals:

not specified

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

4 300 mg/kg bw

Based on:

test mat.

Interpretation of results:

sligthly toxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Executive summary:

LD50 = 4300 mg/kg

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Single page study summary

Qualifier:

no guideline available

Principles of method if other than guideline:

No method stated

GLP compliance:

not specified

Test type:

other: no method stated

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

not specified

Route of administration:

oral: unspecified

Vehicle:

unchanged (no vehicle)

No. of animals per sex per dose:

10

Control animals:

not specified

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

ca. 5 000 mg/kg bw

Based on:

test mat.

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

LD50 approximately 5000 mg/kg

Executive summary:

LD50 approximately 5000 mg/kg

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 300 mg/kg bw

Quality of whole database:

The available information comprises adequate studies used in a Weight-of-Evidence approach. Although the reliability of each study cannot be determined (Klimisch score 4), the results are consistent and are thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5 of Regulation (EC) No. 1907/2006. In fact, both studies were conducted with rats of both genders; in the study reported by Givaudan, a LD50 value of 4300 mg/kg bw was reported, whereas in the study by Moreno, the LD50 is reported as approx. 5000 mg/kg bw. The most sensitive value was retained for assessment of the acute oral toxicity of the compound.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Qualifier:

no guideline followed

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Type of coverage:

not specified

Vehicle:

unchanged (no vehicle)

Doses:

5000 mg/ kg bw

No. of animals per sex per dose:

10

Control animals:

not specified

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

none

Clinical signs:

other: Diarrhea in 1 animal on day 14.

Gross pathology:

Necropsy findings routine

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 >5000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

The available information comprises an adequate study. Although the reliability of the study cannot be determined (Klimisch score 4), the study conduct basically fulfills the standard requirement of a guideline study, and thus the findings are considered reliable data for assessment of the acute dermal toxicity of the compound. The data are therefore considered sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5 of Regulation (EC) No. 1907/2006.

Additional information

Two studies investigating the acute oral toxicity of the registered substance are available. As for both studies only short summaries are available, their reliability cannot be assigned (Klimisch score 4). However, the results obtained are consistent and indicate a low acute toxicity after oral exposure. Both studies are therefore taken into account by means of a Weight-of-Evidence approach.

In the first study (Givaudan, 1971; no guideline stated; no GLP), groups of male and female Wistar rats were dosed with the test substance by oral gavage. Doses applied were 3500 mg/kg bw (5m/4f), 4000 mg/kg bw (4m/5f) and 4500 mg/kg bw (5m/5f). Mortalities occurred as follows: In the low and mid dose groups, 1/9 animal was found dead after 6 h and 2/9 animals died within 24 h post application, respectively. Therefore, 3/9 (33%) animals died during the course of the study at each of these 2 dose levels. In the high dose group 4/10 animals died in the first 6 h after application and 2/10 within 24 h, totalling 6/10 (60%) treatment-related mortalities. The LD50 value was graphically determined to be 4300 mg/kg bw.

The finding of the first study is supported by another investigation of the acute oral toxicity (Moreno, 1977; no guideline stated; no GLP). 10 rats (no further details provided in study summary) were dosed with 5000 mg/kg bw and observed for 14 days after treatment. After application, all animals were comatose for 3 h. 4/10 animals died on day 1 and 1/10 on day 2. Hence, the total number of mortalities observed was 5/10 (50%). In conclusion, the LD50 in this study was determined to be approx. 5000 mg/kg bw

In addition to the acute oral toxicity, the acute dermal toxicity has also been investigated (Moreno, 1977; no guideline stated; no GLP). Again, only a short summary is available and hence the reliability of the study cannot be assessed (Klimisch score 4). 10 rabbits (no further details provided in study summary) were treated with 5000 mg/kg bw of the test substance and observed for 14 days. No mortalities occurred. Clinical signs observed were diarrhea in 1/10 on day 14. The dermal LD50 was therefore established to be > 5000 mg/kg bw.

With regard to Annex VIII, Item 8.5, Column 2, of Regulation (EC) No. 1907/2006 (REACH) performing an acute inhalation toxicity study with cis-Jasmone is not necessary. Studies in addition to the oral route (as required in Annex VII, 8.5.1.) shall be provided for at least one other route. The choice for the second route will depend on the nature of the substance and the likely route of human exposure. Since testing of the acute dermal toxicity has been chosen as the second route of exposure, all information requirements of Annex VIII, Item 8.5, are fulfilled.

Conclusion on acute toxicity

In two independent investigations of the acute oral toxicity and one study on acute dermal toxicity, cis-Jasmone exhibited a very low acute toxicity as indicated by LD50 values well exceeding the criteria for classification and labelling according to Regulation (EC) No. 1272/2008 (CLP) of > 2000 mg/kg bw.

Justification for classification or non-classification

The available data on acute oral and dermal toxicity 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.