L-menthan-3-one

Endpoint summary

Description of key information

Oral: LD50 > 2000 mg/kg body weight, leading to not classification according to CLP.
Dermal: LD50 (Isomenthone) > 5 mL/kg body weight (> 4473 mg/kg bw), leading to not classification according to CLP.
Inhalation: no information available.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Study period:

No study period is specified in the report, but the report was finalized on 1974-04-29.

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Only a short description of the study is gven in the present report and few experimental details are provided. The study was not conducted according to any guideline and did not follow the rules of GLP, as it was performed prior to the implementation of GLP.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

no guideline followed

Principles of method if other than guideline:

The acute oral toxicity of the test item, "d-menthol dest." was determined in female Wistar rats (n=10 per dose ). The test item (10-20 mL/kg) was applied by gavage at dose levels of 1, 1.5, 2, 2,5, and 3 g/kg in peanut oil. The animals were observed for 14 d post-dose. LD50 values were calculated from the experimental data using Probit analysis.

GLP compliance:

not specified

Remarks:

The study was performed prior to the implementation of GLP.

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

no data

Route of administration:

oral: gavage

Vehicle:

peanut oil

Details on oral exposure:

The animals received a single oral dose of the test item via gavage. The test item was administered in peanut oil.

Doses:

The test item was administered at dose levels of 1, 1.5, 2, 2,5, and 3 g/kg.

No. of animals per sex per dose:

10 female animals were used per dose.

Control animals:

no

Details on study design:

Female Wistar rats (n=10 per dose) received a single oral dose dose of the test item in peanut oil item via gavage. The test item was administered at dose levels of 1, 1.5, 2, 2,5, and 3 g/kg.The animals were observed for 14 d post-dose. LD50 values were calculated from the experimental data using Probit analysis.

Statistics:

LD50 values were calculated from the experimental data using Probit analysis.

Preliminary study:

no preliminary study

Sex:

female

Dose descriptor:

LD50

Effect level:

2 046 mg/kg bw

95% CL:

> 1 777 - 2 303

Mortality:

Please, see section "Any other information on results incl. tables" for the mortality rates observed at the different dose levels. In the animals that died, death occurred within 1 to 2 d after administration of the test item.

Clinical signs:

other: Animals were in a narcosis-like state.

Gross pathology:

no data

Other findings:

no data

Table 1: Acute toxicity of "d-menthol dest." in rats

Dose (g/kg)	No. of animals used	No. of animals that died
1	10	0
1.5	10	1
2	10	5
2.5	10	7
3	10	10

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In this acute oral toxicity study in female Wistar rats, the LD50 of "d-menthol dest." was determined as 2.046 g (range: 1.777-2.303 g). Accordingly, the acute toxicity of the test item in rats after oral administration can be considered low.

Executive summary:

In an acute oral toxicity study in female Wistar rats (n=10 per dose), "d-menthol dest." was administered by gavage at dose levels of 1, 1.5, 2, 2,5, and 3 g/kg in peanut oil. The animals were observed for 14 d post-dose. LD₅₀ values were calculated from the experimental data using Probit analysis.

The LD₅₀ of "d-menthol dest." was determined as 2.046 g/kg (range: 1.777-2.303 g). Accordingly, the acute toxicity of the test item in rats after oral administration can be considered low.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 046 mg/kg bw

Quality of whole database:

Only one study with restricted reliablity is available for L-menthane-3-one, other two studies are reliable with restrictions and describe the acute toxicity of racemic menthol and d-menthol. These two last studies are considered as read across studies.

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:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Limited level of detail documented

Qualifier:

no guideline followed

Principles of method if other than guideline:

4 animals were used, one dose level, abraded skin

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: yes
- Fasting period before study: no data
- Housing: in a multiple animal holder for 24 h of exposure and following 14 day period in metabolism cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least two weeks

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 2-3 cm longitudinally
- Type of wrap if used: covered with a rubber sleeve or dam

REMOVAL OF TEST SUBSTANCE
- Washing (if done): wiped down
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5 mL/kg
- Concentration (if solution): pure

Duration of exposure:

24 h

Doses:

5 mL/kg

No. of animals per sex per dose:

4

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily
- Other examinations performed: clinical signs, body weight

Statistics:

no data

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 5 mL/kg bw

Based on:

test mat.

Remarks on result:

other: No deaths

Sex:

not specified

Dose descriptor:

LD0

Effect level:

> 5 mL/kg bw

Based on:

test mat.

Remarks on result:

other: No deaths

Mortality:

No deaths

Clinical signs:

other: All animals showed a mild erythema on both the intact and abraded areas.

Gross pathology:

No data

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The substance was acutely not toxic to rabbits in an acute dermal toxicity test with LD50 value >5 mL/kg bw. The substance is not classified according to CLP.

Executive summary:

The acute dermal toxicity of DL Isomenthone (CAS 491-07-6) was studied in a non-GLP test. A group of four animals were exposed to single dermal dose of 5 mL/kg bw. Animals were observed during a period of 14 days. No deaths occured at a level of 5 mL/kg bw. All the animals showed a mild erythema on both the intact and abraded areas.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

- oral toxicity:

The micronucleus assay in bone marrow cells of the mouse with L-menthone (Honavar 2009) is considered as only one study where the test item correspond to the registration test item L-menthan-3-one. However the duration of toxicity observation is only 48-hours before animal sacrifice, as required by micronucleus test guideline. Since during 2-day observation period one male mouse died at 2000 mg/kg bw, the LD50 for L-menthan-3-one is considered above 2000 mg/kg bw. Two other reliable with restrictions studies show the LD50 at 2602 and 2046 mg/kg bw of racemic Menthol and d-menthol, respectively, after 14-day observation period (Steinhoff 1974). This could be supported as read across information for L-menthan-3-one. Considering all these three studies as WoE data, it could be concluded that LD50 of L-menthan-3-one is above 2000 mg/kg bw.

- dermal toxicity:

The read-across substance Isomenthone is not acutely toxic in an acute dermal toxicity study in rabbits with a dermal LD50 value above 5 mL/kg body weight, i.e. above 4473 mg/kg body weight (Levenstein 1973).

Justification for selection of acute toxicity – oral endpoint
Only one WoE study is available for L-menthan-3-one.

Justification for selection of acute toxicity – dermal endpoint
Only one study as read-across from Isomenthone is available than could be considered as key study.

Justification for classification or non-classification

- oral toxicity:

Based on the above stated assessment of the acute oral toxicity of L-menthan-3-one, the results from WoE studies are above the threshold value given in the CLP Regulation. Therefore L-menthan-3-one does not need to be classified according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and according to CLP (Regulation (EC) No 1272/2008 of the European Parliament and of the Council) as implementation of UN-GHS in the EU.

- dermal toxicity:

Based on the above stated assessment of the acute dermal toxicity of Isomenthone, the results of the read-across study are above the threshold value given in the CLP Regulation. Therefore L-menthan-3-one does not need to be classified according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and according to CLP (Regulation (EC) No 1272/2008 of the European Parliament and of the Council) as implementation of UN-GHS in the EU.

- inhalation toxicity:

No inhalation studies are available and due to exposure considerations the conduction of studies and the classification and labelling for this endpoint is deemed not to be necessary.