2-isopropyl-5-methyl-cyclohexanone

Endpoint summary

Description of key information

Oral: LD50 (Isomenthone) = 2119 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:

key study

Study period:

from 1998-11-10 to 1999-11-02

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study according to OECD TG 401 and EU Method B.1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

GLP compliance:

yes (incl. QA statement)

Remarks:

The Department of Health of the Government of the United Kingdom, 23rd March 1998

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent
- Age at study initiation: eight to twelve weeks old
- Weight at study initiation: 214-246 g (males), 201-236 g (females)
- Fasting period before study: an overnight fast immediately before dosing and for approximately three to four hours after dosing
- Housing: in groups of up to five by sex
- Diet (e.g. ad libitum): (Rat and Mouse Expanded Diet No. 1, Special Diets Services Limited, Witham, Essex, UK, ad libitum
- Water (e.g. ad libitum): mains drinking water, ad libitum
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 1999-09-09 To: 1999-10-12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2.24 mL/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: based on the results of the range-finding study

Doses:

1000, 1414 and 2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity 1/2, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days. Individual bodyweights were recorded prior to dosing on Day 0 and on Days 7 and 14 or at death.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross lesions and other toxicological effects

Statistics:

LD50 and 95% confidence limits were calculated by the method of Thompson. (Thompson, W.R., Bact. Reviews, 11, 115-145 (1947).

Sex:

female

Dose descriptor:

LD50

Effect level:

2 119 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 322 - <= 3 396

Mortality:

2 out of 5 female rats and 1 out of 5 male rats of highest dose died one and two days after dosing. One female animal treated with 2000 mg/kg was killed in extremis one day after dosing.

Clinical signs:

other: Clinical signs of toxicity commonly noted in all dose groups were hunched posture and lethargy. Ataxia was noted in animals treated with 1414 or 2000 mg/kg. Decreased respiratory rate and laboured respiration were noted in animals treated with 1000 or 200

Gross pathology:

Abnormalities noted at necropsy of the animal that was killed in extremis or animals that died during the study were haemorrhagic or abnormally red lungs, pale liver or patchy pallor of the liver, dark kidneys, slightly haemorrhagic or pale gastric mucosa, sloughing of the non-glandular epithelium of the stomach and haemorrhage of the small and large intestines. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral LD50 of the test material, Isomenthone, in the Sprague-Dawley CD strain female rat was 2119 mg/kg body weight. Male animals were considered not to be markedly more sensitive to the test material than female animals.

Executive summary:

The acute oral toxicity of the test substance Isomenthone was studied in a GLP test according to OECD TG 401 and EU Method B.1. Groups of five animals were exposed to single oral (gavage) doses of 1000, 1414 and 2000 mg/kg bw in females and of 2000 mg/kg bw in males. Animals were observed during a period of 14 days. No mortality was observed in the low ad the mid-dose groups, whereas 2 females and 1 male of the high-dose group died within one and two days after dosing. One female animal

treated with 2000 mg/kg bw was killed in extremis one day after dosing. The LD50 and 95 % confidence limits were calculated by the method of Thompson. (Thompson, W.R., Bact. Reviews, 11, 115-145 (1947).)

The LD50 value for females was 2119 mg/kg bw with a 95 % confidence interval of 1322 to 3396 mg/kg bw. Male animals were considered not to be markedly more sensitive to the test material than female animals. Clinical signs of toxicity were ataxia, hunched posture, lethargy, increased lacrimation, pilo-erection, ptosis, decreased respiratory rate, laboured respiration, redlbrown staining around the eyes, loss of righting reflex and splayed or tiptoe gait. Surviving animals recovered one to four days after dosing.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 119 mg/kg bw

Quality of whole database:

Only one study is available in whole database for the acute oral toxicity.

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 based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Limited level of detail documented

Reason / purpose for cross-reference:

reference to same study

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

Quality of whole database:

Only one study is available in whole database for the acute dermal toxicity.

Additional information

-oral toxicity:

The read-across substance Isomenthone is not acutely toxic to rats in a reliable and valid acute oral toxicity study and the oral LD50 value is 2119 mg/kg body weight in female rats, whereas male rats were considered not to be markedly more sensitive to the test material than female rats (Sanders 1999).

- 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 reliable study as read-across from Isomenthone is available that could be considered as key study.

Justification for selection of acute toxicity – dermal endpoint
Only one study as read-across from Isomenthone is available that 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 Isomenthone, the results from reliable read-across study are above the threshold value given in the CLP Regulation. Therefore Reaction mass of isomenthone and trans-menthone 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 Reaction mass of isomenthone and trans-menthone 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.