[1R-(1α,2β,5α)]-1-(isopropyl)-2-methoxy-4-methylcyclohexane

Endpoint summary

Description of key information

Oral (OECD 423), rat: LD50 > 2000 mg/kg bw (limit test)

Dermal (OECD 402), rat: LD50 > 2000 mg/kg bw (limit test)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20 Feb - 8 Mar 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

adopted in Mar 1996

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

(96/54/EC)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

The Department of Health of the Government of the United Kingdom

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

other: CD (Crl:CD (SD) IGS BR)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: approx. 8 weeks
- Weight at study initiation: 232-250 g (males), 204-224 g (females)
- Fasting period before study: Animals were fasted overnight prior to administration and for approx. 3-4 h after dosing.
- Housing: 3 animals of the same sex per cage in solid-floor polypropylene cages, bedding woodflakes
- Diet: Rat and Mouse Expanded Diet No.1 (Special Diets Services Limited, Witham, UK), ad libitum
- Water: mains drinking water, ad libitum
- Acclimation period: at least 5 days

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

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2.29 mL/kg bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed 30 min and 1, 2 and 4 hours after administration and subsequently once daily for 14 days. Individual body weights were determined prior to dosing and 7 and 14 days after administration.
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 500 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: Hunched posture was noted in all females one day after dosing. No clinical signs of toxicity were observed up to the end of the 14-day observation period in males.

Gross pathology:

No abnormalities were noted at necropsy.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

In this acute oral toxicity study a LD50 value > 2000 mg/kg bw in male and female rats was found.

Executive summary:

No mortalities were noted in animals treated with 2000 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 1), and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

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:

key study

Study period:

26 Feb - 12 Mar 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

adopted in Feb 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

(92/69/EEC)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

The Department of Health of the Government of the United Kingdom

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Sprague-Dawley CD (Crl:CD (SD) IGS BR)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: approx. 8 weeks
- Weight at study initiation: 265-275 g (males), 206-216 g (females)
- Housing: 5 animals of the same sex per cage in suspended polypropylene cages, bedding woodflakes, individually during the 24-hour exposure period
- Diet: Rat and Mouse SQC Expanded Diet No. 1 (Special Diets Services Limited, Witham, UK), ad libitum
- Water: mains drinking water, ad libitum
- Acclimation period: at least 5 days

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

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: clipped skin of back and flanks
- % coverage: 10%
- Type of wrap: The treated skin was covered with a piece of surgical gauze, which was held in place with a piece of self-adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: Residual test material was removed with a suitable solvent.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied: 2.29 mL/kg bw
- Constant volume or concentration used: yes

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for deaths or overt signs of toxicity 30 min and 1, 2 and 4 hours after administration and subsequently once daily for up to 14 days. Individual body weights were determined prior to application of the test substance on day 0 and on days 7 and 14 or at death.
- Necropsy of survivors performed: yes
- Other examinations performed: After removal of the dressings and subsequently once daily for 14 days, the test sites were examined for evidence of primary irritation and scored according Draize.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

One male died at day 13 post-dose.

Clinical signs:

other: No clinical signs of systemic toxicity were observed up to the end of the 14-day observation period.

Gross pathology:

Abnormalities noted in the male that died during the study were haemorrhagic lungs, dark liver and dark kidneys. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

Other findings:

There were no signs of dermal irritation. All scores for erythema and oedema were 0 at all reading time points.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

In this acute dermal toxicity study in rats a LD50 value > 2000 mg/kg bw was found in both sexes.

Executive summary:

The acute dermal median lethal dose (LD50) of the test material, in the Sprague-Dawley CD (Cr1:CD® ( SD) IGS BR) strain rat was found to be greater than 2000 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 1), and is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, of Regulation (EC) No 1907/2006.

Additional information

Oral

The acute oral toxicity of the test substance was assessed in a limit test according to OECD Guideline 423 and in compliance with GLP (2001). A total dose of 2000 mg/kg bw of the test substance was administered to 3 male (step 1) and 3 female rats (step 2). Animals were observed for clinical signs 30 and 60 min, as well as 2, 4 and 24 hours and subsequently once daily for 14 days after administration. Furthermore, individual body weights were determined before administration and thereafter in weekly intervals. Macroscopic examination was performed on test Day 15 (14 days after administration) at terminal sacrifice. There were no mortalities during the observation period and body weight gain of all animals was considered to be normal. Hunched posture was noted in all females one day after dosing. No signs of systemic toxicity were noted in male animals. Macroscopic post mortem examination did not reveal any abnormalities. Based on the results of this study, the LD50 value was determined to be > 2000 mg/kg bw in rats. In accordance with the recent OECD Guideline 423, a cut-off value of 5000 mg/kg bw can be derived, since no mortality occurred at 2000 mg/kg bw.

Dermal

The acute dermal toxicity of the test substance was assessed in a limit test according to OECD Guideline 402 and in compliance with GLP (2001). A group of ten rats (five/sex) was given a single, semioccluded dermal application of the undiluted test material to the intact skin at a dose level of 2000 mg/kg bw for 24 hours. Clinical signs and body weight development were monitored during the study. All animals were observed for 14 days and animals were subjected to gross necropsy at the end of the observation period. One mal animal was found dead on Day 13 after administration. There were no signs of systemic toxicity and body weight gain of all animals was considered to be normal. No signs of dermal irritation were observed. Abnormalities noted in the male that died during the study were haemorrhagic lungs, dark liver and dark kidney. No abnormalities were noted at necropsy of animals that were killed at the end of the study. Based on the results of this study, the LD50 value was determined to be > 2000 mg/kg bw in rats.

Justification for classification or non-classification

The available data on acute oral and dermal toxicity of the test substance do not meet the criteria for classification according to Regulation (EC) No 1272/2008, and are therefore conclusive but not sufficient for classification.