Methyl 2,6,6-trimethylcyclohex-2-ene-1-carboxylate

Endpoint summary

Description of key information

Oral: LD50 = 4100 mg/kg bw, male/female rat, equiv. to OECD 401, 1981

Dermal: LD50 = > 2000 mg/kg bw, male/female rabbit, equiv. to OECD 402, 1981

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:

1981

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study following a method equivalent to a recognised guideline.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Principles of method if other than guideline:

The principles of the method were in accordance with the US 16 CFR 1500.3 definitions.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Recognised animal supplier
- Age at study initiation: Not reported.
- Weight at study initiation: 200 - 300 g
- Fasting period before study: Overnight.
- Housing: Not reported but in compliance with Animal Welfare Act (Pub. L-94-279) 9 CFR Part 3 (USA).
- Diet: rat chow ad libitum
- Water: ad libitum
- Acclimation period: Not reported.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not reported.
- Humidity (%): Not reported.
- Air changes (per hr): Not reported.
- Photoperiod (hrs dark / hrs light): Not reported.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The test material was given orally by syringe and dosing needle. The sample was dosed as supplied.

Doses:

2000, 2510, 3160, 3980, 5000 and 6310 mg/kg bw

No. of animals per sex per dose:

Six groups of 10: 5 per sex per dose; 10 total per dose level.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Within first six hours and observations daily for 14 days; body weights before dose and at end of observation period
- Necropsy of survivors performed: Yes.

Sex:

male

Dose descriptor:

LD50

Effect level:

4 200 mg/kg bw

Based on:

test mat.

95% CL:

3 700 - 4 900

Sex:

female

Dose descriptor:

LD50

Effect level:

4 100 mg/kg bw

Based on:

test mat.

95% CL:

3 300 - 4 900

Mortality:

2000 mg/kg bw: No mortalities
2510 mg/kg bw: No mortalities
3160 mg/kg bw: 1 female mortality
3980mg/kg bw: 2 male and 2 female mortalities
5000 mg/kg bw: 4 male and 4 female mortalities
6310 mg/kg bw: Complete mortality.

Clinical signs:

other: 3160 mg/kg bw: slightly depressed and ruffled after 2 hours. They appeared essentially normal within 24 hours. 3980 mg/kg bw: depressed, ruffled, drooling and dirty after 2-4 hours. They were severely depressed after 6 hours. The surviving animals were in

Gross pathology:

No significant findings on necropsy were observed.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study the LD50 was determined to be 4100 mg/kg bw in male/female wistar rats.

Executive summary:

The GLP study was performed following a method similar to OECD TG 401 to assess the acute oral toxicity potential of the test substance to male/female Wistar rats. The test material was administered as a single oral dose to groups of 5 male and 5 female rats orally, at several dose levels of 2000, 2510, 3160, 3980, 5000 and 6310 mg/kg bodyweight. All animals were observed for a fourteen day period for any signs of toxicity or other effects of treatment. Animals were examined for gross pathology. At 2000 mg/kg bw there was no mortality and no significant systemic toxicity. No remarkable findings were noted on necropsy. Under the conditions of this study the LD50 was determined to be 4100 mg/kg bw (female; C.I. = 3300 - 4900) and 4200 mg/kg bw (male; C.I. = 3700 - 4900).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 100 mg/kg bw

Quality of whole database:

The available information as a whole meets the tonnage driven information requirements of REACH.

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:

1981

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

GLP study following a method equivalent to a recognised guideline at a limit dose. Minor deviations (abraded skin plus occlusive dressing) to recognised OECD guideline that do not impact the reliability of the study. Since by expert assessment would increase the potential for positive response (evidence of toxicity) by increasing dermal permeability relative to intact skin within the OECD guideline.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

Limit test of 2000 mg/kg bw on clipped-abraded skin.

Qualifier:

according to guideline

Guideline:

other: 16 CFR 1500.40

Deviations:

no

Principles of method if other than guideline:

The principles of the method were in accordance with the US 16 CFR 1500.40 method and utilised US 16 CFR 1500.3 definitions.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Recognised animal supplier
- Age at study initiation: Not reported.
- Weight at study initiation: Between 2.0 and 3.0 kg
- Housing: The animals were housed in compliance with US 9 CFR Part 3.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: Not reported.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not reported.
- Humidity (%): Not reported
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): Not reported

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: All rabbits were weighed and the correct amount of experimental material was applied to the back of each animal
- Type of wrap if used: covered with large gauze patches and an impervious material was wrapped snugly around the trunk of each animal. The dressings were removed after twenty-four hours and any excess material was removed and the approximate amount remaining was noted.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the exposure site was wiped, but not washed, to remove excess material as per US 16 CFR 1500.40.
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg

Duration of exposure:

24h

Doses:

2000 mg/kg

No. of animals per sex per dose:

3 males and 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observed for signs of toxicity and for mortalities. Gross autopsies were performed on all animals which died during the 14 day observation period and also on all survivors of the 14 day observation period.
- Necropsy of survivors performed: Yes.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortalities.

Clinical signs:

other: There were no unusual behavioral signs noted.

Gross pathology:

Gross pathologic examination revealed nothing remarkable.

Other findings:

No other observations (such as local responses) were noted within the report.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study the LD50 was determined to be > 2000 mg/kg via the dermal route in male/female rabbits.

Executive summary:

The GLP study was performed following a method similar to OECD 402 to assess the dermal toxicity of the test material to the albino rabbit. The test substance was evaluated in six rabbits. A dose of 2000 mg/kg test substance (undiluted), was applied to the back clipped-abraded skin site of the rabbit under a occlusive dressing for 24 hours. After twenty-four hours and any excess material was removed and the approximate amount remaining was noted. The animals were observed for a 14 day period for signs of toxicity and for mortalities. Gross autopsies were performed on all animals. There were no unusual behavioural signs noted and gross pathologic examination revealed nothing remarkable. Under the conditions of this study the LD50 was determined to be greater than 2000 mg/kg via the dermal route in male/female albino rabbits.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

The available information as a whole meets the tonnage driven information requirements of REACH.

Additional information

Acute Oral:

The GLP study was performed following a method similar to OECD 401 to assess the acute oral toxicity potential of the test substance to male/female Wistar rats. The test material was administered as a single oral dose to groups of 5 male and 5 female rats orally, at several dose levels of 2000, 2510, 3160, 3980, 5000 and 6310 mg/kg bodyweight. All animals were observed for a fourteen day period for any signs of toxicity or other effects of treatment. Animals were examined for gross pathology. At 2000 mg/kg bw there was no mortality and no significant systemic toxicity. No remarkable findings were noted on necropsy. Under the conditions of this study the LD50 was determined to be 4100 mg/kg bw (female; C.I. = 3300 - 4900) and 4200 mg/kg bw (male; C.I. = 3700 - 4900).

 

Acute Dermal:

The GLP study was performed following a method similar to OECD 402 to assess the dermal toxicity of the test material to the albino rabbit. The test substance was evaluated in six rabbits. A dose of 2000 mg/kg test substance (undiluted), was applied to the back clipped-abraded skin site of the rabbit under a occlusive dressing for 24 hours. After twenty-four hours and any excess material was removed and the approximate amount remaining was noted. The animals were observed for a 14 day period for signs of toxicity and for mortalities. Gross autopsies were performed on all animals. There were no unusual behavioural signs noted and gross pathologic examination revealed nothing remarkable. Under the conditions of this study the LD50 was determined to be greater than 2000 mg/kg via the dermal route in male/female albino rabbits.

Justification for classification or non-classification

The substance does not meet classification criteria under Regulation (EC) No 1272/2008 for acute toxicity.