2-methylcyclohexyl acetate

Endpoint summary

Description of key information

Acute toxicity: oral: Test method EEC B.1. GLP study. The acute oral LD50 for 2-methylcyclohexyl acetate was determined to be >2000 mg/kg bw in rats.

Acute toxicity: inhalation: Test method EEC B.2. GLP study. The acute 4h-LD50 for 2-methylcyclohexyl acetate was determined to be >5.32 mg/L of air in rats.

Acute toxicity: dermal: Test method EEC B.3. GLP study. The acute dermal LD50 for 2-methylcyclohexyl acetate was determined to be >2000 mg/kg bw in rats.

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:

July 30, 1996 - August 13, 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Ltd, Bicester, Oxon, England.
- Age at study initiation: 4-7 weeks
- Weight at study initiation: 90-103 g
- Fasting period before study: Food was only prevented overnight prior to and approximately 4 hours after dosing.
- Housing: Five rats per sex, in metal cages with wire mesh floors.
- Diet (e.g. ad libitum): Ad libitum (SDS LAD 1).
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3 ºC
- Humidity (%): Not controlled but anticipated in the range of 30-70%.
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light (artificial light).

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2.1 ml/kg bw

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 animals per sex and per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality: at least twice daily
Clinical signs: soon after dosing, every 4 hours during day 1, twice daily on subsequent days (with exception of day 15, morning only).
Body weight: day 1 (prior to dosing), day 8 and 15 or at death.
- Necropsy of survivors performed: yes, all animals surviving treatment were killed on day 15 by cervical dislocation.
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Macroscopic pathology: opening the cranial, abdominal and thoracic cavities, and macroscopic appearance of all tissues.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

One female rat died shortly after dosing.

Clinical signs:

other: Clinical signs prior to death were piloerection and increased salivation. Piloerection persisted on day 1 and was accompanied by hunched posture, waddling gait, lethargy, decreased respiration, partially closed eyelids, pallor of extremities, unsteadiness

Gross pathology:

Female rat dead shortly after dosing: Congestion of stomach (characterised by injected blood vessels), duodenum and small intestine. The stomach contained a clear liquid (assumed to be the test material).
Animals killed on day 15: No macroscopic abnormalities were observed.

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The acute oral LD50 for 2-methylcyclohexyl acetate was determined to be >2000 mg/kg bw in rats.

Executive summary:

An acute oral toxicity test was performed on 2 -methylcyclohexyl acetate in accordance with EEC method B.1. Five male and five female rats were exposed to 2000 mg/kg bw by gavage. Mortality, clinical signs and bodyweight were observed for 14 days after dosing. All animals surviving were killed on day 15 and macroscopic examinations were conducted. One female rat died shortly after dosing (macroscopic examination revealed congestion of the stomach, duodenum and small intestine). Clinical signs were observed but recovery was complete by day 4. No macroscopic abnormalities were observed for animals killed on day 15. Based on these result the acute oral LD50 for 2 -methylcyclohexyl acetate was determined to be >2000 mg/kg bw in rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The study is a GLP compliant and has a Klimisch score 1. The quality of the database was determined as appropriate for assessment.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

January 8, 1997 - February 4, 1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK Ltd, Manston Road, Margate, Kent, England.
- Weight at study initiation: males: 248-281 g; females: 196-230 g.
- Housing: By sex in groups of 5. Stainless steel sheet and wire mesh cages, 35cm x 53cm x 25cm.
- Diet (e.g. ad libitum): Ad libitum (SDS RM1)
- Water (e.g. ad libitum): Ad libitum (tap water)
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-22 ºC
- Humidity (%): 36-58%
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light (artificial light, 8 am - 8 pm).

Route of administration:

other: inhalation: liquid droplet aerosol and vapour.

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Aerosol generator
- Exposure chamber volume: Snout-only exposure chamber (ADG Developments), cylindrical form (30 cm i.d., 45 cm height), made of aluminium alloy, with and enclosed volume of approx. 30 litres.
- Method of holding animals in test chamber: The rats were held in moulded polycarbonate restraining tubes which were attached at evenly spaced ports in the cylindrical section of the chamber. Each rat was restrained in a forward position by an adjustable foamed plastic stopper.
- Source and rate of air: A supply of clean dried air was connected to the aerosol generator giving a flow rate of 15 litres/minute at the atomising jet. The test item was introduced into the generator through a syringe pump, with an initial flow rate of 0.3 ml/minute. This flow rate was expected to give a concentration of 2-methylcyclohexyl acetate in air slightly in excess of 5 mg/L. Equilibration period: 5 minutes.
- Treatment of exhaust air: Each chamber was equipped with an extract fan exhausting to atmosphere through an absolute filter.
- Temperature, humidity, pressure in air chamber:
Temperature (mean): 20 ºC (both control and treatment chambers)
Relative humidity (mean): 42 % (control), 45 % (treatment)

TEST ATMOSPHERE
- Brief description of analytical method used:
Test item concentration in the chamber: Gas chromatography (Hewlett Packard 5890A fitted with a model 7673 autosampler). Five samples (every 30 minutes) were taken during the exposure.
Particle size distribution: Two additional samples (at 90 and 210 minutes following the equilibration period) were taken during the exposure.
The nominal concentration was calculated from the amount of 2-methylcyclohexyl acetate dispersed in the generator and the total air flow through the generator during exposure.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

(see above)

Duration of exposure:

4 h

Concentrations:

0 (control), 5.32 mg/L

No. of animals per sex per dose:

5 animals per sex and per dose

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality and clinical signs: at the end of chamber equilibration period, at 0.25, 0.5 and 1.0 hours and then at hourly intervals during the exposure. During the observation period, once in the morning and then as necessary following a later check.
Body weight: daily from the day of delivery until the end of the observation period.
Food and water consumption: daily from the day of arrival.
- Necropsy of survivors performed: yes, at the end of the 14-day observation period by intraperitoneal injection of pentobarbitone sodium and exsanguinated when clinically dead.
Gross pathology: all rats were subjected to a detailed macroscopic examination.
Organ weights: lungs
Histopathology: lungs, liver and kidneys (buffered 10% formalin)

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.32 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

There were no deaths.

Clinical signs:

other: There were no clinical signs during the exposure nor observation periods related to treatment.

Body weight:

The rate of bodyweight gain for rats following the exposure was similar to that of the control rats.

Gross pathology:

There were no macroscopic abnormalities in test or control rats.

Other findings:

- Food and water consumption: A slight reduction in the food consumption of male test rats was recorded for 1 day following exposure, but were otherwise similar to the control values.
- Organ weights: The mean lung weights for male and female test rats were similar to the respective control values.
- Histopathology: no data available.

Concentration of 2 -methylcyclohexyl acetate in the chamber air: 5.32 ± 0.230 mg/L

Nominal concentration: 20.3 mg/L

Particle size distribution: c.a. 85% of the test atmosphere was present as vapour or droplets of a respirable size (<6 mm).

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The acute 4h-LD50 for 2-methylcyclohexyl acetate was determined to be >5.32 mg/L of air in rats.

Executive summary:

An acute inhalation toxicity test was performed on 2 -methylcyclohexyl acetate in accordance with EEC method B.2. Five rats per sex were exposed to the test item for 4 hours in a snout-only exposure system (liquid droplets aerosol and vapour). The concentration of 2 -methylcyclohexyl acetate was 5.32 mg/L. An additional group of control rats (five male and five females) was exposed to air only for 4 hours. The groups were observed for 14 days post-exposure and necropsy was performed at study termination. There were no deaths nor clinical signs during and following exposure. The rate of bodyweight gain for test rats was similar to that of the control rats. A slight reduction in food consumption was recorded for male rats on the day following exposure but were otherwise similar to that of the control rats. The lung weights were similar to control values and there were no macroscopic abnormalities. Based on these results, the acute 4h-LC50 for 2 -methylcyclohexyl acetate was determined to be >5.32 mg/L of air in rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

0.005 mg/m³ air

Quality of whole database:

The study is a GLP compliant and has a Klimisch score 1. The quality of the database was determined as appropriate for assessment.

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:

August 15, 1996 - August 29, 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Ltd, Bicester, Oxon, England.
- Age at study initiation: 7-10 weeks
- Weight at study initiation: 214-287 g
- Housing: individually in metal cages with wire mesh floors.
- Diet (e.g. ad libitum): Ad libitum (SDS LAD 1).
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 28 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3 ºC
- Humidity (%): Not controlled but anticipated in the range of 30-70%.
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light (artificial light).

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 50 mm x 50 mm (dorso-lumbar region). One day prior to treatment hair was removed with electric clippers.
- % coverage: 10% of the total body surface
- Type of wrap if used: the treated area was promptly covered with gauze which was held in place with a non-irritative dressing encircled firmly around the trunk.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After treatment, the treated area was washed with warm (30-40 ºC) water and blotted dry with absorbent paper.
- Time after start of exposure: 24 hours.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.09 ml/kg bw

Duration of exposure:

24 hours.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 rats per sex and per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality: at least twice daily
Clinical signs: soon after dosing, every 4 hours during day 1, twice daily on subsequent days (with exception of day 15, morning only).
Body weight: day 1 (prior to dosing), day 8 and 15 or at death.
- Necropsy of survivors performed: yes, all animals surviving treatment were killed on day 15 by cervical dislocation.
Macroscopic pathology: opening the abdominal and thoracic cavities, and macroscopic appearance of all organs.
- Others: Local dermal irritation at the treatment site was assessed daily by draize scoring method (erythema and oedema).

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: There were no signs of systemic reaction to treatment.

Gross pathology:

No macroscopic abnormalities were observed at necropsy.

Other findings:

- Other observations: Slight irritation (grade 1 or 2 erythema/oedema) was evident in two female animals following removal of the dressing. This was fully resolved by the following day in one animal and by day 6 in the remaining animal.

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The acute dermal LD50 for 2-methylcyclohexyl acetate was determined to be >2000 mg/kg bw in rats.

Executive summary:

An acute dermal toxicity test was performed on 2 -methylcyclohexyl acetate in accordance with ECC method B.3. Five male and five female rats were given a single dermal application of 2000 mg/kg bw test item. Mortality, clinical signs, bodyweight and dermal responses were observed for 14 days after dosing. All animals surviving were killed on day 15 and macroscopic examinations were conducted. There were no deaths and no signs of systemic reactions to treatment. Slight irritation was evident in two female rats following removal, and were fully resolved by the following day and by day 6 respectively. A loss of body weight was only recorded for one female rat on day 8. No abnormalities were observed at the macroscopic examinations. One female rat died shortly after dosing (macroscopic examination revealed congestion of the stomach, duodenum and small intestine). Based on these result the acute dermal LD50 for 2 -methylcyclohexyl acetate was determined to be >2000 mg/kg bw in rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The study is a GLP compliant and has a Klimisch score 1. The quality of the database was determined as appropriate for assessment.

Additional information

Acute toxicity: oral. Key study: An acute oral toxicity test was performed on 2 -methylcyclohexyl acetate in accordance with EEC method B.1. Clinical signs were observed but recovery was complete by day 4. No macroscopic abnormalities were observed for animals killed on day 15. The acute oral LD50 for 2 -methylcyclohexyl acetate was determined to be >2000 mg/kg bw in rats.

Acute toxicity: inhalation. Key study: An acute inhalation toxicity test was performed on 2 -methylcyclohexyl acetate in accordance with EEC method B.2. There were no deaths nor clinical signs during and following exposure. There were no macroscopic abnormalities. The acute 4h-LC50 for 2 -methylcyclohexyl acetate was determined to be >5.32 mg/L of air in rats.

Acute toxicity: dermal. Key study: An acute dermal toxicity test was performed on 2 -methylcyclohexyl acetate in accordance with EEC method B.3. There were no deaths and no signs of systemic reactions to treatment. Slight irritation was evident in two female rats following removal, and were fully resolved by the following day and by day 6 respectively. No abnormalities were observed at the macroscopic examinations. The acute dermal LD50 for 2 -methylcyclohexyl acetate was determined to be >2000 mg/kg bw in rats.

Justification for selection of acute toxicity – oral endpoint

Only one study available.

Justification for selection of acute toxicity – inhalation endpoint

Only one study available.

Justification for selection of acute toxicity – dermal endpoint

Only one study available

Justification for classification or non-classification

Taking into account the available data, acute oral LD50 > 2000 mg/kg bw, acute dermal LD50 >2000 mg/kg bw and inhalation 4h-LC50 > 5.32 mg/L (mists), the substance is not classified according to CLP Regulation (EC) No 1272/2008.