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Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report date:
1997

Materials and methods

Test guideline
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

Test material

Constituent 1
Chemical structure
Reference substance name:
2-methylcyclohexyl acetate
EC Number:
227-231-1
EC Name:
2-methylcyclohexyl acetate
Cas Number:
5726-19-2
Molecular formula:
C9H16O2
IUPAC Name:
2-methylcyclohexyl acetate
Details on test material:
- Name of test material (as cited in study report): 2-Methyl cyclohexyl acetate
- Physical state: Liquid
- Analytical purity: >95%
- Lot/batch No.: 36586
- Expiration date of the lot/batch: June 1997
- Storage condition of test material: Room temperature in the dark.

Test animals

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).

Administration / exposure

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)

Results and discussion

Effect levels
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.

Any other information on results incl. tables

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).

Applicant's summary and conclusion

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.

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