2-(1-methylethoxy)ethyl acetate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23 Jul - 06 Sep 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

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

Test material

Test material information

Constituent 1

Reference substance name:

2-(1-methylethoxy)ethyl acetate

EC Number:

242-901-3

EC Name:

2-(1-methylethoxy)ethyl acetate

Cas Number:

19234-20-9

Molecular formula:

C7H14O3

IUPAC Name:

2-(propan-2-yloxy)ethyl acetate

Test material form:

liquid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 57033
- Expiration date of the lot/batch: 25 November 2014

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature in the dark.

Test animals

Species:

rat

Strain:

other: RccHan™:WIST

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Oxon, UK
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: 200-350 g
- Housing: animals were housed in groups of five by sex in solid-floor polypropylene cages with stainless steel lids, furnished with softwood flakes and provided with environmental enrichment items: wooden chew blocks and cardboard "fun tunnels" (Datesand Ltd., Cheshire, UK).
- Diet: Harlan 2014C Rodent Diet (Harlan Laboratories UK Ltd., Oxon, UK), ad libitum
- Water: main drinking water, ad libitum
- Acclimation period: at least 5 days

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

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

clean air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: cylindrical exposure chamber
- Exposure chamber volume: 30 L (28 cm diameter x 50 cm high)
- Method of holding animals in test chamber: animals were individually held in a tapered, polycrbonate restraining tube fitted onto a single tier of the exposure chamber and sealed by means of a rubber "O" ring.
- Source and rate of air: compressed air was supplied by means of an oil free compressor and passed through a water trap and respiratory quality filters before it was introduced to the nebuliser. The chamber flow rate was maintained at 40 L/min providing 80 air changes per hour.
- System of generating aerosols: the test item was aerosolised using a glass concentric jet nebuliser (Radleys, Saffron Walden, UK).
- Method of particle size determination:
- Temperature, humidity, pressure in air chamber: temperature, relative humidity and oxygen levels were measured by an electronic thermometer/humidity meter (Hanna Instruments Ltd, Beds, UK) or oxygen analyser (Servomex Ltd, Crowborough, UK) located in a vacant port in the animals’ breathing zone of the chamber.

TEST ATMOSPHERE
- Brief description of analytical method used: the actual concentration of the test item was measured off-line by gas chromatography (GC).
- Samples taken from breathing zone: yes

TEST ATMOSPHERE
- Particle size distribution: Inhalable fraction
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.):

Analytical verification of test atmosphere concentrations:

yes

Remarks:

GC

Duration of exposure:

4 h

Concentrations:

12.3 mg/L (mean achieved concentration)
35.6 mg/L (nominal concentration)

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: bodyweights were recorded on arrival, prior to treatment on the day of exposure and on Days 1, 3, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: animals were observed for clinical signs and the respiratory tract was subjected to a detailed macroscopic examination for signs of irritancy or local toxicity.

Results and discussion

Preliminary study:

In a preliminary study, two rats (one male, one female) were exposed to an atmosphere of the test item at a mean achieved atmosphere concentration of 2.83 mg/L for approx. 4 hours. No significant effects were noted in either animal.

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 12.3 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: No animal died at the limit dose of 12.3 mg/L.

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: The following abnormalities were detected: (during exposure and directly after exposure): increased respiratory rate; (one day after exposure): hunched posture, pilo-erection (all animals), increased respiratory rate and red/brown staining around the eyes

Body weight:

5/5 males and 4/5 females exhibited bodyweight losses on the first day post-exposure. Further bodyweight losses or no bodyweight gain were noted in 4 males and 3 females from days 1 to 3 post-expossure. Reasonable bodyweight development was noted in all animals during the remainder of the recovery period.

Gross pathology:

No macroscopic abnormalities were detected in any animal at necropsy.

Any other information on results incl. tables

Table 1. Mean achieved atmosphere concentration

Atmosphere concentration
Mean achieved (mg/L)	Standard deviation	Nominal (mg/L)
12.3	0.15	35.6

 

Table 2. Results of the acute inhalation study: Mortality

Mean achieved atmosphere concentration (mg/L)	Deaths
	Male	Female	Total
12.3	0/5	0/5	0/10

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified