Isobutyl acetate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Methodological deficiencies, limited reporting (LC50 value not statistically determined, no actual concentrations and particle size distribution measured, only 6 rats used, reporting not according to test guideline)

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Unnamed

Year:

1962

Report date:

1962

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

1957

Report date:

1957

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

: no concentrations and particle size distribution measured, only 6 rats used, reporting limited and not according to test guideline

Principles of method if other than guideline:

Pre-guideline study, but method is similar to OECD TG 403. A test with graduate doses (standard test) and an inhalation hazard test were performed.

GLP compliance:

no

Remarks:

pre-GLP study

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Isobutyl acetate

EC Number:

203-745-1

EC Name:

Isobutyl acetate

Cas Number:

110-19-0

Molecular formula:

C6H12O2

IUPAC Name:

isobutyl acetate

Details on test material:

- Name of test material (as cited in study report): Acetic acid, isobutyl ester; isobutyl acetate
- no further information on test substance
- Analytical purity: no data, but as iso-butyl acetate is usually available as high quality / purity, it can probably be assumed that test item purity was high

Test animals

Species:

rat

Strain:

other: Albino

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: own breeding facility
- Age at study initiation: 4 to 5 weeks
- Weight at study initiation: 90 to 120 g
- Fasting period before study: no
- Housing: no data
- Diet (e.g. ad libitum): Rockland rat diet, complete, ad libitum
- Water (e.g. ad libitum): ad libitum

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

Test with graduate doses (standard test)
Test atmosphere was generated by injecting definite amounts of test substance into the flowing stream of breathing air using a suitable proportioning pump.
Inhalation hazard test
Test atmosphere was generated by passing a stream of dried air at 2.5 L/min at room temperature through a fritted glass disc immersed to a depth of at least 1 inch in approximately 50 mL of the test substance contained in a gas washing bottle. Six female albino rats were exposed for different exposure times to this atmosphere (flowing stream of air saturated or close to saturation with vapour).

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

4 h

Remarks on duration:

test with graduate doses

Concentrations:

For the standard test, doses were spaced in a logarithmic series with a factor of 2. Doses of 4000, 8000, and 16000 ppm (19.3, 38.6, and 77.3 mg/L) are reported.
For the inhalation hazard test, the test atmosphere was saturated or close to saturation with test substance vapor as indicated by the generation method of test atmosphere (saturated vapor concentration of isobutyl acetate: 95 mg/L at 20°C according to Auer Technikum Edition 12, Auergesellschaft GmbH, Berlin, 1988)

No. of animals per sex per dose:

six female animals per dose

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: no data
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: no data

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LC50

Effect level:

30 mg/L air

Remarks on result:

other: deduction based on study data (see under Remarks on results)

Effect levels 2

Sex:

female

Dose descriptor:

LC0

Effect level:

19.3 mg/L air (nominal)

Remarks on result:

other: Standard test: at the given dose, 0 of 6 animals died. Dose is converted from ppm as reported by the authors (4000 ppm)

Effect levels 3

Sex:

female

Dose descriptor:

other: LC67

Effect level:

38.6 mg/L air (nominal)

Exp. duration:

4 h

Remarks on result:

other: Standard test: at the given dose, 4 of 6 animals died. Dose is converted from ppm as reported by the authors (8000 ppm)

Effect levels 4

Sex:

not specified

Dose descriptor:

discriminating conc.

Effect level:

ca. 95 mg/L air (nominal)

Exp. duration:

1 h

Remarks on result:

other: Inhalation Hazard Test: as discriminating dose the saturated vapor concentration of test substance is given. Exposure duration is the longest exposurte time resulting in no death

Mortality:

Standard test: Dose [mg/L] Mortality
19.3 0 / 6
38.6 4 / 6 (death occured during exposure between 3rd and 4th h)
77.3 6 / 6 (death occured during exposure within 3.4 h)
Hazard Inhalation Test: Maximum exposure time for no death: 1 hour.

Clinical signs:

other: Anesthesia

Body weight:

The surviving rats of the medium dose group (38.6 mg/L) and the rats of the low dose group (19.3 mg/L) gained weight during the 14 d observation period (ca. 30 g).

Gross pathology:

Deaths were caused by breakdown of the capillary bed of the lungs.

Any other information on results incl. tables

Reported data (ppm) are converted to mg/L using a conversion factor of 4.83 (Auer Technikum Edition 12, Auergesellschaft GmbH, Berlin, 1988).

 

A LC50 value was not derived by the authors. Based on mortality data of the standard test, it is evident that the LC50 falls within the range of 19.3 to 38.6 mg/L (mortality 0 and 4 of 6 animals respectively) being closer to 38.6 mg/L. As conservative estimate, the LD50 is determined to be 30 mg/L.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Exposure to isobutyl acetate vapors in air at concentrations of 19.3 and 38,6 mg/L for 4 hours resulted in the death of 0 and of 4 out of 6 animals respectively (observation period 14 days). From this data, a LC50 of 30 mg/L can be estimated.
With a saturated or nearly saturated vapor concentration in air (ca. 95 mg/L), the exposure period was restricted to one hour in order not to cause any mortality. This coincides with the LC50 estimate.

Executive summary:

For this acute inhalation toxicity study, a standard graduate dose test and an inhalation hazard test were performed. The observation period for both tests was 14 days.

 

Groups of six female albino rats were exposed for 4 hours to graduate doses of isobutyl acetate vapor in the breathing atmosphere of test animals. Doses were spaced in a logarithmic series with a factor of 2 (4000, 8000, and 16000 ppm; 19.3, 38.6, and 77.3 mg/L respectively).

 

In the inhalation hazard test, test animals were exposed for various time periods starting from one forth hour up to 8 hours (spacing factor of 2) to an atmosphere saturated or close to saturation with vapors of isobutyl acetate. Actual atmosphere concentrations were not measured but can be estimated to be saturated or close to saturation by the method the atmosphere was generated. Saturated vapor concentration of isobutyl acetate at 20°C in air is 95 mg/L (Auer Technikum, Edition 12, Auergesellschaft GmbH, Berlin, 1988).

 

In the standard test, concentrations of 4000 and 8000 ppm (ca. 19.3 and 38,6 mg/L) caused a mortality of 0 and of 4 out of 6 animals, respectively. From this data a LC50 of 30 mg/L is estimated.

 

In the inhalation hazard test (saturated vapor), the exposure time was restricted to 1 hour in order to produce no mortality.

 

The LC50 value for isobutyl acetate can be estimated to be 30 mg/L (Smyth, 1962).

 

Standards of the OECD test guideline 403 (Acute Inhalation Toxicity) are only met with restrictions by this investigation (only 6 rats used, no concentrations measured, deficiencies in reporting).