Registration Dossier

Toxicological information

Acute Toxicity: inhalation

Currently viewing:

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given comparable to guideline study (deviations: only two concentrations tested, no concentrations and particle size distribution measured, only 6 rats used, sex not specified, reporting not according to test guideline)

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
1974
Report Date:
1974
Reference Type:
study report
Title:
Unnamed
Year:
1970
Report Date:
1970

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
: only two concentrations tested, no concentrations and particle size distribution measured, only 6 rats used, sex not specified, reporting 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

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 3-Methylbutyraldehyde
- no further information on test substance

Test animals

Species:
rat
Strain:
other: Albino
Sex:
not specified
Details on test animals 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 using a suitable proportioning pump by injecting definite amounts of test substance at a constant rate inside of a spirally corrugated surface of a minimally heated one inch Pyrex tube through which metered air is passed.
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 male or 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:
Standard test
8000 and 16000 ppm (28.64 and 57.28 mg/L); doses were spaced in a logarithmic series with a factor of 2
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 isovaleraldehyde: 233 mg/L at 25°C according to Auer Technikum Edition 12, Auergesellschaft GmbH, Berlin, 1988)
No. of animals per sex per dose:
six male or 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
Statistics:
LC50 was calculated by the moving average method based on a 14-day observation period.

Results and discussion

Effect levels
Sex:
not specified
Dose descriptor:
LC50
Effect level:
42.7 mg/L air (nominal)
95% CL:
34.6 - 53
Exp. duration:
4 h
Remarks on result:
other: LC50 in mg/L is taken as reported by the authors (LC50 in ppm: 12,100 ppm)
Mortality:
Standard test
Concentration Mortality
8000 ppm (28.64 mg/L) 0 / 6
16000 ppm ( 57.28 mg/L) 5 / 6 (during exosure)
Inhalation hazard test
Time Mortality
15 min 0 / 6
25 min 6 / 6 LT50 = 21.2 min (17.1 to 26.3 min) (LT50 = time to death of half of rats exposed to saturated vapor
Clinical signs:
other: Standard test 8000 ppm: eye irritation and slight loss of coordination within 10 min, salivation and irritation of extremities within 20 min, prostrate at 1 h 16000 ppm: Salivation and eye irritation by 8 min, poor coordination by 40 min, and prostra
Gross pathology:
Only Inhaltaion Hazard Test
Victims: froth in trachea
Survivors: nothing remarkable

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Exposure to isovaleraldehyde vapor in air at concentration of 28.64 and 57.28 mg/L (8000 and 16000 ppm) for 4 hours resulted in the death of 0 and 5 out of 6 animals (observation period 14 days). From this data, a LC50 of ca. 42.7 mg/L is calculated.
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 albino rats were exposed for 4 hours to graduate doses of isovaleraldehyde vapor in the breathing atmosphere of test animals. Doses were spaced in a logarithmic series with a factor of 2 (28.64 and 57.28 mg/L).

 

In the inhalation hazard test, test animals were exposed for various time periods starting from one forth hour up to 8 hours (if appropriate, spacing factor of 2) to an atmosphere saturated or close to saturation with vapor of isovaleraldehyde. 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 isovaleraldehyde at 25°C in air is 233 mg/L (Auer Technikum, Edition 12, Auergesellschaft GmbH, Berlin, 1988).

 

In the standard test, a mortality of 0 and 5 animals was observed for the two concentrations tested. The LC50 was calculated as 42.7 mg/L.

 

In the inhalation hazard test (saturated vapor), the exposure time to death of half of the rats exposed (LT50) was determined to be 21.7 min.

 

The LC50 for isovaleraldehyde was determined to be 42.7 mg/L in rats (Carpenter 1974).

 

Standards of the OECD test guideline 403 (Acute Inhalation Toxicity) are only met with restrictions by this investigation (only two concentrations tested, no concentrations and particle size distribution measured, only 6 rats used, sex not specified, reporting not according to test guideline). But the results are estimated to be sufficiently valid to assess the acute inhalation toxicity potential of isovaleraldehyde.