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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1941
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Cross-reference
Reason / purpose:
reference to same study
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1941
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Reason / purpose:
reference to same study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
Incomplete experimental data, exposure durations from 1-24h
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): Diisobutyl Ketone
- Physical state: Liquid
- Analytical purity: Usual commercial grade, no further specification
Species:
guinea pig
Strain:
not specified
Sex:
not specified
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The apparatus used for producing the continuous flow of vapour was an adaptation of that used by Irish and Adams in their studies on methods for testing the toxicity of vapours. A measured stream of pure air was drawn through a heated tube to which Diisobutyl Ketone was furnished by means of a displacement pump. A loose fitting plunger was lowered into a liquid reservoir by a constant speed electric clock motor. The liquid was displaced and flowed through a side arm into the heated tube through which pure air was being drawn at the desired rate to produce a given concentration of vapour, Prolonged recirculation over a wick saturated with the solvent was utilized to obtain saturated air at room temperature.
- Exposure chamber volume: 200L
- Source and rate of air: The air flow was equivalent to one complete change in 5 to 10 minutes


TEST ATMOSPHERE
- Brief description of analytical method used: During exposures, concentrations were checked with a 50 cm. portable Zeiss interferometer. Each division on the scale was found to be equivalent to 86ppm of Diisobutyl Ketone. This established a reasonable control, on concentrations
- Samples taken from breathing zone: no
Analytical verification of test atmosphere concentrations:
yes
Remarks:
During exposures, concentrations were checked with a 50 cm portable Zeiss interferometer. Each division on the scale was found to be equivalent to 86 ppm of Diisobutyl Ketone. This established a reasonable control, on concentrations.
Duration of exposure:
>= 1 - <= 24 h
Remarks on duration:
Different durations of exposure were performed combined with the different concentrations
Concentrations:
500, 750, 1000, 1500, 2000 and 2500ppm
No. of animals per sex per dose:
6
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, blood counts
Sex:
not specified
Dose descriptor:
LC50
Effect level:
> 14.5 mg/L air (nominal)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: According to 14500 mg/m³ air
Mortality:
Deaths occured only in the high dose group of 2500ppm after exposure time of >4h. From 4 tested animals in this group 1 was found dead. Deaths were usually rapid when they occurred, indicating that the constitutionally weaker animals succumbed promptly.
Clinical signs:
other: The symptoms exhibited by the animals during exposure naturally varied from animal to animal but generally were perceived in the following order of development: irritation of the eyes and nose, increased salivation, instability, respiratory difficulty or
Body weight:
No abnormal bodyweight changes in surviving animals were observed
Gross pathology:
A concentration of 750ppm gave rise to only minor lung pathology after a continuous exposure of 24 hours duration.
Other findings:
- Histopathology: Micropathology of the lung, kidney, liver, spleen and adrenal of those animals surviving exposure by 14 days was never severe, with frequency of involvement in that order. A concentration of 750ppm gave rise to only minor lung pathology after a continuous exposure of 24 hours duration.
- Other observations: There is no distinctive alteration in the blood picture except the usual variation seen in blood counts on small animals which is a normal occurrence.

According to guideline OECD 403 the usual exposure time is 4h (240min). All results for this duration are sufficient for determination of an appropriate LC50 and are summarised in table 1:

Table 1: Mortality after 4h exposure to guinea pig

ppm

exposure time

deaths occurred/tested animals

2500

4h

0/6

2000

4h

0/5

The LC50 for Diisobutyl Ketone administered by the inhalative route as vapour to guinea pigs is therefore specified as >2500ppm which is equivalent to 14.5 mg/L and 14500 mg/m³. According to DSD and CLP Diisobutyl Ketone has not to be classified.

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute inhalation LC50 of DIBK in guinea pigs is greater than 14500 mg/m3 (highest concentration tested). Hence, no calssification for acute inhalation toxicity is required according to EU criteria.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1941
Report Date:
1941

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
Incomplete experimental data, exposure durations from 1-24h
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
- Name of test material (as cited in study report): Diisobutyl Ketone
- Physical state: Liquid
- Analytical purity: Usual commercial grade, no further specification

Test animals

Species:
rat
Strain:
not specified
Sex:
not specified

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The apparatus used for producing the continuous flow of vapour was an adaptation of that used by Irish and Adams in their studies on methods for testing the toxicity of vapours. A measured stream of pure air was drawn through a heated tube to which Diisobutyl Ketone was furnished by means of a displacement pump. A loose fitting plunger was lowered into a liquid reservoir by a constant speed electric clock motor. The liquid was displaced and flowed through a side arm into the heated tube through which pure air was being drawn at the desired rate to produce a given concentration of vapour, Prolonged recirculation over a wick saturated with the solvent was utilized to obtain saturated air at room temperature.
- Source and rate of air: The air flow was equivalent to one complete change in 5 to 10 minutes


TEST ATMOSPHERE
- Brief description of analytical method used: During exposures, concentrations were checked with a 50 cm. portable Zeiss interferometer. Each division on the scale was found to be equivalent to 86 ppm of Diisobutyl Ketone. This established a reasonable control, on concentrations
- Samples taken from breathing zone: no


Analytical verification of test atmosphere concentrations:
yes
Remarks:
During exposures, concentrations were checked with a 50 cm portable Zeiss interferometer. Each division on the scale was found to be equivalent to 86 ppm of Diisobutyl Ketone. This established a reasonable control, on concentrations.
Duration of exposure:
>= 1 - <= 24 h
Remarks on duration:
Different durations of exposure were performed combined with the different concentrations
Concentrations:
500, 750, 1000, 1500, 2000 and 2500ppm
No. of animals per sex per dose:
6
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, blood counts

Results and discussion

Effect levels
Sex:
not specified
Dose descriptor:
LC50
Effect level:
> 14.5 mg/L air (nominal)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: According to 14500 mg/m³ air
Mortality:
Deaths occured only in the high dose groups of 2000 and 2500ppm after exposure times of >2h. From 36 tested animals in these groups 4 were found dead. Deaths were usually rapid when they occurred, indicating that the constitutionally weaker animals succumbed promptly
Clinical signs:
other: The symptoms exhibited by the animals during exposure naturally varied from animal to animal but generally were perceived in the following order of development: irritation of the eyes and nose, increased salivation, instability, respiratory difficulty or
Body weight:
No abnormal bodyweight changes in surviving animals were observed
Gross pathology:
A concentration of 750ppm gave rise to only minor lung pathology after a continuous exposure of 24 hours duration.
Other findings:
- Histopathology: Micropathology of the lung, kidney, liver, spleen and adrenal of those animals surviving exposure by 14 days was never severe, with frequency of involvement in that order. A concentration of 750ppm gave rise to only minor lung pathology after a continuous exposure of 24 hours duration.
- Other observations: There is no distinctive alteration in the blood picture except the usual variation seen in blood counts on small animals which is a normal occurrence.

Any other information on results incl. tables

According to guideline OECD 403 the usual exposure time is 4h (240min). All results for this duration are sufficient for determination of an appropriate LC50 and are summarised in table 1:

Table 1: Mortality after 4h exposure to rats

ppm

exposure time

deaths occurred/tested animals

2500

4h

1/6

2000

4h

0/6

The LC50 for Diisobutyl Ketone administered by the inhalative route as vapour to rats is therefore specified as >2500ppm which is equivalent to 14.5 mg/L air and 14500 mg/m³. According to DSD and CLP Diisobutyl Ketone has not to be classified.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute inhalation LC50 of DIBK in rats is greater than 14500 mg/m3 (highest concentration tested). Hence, no calssification for acute inhalation toxicity is required according to EU criteria.