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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable study report which meets generally accepted scientific principles. Study is well documented, before OECD TG and GLP existed. The study is fully sufficient for endpoint evaluation.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report Date:
1978

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
no
Remarks:
GLP was not compulsory at the time the study was conducted
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): Diisopropylamin
- Physical state: liquid
- Analytical purity: >= 99.0 %

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: WIGA, Sulzfeld, Germany
- Weight at study initiation: 185 +/- 15 g
- Diet: Herilan MRH (H. Eggersmann KG, Rinteln/Weser, Germany), ad libitum
- Water: tap water, ad libitum


Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
The exposure apparatus was a whole body inhalation system:
An infusion pump (Unita I, B. Braun, Melsungen) was used to transport a constant amount of the test material to an evaporator, which had a temperature of 36 °C. The arising vapours were mixed with a stream of fresh air and then poured into an inhalation chamber with a volume of ca. 180 l. After a prestreaming period of ca. 20 minutes the animals were transferred inward by using two locks.
The animals were exposed to the inhalation mixture for 4 hours.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
Analytic verification of the test atmosphere concentrations was conducted with a HP5840A gas chromatograph. The samples were taken near the noses of the animals, 1 l per min was taken out using a 4 mm diameter sample probe
Duration of exposure:
4 h
Concentrations:
nominal: 14.3, 8.6, 4.3, 1.1 mg/l (Group 1, 2, 3, 4)
analytic: 9.1, 5.3, 3.2, 0.86 mg/l
No. of animals per sex per dose:
10 animals per sex per dose.
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of weighing: at study initiation, on day 7 and 14
- Frequency of observations: daily
- Necropsy of survivors performed: yes
- Other examinations performed: mortality, clinical signs, body weight,organ weights, histopathology
Statistics:
Probit-Analysis according to Finney (p. 1-150, Cambridge University Press, 1971)

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
5.35 mg/L air (analytical)
Exp. duration:
4 h
Mortality:
In group 1, 10/10 females and 8/10 males died, in group 2, 7/10 males and 3/10 females died, in group 3, 2/10 males and 0/10 females died and in group 4, 0/10 males and 0/10 females died. No mortality was seen in the control group.
The death of the animals occured between day 1 to day 7 after exposure to the test material.
Clinical signs:
All animals in all dose groups showed clinical signs of toxicity:
In the groups 1 to 3 closed eyelids, aqueous to red coloured nasal discharge, corneal opacity, dyspnea, spastic walk, a crouched down position, tremor, unkempt fur and ventral position was observed.
In group 4 closed eyelids, snout-wiping and intermittent breath was seen. After 2 days there were no more symptoms recorded.
Body weight:
In the male dose groups a clearly reduced body weight gain was recorded when compared to control animals. For the females in groups 2 and 3 the same finding was seen, whereas the the body weight in group 3 was widely adapted to the controls.
The body weights of group 4 did not differ compared to the control group.

For further details see table 1.
Gross pathology:
Animals that died during the study:
In the groups 1 to 3 an acute dilatation in the heart was seen as well as an acute congestional hyperemia was seen, in the lung an acute exhalation was observed and in the liver there were sporadic peripheral lobe structures.

Any other information on results incl. tables

Table 1: Absolute body weights of male and female rats:

Mean body weight

day 0

day 7

day 14

male

female

male

female

male

female

 Group 1

weight (g) /

number of animals

186 /

10

180 /

10

167 /

10

- /

-

190 /

2

- /

-

Group 2

weight (g) /

number of animals

177 /

10

173 /

10

173 /

3

143 /

7

218 /

3

169 /

7

Group 3

weight (g) /

number of animals

181 /

10

181 /

10

168 /

8

174 /

10

230 /

8

204 /

10

Group 4

weight (g) /

number of animals

178 /

10

170 /

10

198 /

10

190 /

10

226 /

10

199 /

10

Control Group

weight (g) /

number of animals

188 /

10

178 /

10

223 /

10

198 /

10

264 /

10

208 /

10

Applicant's summary and conclusion

Interpretation of results:
toxic
Remarks:
Migrated information Toxicity Category III Criteria used for interpretation of results: EU
Conclusions:
Under the experimental conditions of this test for acute toxicity after inhalation, a LC50 of 5.35 mg/l air was obtained for male and female rats after 4 hours of whole body exposure to vapour containing DIPA.
Executive summary:

The acute inhalation toxicity of Diisopropylamine (DIPA) was evaluated in a 4-hour, single-exposure study in rats according to a protocol similar to the OECD Guideline 403.

DIPA was administered to a single group of five male and five female Sprague Dawley rats via whole-body vapor exposure at nominal concentrations of 14.3, 8.6, 4.3, 1.1 mg/l (Group 1, 2, 3, 4, respectively), leading to analytic concentrations of 9.1, 5.3, 3.2, 0.86 mg/l.

Mortality, clinical observations for clinical signs and body weight changes were evaluated over a 14-day observation period. All animals were subjected to a gross necropsy.

In group 1, 10/10 females and 8/10 males died, in group 2, 7/10 males and 3/10 females died, in group 3, 2/10 males and 0/10 females died and in group 4, 0/10 males and 0/10 females died. No mortality was seen in the control group. The death of the animals occurred between day 1 to day 7 after exposure to DIPA.

All animals in all dose groups showed clinical signs of toxicity: In the groups 1 to 3 closed eyelids, aqueous to red colored nasal discharge, corneal opacity, dyspnea, spastic walk, a crouched down position, tremor, unkempt fur and ventral position was observed. In group 4 closed eyelids, snout-wiping and intermittent breath was seen. After 2 days there were no more symptoms recorded.

In the male dose groups a clearly reduced body weight gain was recorded when compared to control animals. For the females in groups 2 and 3 the same finding was seen, whereas the body weight in group 3 was widely adapted to the controls. The body weights of group 4 did not differ compared to the control group.

In the groups 1 to 3 an acute dilatation in the heart was seen as well as an acute congestional hyperemia was seen, in the lung an acute exhalation was observed and in the liver there were sporadic peripheral lobe structures.

Based on the results of this study, the LC50 of DIPA was calculated to be 5.35mg/l when male and female rats were exposed whole-body to a vapor of DIPA for a single, 4-hour period.