Diisopropylamine

Acute Toxicity: inhalation

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

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

Test material information

Constituent 1

Reference substance name:

Diisopropylamine

EC Number:

203-558-5

EC Name:

Diisopropylamine

Cas Number:

108-18-9

Molecular formula:

C6H15N

IUPAC Name:

bis(propan-2-yl)amine

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 or test system 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:

other: 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

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.