Ethyldiisopropylamine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to Guideline study (GLP; ATC method, dose steps: 2000, 500 and 200 mg/kg bw, respectively, instead of 2000, 300 and 50 mg/kg bw.)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method; Dec 29, 1992)

Deviations:

yes

Remarks:

dose steps: 2000, 500 and 200 mg/kg bw, respectively, instead of 2000, 300 and 50 mg/kg bw.

GLP compliance:

yes

Test type:

acute toxic class method

Test material

Test material information

Constituent 1

Reference substance name:

Ethyldiisopropylamine

EC Number:

230-392-0

EC Name:

Ethyldiisopropylamine

Cas Number:

7087-68-5

Molecular formula:

C8H19N

IUPAC Name:

ethylbis(propan-2-yl)amine

Details on test material:

- Name of test material (as cited in study report): N-Ethyldiisopropylamin (Lab test substance number: 96/479)
- Physical state: liquid, colourless
- Analytical purity: 99.3 %
- Lot/batch No.: K 79 PD
- Storage condition of test material: Refrigerator
- Stability under test conditions: the stability of the test substance in olive oil for a time period of 4 hours was confirmed by analysis. The stability of the test substance over the study period has not been investigated by reanalysis, because the study was terminated only about 4 weeks after the characterization. It can be assumed, that the test substance was stable for the duration of the study.
- Other: the test substance was homogeneous by visual inspection.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: DR. K. THOMAE GMBH, Biberach, Germany
- Age at study initiation: young adult animals
- Weight at study initiation: 173 - 194 g (±20% of the mean weight)
- Fasting period before study: at least 16 h before administration, but water was available ad libitum
- Housing: single housing in stainless steel wire mesh cages, Type DK-III (Becker & Co., Castrop-Rauxel, FRG)
- Diet: KLIBA-LABORDIAET 343, Klingenthalmuehle AG, Kaiseraugst, Switzerland; ad libitum
- Water: tap water; ad libitum
- Acclimation period: at least 1 week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24 °C
- Humidity (%): 30-70 %
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Remarks:

DAB 10

Details on oral exposure:

VEHICLE
- Justification for choice of vehicle: test substance is unsoluble in water
- Concentration in vehicle: 4.0, 10.0 and 40.0 g/100 ml, respectively for the low, mid and high dose groups
MAXIMUM DOSE VOLUME APPLIED: 5 ml

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: based on the physical and chemical characteristics of the test substance and its composition no pronounced acute oral toxicity was expected. Therefore a starting dose of 2000 mg/kg bw was chosen in a first step with 3 female animals. As all animals died, 500 mg/kg bw were used with 3 female animals in a second step. Because 100% mortality occurred, 200 mg/kg bw were tested in a third step with 3 female rats. Because no mortality occurred in this third step, 3 male animals were treated in a fourth step with the same dose (200 mg/kg bw).

Doses:

200, 500, 2000 mg/kg

No. of animals per sex per dose:

3 females (high and mid dose levels); 3 males and 3 females (low dose level)

Control animals:

no

Details on study design:

- Duration of observation period following administration: up to 14 days (depending on survival)
- Frequency of observations: clinical signs daily (several times on the day of administration, and at least once each workday); check for mortality and moribund animal twice each workday and once on Saturdays, Sundays and public holidays
- Frequency of weighing: day 0, 7 and 14
- Necropsy of survivors performed: yes; necropsy at the last day of the observation period. Withdrawal of food at least 16 hours before killing with CO2, then necropsy with gross-pathology examination. Necropsy of all animals that died before as early as possible.
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 200 - < 500 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality occurred at 200 mg/kg bw (3 male and 3 female animals), whereas 100% mortality was observed at 500 and 2000 mg/kg bw (only females)

Effect levels 2

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 317 mg/kg bw

Based on:

test mat.

95% CL:

15 - 1 360

Remarks on result:

other: LD50 point estimate (re-calculated)

Mortality:

- 2000 mg/kg bw: all 3 animals died within 1 hour;
- 500 mg/kg bw: 1 animal died within 1 hour, the remaining 2 within 3 hours;
- 200 mg/kg bw: no mortality.

Clinical signs:

other: - 200 mg/kg: impaired general state (day 2), poor general state (hour 0-day 1), dyspnoea (hour 0-day 2), apathy (hour 0-day1), staggering (hour 0-hour 5), piloerection (hour 0-day 2) in all male animals. Poor general state, dyspnoea, apathy, staggering, t

Gross pathology:

Animals that died:
- 2000 mg/kg bw: glandular stomach: slight hyperemia of the glandular stomach, moderate erythema of the small intestine;
- 500 mg/kg bw: slight thickening of fore stomach and glandular stomach walls;
- 200 mg/kg bw (sacrificed animals): organs without particular findings.

Any other information on results incl. tables

Mortality:

Dose (mg/kg bw)	Gender	1 h	3 h	14 days
200	male	0/3	0/3	0/3
200	female	0/3	0/3	0/3
500	female	1/3	3/3	3/3
2000	female	3/3	3/3	3/3

Weight (g):

Dose (mg/kg)	Gender	day 0	day 7	day 14
200	male	181	243	283
200	female	176	210	224
500	female	188	-	-
2000	female	177	-	-

There is indication that the test substance causes local irritation to the exposed tissue.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 value is between 200 and 500 mg/kg and calculated to be 317 mg/kg bw.

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Executive summary:

To assess the acute oral toxicity after a single oral administration of ethyldiisopropylamine, a GLP study according to the acute toxic class method was conducted.

None of the animals (0/6, m/f) died after administration of 200 mg/kg bw. However clinical symptoms of toxicity were observed (poor general state, dyspnoea, apathy, staggering, tremor and twitching). All animals (3/3, f) died after receiving a dose of 500 mg/kg or 2000 mg/kg bw. Clinical symptoms were the same as observed for the 200 mg/kg dose group. Necropsy of the animals that died revealed hyperemia of the gastro-intestinal tract pointing to the irritating/caustic properties of the test substance. The test substance was applied in olive oil, which might have influenced the resorption properties and necropsy findings of this caustic substance to some extend.  The LD50 value is between 200 and 500 mg/kg and calculated to be 317 mg/kg bw.

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