N-methylisopropylamine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study conducted according to GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(2001)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

(2004)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

(2002)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japan MAFF Testing Guideline of 12 Nosan No. 8147 as this in line with OECD 423

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N-methylisopropylamine

EC Number:

225-266-7

EC Name:

N-methylisopropylamine

Cas Number:

4747-21-1

Molecular formula:

C4H11N

IUPAC Name:

methyl(propan-2-yl)amine

Details on test material:

- Name of test material (as cited in study report): N-Methylisopropylamine
- Physical state: liquid, yellowish
- Analytical purity: >99.9%
- Lot/batch No.: 8078/06/056
- Stability under test conditions: the stability of the test substance under storage conditions over the test period was guaranteed by the manufacturer, and the manufacturer holds this responsibility
- Storage condition of test material: room temperature, in the dark, under N2

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd Laboratory Animal Services, CH-4414 Füllinsdorf, Switzerland
- Age at study initiation: 9 to 11 weeks
- Mean weight at study initiation: about 176 g
- Fasting period before study: at least 16 hours before administration
- Housing: single housing in Makrolon cage, type III
- Diet (e.g. ad libitum): VRF1(P); SDS Special Diets Services, Altrip, Germany), ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 – 24
- Humidity (%): 20 – 80
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

DOSAGE PREPARATION AND APPLICATION
For the high dose, the liquid test substance was administered undiluted at an application volume of 2.99 mL/kg bw.
For the lower doses, test substance preparations in bidistilled water were used and the application volume was 3 mL/kg bw.

Doses:

2000 (one test group), 300 (one test group), 50 mg/kg bw (two test groups)

No. of animals per sex per dose:

As suggested by the OECD guideline nulliparous and nonpregnant female animals were used for the test, because there is no indication that male animals are likely to be more sensitive to the acute effects of the test substance.
Three females per test group were used.

Control animals:

no

Details on study design:

OBSERVATION PERIOD
Treatment was followed by an observation period of at least 21 days.
CLINICAL SIGNS AND MORTALITY
Observation for clinical signs was done several times on the day of administration and at least once each workday thereafter; check for any dead or moribund animal was made twice each workday and once on Saturdays, Sundays and on public holidays.
BODY WEIGHT
Individual body weights were recorded shortly before administration (day 0), weekly thereafter and on the last day of observation. Additionally, at day of death in animals that died or were sacrificed moribund starting with study day 2.
NECROPSY
At the end of the observation period the animals were sacrificed by CO2-inhalation and were subjected to gross pathology. No histological examinations were performed.
Examination of all animals that died before test ending was conducted as early as possible after death.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

50 - 300 mg/kg bw

Based on:

test mat.

Remarks on result:

other: All animals of the 2000 mg/kg bw group died within 1 hr post-treatment. One animal of the 300 mg/kg bw group died on day 2 and a further one was sacrificed in extremis on day 17 because of moribund state. All animals treated with 50 mg/kg bw survived.

Mortality:

All animals of the 2000 mg/kg bw group died within the first hour after administration. Thus, mortality at 2000 mg/kg bw was 100%.
One animal of the 300 mg/kg bw group was found dead on day 2 of observation whereas a further one needed to be sacrificed on day 17 because of moribund state. Thus, mortality at 300 mg/kg bw was about 70%.
All animals treated with 50 mg/kg bw survived.

Clinical signs:

other: Because the animals in the 2000 mg/kg bw group died immediately after administration, no clinical signs and findings were observed. Clinical signs seen in the 300 mg/kg bw group included impaired general state, dyspnoea, piloerection, red to orange-red di

Gross pathology:

Necropsy of animals that died:
Gross pathological examination of animals that died during the experiment (3/3 in the 2000 mg/kg bw group and 1/3 in the 300 mg/kg bw group) revealed dark red to brown discoloration of lung, black discoloration of heart, clotted blood in the thorax, petechial bleeding in the stomach and dark discoloration of liver, stomach, spleen, heart and small intestine.
Necropsy of animals sacrificed in extremis or at the end of the observation period:
Gross pathological examination of animals that were sacrificed revealed no abnormalities (2/3 in the 300 mg/kg bw group and 6/6 in the 50 mg/kg bw group).

Any other information on results incl. tables

N-Methylisopropylamine (MIPA): Acute oral toxicity test, individual body weight changes

Dose	2000 mg/ kg bw				300 mg/kg bw
	Individual weights (g)			Mean weight (g)	Individual weights (g)			Mean weight (g)
Animal	1	2	3		1	2	3
Day 0	176	179	178	178	171	175	176	174
Day 2	n.a.	n.a.	n.a.	n.a.	150*	n.r.	n.r.	n.r
Day 7	n.a.	n.a.	n.a.	n.a.	n.a.	174	161	168
Day 14	n.a.	n.a.	n.a.	n.a.	n.a.	197	157	177
Day 17	n.a.	n.a.	n.a.	n.a.	n.a.	n.r.	139**	n.r.
Day 21	n.a.	n.a.	n.a.	n.a.	n.a.	214	n.a.	214
Dose	50 mg/ kg bw				50 mg/kg bw
	Individual weights (g)			Mean weight (g)	Individual weights (g)			Mean weight (g)
Animal	1	2	3		1	2	3
Day 0	206	206	190	201	196	194	199	196
Day 7	226	226	210	221	218	215	218	217
Day 14	243	242	217	234	229	225	227	227
Day 17	n.r.	n.r.	n.r.	n.r.	n.r.	n.r.	n.r.	n.r.
Day 21	n.r.	n.r.	n.r.	n.r.	n.r.	n.r.	n.r.	n.r.
n.a., not applicable since animal died; n.r., not recorded; *, animal died; **,animal was sacrificed in extremis because of moribund state

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria