Dimethyl(propyl)amine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

01 June - 07 June 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

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:

1996

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1996

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dimethyl(propyl)amine

EC Number:

213-139-9

EC Name:

Dimethyl(propyl)amine

Cas Number:

926-63-6

Molecular formula:

C5H13N

IUPAC Name:

dimethyl(propyl)amine

Specific details on test material used for the study:

- Lot/batch No.: K322/1

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Boehringer Ingelheim Pharma KG
- Age at study initiation: adult animals
- Weight range at study initiation: 150 - 300 g
- Housing: single housing in stainless steel wire mesh cages, type DK-III ( Becker & Co., Castrop-Rauxel)
- Diet: Kliba-Labordiet, Klingenthalmuehle AG Kaiseraugst, ad libitum
- Water: tap water, ad libitum
- Acclimation period: 1 week
- Fasting period before study: 16 h

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

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle:
1.) 200 mg/kg: 2g/100 mL
2.) 500 mg/kg: 5 g/100 mL
3.) 2000 mg/kg: 20 g/100 mL
- Amount of vehicle: 10 mL/kg
- Justification for choice of vehicle: corresponds to the physiological medium

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

CLASS METHOD:
According to the guideline OECD 423 adopted from 1996, 25, 200 or 2000 mg/kg bw can be selected as starting dose. Due to the physical and chemical characteristics of the substance and composition the mid dose was seen as the best choice. At first this value was tested on 3 male animals. In this experiment no mortality was observed. In the next step substance was tested with the same dosis on 3 female rats. Again, no mortality was observed. According to the guideline 2000 mg/kg bw was tested with 3 rats on male rats. Again 3 animals died. In the next step 500 mg/kg bw was tested with 3 male animals. Due to mortality in this group the same dose was applied at 3 animals of the other sex.

Doses:

200, 500, 2000 mg/kg bw

No. of animals per sex per dose:

200 mg/kg bw: 3/ sex (males and females)
500 mg/kg bw: 3/ sex (males and females)
2000 mg/kg bw: 3/ sex (males)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: body weight determination individually before administration, weakly thereafter and at the end of the study; signs and symptoms were recorded individually several times at day of administration, at least once each workday for each animal; mortality was checked twice each workday and once on other days.
- Necropsy of survivors performed: yes (gross pathology)

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

500 mg/kg bw

Based on:

test mat.

Mortality:

200 mg/kg bw: no mortality was observed (0/3 male animals; 0/3 female animals).
500 mg/kg bw: 1/3 male animals and 2/3 female animals died.
2000 mg/kg bw: all 3 treated male animals died.

Clinical signs:

other: At 200 mg/kg bw: no symptoms were detected for male and female animals. At 500 mg/kg bw: all female animals showed impaired, poor general state, dyspnoea, abdominal position, staggering, tremor, twitching, clonic convulsions, salivation, and lacrimation.

Gross pathology:

Animals that were sacrificed showed no particular findings in organs.
Animals that died had following findings:
At 2000 mg/kg bw, all animals showed severe hemorrhage in forestomach, glandular stomach and small intestine; the stomach muscles showed severe erythema
At 500 mg/kg bw, one male that died showed watery contents in the small intestine; one of the 2 females that died showed dilation (slight to moderate) of the stomach and small intestine, with watery contents. The second female that died showed slight hyperemia of the glandular stomach and in the liver, numerous foci were seen, with a diameter up to 2 mm, beige in colour, mainly affecting the right lateral lobe, and caudate process.

Any other information on results incl. tables

Table 1: Mortality

Male animals
dose [mg/kg] bw	200	500	2000
No of animals	3	3	3
Immediately  after application	0	0	1
after 1hr	0	0	3
after 1 day	0	1
after 14 days	0	1
overall mortality	0	2	3
Female animals
dose [mg/kg] bw	200	500
No of animals	3	3
Immediately  after application	0	0
after 3 hrs	0	1
after 1 day	0	1
after 14 days	0	0
overall mortality	0	2

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

An acute oral toxicity study with rat according to the OECD TG 423 (1996) was conducted, and the test item was applied at following dose levels: 200, 500 and 2000 mg/kg bw. At low and medium dose 3 male and 3 female rats and at high dose 3 male animals were tested.
Mortality was observed at highest dose (all 3 males died) and at medium dose (1 of 3 males and 2 of 3 females died). Therefore, the LD50 for DPMA is 500 mg/kg bw.