2-(dimethylamino)-2-methylpropan-1-ol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

03 Nov - 02 Dec 1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions. The documentation of materials and methods, and results is limited.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1982

Report date:

1982

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

limited documentation

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-(dimethylamino)-2-methylpropan-1-ol

EC Number:

230-279-6

EC Name:

2-(dimethylamino)-2-methylpropan-1-ol

Cas Number:

7005-47-2

Molecular formula:

C6H15NO

IUPAC Name:

2-(dimethylamino)-2-methylpropan-1-ol

Details on test material:

- Name of test material (as cited in study report): 2-Dimethylamino-2-methyl-1-propanol, 73% DMAMP, Polymeen A (P-2614)
- Substance type: clear, pale yellow liquid
- Analytical purity: 72.03%
- Lot/batch No.: 730H18DF36
- pH: 12.5

Test animals

Species:

rat

Strain:

other: Cox-SD albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 187 ± 8.8 g
- Fasting period before study: yes

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Justification for choice of vehicle: test substance is soluble in the vehicle (water)

Doses:

950, 1500, 1900, 2400 and 3000 mg/kg bw

No. of animals per sex per dose:

10

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: the animals were observed for mortality and signs of toxicity several times during the first day after dosing and daily thereafter. All animals were weighed before dosing, on day 7 and on day 14.
- Necropsy of survivors performed: yes. Animals that died during the study period were necropsied immediately and the surviving animals were necropsied after sacrifice on day 14.

In a range-finding study, the maximum dose possible to administer was 3000 mg/kg bw. Therefore this was selected as the highest dose in the main study.

Statistics:

The oral LD50 values, the 95% confidence limits (shown in parenthesis), and the slope (+SE) were calculated according to Finney (Probit Analysis, Cambridge University Press, 1971) adapted to BASIC computer program.

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

1 656 mg/kg bw

Based on:

test mat.

95% CL:

1 395 - 1 878

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

1 767 mg/kg bw

Based on:

test mat.

95% CL:

1 600 - 1 946

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 712 mg/kg bw

Based on:

test mat.

Mortality:

950 mg/kg bw: 1/10 males and 0/10 females died
1500 mg/kg bw: 1/10 males and 4/10 females died
1900 mg/kg bw: 7/10 males and 7/10 females died
2400 mg/kg bw: 10/10 males and 9/10 females died
3000 mg/kg bw: 10/10 males and 10/10 females died

Most of the animals died within 24 hours of dosing, while one female administered 2400 mg/kg bw and 2 males administered 1900 mg/kg bw died on day 5, 5 and 6, respectively. The mortality was caused by the local irritating effect of the test substance, as the main findings were hemorrhaging in the stomach and intestines.

Clinical signs:

other: 1500 mg/kg bw: lethargy, eye squint, hunched posture, and ataxia by the fourth hour after dosing in females, fully reversible within 24 h. 1900 mg/kg bw: lethargy, eye squint, hunched posture, and ataxia by the fourth hour after dosing in females and male

Gross pathology:

In the animals that died during the study period, the stomach and intestine were severely haemorrhaged. These effects are probably due to local irritation by the very alkaline test substance.

The presence of dark organs is not dose-related and may be a result of the method of sacrifice (the method was not reported).

1900 mg/kg bw: 5/10 males and 6/10 females had a dark spleen, while 1/10 females also had dark adrenals
2400 mg/kg bw: 3/10 females had a dark spleen
3000 mg/kg bw: 4/10 females had a dark spleen, kidneys and adrenals

One female administered 950 mg/kg bw had severe lung infection. This is not considered to be a treatment-related effect, as only one animal had this condition and no dose-related trend was observed. All other organs were grossly normal.

Any other information on results incl. tables

Table 1. Results, acute oral toxicity study

 

Dose [mg/kg bw]	Toxicological results*	Duration of clinical signs	Time of death	Mortality (%)
Males
950	1/0/10	-	Day 5	10
1500	1/0/10	-	Day 1	10
1900	7/10/10	3 h – day 5	Day 1 (5 rats), Day 5 (1 rat), Day 6 (1 rat)	70
2400	10/10/10	1 h - death	Day 1	100
3000	10/10/10	1 h - death	Day 1	100
LD50 = 1767 mg/kg bw (male)
Females
950	0/0/10	---	---	0
1500	4/10/10	3 h – day 1	Day 1	40
1900	7/10/10	3 h – day 6	Day 1	70
2400	9/10/10	2 h - death	Day 1 (8 rats) and 5 (1 rat)	90
3000	10/10/10	1 h - death	Day 1	100
LD50 = 1656 mg/kg bw (female)

                                                                                   

* first number = number of dead animals                                   

 second number = number of animals with clinical signs           

 third number = number of animals used                                 

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: Acute oral toxicity 4, H302
DSD: Xn, R22