Trimethylamine, N-oxide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

22. Aug 1978 - 11. Oct 1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well documented report which meets basic scientific principles.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

BASF-Test: The study was conducted according to an internal BASF method which in principle is comparable to the OECD Guideline 401.
A test group consisting of 5 animals/sex was treated by single gavage application with an aqueous solution of the test substance. The animals were observed for mortality and for clinical symptoms of toxicity. At the end of the observation period of 7 days, the surviving animals were sacrificed for the purpose of necropsy; animals that died during the observations period also were subjected to necropsy.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Trimethylamine

EC Number:

200-875-0

EC Name:

Trimethylamine

Cas Number:

75-50-3

Molecular formula:

C3H9N

IUPAC Name:

N,N-dimethylmethanamine

Details on test material:

- Name of test material (as cited in study report): Trimethylamin 45 % (liquid)
CAS 75-50-3 (trimethylamine), purity not specified;

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: WIGA
- Weight at study initiation: male: 220 g (mean); female: 178 g (mean)
- Fasting period before study: 15 - 20 h before application
- Diet: Herlian MRH; Eggermann; Germany, ad libitum
- Water: tap water ad libitum

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Doses:

215, 316, 464, 681 and 1000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: days 2-4, 7 and 13
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Animals were weighed before the experiment, and then on days 2-4, 7 and 13 of the experiment. Food was withheld from animals for a period of 15-20 hours before the application of the test substance, but water was available.  

Statistics:

A probit analysis was used to determine the LD50 value.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

766 mg/kg bw

95% CL:

654 - 901

Mortality:

No animals died in the three lowest groups, but 3/10 and 9/10 died in the two highest dose groups. No animals died in the first hour after administration of the test substance, but animals did die within the first 24 hours.

Clinical signs:

other: Animals of the two highest doses showed dyspnoea, apathy, aggressiveness, staggering, tremor, spastic gait, ruffled fur, diarrhea, exsiccosis, agglutinated snouts and poor general state.

Gross pathology:

Animals that died:
Heart: acute dilatation and congestive hyperemia;
Lung: slight acute swelling;
Liver: peripheral lobule marking;
Stomach: corroded mucous membranes of glandular stomach, bloody content;
Intestine: atonic, corroded mucous membranes, slight hydrothorax

Any other information on results incl. tables

Mortality:

Dose (mg/kg bw)

1 h

24 h

48 h

7 days

14 days

male

female

male

female

male

female

male

female

male

female

1000

0/5

0/5

4/5

4/5

4/5

5/5

4/5

5/5

4/5

5/5

681

0/5

0/5

0/5

1/5

0/5

1/5

1/5

2/5

1/5

2/5

464

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

316

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

215

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

Mean weight (g):

Dose (mg/kg)	gender	day 0	day 2-4	day 7	day 13
1000	male	260	212	269	324
	female	190	-	-	-
681	male	190	170	217	259
	female	170	160	188	208
464	male	190	198	245	279
	female	170	185	201	210
316	male	190	211	249	254
	female	170	189	203	214
215	male	270	272	320	340
	female	190	199	214	222

The test substance caused systemic toxicity (including mortality) and local irritation in a dose dependend manner.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Criteria used for interpretation of results: not specified

Conclusions:

The test substance caused systemic toxicity (including mortality) and local irritation in a dose dependent manner.

Executive summary:

An acute toxicity study was performed by BASF AG in 1979 comparable to the OECD Guideline 401. A test group consisting of 5 rats (strain: Sprague-Dawley)/sex was treated by single gavage application with an aqueous solution of the test substance trimethylamine. The animals were observed for mortality and for clinical symptoms of toxicity. At the end of the observation period of 7 days, the surviving animals were sacrificed for the purpose of necropsy; animals that died during the observations period also were subjected to necropsy. The initial concentrations were 215, 316, 464, 681, and 1000 mg/kg bw. As effect level LD50 was 766 mg/kg bw. No animals died in the three lowest groups, but 3/10 and 9/10 died in the two highest dose groups. No animals died in the first hour after administration of the test substance, but animals did die within the first 24 hours. Animals of the two highest doses showed dyspnoea, apathy, aggressiveness, staggering, tremor, spastic gait, ruffled fur, diarrhea, exsiccosis, agglutinated snouts and poor general state. The test substance caused systemic toxicity (including mortality) and local irritation in a dose dependend manner.