Tetramethylammonium chloride

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study performed before test guidelines and GLP principles were in place. However missing information and shortcomings in description of the methods. No details on test substance (Lot/Batch number; purity).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1978

Report date:

1978

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Remarks:

Experiment was done before GLP principles were implemented.

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Tetramethylammonium chloride

EC Number:

200-880-8

EC Name:

Tetramethylammonium chloride

Cas Number:

75-57-0

Molecular formula:

C4H12N.Cl

IUPAC Name:

N,N,N-trimethylmethanaminium chloride

Details on test material:

- Name (as cited in test report): tetramethylammonium chloride

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: TNO in house breeding
- Age at study initiation: not described
- Weight at study initiation: males 197 - 352 g; female 105 - 200 g
- Fasting period before study: yes, overnight
- Housing: in groups of 5, in stainless steel cages
- Diet: ad libitum, stock diet
- Water: ad libitum, tap water
- Acclimation period: not necessary (in house breeding)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23-25C
- Humidity (%): not described
- Air changes (per hr): not described, "well-ventilated"
- Photoperiod (hrs dark / hrs light): not described

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 2% v/v

MAXIMUM DOSE VOLUME APPLIED: 6.2 ml/kg bw

Doses:

single doses of 0.06, 0.072, 0.086, 0.104 and 0.124 ml/kg body weight (corresponds to 30, 36, 43, 52 and 62 mg TMAC /kg bw)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: none performed
- Necropsy of survivors performed: yes
- Other examinations performed: no

Statistics:

The LD50 was calculated according to the method of Weil (Biometrics (1952) 249-263)

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

47 mg/kg bw

Based on:

other: TMAC

95% CL:

> 41 - < 50.5

Mortality:

Deaths occurred between 1 and 18 hours after dosing.

Clinical signs:

other: Within a few hours after treatment the rats showed sedation, clonic convulsions and dacryorrhoea. Coma was frequently observed. The survivors recovered gradually and looked quite healthy again at the end of the observation period.

Gross pathology:

Macroscopic examination of the survivors at autopsy did not reveal any treatment-related gross alterations.

Any other information on results incl. tables

dose		mortality
Solution ml/kg	Test substance (50% aqueous sol.) ml/kg	number		%
		males	females
3.0	0.060	0/5	0/5	0
3.6	0.072	0/5	1/5	10
4.3	0.086	2/5	2/5	40
5.2	0.104	2/5	5/5	70
6.2	0.124	3/5	4/5	70

Applicant's summary and conclusion

Interpretation of results:

highly toxic

Remarks:

Migrated information category 2 Criteria used for interpretation of results: EU

Conclusions:

In an oral toxicity study with rats in general according to OECD 401 (1987), the LD50 of a 50% aqueous solution of TMAC was found to be 0.094 ml/kg bw. This is equivalent to an LD50 of 47 mg/kg bw for pure TMAC. Therefore the substance is classified for oral toxicity in category 2 according to CLP Regulation (EC) 1272/2008.

Executive summary:

In an oral toxicity study with male and female rats in general according to OECD guideline 401 (1987), the rats were orally exposed to dilutions of a 50% aqueous solution of TMAC. Deaths occurred between 1 and 18 hours after dosing. Within a few hours after treatment the rats showed sedation, clonic convulsions and dacryorrhoea. Coma was frequently observed. The survivors recovered gradually and looked quite healthy again at the end of the observation period. The LD50 of the 50% aqueous solution of the test substance was found to be 0.094 ml/kg bw. This is equivalent to an LD50 of 47 mg/kg bw for pure TMAC. The substance is classified for oral toxicity in category 2 according to CLP Regulation (EC) 1272/2008.