Tetramethylammonium hydroxide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

April - May 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study has been performed in accordance with OECD/EC guidelines and GLP principles.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: JMAFF, 12 Nohsan, Notification no 8147, November 2000, including the most recent partial revisions

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Tetramethylammonium hydroxide

EC Number:

200-882-9

EC Name:

Tetramethylammonium hydroxide

Cas Number:

75-59-2

Molecular formula:

C4H12N.HO

IUPAC Name:

N,N,N-trimethylmethanaminium hydroxide

Test material form:

other: 2.5% aqueous solution

Details on test material:

- Name of test material (as cited in study report): TMA248WA
- Physical state: clear colourless liquid
- Analytical purity: 2.5% (solution in water)
- Lot/batch No.: 05C14001B
- Expiration date of the lot/batch: 13 February 2007
- Storage condition of test material: at room temperature in the dark
- pH 13.21 (determined at test lab)

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: young adults (approx. 11 weeks old)
- Weight at study initiation: 195-258 g
- Fasting period before study: yes, overnight
- Housing: group housing of 3 animals per cage in Macrolon cages containing purified sawdust as bedding material and paper as cage enrichment
- Diet: free access to standard pelleted laboratory animal diet (Altromin (code VRF 1), Lage, Germany)
- Water: free access to tap-water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.6-22.6
- Humidity (%): 27-73; deviations from the minimum level of humidity occurred; based on laboratory historical data these deviations were considered not to have affected the study results
- Air changes (per hr): approx. 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 15 April to 3 May 2005

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Remarks:

= 2.5% aqueous solution

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2.02 ml/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: no rationale given

Doses:

two groups at 300 mg/kg bw followed by a group at 2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

OBSERVATIONS:
- Mortality/viability: twice daily
- Clinical signs: at periodic intervals on day of dosing and once daily thereafter
- Body weights: pre-administration (day 1) and on day 8 and 15
- Necropsy of survivors performed: yes, all animals

Statistics:

Not applicable

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

300 - 2 000 mg/kg bw

Based on:

dissolved

Remarks:

(2.5% TMAH)

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

7.5 - 50 mg/kg bw

Based on:

other: (pure TMAH)

Mortality:

No mortality occurred in females dosed at 300 mg/kg bw. Two females at 2000 mg/kg bw were found dead and the remaining animal was sacrificed for humane reasons on day 1.

Clinical signs:

other: 300 mg/kg bw: hunched posture on day 1 2000 mg/kg bw: hunched posture, lethargy, flat posture, slow breathing, laboured respiration and/or ptosis

Body weight:

other body weight observations

Remarks:

Reduced body weight gain and body weight loss was noted among animals at 300 mg/kg bw.

Gross pathology:

No abnormalities were observed at macroscopy of surviving animals. Macroscopic examination of animals found dead revealed reddish discolouration of the glandular mucosa of the stomach in one female.

Applicant's summary and conclusion

Interpretation of results:

other: Category 2

Remarks:

according to EC 1272/2008

Conclusions:

The oral LD50 of TMA248WA in Wistar rats was established to be within the range of 300-2000 mg/kg bw, which corresponds to an LD50 of 7.5-50 mg/kg bw for the pure substance.
According to EC Regulation 1272/2008, pure TMAH is classified in category 2.

Executive summary:

In an acute oral toxicity test performed according to OECD 423, no mortality occurred at 300 mg/kg bw, but all three animals died/were killed at 2000 mg/kg bw. Hunched posture was noted at 300 mg/kg bw on day 1. At 2000 mg/kg bw hunched posture, lethargy, flat posture, slow breathing, laboured respiration and/or ptosis were seen. Reduced body weight gain and body weight loss was noted at 2000 mg/kg bw. Macroscopic examination of animals that died revealed reddish discolouration of the glandular mucosa of the stomach in one female. The LD50 was determined to be within the range of 300 -2000 mg/kg bw, which corresponds to an LD50 of 7.5-50 mg/kg bw for the pure substance. According to EC Regulation 1272/2008 pure TMAH is classified in category 2.