Tetramethylammonium hydroxide

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

April-June 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 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

3 animals instead of 5 animals (as required by the guidelines) were used at 200 and 2000 mg/kg bw and at the discriminating level for classification 5 animals/sex were used

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

yes

Remarks:

idem

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

idem

Test guideline 4

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

TMA248WA

IUPAC Name:

TMA248WA

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:

male/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. 9-12 weeks old)
- Weight at study initiation: 344-366 g for males; 184-294 g for females; one female at 1000 mg/kg bw exceeded the +/- 20% sex mean body weight range, but this is not considered to have influenced the study results
- Housing: individually housed 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): 19.6-22.7
- 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

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: approx. 25 cm2 for males and 18 cm2 for females
- % coverage: 10
- Type of wrap if used: surgical gauze covered with aluminium foil and Coban elastic bandage

REMOVAL OF TEST SUBSTANCE
- Washing: with water
- Time after start of exposure: 24 hrs

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 200, 1000 or 2000 mg/kg bw
- Constant concentration used: yes

Duration of exposure:

24 hours

Doses:

200, 1000 and 2000 mg/kg bw; initially 3 females were treated at 200 mg/kg bw. In a stepwise procedure 3 females were dosed at 1000 and 2000 mg/kg bw and 2 females and 5 males at 1000 mg/kg bw to complete the set of animals at the highest possible dose. The test was performed with less animals combining the procedures from the acute oral toxic class method and OECD 402, which is considered not to have affected the integrity of the study.

No. of animals per sex per dose:

3 females at 200 and 2000 mg/kg bw; 5/sex at 1000 mg/kg bw

Control animals:

not required

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 weight: pre-administration (day 1), day 8 and 15
- Necropsy of survivors performed: yes, all animals

Statistics:

Not applicable

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 000 - 2 000 mg/kg bw

Based on:

dissolved

Remarks:

(2.5% aqueous solution)

Effect levels 2

Sex:

male/female

Dose descriptor:

LD50

Effect level:

25 - 50 mg/kg bw

Based on:

other: (pure substance)

Mortality:

2000 mg/kg bw: all three animals died/were sacrificed
1000 and 200 mg/kg bw: no mortality observed

Clinical signs:

other:

Body weight:

lower than 10% body weight loss

Remarks:

No effect on body weight was noted.

Gross pathology:

No abnormalities were found at macroscopic examination of all animals.

Applicant's summary and conclusion

Interpretation of results:

other: Category 1

Remarks:

according to EC 1272/2008

Conclusions:

The dermal LD50 of TMA248WA in Wistar rats was established to be in the range of 1000-2000 mg/kg bw, which is equivalent to 25 - 50 mg/kg bw for the pure substance.
According to EC Regulation 1272/2008 the pure substance should be classified in category 1.

Executive summary:

In an acute dermal toxicity study with TMA248WA performed according to OECD 402, the three animals exposed to 2000 mg/kg bw died/were sacrificed. At 200 and 1000 mg/kg bw no mortality occurred. Clinical signs observed at 2000 mg/kg bw included restless behaviour, clonic spasms, hunched posture, uncoordinated movements and laboured respiration. At 1000 and 200 mg/kg bw flat posture and/or chromodacryorrhoea were seen. No abnormalities were observed at macroscopic examination.

The dermal LD50 of TMA248WA in Wistar rats was established to be in the range of 1000-2000 mg/kg bw, which is equivalent to 25 - 50 mg/kg bw for the pure substance.

According to EC Regulation 1272/2008 the pure substance is classified in category 1.