Trimethylamine, N-oxide

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well documented report which meets basic scientific principles. Similar to guideline study; not GLP, no information regarding gross necropsy

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Similar to guideline study; not GLP, no information regarding gross necropsy

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Principles of method if other than guideline:

BASF Internal Procedure

GLP compliance:

no

Test type:

standard acute method

Species:

rat

Strain:

not specified

Sex:

male/female

Type of coverage:

occlusive

Vehicle:

not specified

Details on dermal exposure:

no details available

Duration of exposure:

24 hours

Doses:

2000, 5000 mg/kg bw

No. of animals per sex per dose:

3/sex/dose

Control animals:

not specified

Details on study design:

Animals were observed for 14 days after the application of the test substance to the shaved dorsal surface of the rat.
The average weight of the animals was 221 g (males) and 180 g (females).

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Remarks on result:

other: no further details available

Mortality:

No animals died.

Clinical signs:

other: Irregular breathing, staggering, spastic gait and apathy were observed. After 14 days animals were mostly free of clinical signs.

Interpretation of results:

GHS criteria not met

Conclusions:

Only clinical symptons were observed: irregular breathing, staggering, spastic gait and apathy. After 14 days animals were mostly free of clinical signs.

Executive summary:

According to an internal BASF procedure (1979), which is equivalent to OECD guideline 402 the acute dermal toxicity was investigated on 3 male and female rats each. As type of coverage occlusive was chosen, the exposure duration was 24 hours and the doses were 2000 and 5000 mg/kg bw. An LD50 greater than 5000 mg/kg bw was reported, due to the fact that no animal died at the highest dose concentration. Only clinical symptoms as irregular breathing, staggering, spatic gait and apathy were observed. After 14 days the animals were mostly free of these clinical signs.

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 402 (Acute Dermal Toxicity)

Principles of method if other than guideline:

BASF test: The product was applied once for 24 hours to the clipped skin of the back and flank (area about 42 cm²) unchanged in a dose of 5000 , 2000 or 400 mg/kg bw. The treated area of skin was then covered with an inert foil, which was secured in position with adhesive tape. The bandage was removed after an exposure period of 24 hours; subsequently, the test substance was washed off with warm water or a mixture of water/Lutrol and dried with cellulose.

GLP compliance:

no

Test type:

standard acute method

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)

Test animals

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: WIGA
- Weight at study initiation: male: 221 g (mean); female: 180 g (mean)
- Diet: Herlian MRH, ad libitum
- Water: tap water ad libitum

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE - Area of exposure: 42 cm
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Lutrol and Lutrol/water (1:1)
- Time after start of exposure: 24 h

Duration of exposure:

24 h

Doses:

400, 2000, 5000 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: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Remarks on result:

other: No mortalities occurred at highest dose.

Mortality:

No mortality occured

Clinical signs:

other: Systemic toxicity: irregular respiration, staggering, apathy, spastic gait. Local symptoms: after 24 h skin irritation was noted and after 14 days scaling of the skin was observed.

Gross pathology:

no abnormalities observed.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

No mortality occured at highest dose rate of 5000 mg/kg bw. Only clinical symptons were observed: irregular breathing, staggering, spastic gait and apathy. After 14 days animals were mostly free of clinical signs.

Executive summary:

BASF AG performed a test for acute toxicity by dermal application in 1979. Trimethylamine was applied once for 24 hours to the clipped skin of the back and flank (area about 42 cm²) unchanged in a dose of 5000 , 2000 or 400 mg/kg bw. The treated area of skin was then covered with an inert foil, which was secured in position with adhesive tape. The bandage was removed after an exposure period of 24 hours; subsequently, the test substance was washed off with warm water or a mixture of water/Lutrol and dried with cellulose. No mortality was observed, as well as no changes in body weight and no abnormalities in gross pathology. Clinical signs were differentiated in systemic (irregular respiration, staggering, apathy, and spastic gait) and local symptoms (skin irritation after 24 hours, scaling of the skin after 14 days).