Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable well-documented study report, which meets basic scientific principles.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1984

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
Trimethylamine hydrochloride was administered to HC/CFY rats by gavage at a single dose of 2000 mg/kg bw.
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Trimethylamine hydrochloride salt, 58 % solution;
- Physical state: a clear liquid (received on 31. Jan 1984 and stored at ambient temperature).
- Stability under test conditions: Stability and absorption ot the test substance were not determined.

Test animals

Species:
rat
Strain:
other: HC/CFY (Remote Sprague-Dawley)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: not specified
- Age at study initiation: approximately four to six weeks of age
- Weight at study initiation: 86 to 111 g
- Fasting period before study: no. Access to food was only prevented overnight prior to and approximately 4 hours after dosing.
- Housing: housed in groups by sex in metal cages with wire mesh floors.
- Diet (e.g. ad libitum): ad libitum (a standard laboratory rodent diet (Laboratory Diet No. 1 Spratt's Rodent Breeding Diet (LAD1) Expanded obtained from Spratt's Specialist Services Division, new Malden, Surrey, England).
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 -23
- Humidity (%): 38 (mean)
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: the substance was administered as supplied by the sponsor at a volume not exceeding 1.9 mL/kg (S.G.1.038).
Doses:
2.0 g/kg bw (single oral dose).
No. of animals per sex per dose:
5 males and 5 females in total.
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days. Animals were observed soon after dosing, then at frequent intervals for the remainder of Day 1. On subsequent days the animals were observed at least twice. Clinical signs were recorded at each observation.
- Frequency of observations and weighing: daily observations; individual bodyweights of rats were recorded on days 1 (day of dosing), 8 and 15 and at death.
- Necropsy of survivors performed: yes. Surviving animals were killed on day 15 by cervical dislocation. All animals were subjected to a macroskopic post mortem examination (opening the abdominal and thoracic cavities). The macroskopic appearance of abnormal organs was recorded.
- Other examinations performed: approximate time of death of individual rats; nature, severity, approximate time of onset and duration of each toxic sign.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 2 000 mg/kg bw
Mortality:
3 rats dies following treatment at 2.0 g/kg bw within 3 and 20 hours of dosing.
Clinical signs:
- Pilo-erection, lethargy, decreased resypiratory rate and pallor pf the extremities.
The signs were accompanied by:
- abnormal body carriage (hunched posture),
- abnormal gait (waddling) and
- ptosis
amongst treated rats,
as well as
- body tremor and
- ataxia in the rats that subsequently died.
Body weight:
Slight bodyweight losses were recorded for male rats that died.
Bodyweight gains of survinving rats were normal on Day 8 and 15.
Gross pathology:
Autopsy revealed haemorrhage of the lungs and pallor of liver in the two male rats, with pallor of the spleen in one and pallor of the kidneys in the other one.
One male rats showed thickening of the glandular region of the stomach and intestine. The female rats was cannibalised so a meaningsful autopsy could not be undertaken.

Terminal autospy findings of surviving rats was normal.

Applicant's summary and conclusion

Interpretation of results:
other:
Remarks:
EU-GHS criteria not met
Conclusions:
Deaths occurred amongst rats treated at 2.0 g/kg bodyweight with trimethylamine hydrochloride salt, 58 % soultion. The acute median lethal dose (LD 50) is expected to be in the region of 2.0 g/kg body weight.
Executive summary:

The acute oral toxicity of trimethylamine hydrochloride was investigated in HC/CFY rats by standard acute method (OECD 401, Huntingdon Research Centre plc., 1984). At a single oral dose of 2 g/kg bw 3 out of 10 rats died. The clinical signs were pilo-erection, lethargy, decreased respiratory rate and pallor of the extremities. The signs were accompanied by abnormal body carriage (hunched posture), abnormal gait (waddling) and ptosis or body tremor and ataxia in the rats that subsequently died. Slight bodyweight losses were recorded for male rats that died. Bodyweight gains of survinving rats were normal on Day 8 and 15. Autopsy revealed haemorrhage of the lungs and pallor of liver in the two male rats, with pallor of the spleen in one and pallor of the kidneys in the other one. One male rats showed thickening of the glandular region of the stomach and intestine. The female rats was cannibalised so a meaningsful autopsy could not be undertaken. Terminal autospy findings of surviving rats was normal.

In conclusion, an approximate lethal dosis is around 2 g/kg bw or 2000 mg/kg bw.

Based on the LD50 around 2 g/kg bw, classification is not warranted according to the criteria of EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.