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Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
November 2013 - January 2014
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report date:
2014

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
There was a deviation to the OECD Guideline 423 in one case: the first clinical observation was 50 minutes after the treatment instead of 30 minutes after the treatment in group I. This difference does not influence the result of the study.
Principles of method if other than guideline:
There was a deviation to the OECD Guideline 423 in one case: the first clinical observation was 50 minutes after the treatment instead of 30 minutes after the treatment in group I. This difference does not influence the result of the study.
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Triethylammonium bromide
EC Number:
211-263-8
EC Name:
Triethylammonium bromide
Cas Number:
636-70-4
Molecular formula:
C6H15N.BrH
IUPAC Name:
N,N-diethylethanaminium bromide
Test material form:
solid: crystalline
Details on test material:
Name triethylammonium bromide
Batch no. 32541
Appearance white crystals
Composition triethylammonium bromide, water
CAS No. 636-70-4
EINECS-No. 211-263-8
Molecular formula C6H16BrN
Molecular weight 182.10 g/mol
Purity 98.2 % (argentometry)
Homogeneity homogeneous
Production date 11. Sep. 2013
Expiry date 10. Sep. 2028
Storage room temp. (20 ± 5 °C); kept away from light

Test animals

Species:
rat
Strain:
other: Crl:(WI)BR rats
Sex:
female
Details on test animals or test system and environmental conditions:
Experimental Animals
Species and strain: Crl:(WI)BR rats
Source: TOXI COOP ZRT. Cserkesz u. 90.
1103 Budapest, Hungary
Hygienic level at arrival: SPF
Hygienic level during the study: Good conventional
Justification of strain: The Wistar rats as a rodent is one of the standard species
of acute toxicity studies
Number of animals: 3 animals/group
Sex: Female, nulliparous and non pregnant animals
Age of animals: Young adult rat, 8 weeks old in first and second step
Body weight range
at starting (first step): 194 - 200 g
Body weight range
at starting (second step): 190 - 200 g
Acclimatization time: 5 days in first step and 6 days in second step

Husbandry
Animal health: Only healthy animals were used for the study. Health
status was certified by the study director.
Room: 5/I (E building)
Housing: Group caging (3 animals/cage)
Cage type: Type II polypropylene/polycarbonate.
Bedding: Laboratory bedding.
Light: Artificial light, from 6 a.m. to 6 p.m.

Food and Water Supply
Animals received ssniff® SM R/M-Z+H complete diet for rats and mice produced by ssniff Spezialdiäten GmbH, D-59494 Soest Germany and tap water from municipal supply, as for human consumption from bottle ad libitum.
The diet and drinking water are periodically analysed and are considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study. Copies of the relevant Certificates of Analysis are maintained in Toxi-Coop Zrt.’s archive.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
Vehicle
Name: Aqua purificata Ph.Hg. VIII.
Batch number: 1306-5519
Date of expiration: 19.12.2013
Produced by: Parma Produkt Kft.
Doses:
Starting dose was selected on the basis of the available information about the test item. The acute toxic class method was carried out involving a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats. Only one animal died in the first step at 2000 mg/kg bw dose level, so treatment with 2000 mg/kg bw was repeated on further three female rats. Only one animal died in the second step, too, so the test was finished, the stopping criteria of Annex 2d of OECD Guideline No. 423 (presented in Appendix VII) was met.
No. of animals per sex per dose:
6
Control animals:
no

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
dissolved
Remarks on result:
other: The method used, was not intended for the precise calculation of a precise LD50 value.
Mortality:
Altogether two animals treated with 2000 mg/kg single oral dose of the test item triethylammonium bromide died during the study.
One rat (No.: 9530) of group 1 died on the treatment day 1 hour after the treatment and one rat (No.: 9534) of group 2 died on the treatment day 1 hour after the treatment, as well. Deaths seemed to be consequences of systemic toxic effect of the test item. Four animals (No.: 9527, 9529, 9535, 9536) survived until the end of the 14-day observation period.
Clinical signs:
other: In group 1 treated with 2000 mg/kg bw dose clinical sign of reaction comprised of increased activity (2 cases of 39 observations), decreased activity (11/39), pain reaction (11/39), vocalization (8/39), restlessness (12/39), irritability (8/39), tremor (1
Gross pathology:
Two rats (No.: 9530, 9534) treated with 2000 mg/kg bw dose of the test item spontaneously died during the study. The other animals survived until the scheduled necropsy on Day 15. Internal necropsy finding as pale kidneys was observed in animal No.: 9529 of group 1 and in animal No.: 9536 of group 2. This alteration could not be related to the test item toxic effect, but was regarded an individual variation. Most likely the observation is a congenital anomaly.

Any other information on results incl. tables

Evaluation Two out of six animals treated with 2000 mg/kg bw dose of the test item died during the study. One animal died in group 1 and one animal died of group 2. The observed clinical signs were related to the effect of the test item. The test item did not influence the body weights of animals. Autopsy revealed no treatment related pathological changes.

Applicant's summary and conclusion

Interpretation of results:
other: GHS category 5
Remarks:
Criteria used for interpretation of results: expert judgment
Conclusions:
The method used, was not intended for the precise calculation of a precise LD50 value.
The test item was ranked into classes of Globally Harmonized Classification System (GHS) described in the OECD Guideline No. 423 as below:

Dose (mg/kg bw): 2000
Mortality (dead/treated): 2/6
LD50 (mg/kg bw): above 2000
GHS category: 5
Executive summary:

General information:

An acute toxic class method was carried out involving a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats. Only one animal died in the first step at 2000 mg/kg bw dose level, therefore treatment with 2000 mg/kg bw was repeated on further three female rats. Only one animal died in the second step, too, so the test was finished, the stopping criteria of Annex 2d of OECD Guideline No. 423 was met. Animals were weighed, observed for lethality and toxic symptoms for 14 days after the treatment. Gross pathological examination was carried out in animals died on the Day 1, as well as 15th day after the treatment in survivor animals.

Lethality, Clinical symptoms and Body weight:

Two rats dosed at 2000 mg/kg bw test item died on Day 1, all other rats survived until the end of the 14-day observation period.

In the first step, CNS symptoms (decreased activity, increased activity, pain reaction, vocalization, restlessness, irritability, tremor, tonic convulsion, crouching, closed eyes), disturbance of coordination (abnormal gait) and disturbances of autonomic functions

(salivation, piloerection, dyspnoea) were observed in animals between treatment day and Day 1.

In the second step, CNS symptoms (decreased activity, increased activity, pain reaction, vocalization, restlessness, irritability, tremor, tonic convulsion, crouching, closed eyes), disturbance of coordination (abnormal gait) and disturbances of autonomic functions

(piloerection, dyspnoea) were observed in animals between treatment day and Day 1.

The body weight development was undisturbed in all survivor animals.

Gross pathology:

Two animals treated with 2000 mg/kg bw dose died spontaneously during the study. Four animals were sacrificed as scheduled during the study. All organs of all experimental animals proved to be free of treatment related gross pathological changes.