Tribenzylamine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2021-01-26 to 2021-03-30

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2021

Report date:

2021

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

December 17, 2001

Deviations:

yes

Remarks:

Please refer to "Principles of method if other than guideline".

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2008

Deviations:

yes

Remarks:

Please refer to "Principles of method if other than guideline".

Principles of method if other than guideline:

The relative humidity varied from 26.5 – 55.0 %. Therefore, the relative humidity was transiently outside the guideline range of 30 - 70 %. This minor transient deviation did not influence the integrity or outcome of the study.

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Tribenzylamine

EC Number:

210-638-3

EC Name:

Tribenzylamine

Cas Number:

620-40-6

Molecular formula:

C21H21N

IUPAC Name:

tribenzylamine

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Crl:WI (Han)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River GmbH, Sulzfeld, Germany
- Females nulliparous and non-pregnant: not specified
- Age at study initiation: 9 weeks
- Weight at study initiation: 167 g (range from 151 to 177 g)
- Fasting period before study: yes. Diet was withheld from about 17 to 20 hours before start of treatment until 4 hours after administration.
- Housing: group-housed before treatment (type IV Makrolon® cages), single after treatment (type III Makrolon® cages), group-housed starting 1 day after treatment; on softwood bedding material (ABEDD LTE E-001, ABEDD LAB&VET Service GmbH, Austria) with play tunnels (Ref. 14153, Plexx BV, Netherlands)
- Diet: ad libitum; with fasting before treatment; maintenance diet (VI534, ssniff Spezialdiaten GmbH, Germany)
- Water: ad libitum; community water
- Acclimation period: at least 5 days
- Microbiological status when known: not specified; The health status of the rats was checked upon arrival and immediately before start of the experimental phase.
- Method of randomisation in assigning animals to test and control groups: not specified

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.2 - 23.3
- Humidity (%): 26.5 - 55.0
- Air changes (per hr): not specified; fully air-conditioned room
- Photoperiod (hrs dark / hrs light): not specified

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 0.25 % aqueous hydroxypropylcellulose

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 and 200 g/L
- Amount of vehicle: 10 mL/kg
- Justification for choice of vehicle: A well-tolerated and established standard vehicle was used.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION: The test item preparation was made directly before administration. Appropriate amounts of the test item were suspended in the vehicle using a spatula, a mini shaker (Vortex Genie 2®, Scientific Industries Inc, New York, USA), Ultra-Turrax device (Ultra-Turrax T25, IKA®-Werke GmbH & Co. KG, Staufen, Germany) and a magnetic stirrer. The test item preparation was administered within less than 1 hour after preparation. The stability of the test item in the vehicle was not investigated.

CLASS METHOD
- Rationale for the selection of the starting dose: The toxic potential of the test item could not be estimated Therefore, the study was started in 3 females with 300 mg/kg.

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

6 females per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: On the day of treatment, each animal was observed for mortality and for symptoms of intoxication for at least 6 hours after administration. On the following days, the rats were examined once daily. All animals were weighed before treatment (day 1) and on day 2, 4, 6, 8, 11, 13 and 15. The animals treated with 2000 mg/kg were additionally weight on day 3.
- Necropsy of survivors performed: yes
- Clinical signs including body weight: yes

Statistics:

No statistical analysis was conducted.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was seen.

Clinical signs:

other: No clinical signs of toxicity were observed.

Gross pathology:

No organ alterations were identified during the gross pathological examination.

Other findings:

No other findings observed.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test item has no acute toxic potential under the conditions of the present study, and the LD50 value is higher than 2000 mg/kg after single oral administration in female rats.

Executive summary:

A study according to OECD TG 423 was conducted to identify potential toxic effects of the test item, after single oral administration to rats in a stepwise procedure. The study was started with 300 mg/kg bw in 3 female rats, continued with further 3 females treated with 300 mg/kg bw. Due to the fact, that no mortality was seen after treatment with 300 mg/kg bw, further 6 females were treated with 2000 mg/kg bw. Mortality and clinical signs were monitored for at least 6 hours after administration and then daily. All animals were weighed before treatment (day 1) and on days 2, 4, 6, 8, 11, 13, and 15. At the end of the observation period, all surviving rats were sacrificed and subjected to a detailed necropsy. No mortality occurred during the course of this study. No clinical signs of toxicity were observed. The body weight gain on day 2 of three rats treated with 2000 mg/kg bw was lower compared to all other rats. The body weight development of all other rats was inconspicuous throughout the study. The gross pathological examination revealed no organ alterations. The test item has no acute toxic potential under the conditions of the present study, and the LD50 value is higher than 2000 mg/kg after single oral administration in female rats.