Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2019

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
not specified
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Trifluoro(piperidine)boron
EC Number:
209-752-6
EC Name:
Trifluoro(piperidine)boron
Cas Number:
592-39-2
Molecular formula:
C5H11BF3N
IUPAC Name:
piperidine; trifluoroborane
Test material form:
solid: crystalline

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
Species Wistar rats
Source Slovak Academy of Sciences Dobrá Voda, Slovak Republic
Number and Sex of Animals 9 females
Age at First Dose 8-9 weeks; female animals were non-pregnant and nulliparous
Animal Health Health condition of animals was examined by a veterinarian before initiation of the study.
Acclimation The animals were acclimated under the conditions identical to the conditions during the experiment 5 days prior to the start of treatment.
The acclimation was according to the standard operation procedure.
Housing Condition The animals were housed in plastic cages suspended on stainless steel racks, 3 animals per cage in a room equipped with central airconditioning. The average room temperature was maintained within the range of 22.95 ± 0.46 °C, relativ e humidity within 54.84 ± 2.66 %. The light regimen was set to a 12-hour light /12-hour dark cycle. Sanitation was perf ormed according to the standard operation procedures.
Diet The laboratory food ssniff (ssniff Spezialdiäten GmbH, Germany) was offered at recommended doses each day appr oximately at the same time. The certificate of analysis is included in the raw data.
Water The animals received tap water for human consumption. Supply of drinking was unlimited. The quality of drinking wate r is periodically analysed and recorded; certificate of analysis is included in the raw data.
Bedding Lignocel S3/4, Lufa - ITL GmbH, Germany
Animals Identification The animals in the cage were marked by a line (I-III) on the tail with a waterproof marker. Each cage was marked with the study code, ID of animals and date of administration of the test item.
Justification for the Choice of Species Normally females are used for testing according to OECD TG 423 because females are typically the more sensitive gender.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
The test item was administered in a single dose by gavage using a metal stomach tube. Animals were fasted 10-12 h prior to dosing (food but not water was withheld over-night). Following a period of fasting, animals were weighed and the test item administered. After test item administration, food was withheld for further 3-4 hours.
Doses:
The starting dose could be selected from the fixed dose levels of 5, 50, 300, and 2000 mg/kg body weight. A dose of 50 mg/kg body weight was used as a starting dose. One group of 3 females was dosed. Test item-related mortality was observed within few minutes after administration of the test item. In a second step 3 females were treated with the dose of 5 mg/kg body weight. All females survived 24 hours and therefore another 3 females (third step) were treated with the same dose of 5 mg/kg body weight.
No. of animals per sex per dose:
The starting dose could be selected from the fixed dose levels of 5, 50, 300, and 2000 mg/kg body weight. A dose of 50 mg/kg body weight was used as a starting dose. One group of 3 females was dosed. Test item-related mortality was observed within few minutes after administration of the test item. In a second step 3 females were treated with the dose of 5 mg/kg body weight. All females survived 24 hours and therefore another 3 females (third step) were treated with the same dose of 5 mg/kg body weight.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50 cut-off
Effect level:
25 mg/kg bw
Based on:
test mat.
Mortality:
Mortality of 3/3 females at a dose of 50 mg/kg body weight was noted. All 6/6 females survived the dose of 5 mg/kg body weight.
Clinical signs:
Test item-related mortality in females treated with the test item at a dose of 50 mg/kg body weight was observed within few minutes after administration of the test item in animals No 1, 2, 3. Tremor and spasms were registered in all three animals immediately after administration.
No mortality was observed in females treated with the test item at a dose of 5 mg/kg body weight. In animals No 7, 8 ,9, lethargy was noted immediately after administration of the test item and it persisted next 30 minutes. 2 hours after administration, piloerection was observed in the same three animals. The rest animals treated with the dose of 5 mg/kg (No 3, 4, 5) did not display signs of intoxication, change of health, nor any other adverse reaction.
Body weight:
The body weights of all survived animals increased during the study. A stagnation of the body weights in animal No 8 and No 9 was observed between the first and the second week after administration.
Gross pathology:
All animals were necropsied. During necropsy, no macroscopic findings were observed

Any other information on results incl. tables

The test item “BF3-piperidine-complex” administered to 3 females at a dose of 50 mg/kg body weight caused death of 3/3 animals. Spasm and tremor were observed immediately after administration. 6/6 animals survived a dose of 5 mg/kg body weight. Lethargy and piloerection were observed during the observation period in three animals. The rest animals did not display signs of toxicity during the first 4 hours and the 14-day observation period. The body weights of all animals increased during the study. A stagnation of the body weights in two animals was observed between the first and the second week after administration. During necropsy, no macroscopic findings were observed in animals treated with the dose of 50 mg/kg or 5 mg/kg. 

Applicant's summary and conclusion

Interpretation of results:
Category 2 based on GHS criteria
Conclusions:
The LD50 of the test item “BF3-piperidine-complex” is higher than 5 mg/kg body weight and lower than 50 mg/kg body weight after single oral administration to Wistar rats.
Based on Annex 2d Test Procedure with a Starting Dose of 50 mg/kg body weight of OECD Guideline 423 it can be concluded that the test item “BF3-piperidine-complex” is according to GHS criteria classified in Category 2 with a LD50 cut off value 25 mg/kg body weight, after single oral administration to Wistar rats
Executive summary:

The purpose of the study was to evaluate the potential toxic effect of the test item “BF3-piperidinecomplex” when administered as a single oral dose to Wistar rats.

The procedure according to OECD Guideline 423 Acute Toxic Class (ATC) method was used. 

The test item “BF3-piperidine-complex” administered to 3 females at a dose of 50 mg/kg body weight caused death of 3/3 animals within few minutes after administration Spasm and tremor were observed immediately after administration. 

6/6 animals survived a dose of 5 mg/kg body weight. Lethargy and piloerection were observed during the observation period in three animals. The rest animals did not display signs of toxicity during the first 4 hours and the 14-day observation period. The body weights of all survived animals increased during the study. A stagnation of the body weights in two animals was observed between the first and the second week after administration. During necropsy, no macroscopic findings were observed in animals treated with the dose of 50 mg/kg or 5 mg/kg. 

The LD50of the test item “BF3-piperidine-complex” is higher than 5 mg/kg body weight and lower than 50 mg/kg body weight after single oral administration to Wistar rats.

Based onAnnex 2d Test Procedure with a Starting Dose of 50 mg/kg body weight of OECD Guideline 423it can be concluded that the test item “BF3-piperidine-complex” is according to GHScriteria classified in Category 2 with a LD50cut off value 25 mg/kg body weight, after single oral administration to Wistar rats.