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Acute Toxicity: oral

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acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2018-06-25 - 2018-08-09
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference Type:
study report
Report Date:

Materials and methods

Test guideline
according to
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
Adopted: 17th December 2001
GLP compliance:
yes (incl. certificate)
The study was conducted in compliance with principles of Good Laboratory Practice: -OECD Principles on Good Laboratory Practice (as revised in 1997), ENV/MC/CHEM (98)17 -EC Commission Directive 2004/10/EC of 11 February 2004 (Official Journal No L 50/44)
Test type:
acute toxic class method
Limit test:

Test material

Test material form:
solid: crystalline
Specific details on test material used for the study:
Test Item: BF3-Ethylamine-Complex
Lot Number: 24002194
CAS No: 75-23-0
EINECS-No: 200-852-5
Molecular formula: C2H7BF3N
Molecular weight: 112.9 g/mol
Purity: 97.1% (m/m) (Kieldahl titration, total organic nitrogen, TON)
Appearance: white crystalline powder
Composition: Boron trifluoride-monoethylamine-complex
Homogeneity: homogeneous
Production Date: 29.11.2017
Expiry Date: 29.11.2020
Storage: Room Temperature (20 ± 5°C)
Test Item Handling and Storage: According to SPPA-00147-BIO, Test and Reference Items

Test animals

Details on test animals 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, relative humidity within 54.84 ± 2.66 %. The light regimen was set to a 12-hour light /12-hour dark cycle. Sanitation was performed according to the standard operation procedures.
Diet: The laboratory food ssniff (ssniff Spezialdiäten GmbH, Germany) was offered at recommended doses each day approximately 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 water 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
olive oil
Vehicle: Olive oil Lot Number: L71143 Expiry Date: 10/2018 Manufacturer: Oleificio Luca, Italy Storage: 20 ± 5 °C Justification for the Choice of Vehicle: Olive oil is a common vehicle in toxicity studies like OECD TG 423
Details on oral exposure:
The required amount of the test item (according to the body weight and dose) was mixed with vehicle
(Olive oil) shortly before administration. The doses of 300 mg/kg was administered in a volume of 5
mL/kg body weight and the dose of 2000 mg/kg was administered in a volume of 10 mL/kg.
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.
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 300 mg/kg body weight was used as a starting dose. One group of 3 females was
dosed. Test item-related mortality was not observed during 48 hours and therefore, in a second step,
another 3 females were treated at the same dose. All females survived 24 hours and therefore another
3 females (third step) were treated at the limit dose of 2000 mg/kg body weight.
Control animals:

Results and discussion

Effect levels
Key result
Dose descriptor:
Effect level:
500 mg/kg bw
Based on:
test mat.
Clinical signs:
Animals were observed individually immediately after administration of the test item and 0.5, 1, 2,
and 4 hours later. Each animal was inspected daily for the next 14 days.
Observations included: changes in skin, fur, eyes, mucous membranes, respiratory, circulatory,
autonomic and central nervous systems, somatomotor activity, and behavioural pattern. Particular
attention was given to potential neurologic endpoints such as tremors, convulsions, salivation,
diarrhoea, lethargy, sleep and coma.
Body weight:
Individual weights of animals were measured immediately prior to administration of the test item and
weekly thereafter. Weight differences after first and second weeks after administration were
calculated and recorded.
Gross pathology:
All test animals were subjected to gross necropsy and the results were recorded for each animal.
All animals were necropsied. During necropsy, no macroscopic findings were observed in animals
treated with the dose of 300 mg/kg body weight.
In animals treated with the dose of 2000 mg/kg, diffusely red coloured mucosa of the small intestine
and stomach was registered.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
The LD50 of the test item “BF3-Ethylamine-Complex” is higher than 300 mg/kg body weight and
lower than 2000 mg/kg body weight after single oral administration to Wistar rats.
Based on Annex 2c Test Procedure with a Starting Dose of 300 mg/kg body weight of OECD
Guideline 423 it can be concluded that the test item “BF3-Ethylamine-Complex” is according to GHS
criteria classified in Category 4 with a LD50 cut off value 500 mg/kg body weight, after single oral
administration to Wistar rats.
Executive summary:

The test item “BF3-Ethylamine-Complex” administered to 6 females at a dose of 300 mg/kg body

weight did not cause death. Four hours after administration of the test item, piloerection was noticed

in two animals. The rest animals did not display signs of toxicity during the observation period. The

body weights of all animals increased during the study. During necropsy, no macroscopic findings

were observed.

3/3 animals did not survive a limit dose of 2000 mg/kg body weight. Lethargy and tremor were

observed during the observation period. During necropsy, diffusely red coloured mucosa of the small

intestine and stomach was registered.