Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2018-06-28 - 2018-08-09
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report date:
2018

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity: Fixed Dose Procedure)
Version / remarks:
revised in 1997
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
yes

Test material

1
Chemical structure
Reference substance name:
Ethylamine--boron trifluoride
EC Number:
200-852-5
EC Name:
Ethylamine--boron trifluoride
Cas Number:
75-23-0
Molecular formula:
C2H7BF3N
IUPAC Name:
ethanamine; trifluoroborane
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

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
Species: Wistar rats
Source: Dobrá Voda, Slovak Republic
Number and Sex of Animals: 3 females
Age at First Dose: 8-9 weeks; female animals were non-pregnant and nulliparous
Animal Health: The health condition of animals was examined by a veterinarian before initiation of the study.
Acclimation: The animals were acclimated to the condition 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, 1-3 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. The sanitation was performed according to the standard operation procedures.
Diet: A laboratory food ssniff (ssniff Spezialdiäten GmbH) was available ad libitum. The certificate of analysis is included in the raw data.
Water: The animals received tap water for human consumption. Supply of drinking water was unlimited. The quality of drinking water is periodical analysed (including microbiological control) and recorded; certificate of analysis is included in raw data.
Bedding: Lignocel S3/4, Lufa - ITL GmbH, Germany
Animals Identification: Each animal was marked with an ID number. Each cage was affixed with a cage card containing pertinent animal and study information. The animals in cages were marked by a line (I-III) on the tail with an ink marker.
Justification for the Choice of Species: Normally females are used in the test according to OECD TG 402 because mostly females are the more sensitive gender.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
olive oil
Details on dermal exposure:
Approximately 24 hours before the test, fur was removed from the dorsal area of the trunk of the test animals by clipping and shaving. A precise amount of the test item was aspirated into an adjustable pipette and applied directly on the shaved skin of the back in a single dose uniformly over an area approximately 10 % of the total body surface area. Test item was held in contact with the skin by using semi-occlusive dressing with non-irritating tape throughout the 24-hours exposure period. At the end of the exposure period, any residuals of the test item were removed by using lukewarm water without altering the existing response or integrity of the epidermis.
Doses:
The required amount of the test item (according to the body weight and dose) was mixed with the vehicle (olive oil) shortly before application according to the actual body weight.
No. of animals per sex per dose:
Sighting Study
The purpose of the sighting study was to select the appropriate starting dose for the main test. The
starting dose for sighting study could be selected from the fixed dose levels of 50, 200, 1000, and
2000 mg/kg body weight. A limit dose of 2000 mg/kg body weight was used as a starting dose. One
female was dosed. Test item-related mortality was not observed during 48-hours exposure period.
The sighting study was finished; the main test was started with dose of 2000 mg/kg body weight.
Main Study
The additional 2 females were dosed in the Main Study with the dose of 2000 mg/kg body weight.
Control animals:
not required

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All 3/3 females at the limit dose of 2000 mg/kg body weight survived.
Clinical signs:
Animals were observed individually immediately after the application of the test item and then 0.5,
1, 2, 4 and 6 hours later. Each animal was inspected daily for the next 14 days.
Observations included changes in skin and fur, eyes and mucous membranes, and also respiratory,
circulatory, autonomic and central nervous systems, and somatomotor activity and behaviour pattern.
Attention was directed to observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep
and coma. In addition, the treatment site was observed at 24, 48 and 72 hours after removal of test
chemical using the Draize criteria.

No mortality was observed during the study. Animals lived through the observation period without
signs of intoxication. 24 hours after remove the test item, all three animals had a slight erythema at
the test site which persisted to the next day.
Gross pathology:
All animals were necropsied. During necropsy, no macroscopic changes were noticed.

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
Based on OECD Guideline 402 it can be concluded, that the test item “BF3-Ethylamine-Complex”
according to the Globally Harmonised System can be classified in Category 5/Unclassified after
single dermal application to Wistar rats.
Executive summary:

The test item “BF3-Ethylamine-Complex” applied to 3 females at a limit dose of 2000 mg/kg body

weight did not cause death. The body weights of all animals were increasing during the study. No

signs of toxicity were observed at the dosage of 2000 mg/kg body weight during the first 4 hours or

14-day observation period. 24 hours after removal of the test item, all three animals had a slight

erythema at the test site which persisted next 24 hours. During necropsy no macroscopic findings

were noticed.