Registration Dossier

Diss Factsheets

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:
2016
Report date:
2016

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Benzyltris(dimethylaminato)phosphorus(1+) tetrafluoroborate(1-)
EC Number:
302-080-5
EC Name:
Benzyltris(dimethylaminato)phosphorus(1+) tetrafluoroborate(1-)
Cas Number:
94088-77-4
Molecular formula:
C13H25BF4N3P
IUPAC Name:
benzyltris(dimethylaminato)phosphorus(1+) tetrafluoroborate(1-)
Test material form:
solid: crystalline

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Dobrá Voda, Slovak Republic

- Females (if applicable) nulliparous and non-pregnant: yes

- Age at study initiation: 8-12 wk

- Weight at study initiation:
Individual weights of animals were determined shortly before the test item was administered and weekly thereafter. Weight differences after first and second weeks after administration were calculated and recorded.

Dose Animal BW (g)
300 mg/kg 1 175
2 165
3 170
2000 mg/kg 4 170
5 170
6 190
7 175
8 190
9 170

- Fasting period before study:
Animals were fasted prior to dosing (food but not water were withheld over-night).

- Housing:
The animals were housed in plastic cages suspended on stainless steel racks, up to 3 animals per cage in a room equipped with central air-conditioning.

- Diet (e.g. ad libitum):
A laboratory food ssniff (Spezialdiäten GmbH, Germany) was offered in recommended doses each day approximately at the same time. The certificate of analysis is included in the raw data.

- Water (e.g. ad libitum):
The animals received tap water for human consumption. Supply of drinking was unlimited. The quality of drinking water is periodical analysed (including microbiological control) and recorded; certificate of analysis is included in raw data.

- Acclimation period:
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.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.6 +/- 0.4°C
- Humidity (%): 55.5 +/- 2.5 %
- Photoperiod (hrs dark / hrs light): 12-hour light /12-hour dark cycle

IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle:
The required amount of the test item (according to the body weight and dose) was mixed with vehicle (olive oil) shortly before administration.

- Justification for choice of vehicle:
Olive oil is a standard vehicle according to OECD TG 423.

- Lot/batch no. (if required): L52897 (Oleificio Luca, Italy)

The test item was administered in a single dose by gavage using a metal stomach tube. Animals were fasted prior to dosing (food but not water were withheld over-night). Following the period of fasting, the animals were weighted and the test item administered. After the test item had been administered, food was withheld for further 3-4 hours.

CLASS METHOD (if applicable)

- Rationale for the selection of the starting dose:
The starting dose could be selected from the fixed dose levels of 5, 50, 300, and 2000 mg/kg body weight. It was suspected, that the substance may be toxic. 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 24 hours and therefore in a second step 3 females were treated with the dose of 2000 mg/kg body weight. Test item-related mortality was not observed; in the step 3 females were treated with the same dose.
Doses:
300 and 2000 mg/kg BW
No. of animals per sex per dose:
3 Animals at 300 mg/kg BW
6 Animals at 2000 mg/kg BW
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing:
The animals were observed individually immediately after the administration of the test item and then 0.5, 1, 2, and 4 hours later. Then each animal was inspected daily for the next 14 days.

- Necropsy of survivors performed: yes
All test animals were subjected to gross necropsy and result were recorded for each animal.

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
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.
Individual weights of animals were determined shortly before the test item was administered and weekly thereafter. Weight differences after first and second weeks after administration were calculated and recorded.

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Key result
Sex:
female
Dose descriptor:
LD50 cut-off
Effect level:
>= 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed during the study.
Clinical signs:
Animals lived through observation period without signs of intoxication. Neither change of health nor negative reactions were registered.
Body weight:
The body weights of all animals were increasing during the study. Stagnation of the body weight in one animal (dose 300 mg/kg body weight), 2 animals (dose 2000 mg/kg body weight) and mild increase of the body weight in the rest animals were observed between first and second week after administration.
Gross pathology:
All animals were necropsied. During necropsy, no macroscopic findings were noticed.

Applicant's summary and conclusion

Interpretation of results:
other: Category 5 or unclassified based on GHS criteria.
Conclusions:
The LD50 of the test item Tecnoflon BA 104 is higher 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 Tecnoflon BA 104 is classified in Category 5/Unclassified with a LD50 cut off value equal to or greater than 5000 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 Tecnoflon BA 104 when administered as a single oral dose to Wistar rats.

The procedure according to OECD Guideline 423 Acute Toxic Class(ATC)method was used. Available information indicated that the test item is likely to be toxicwith regardto acute toxicity. 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 24 hours and therefore in a next steps 6 females were treated with the dose of 2000 mg/kg body weight.

All 6 females survived the limit dose. The limit dose of 2000 mg/kg body weight did not cause death, evident signs of toxicity or body weight loss during the 14-day long observation period.

The LD50of the test item Tecnoflon BA 104 is higher 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 thetest item Tecnoflon BA 104 is classified in Category 5/Unclassified with a LD50 cutoff value equal to or greater than 5000 mg/kg body weight, after single oral administration to Wistar rats.

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