3A-Flux

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 18 February 2021 to 19 March 2021

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

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Potassium hydrogen fluoride, reaction product with boric acid and dipotassium salt of boric acid

Cas Number:

2787482-26-0

Molecular formula:

not applicable (UVCB)

IUPAC Name:

Potassium hydrogen fluoride, reaction product with boric acid and dipotassium salt of boric acid

Test material form:

solid - liquid: suspension

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

- Source: Institute of Experimental Pharmacology and Toxicology, Center of
Experimental Medicine of the Slovak Academy of Sciences, Dobrá
Voda, Slovak Republic

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

- Age at study initiation: 8-12 weeks

- 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 airconditioning.
The room temperature was maintained within the range of
22±2 °C. The relative humidity will be 55±10 %. The light regime was
set to a 12-hour light / 12-hour dark cycle. The sanitation was performed
according to standard operation procedures. For bedding AlpenSpan Eco, Johann Pabst Holzindustrie GmbH, Zeltweg, Austria was used

- Diet (e.g. ad libitum): A standard laboratory food KKZ-P/M (UEFT CEM SAS) was available
ad libitum. Animals were fasted prior to dosing.

- Water (e.g. ad libitum): The animals received tap water for human consumption. Supply of
drinking water was unlimited. The quality of drinking water is periodical
monitored (including microbiological control) and recorded

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle:
- Amount of vehicle (if gavage):
- Justification for choice of vehicle: Ultra pure water such as API is a common vehicle for water soluble items in toxicity studies like OECD TG 423
- Lot/batch no. (if required): 19L1001
- Purity:

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Available information indicated that the test item was likely to be non-toxic regarding acute toxicity therefore we chose a dose of 2000 mg of 3A-Flux per kg body weight to be used as a starting dose.

Doses:

2000 mg/kg bw
300 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations: Immediately after the administration of the test item and then
0.5, 1, 2 and 4 hours later and daily afterwards

- Frequency of weighing: Before administration and weekly thereafter

- Necropsy of survivors performed: All animals were subject to gross necropsy

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

500 mg/kg bw

Based on:

test mat.

Remarks on result:

other: LD50 between 300 mg/kg bw and 2000 mg/kg bw

Mortality:

Mortality of 3/3 females at limit dose of 2000 mg/kg body weight was observed.

Clinical signs:

lethargy (hypoactivity)

sleep

other: Depression of CNS

Body weight:

other body weight observations

Remarks:

No effects observed

Gross pathology:

For animals treated with 2000 mg/kg bw ulcerative lesions in small intestine were observed.
No observations in animal treated with 300 mg/kg bw.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 of the test item 3A-Flux is greater than 300 mg/kg and lower than 2000 mg/kg body weight after single oral administration to Wistar rats.
Based on Annex 2d Test Procedure with a Starting Dose of 2000 mg/kg body weight of OECD Guideline 423 it can be concluded that the test item 3A-Flux is classified GHS 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 3A-Flux administered to 3 females Wistar rats at a limit dose of 2000 mg/kg caused reaction within 30 minutes (lethargy, depression of CNS) and after two hours Animals 1 and 2 died and 4 hours after administration of test item Animal 3 died. During necropsy we observed ulcerative lesions in small intestine in all animals at this dose level.

Dose of 300 mg/kg of body weight did not caused death of animals with no signs of intoxication, change of health, or any other adverse reactions during
14-days observation period. During necropsy we did not observe any macroscopic findings in all animals at this dose level.

The body weights of all surviving animals increased in normal range during the study.