Potassium isobutyrate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

30 January 2019 - 15 February 2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

Adopted 17th December 2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Potassium isobutyrate

EC Number:

243-077-8

EC Name:

Potassium isobutyrate

Cas Number:

19455-20-0

Molecular formula:

C4H8O2.K

IUPAC Name:

potassium 2-methylpropanoate

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Sponsor/181101001
- Expiration date of the lot/batch: 31/10/2020
- Purity test date:


STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature (20 ± 5°C); Keep away from humidity
- Stability under test conditions: Stable

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Slovak Academy of Sciences Dobrá Voda, Slovak Republic
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 9-10 weeks
- Weight at study initiation:
- Fasting period before study: 10-12 hours
- Housing: plastic cages suspended on stainless steel racks, 3 animals per cage in a room equipped with central air-conditioning.
- Diet (e.g. ad libitum): The laboratory food ssniff (ssniff Spezialdiäten GmbH, Germany) was available at libitum.
- Water: ad libitum - The animals received tap water for human consumption.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.12 ± 0.24 °C
- Humidity (%): 54.92 ± 2.46 %
- Photoperiod (hrs dark / hrs light): 12-hour light /12-hour dark cycle

IN LIFE DATES: 24/01/2019 - 15/02/2019

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Aqua pro injectione

Remarks:

Aqua pro injectione is a common vehicle in toxicity studies like OECD TG 423

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/kg
- Amount of vehicle (if gavage): 5mL/kg bw
- Justification for choice of vehicle: Aqua pro injectione is a common vehicle in toxicity studies like OECD TG 423
- Lot/batch no. (if required): 18E2302
- Purity: certificate of analysis provided in study report.


CLASS METHOD
- 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. A limit dose of 2000 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, another 3 females were treated at the same dose.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
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.
Individual weights of animals were measured immediately prior to administration of the test item and weekly thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ appearance

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 (6/6 females) animals survived the limit dose of 2000 mg/kg body weight.

Clinical signs:

other: During the follow up period, no animals displayed signs of intoxication, change of health, nor any other adverse reaction.

Gross pathology:

All animals were necropsied. During necropsy, no macroscopic findings were observed.

Any other information on results incl. tables

Clinical Observation

Observation	Time After Administration
	Hour					Day
	Immediately	0.5	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
Skin and Hair	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Eyes	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Mucosa	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Respiratory System	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Circulatory System	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
CNS	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Somatomotoric Activity	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Tremor	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Spasms	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Salivation	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Diarrhoea	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Lethargy	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Sleep	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Coma	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Death	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-

 -No observed signs

Body Weight

Sex	Dose	ID	Body Weight (g)			Body Weight Difference (g)
			Initial	Week 1	Week 2	Week 1 - Initial	Week 2 - Initial	Week 2 - Week 1
♀	2000 mg/kg	1	210	243	257	33	47	14
		2	214	223	219	9	5	-4
		3	219	234	243	15	24	9
		4	244	261	324	17	80	63
		5	238	252	268	14	30	16
		6	238	252	267	14	29	15

Necropsy Results

Sex	Dose	ID	Result	Sex	Dose	ID	Result
♀	2000 mg/kg	1	no finding	♀	2000 mg/kg	4	no finding
		2	no finding			5	no finding
		3	no finding			6	no finding

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 of the test item “Potassium isobutyrate” is greater 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 “Potassium isobutyrate” is according to to Regulation (EC) No 1272/2008 (EU CLP) unclassified with a LD50 cut off value of equal to or greater than 2000 mg/kg body weight, after single oral administration to Wistar rats.

Executive summary:

SUMMARY

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

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

A limit dose of 2000 mg/kg body weight was used as a starting dose.The test itemadministeredto 6 females at a limit dose did not cause death.The body weights of all animals increased during the study. A slight decrease of body weight in one animal was observed between the first and second week after administration of the test item.During necropsy, no macroscopic findings were observed.

The LD₅₀ of the test item “Potassium isobutyrate”is greater 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 “Potassium isobutyrate”is according to Regulation (EC) No 1272/2008 (EU CLP) unclassified with a LD₅₀cut off value of equal to or greater than 2000 mg/kg body weight,after single oral administration to Wistar rats.