Potassium isobutyrate

Endpoint summary

Description of key information

One key study is available for the endpoint acute oral toxicity. This study is performed in accordance with OECD 423 and under the conditions of GLP.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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

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

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

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

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

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.

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

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The key study is considered to be a Klimisch reliability 1.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

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.