Potassium propionate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

FACTORS AFFECTING THE DISTRIBUTION OF INGESTED PROPIONIC ACID IN THE RAT FORESTOMACH

Author:

J. E. BUELD and K. J. NETTER

Year:

1992

Bibliographic source:

Fd Chem. Toxic. Vol. 31, No. 3, pp. 169-176, 1993

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: OECD guideline 408 (90 day repaeted dose toxicity study)

Deviations:

yes

Remarks:

rats were exposed to propionic acid via food either as powedered or pelleted feed for 12 or 20 weeks. The occurrence of hyperplasias in the forestomach and the accumulation of propionic acid were evaluated.

Principles of method if other than guideline:

- Principle of test: Exposure of male Wistar rats to 0, 4%, and 8% propionic acid in feed over 12 and 20 weeks respectively, to investigate the occurrence of hyperplasias and the accumulation of propionic acid in the forestomach.
- Short description of test conditions: Groups of six male Wistar rats (approx. 130g) were fed for 24wk a pelleted diet containing 0 or 8% PA . In a second experiment, four groups of male Wistar rats (24 in total; 120-140 g)
were fed either control powdered diet or powdered diet supplemented with 4% PA, 1% L-carnitine or 4%PA and 1% L-carnitine for 12wk. Body weights were taken at the start of the study and weekly thereafter. Food onsumption was determined daily by weighing the containers (after filling and before spilling on the next day at 9 am).
Food spillage was minimized by a special construction of the food containers; therefore it was not considered further. At the end of the study, rats were killed by CO2 inhalation. Parts of the food bolus within the forestomach and glandular stomach were collected and stored at - 20°C to prevent evaporation of PA. The remaining bolus was then removed with icecold saline, and the stomach was flattened and fixed while attached to a piece of cardboard and examined macroscopically. Sections taken parallel to the lesser curvature, including the forestomach, limiting ridge and glandular stomach, were pinned flat in Bouin's solution (saturated picric acid-37% formalin-glacial acetic acid; 15:4:1, by vol.) and prepared for haematoxylin and eosin staining.
- Parameters analysed / observed: macroscopically determination of hyperplasias, accumulation of propionic acid in the forestomach tissues.

GLP compliance:

no

Test type:

other: repeated dose oral toxicity study over at least 84 days

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Propionic acid

EC Number:

201-176-3

EC Name:

Propionic acid

Cas Number:

79-09-4

Molecular formula:

C3H6O2

IUPAC Name:

propionic acid

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: approx. 130 g in the first experiment and 120-140 g in the second experiment
- Fasting period before study: no
- Housing: In each experiment rats were housed two in Macrolon cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55-60
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: feed

Vehicle:

water

Details on oral exposure:

For the preparation of food pellets, the appropriate amount of PA was diluted with water before being mixed with the powder. Pellets of about 10 g were pressed and air-dried for at least 3 days but stored not longer than 10 days.

Doses:

0, 4, and 8% in feed

No. of animals per sex per dose:

6

Control animals:

yes

Details on study design:

- Duration of observation period following administration: n/a; repeated dose study over 12 or 20 wk
- Frequency of observations and weighing: Body weights were taken at the start of the
study and weekly thereafter. Food consumption was determined daily by weighing the containers (after filling and before filling on the next day at 9 am).
- Necropsy of survivors performed: not specified
- Other examinations performed: body weight, macroscopically observation of the forestomach

Results and discussion

Effect levels

Key result

Sex:

male

Dose descriptor:

other: macroscopical observation of changes in tissues of the forestomach; effects observed

Effect level:

3 600 mg/kg bw

Based on:

test mat.

Remarks:

dose calculated according to EFSA Scientific Commitee (2012), concentration as stated in the publication 4% propionic acid in the diet

Mortality:

not observed

Clinical signs:

other: other: not observed

Gross pathology:

When pelleted diet was used, no
hyperplasias were observed. Macroscopical and
histopathological examinations showed no changes in various parts of the gastric mucosa; this could be attributed to the administration of PA in pelleted food for 24 wk. After 12wk of administration, powdered PA produced severe changes in the forestomach but not in the glandular stomach.
Grossly, crater-like growths with marginal hyperplasias and central ulceration were found in the forestomachs of all animals, particularly in the prefundic region (area proximate to the glandular stomach). The limiting ridge was substantially thickened. No histological examinations were made.

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Conclusions:

The present study was conducted to examine the effects of 0, 4, and 8% propionic acid in the diet of the rats forestomach. Male wistar rats were exposed to feed containing either powdered diet with 4% propionic acid or pelleted feed containing 8% propionic acid. In the group treated with the pelleted feed no hyperplasias were observed whereas in the group fed with powdered diet hyperplasias occurred. No other signs of toxicity were reported, thus, the dose at which the first adverse effect was observed (i.e. changes in the forestomach tissues) was 3600 mg/kg bw. after 12 weeks repeated exposure.

Executive summary:

The study of Bueld and Netter (1992) was conducted to examine the effects of 0, 4, and 8% propionic acid in the diet to the rats forestomach. Groups of 6 male Wistar rats weighing approximately 130g were exposed to feed containing pelleted diet with 0 or 8% propionic acid for 24 weeks. In a second experiment six male Wistar rats each group were fed powdered diet containing 4% propionic acid for 12 weeks. In the group treated with the pelleted feed no hyperplasias were observed whereas in the group fed with powdered diet hyperplasias occurred. No other signs of toxicity were reported, thus, the dose at which the first adverse effect was observed (i.e. changes in the forestomach tissues) was 3600 mg/kg bw after 12 weeks repeated exposure. Based on the determined value propionic acid does not need to be classified with regard to acute oral toxicity according to Regulation (EU) No. 1272/2008 (CLP) under the conditions of the test.