Registration Dossier

Administrative data

Description of key information

Acute oral toxicity
- LD50 (male and female: rat): 3455.1 mg/kg bw (2978.9-4007.5) (BASF AG 1969)
Acute inhalation toxicity:
LC50 is supposed to be > 20 mg/L /4h (vapor) based onthe available information (BASF 1969; Smyth et al. 1962)
Acute dermal toxicity
- LD50 (female: rat): 3235 mg/kg bw (Hoechst 1975)

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions (no GLP)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Principles of method if other than guideline:
The study was conducted according to an internal BASF method which was in principle comparable to the OECD guideline 401. A test group consisting of 5 animals/sex/dose was treated by single gavage with an aqueous solution of the test substance. The animals were weighed prior treatment only. The animals were observed for mortality and for clinical signs of toxicity for a period of 14 days. Decedents were subjected to necropsy. At the end of the observation period, the surviving animals were sacrificed (CO2 aphyxiation) for the purpose of necropsy. The LD50 value was estimated on the basis of the observed mortalities using the Lichtfield and Wilcoxon method

GLP compliance:
no
Test type:
standard acute method
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Firma Gassner/Ottobrunn
- Age at study initiation: no data
- Mean weight at study initiation: ♀ = 150g; ♂ = 160g
- Diet: ad libitum (Altromin "R" from Altromin GmbH, Lage)
- Water: ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- no data
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 - 21.3 ml/kg bw

DOSAGE PREPARATION (if unusual):
The test substance was administered as a 20 and 30% aqueous solution
Doses:
2, 2.5, 3.2, 4, 5, 6.4 ml/kg bw
conversion with density 0.99g/ml) = 1980, 2475, 3168, 3960, 4950, 6336 mg/kg bw
No. of animals per sex per dose:
5/sex/dose for all doses except 3168 mg/kg bw where 10/sex/dose were employed
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of mortality check: after 1 hour, 24 hours, 48 hours, 7 days and 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 455.1 mg/kg bw
95% CL:
2 978.9 - 4 007.5
Remarks on result:
other: At all doses symptoms included: apathy, dyspnoea, partly cyanosis, intermittent breathing, crouching position, agitation.
Mortality:
- 1980 mg/kg bw: 1/5♀, 0/5♂
- 2475 mg/kg bw: 1/5♀, 0/5♂
- 3168 mg/kg bw: 5♀, 3♂
- 3960 mg/kg bw: 5/5♀, 3/5♂
- 4950 mg/kg bw: 3/5♀, 4/5♂
- 6336 mg/kg bw: 5/5♀, 5/5♂
Clinical signs:
At all doses symptoms included: apathy, dyspnoea, partly cyanosis, intermittent breathing, crouching position, agitation.
Body weight:
no data
Gross pathology:
- Decedents: liquid accumulation in the abdomen (10 animals), smudgy snout (4 animals), liver necrosis (1 animal)
- Sacrificed animals: multiple cases (9 animals) of reduced retroperitoneal fat pads, distended gastrointestinal tract
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
3 455 mg/kg bw

Additional information

Oral

Several valid studies exist for the assessment of the acute oral toxicity of propionic acid.

 

In an acute oral toxicity study similar to OECD 401, groups of 5-10 Sprague Dawley rats per sex weighing 150-160g were given a single oral dose of propionic acid (100 % pure) in water at doses of 2, 2.5, 3.2, 4, 5, 6.4 ml/kg bw (1980, 2475, 3168, 3960, 4950, 6336 mg/kg bw; density = 0.99 g/ml) and observed for 14 days. LD 50 in this study was 3455.1 mg/kg bw (2978.9-4007.5). Symptoms exhibited by the animals at all doses included; apathy, dyspnoea, partly cyanosis, intermittent breathing, crouching position, agitation. Multiple cases of reduced retroperitoneal pads and distended gastrointestinal tract were noticed at necropsy in surviving animals. Accumulation of liquids in the abdomen and smudgy snouts were noticed in moribund or descendent animals (BASF AG 1969).

 

In another acute oral study, 4-5 weeks old non-fasted male Carworth-Wistar rats weighing 90-120 g were treated (5 animals/ dose) once with propionic acid (no data on purity, no data on vehicle, and no data on doses) by means of gavage. Based upon mortalities during a 14-day observation period, the LD50 value and its fiducial range are estimated by the method of Thompson using the tables of Weil. LD 50 in this study was 4290 mg/kg bw (3070-5980) (Smyth et al 1962).

In another acute oral study, groups of 10 female SPF-Wistar rats (bw 90 -110 g) were given a single oral dose of propionic acid (10% in water) at doses of 1000, 1600, 2500 and 4000 mg/kg bw and observed for 14 days. The LD50 in this study was 2271 mg/kg bw. (Hoechst 1975)

In a publication with limited documentation, an LD 50 of 2600 mg/kg bw was reported for propionic acid applied via the oral route in the rat (FAO/WHO 1962).

 

Taken together, available data allows the conclusion that systemic exposure to propionic acid is of low toxicity after a single ingestion.

 

Inhalation

In an acute inhalation toxicity study, groups of adult Sprague Dawley rats (10/sex/group) weighing 200-300 g were exposed head and nose only by the inhalation route to vapors of propionic acid (100% pure) in air for 1 hour at concentrations of  2.69 and 19.7 g/l. Animals were then were observed for 14 days. No mortality occurred in the low dose group while 1/10 females died in the high dose group. LC 50 was > 19.7 mg/l air. In the low dose groups, symptoms included; slightly constricted palpebral fissure (closed eyes), wet fur (from urine) and slight tearing. In the high dose group, clinical symptoms were; reduced respiratory frequency, slight to increased intermittent respiration, tightly closed eyes, slight tearing, slight to heavy salivation, slight to heavy nasal secretion and slight corneal opacity. There were no treatment related changes in body weight. At necropsy, gray-pinkish coloring of the lungs, gaseous intestines and emphysematous and partly atelectatic lungs were noticed in the single female animal that died. Petechiae was seen in 4/19 animals at necropsy (BASF AG 1979).

In another Inhalation hazard test (Smith et al 1962) 6 albino rats per sex were put into an exposure chamber for an 8 h exposure towards a propionic acid vapor atmosphere. The test atmosphere was generated by passing 2.5 liters of air / minute through a fritted glass disk into a 50 ml gas wash bottle containing propionic acid. No mortality was observed. Nominal concentration was 12.2 mg/L. According to the Haber rule this is equivalent to a LC0 of 24.4 mg/L/4h. The result is supported by a further inhalation hazard test. Three male and female rats were exposed by whole-body inhalation to 5.5 mg/L propionic acid as a vapor for a single four hour period. No mortality was observed either during the exposure or during a 7-day post-exposure period. Signs of slight eye and nasal irritation were noted during the exposure and for several hours afterwards. However, the animals quickly recovered and were generally without clinical signs during the remainder of the 7 -day post-exposure observation period. (Hoechst, 1990)

 

 

Dermal

In an acute dermal study groups of female SPF-Wistar rats were treated occlusive dermal exposed for 24 hours with propionic acid at concentrations of 1000, 2500, 3150, 4000 and 5000 mg/kg bw. The area of exposure was 30 cm² and covered with aluminium foil and elastic patch. After 24 hours the test substance was rinsed with warm water. The observation time was 14 – 21 days. Animals found dead died in a narcotic like condition in abdominal position. The skin on the back was dicoloured brown, hard and necrotic. animals found dead: 5000 mg/kg: 3 dead animals showed pale spotted liver and a bloody small intestine. Regarding to autolytic changes, no macroscopic assessement of the other dead animals was possible. No abnormality in the sacrificed animals. All animals died in the group of 4000 and 5000 mg/kg bw. The calculated LD50 was 3235 mg/kg bw. (Hoechst, 1975)

Justification for classification or non-classification

Classification for acute toxicity is not warranted according to the criteria of EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.