Propionic anhydride

Endpoint summary

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)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Dose descriptor:

LD50

Value:

3 455 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Dose descriptor:

LC50

Value:

19 700 mg/m³ air

Additional information

Due to the very short half-life (4 minutes) in aqueous media, propionic acid is a valid read-across substance for propionic anhydride, as it is the primary hydrolysis product.

Oral

Several valid studies exist for 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 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 a 120 l 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 concentrations was 12.2 mg/L. According to the Haber rule this is equivalent to a LCo of 24.4 mg/L/4h. the result is suppuported by the result of the other inhalation hazard test.

 

 

Dermal

No reliable studies for acute dermal toxicity are available for propionic acid. In accordance with Column 2 of REACH Annex VIII, testing for acute dermal toxicity is not required as studies on skin irritation/corrosion indicate that propionic acid is corrosive to the skin.

Justification for classification or non-classification

Classification for acute toxicity is not warranted according to the criteria of EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.