Propionyl chloride

Endpoint summary

Description of key information

Acute oral toxicity data indicate a moderate toxicity: in rats the oral LD50 was 823 mg/kg bw. In the acute inhalation toxicity study a LC50 value of >0.2 mg/L was determined.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Value:

mg/kg bw

Additional information

Oral toxicity

In an acute oral (gavage) toxicity study, comparable to OECD guideline 401, Sprague-Dawley rats (5/sex/dose) were administered propionyl chloride by gavage at 215, 464, 562, 681, 825 and 1000 mg/kg bw and followed by a 14-day observation period (BASF AG, 1980). Clinical signs included dyspnea, apathy, abnormal position, staggering, atony, shivering, spastic walk, ragged skin, exsiccation and paresis. No mortality was observed at 215 and 464 mg/kg bw. At 562 mg/kg bw: 2/5 males and 0/5 females died, at 681 mg/kg bw: 1/5 males and 0/5 females died, at 825 mg/kg bw: 3/5 males and 2/5 females died and at 1000 mg/kg bw: 4/5 males and 4/5 females died. Findings at necropsy included acute dilatation of the heart, acute congestive hyperemia, mordant gastritis, enteritis, diarrhea, liver dystrophy (diseased animals) and thickened stomach wall, scattered aggregation of the stomach and spleen with the peritoneum (euthanized animals). The LD50 was 823 mg/kg bw.

 

In a supporting acute oral toxicity study comparable to OECD guideline 401, Gassner-rats (5/sex/dose) were exposed by gavage to propionyl chloride at 200, 400, 800, 1000, 1250 and 1600 mm³/kg bw, equivalent to 213 to 1704 mg/kg bw and followed by a 14-day observation period (BASF AG, 1969). Clinical signs included dyspnea, apathy and prone and lateral positions. Mortality occurred from 800 mm³/kg bw. Findings at necropsy included hemorrhagic gastritis, blood plethora and lung edema. The LD50 was 1065 mg/kg bw.

 

Inhalation toxicity

The substance was tested in an acute inhalation toxicity study comparable to OECD guideline 403 (BASF AG, 1996). Different exposure durations and concentrations were tested: 10 min exposure to 370 mg/L (3 male and 3 female rats), 3 min exposure to 370 mg/L (3 male and 3 female rats) and 1 hour exposure to 0.82 mg/L (6 male and 6 female rats). The concentrations represent nominal concentrations calculated from mass loss of test substance and volume of air used. The observation period was 7 days.

Immediately after the start of exposure, the animals showed attempts to escape, sever mucosal irritation and gasping. The surviving male and female animals showed cloudy cornea, dyspnea and sever nasal secretion. They were free of clinical signs of toxicity from day six onward. After 3 min exposure to 370 mg/L, 5 of 6 male and all 6 female animals died. After 10 min exposure to 370 mg/L, 2 of 3 males and 2 of 3 female animals died. No mortality was reported after 1 hour exposure to 0.82 mg/L. Necropsy findings in animals that died during the study were acute congestion and edema of the lung.

By means of Haber’s rule, the 4 hour LC92 of propionyl chloride was calculated to be approximately 4.6 mg/L and the LC50 > 0.2 mg/L.

With regard to structure activity, it can be observed that the short chain acid chlorides (e.g. propionyl or butyryl chloride (CAS number: 141-75-3)) affect more the upper tract of the respiratory tract due to their more hydrophilic properties. A lower acute inhalation toxicity is observed for these substances compared to their longer chain analogues showing higher lipophilicity and which can act deeper in the lungs (such as isobutyryl chloride (CAS number: 79-30-1)). Based on this consideration and based on the results of the study, it is estimated that the actual LC50 (vapour) for propionyl chloride would be in the range of the cut off values for a Cat. 3 acute inhalation toxicant (2 mg/l-10 mg/l) (in comparison: the LC50 value estimated for butyryl chloride is 3.6-5.7 mg/l while the LC50 value calculated for isobutyryl chloride is 0.47-1.95 mg/l).

Dermal toxicity

No acute dermal toxicity is available. In accordance with column 2 of REACH Annex VIII, testing for acute dermal toxicity is not necessary as the substance is classified as corrosive to the skin according to Directive 67/548/EEC (C, R34) and according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 (H314, Category 1B).

Justification for classification or non-classification

The available oral acute toxicity data warrants classification with Xn; R22 according to Directive 67/548/EEC and Cat. 4; H302 according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

Regarding the inhalation route, with regard to structure activity, it can be observed that the short chain acid chlorides (e.g. propionyl or butyryl chloride (CAS number: 141-75-3)) affect more the upper tract of the respiratory tract due to their more hydrophilic properties. A lower acute inhalation toxicity is observed for these substances compared to their longer chain analogues showing higher lipophilicity and which can act deeper in the lungs (such as isobutyryl chloride (CAS number: 79-30-1)). Based on this consideration and based on the results of the study, it is estimated that the actual LC50 (vapour) for propionyl chloride would be in the range of the cut off values for a Cat. 3 acute inhalation toxicant (2 mg/l-10 mg/l) (in comparison: the LC50 value estimated for butyryl chloride is 3.6-5.7 mg/l while the LC50 value calculated for isobutyryl chloride is 0.47-1.95 mg/l) and therefore the substance should be classified as follows: according to Directive 67/548/EEC, classification with Xn, R20 is warranted and according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, the classification is H331, Cat. 3.