Propionic anhydride

Endpoint summary

Description of key information

 Propionic acid is corrosive to skin. Severe eye damage is considered implicit

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

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.

In a primary dermal irritation study, 2-4 Vienna White rabbits were dermally exposed to 1 ml of undiluted propionic acid (> 99 % pure), applied under occlusion to the shaved skin (2.5 x 2.5 cm) for 1, 5 and 15 min. At the end of exposure, skins were washed first with lutrol and then with 50% lutrol in water. Animals were observed for up 53 days after application. Irritation was scored regularly using a BASF internal method. The score were later translated in Draize scores. Shortly after removal of the patch, erythema and oedema was evident for all the three exposure durations. Between 24-72 hours following exposure, anaemic to leather like necrosis at the application site was evident in some animals exposed for 5 and 15 mins. Necroses eventually lead to the development of deep and penetrative, sometimes bloody crusts beginning 72 h post application. After the detachment of the crusts which began averagely about 2 weeks after application, the formation of deep penetrative and sometimes haemorrhaging scabs (eschar) were observed by the end of the observation period (53 days). Crust formation (after 8 days) and scaling (day 30) were observed on skin exposed to propionic acid for 1 min. In this study, propionic acid was corrosive to the skin (BASF AG 1957).

The effects of propionic acid to the skin was determined following the Fed Reg 38 No 187§ 1500.41. 0.5 ml of undiluted Pronionic acid (no data on purity) was applied on the shaved skin of 6 New Zealand Albino Rabbits under complete occlusion for a duration of 24 hours. Skin changes were scored 4, 24, 48 72 and 168 hours following termination of exposure. The application sites were not washed. Corrosion was observed with 4 hours. A loosening about edges of scab in fourteen to seventeen days after termination showed injury in depth (Young Labs Inc.1975).

 

Eastman Kodak (1974) reported a study in which a volume of 0.5 ml (500 mg) of undiluted propionic acid (no data on purity) was applied to the skin (occlusive) of 5 guinea pigs (strain not indicated). No data on exposure duration. Skin reaction was observed and recorded at 2, 24, and 48 hrs. At 2 hours after administration, slight to moderate oedema, moderate to severe erythema, and necrosis were observed. After 24 hours the application site was necrotic with peripheral erythema. At 48 hours, eschar covered most of the treatment site on all animals; there was also petechial haemorrhages, erythema, and scattered areas of necrosis. All animals lost weight during the 14-day observation interval (Eastman Kodak, 1974).

In another study reported by Smyth et al (1962), application of 0.01 ml (10 mg) undiluted propionic acid (no data on purity) to the uncovered clipped skin of 5 male rabbits for 24 hours produced necrosis 24 hours after application. Moderate to marked erythema was also seen (grade 6 on a 10-grade ordinal series). Grade 6 indicates necrosis with the undiluted test substance and Grade 10 indicates necrosis from a 0.01% solution (Smyth et al., 1962).

 

In another primary dermal irritation study, the skins (2.5 x 2.5 cm) of 6 rabbits were exposed (occlusive) to 0.5 ml of 15% propionic acid (no data on purity) in aqueous solution for duration of 4 hours. Restrainers were used to preclude the animals from detaching the application patch. Washing was not performed. No data on skin scoring system was reported. 15% solution of propionic acid in water was not corrosive to the skin of the rabbit after the 4 hour occlusive exposure duration (Vernot 1977).

 

Eye irritation

From data on skin irritation/corrosion studies (see above), propionic has been shown to be corrosive to the skin. The risk of severe damage to the eyes is thus considered implicit.

One eye irritation/corrosion study of suitable reliability is however available. 0.1 ml of undiluted propionic acid (no data on purity) was appplied to the eyes of 6 New Zealand Albino rabbits. Eyes were not washed after application. Eyes were observed up till 14 days post instillation. As early as 1 minute post application, propionic acid caused a corrosive effect. 14 days after application, ulcceration was seen in all animals. Severe discomfort with pawing, squealing, and thrashing about the stock were observed immediately after application of the test propionic acid to the eye. In this study, propionic acid causes severe damage to the eye (Young Labs. Inc., 1975).

Respiratory Irritation

Although not tested directly tested clinical symptoms observed in inhalation studies 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. These results suggest that propionic acid vapor can cause respiratory irritation, which can be expected for a caustic substance

 

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Effects on respiratory irritation: irritating

Justification for classification or non-classification

Based on the necrosis seen with 72 hours on the skin of rabbits after 5 -15 min exposure duration, the risk phrase R34 "causes burns" is warranted according to directive 67/548/EEC Annex VI. According to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 a classification as Cat 1B is warranted. The risk of eye injury and raspiratory tract irritation is considered implicit because the corosive effects of propionic acid to the skin (see specific concentration limits).

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