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Administrative data

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

Link to relevant study records
Reference
Endpoint:
skin irritation / corrosion, other
Remarks:
in vivo study already available
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards, well documented and acceptable for assessment
Principles of method if other than guideline:
Before OECD Guideline 404 was established, skin irritation was tested using an internal BASF method. The undiluted substance was applied to the clipped back (2.5 X 2.5 cm) of 2-4 animals for short periods of time (1, 5 and 15 mins). At the end of treatment, the application site was washed first with lutrol and then with 50% aqueous lutrol solution. The animals were observed for up to 53 days and skin changes were assessed and scored.
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.25-2.85 kg

ENVIRONMENTAL CONDITIONS
- no data
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Concentration (if solution): undiluted
Duration of treatment / exposure:
1, 5, 15 min
Observation period:
53 days
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: no data

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes (undiluted lutrol and 50% lutrol in water)
- Time after start of exposure: after 1, 5 and 15 min

SCORING SYSTEM: The test was initially scored using a BASF numerical skin grading system. Later these scores were converted to the scoring system by Draize.
Irritation parameter:
erythema score
Remarks:
(after 1 min of exposure)
Basis:
mean
Remarks:
(4 animal)
Time point:
other: 24 and 72 hour
Score:
1.25
Max. score:
4
Reversibility:
fully reversible within: 30 days
Remarks on result:
other: crust formation (after 8 days) and scaling (till 30 days) were apparent
Irritation parameter:
erythema score
Remarks:
(after 5 mins of exposure)
Basis:
mean
Remarks:
(of 4 animals)
Time point:
other: 24 and 72 hours
Score:
1.9
Max. score:
4
Reversibility:
fully reversible within: 23 days
Remarks on result:
other: Brown and anaemic skin colouration was evident shortly after removal of patch (lasted up to 8 days after application). Necrosis and crusty skin from 24 h post termination of exposure was apparent. Scar tissue at end after 53 days
Irritation parameter:
erythema score
Remarks:
(exposure duration of 15 min)
Basis:
mean
Remarks:
(2 animals)
Time point:
other: 24 and 72 hours
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 15 days
Remarks on result:
other: Necrosis was evident as from 24 h post termination of exposure. Crust formation induced after 72. At termination (53 days) bloody and deep penetrative scars were apparent.
Irritation parameter:
edema score
Remarks:
(after 1 min of exposure)
Basis:
mean
Remarks:
(of 4 animals)
Time point:
other: 24 and 72 hours
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
edema score
Remarks:
(after 5 min of exposure)
Basis:
mean
Remarks:
(of 4 animals)
Time point:
other: 24 and 72 hour
Score:
0.4
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
edema score
Remarks:
(after 15 min of exposure)
Basis:
mean
Remarks:
(of 2 animals)
Time point:
other: 24 and 72 h
Score:
1.5
Max. score:
4
Reversibility:
fully reversible within: 15 days
Irritant / corrosive response data:
- Necrosis after exposure periods of 5 and 15 minutes of exposure
- Crustaceous tissue was present after 1 minutes of exposure

Table 1: Results after 15 min duration

 

Animal

Animal

Erythema

Edema

Further findings

Immediately after removal of patch   (15 min)

1

3

3

Anemic appearance, erythema at edges

2

3

3

Anaemic appearance, erythema at edges and oedema

 

24h

1

3

0

Anemic appearance, erythema at edges

2

3

3

Brown discolouration, anaemic appearance, erythema at elevated edges

 

72h

1

3

0

Anaemic application site with reddened edges and oedema, beginning necrosis

2

3

3

Penetrative crust, reddened edges

8d

1

3

0

Brown and partly anaemic necrosis with reddened edges

2

0

0

necrosis

15d

1

0

0

Hardened penetrative crust

2

 0

0

Bloody penetrative scar

53 d      (8 weeks)

1

0

 0

Scar

2

0

 0

Bloody penetrative scar

Mean scores (24-72h)

1

3

3

 

2

3

0

 

 

Table 2: Results after 5 min exposure duration

Readings

Animal

Erythema

Edema

Further findings

At removal (after 5 min)

1

3

3

Anaemic in the middle with reddened and oedematous edges

2

3

3

3

3

3

4

3

3

24h

1

3

3

Anaemic in the middle with reddened and oedematous edges

2

3

0

Brown discolouration in the middle, partly anaemic with reddened elevated edges

3

3

0

Anaemic in the middle, partly brown necrotic tissue with reddened edges

4

0

0

Anaemic in the middle, partly brown discolouration

72h

1

3

0

Anaemic leather-like crust

2

3

0

Anaemic crust with reddened edges, partly brown

3

0

0

Deep penetrative crust

4

0

0

Anaemic in the middle, partly brown discolouration

8d

1

3

0

Anaemic necrosis with reddened edges

2

3

0

Deep penetrative crust with reddened elevated edges

3

0

0

-

4

0

0

Anaemic crust with reddened edges

15d

1

0

0

Hard deep and penetrative crust

2

0

0

Crust partly detached

3

0

0

-

4

0

0

-

23 d

1

0

0

Hard deep and penetrative crust

2

0

0

Detaching crust/bloody scar

3

0

0

Deep penetrative and bloody crustaceous scar

4

0

0

Thick yellow crust, partly detached

8 weeks (53 d)

1

0

0

Scaring tissue

2

0

0

Bloody scar/extensive scar

3

0

0

Scar with increased hair growth

4

0

0

Deep penetrative and bloody crustaceous scar

MW (24-72h)

1

3

1.5

 

2

3

0

 

3

1.5

0

 

4

0

0

 

 

Table 3: Results after 1 min exposure duration

Readings

Animal

Erythema

Edema

Further findings

At removal (after 1 min)

1

2

0

-

2

2

0

bleeding

3

2

3

-

4

2

3

 

24h

1

1

0

 

2

1

0

 

3

2

2

 

4

2

0

 

72h

1

0

0

 

2

0

0

Symptom free

3

2

2

-

4

2

0

 

8d

1

0

0

scaling

2

0

0

-

3

2

0

Scaling, crusty edges

4

0

0

Symptom free

15d

1

0

0

 

2

0

0

 

3

0

0

 

4

0

0

 

30 d

1

0

0

Increased hair growth

2

0

0

-

3

0

0

scaling

4

0

0

scaling

MW (24-72h)

1

0.5

0

 

2

0.5

0

 

3

2

2

 

4

2

0

 

Interpretation of results:
corrosive
Remarks:
Migrated information
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation, other
Remarks:
in vivo study already available
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guidline study with accepted restrictions
Principles of method if other than guideline:
According to Fed Reg 38 No.187 § 1500.41
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 µl
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
14 days
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: no data


TOOL USED TO ASSESS SCORE: no data
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 1 min
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: corrosive with in 1 min. No evaluation of iris, erythema and chemiosis was done therefore
Irritant / corrosive response data:
Immediately after instillation: Severe discomfort with pawing, squealing, and thrashing about the stock
After 1 min: Corrosive
After 14 days: Ulceration
Interpretation of results:
corrosive
Remarks:
Migrated information
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin irritation

In a primary dermal irritation study, Vienna White rabbits were dermally exposed to undiluted propionic acid, applied under occlusion to the shaved skin for 1, 5 and 15 min. At the end of exposure, skins were washed. Animals were observed for up to 53 days after application. Shortly after removal of the patch, erythema and oedema was evident for all 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 minutes. 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 was applied on the shaved skin of 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 within 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 undiluted propionic acid was applied to the skin (occlusive) of 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 undiluted propionic acid to the uncovered clipped skin of 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 of rabbits were exposed (occlusive) to undiluted test substance for a duration of 4 hours. Skin reaction was observed and recorded at 1, 24 and 72 hours. For all time points, the score for erythema and edema was 4. The primary irritation score was 8.0. In this study, the test substance was corrosive to the skin (Celanese 1972).

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. Undiluted propionic acid was appplied to the eyes of New Zealand Albino rabbits. Eyes were not washed after application. Eyes were observed up to 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 caused severe damage to the eye (Young Labs. Inc., 1975).

Respiratory Irritation

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.

 


Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Effects on respiratory irritation: irritating

Justification for classification or non-classification

According to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, classification for skin corrosion (cat. 1B) and respiratory irritation (STOT SE cat. 3) is warranted.