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Administrative data

Description of key information

Skin irritation (OECD 404): corrosive 
Eye irritation (OECD 405), 70%: irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1981
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Van Zutphen Breeding Centre, Keldonk, The Netherlands
- Weight at study initiation: 2779 g, 2886 g and 2949 g (measured 5 days before dose administration)
- Housing: individually in metal cages with perforated floors
- Diet: standard laboratory animal diet (LK-01, pellet diameter 4 mm)
- Water: tap water, ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-22
- Humidity (%): 50-75
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin sites of same animals
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration: 100%
Duration of treatment / exposure:
4 h
Observation period:
14 days
Reading time points: 1, 24, 48 and 72 h
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: right flank
- Type of wrap if used: 6 cm patch of surgical gauze, which was attached with a bit of petrolatum to aluminium foil and mounted on tape (Micropore@, 3M, St. Paul, USA). Finally, the animals were wrapped in flexible bandage (Coban@, 3M, St. Paul, USA).


REMOVAL OF TEST SUBSTANCE
- Washing (if done): no, removal of substance by tissue
- Time after start of exposure: 4 h


SCORING SYSTEM:
Erythema:
0 - no erythema
1 - very slight erythema (barely pereptible)
2 - well-defined erythema
3 - moderate to severe erythema
4 - severe erythema (beet redness) to slight eschar formation (injuries in deep)

edema:
0 - no edema
1- very slight edema (barely perceptible)
2 - slight edema (edges of area well defined by definite raising)
3 - moderate edema (raised appr. 1 mm)
4 - severe edema (raised >1 mm and extending beyond area of exposure)
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.7
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
other: necrosis
Basis:
animal: #1, #2, #3
Time point:
48 h
Reversibility:
not reversible
Remarks on result:
other: full thickness necrosis was observed at reading time point 48 h in all animals
Irritant / corrosive response data:
Only slight edema and moderate erythema were observed 1, 24, 48, and 72 h after removal of the test material. However, the also observed light-brown staining of the skin proved to indicate skin necrosis, since a crust had formed 48 h after exposure.
In one animal the hairs in the exposed area continued to grow, indicating that the hair roots, lying in the deeper layers of the dermis, had not been affected in this animal. The other two animals revealed no hair growth in the treated area. On day 7, in each of the animals the hairs failed to grow. After the formation and loosening of the crust, the skin had almost returned to normal 14 days after exposure in the two animals, while the one animal showed a rather scurfy skin and only partial restoration of hair growth.
In conclusion, since the test material produced full thickness destruction of the skin tissue in the treated animals, the test material is considered to be corrosive.

Results:

Time Animal Erythema Edema Other findings
1 h 1 1 2
2 1 1 b
3 1 1 b
24 h 1 1 3 b
2 1 2 b
3 1 2 b
48 h 1 4 2 n
2 4 2 n
3 4 2 n
72 h 1 4 0 e
2 4 0 e
3 4 0 e
mean 24 - 48 - 72 h 1 3.0 2.7
2 3.0 1.3
3 3.0 1.3
mean  3.0 1.8

b: exposed skin brownish

n: skin necrotic

e: eschar formation

Interpretation of results:
other: classification as Skin Corr. 1C, H314 required according to Regulation (EC) No 1272/2008
Conclusions:
CLP: Skin Corr. 1C, H314

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
17 Jul - 10 Sep 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted 24 April 2002
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Commission Regulation (EC) No 440/2008, L142, Annex Part B
Version / remarks:
30 May 2008
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Version / remarks:
August 1998
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
BAYRISCHES LANDESAMT FÜR GESUNDHEIT UND LEBENSMITTELSICHERHEIT, LANDESINSTITUT FÜR ARBEITSSCHUTZ UND PRODUKTSICHERHEIT, München, Germany
Species:
rabbit
Strain:
other: New Zealand White Rabbits, Crl:KBL (NZW)
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approx. 20 weeks
- Weight at study initiation: 3.5 - 4.6 kg
- Housing: Rabbits were housed individually in ABS - plastic rabbit cages with a floor of 4200cm²
- Diet: autoclaved hay and Altromin 2123 maintenance diet for rabbits, rich in crude fiber, ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days
The animals were derived from a controlled full-barrier maintained bredding system (SPF).

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr):at least 10 x
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 17 Jul 2011 To: 10 Sep 2011
Vehicle:
other: vaseline
Controls:
other: The untreated eye served as control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration: 70% (v/v)

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): 100%
- Lot/batch no. (if required): 1004025-01
Duration of treatment / exposure:
24 h
Observation period (in vivo):
up to 11 days
Reading time points: 24, 48 and 72 h and every 24 h for up to 11 days
Number of animals or in vitro replicates:
4 females (including 1 animal for the preliminary test)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated eye was rinsed with physiological saline 0.9% NaCl
- Time after start of exposure: 24 h

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 9 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: mean over 24,48 and 72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 6 days
Remarks on result:
other: evaluated after fluoresceine application
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 11 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 6 days
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible within: 4 days
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 4 days
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 3 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
1.67
Max. score:
3
Reversibility:
fully reversible within: 11 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: mean over 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: mean over 24, 48 and 72 h
Score:
0.66
Max. score:
4
Reversibility:
fully reversible within: 3 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: mean over 24, 48 and 72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 6 days
Irritant / corrosive response data:
The test item produced irritant ocular effects after application in 3 animals.
Conjunctival rednesses, chemosis and discharge were observed in 3 animals.
Upon fluoresceine examinations, corneal lesions were determined in 2 animals after 72 h.

A 70% mixture of octanoic acid in vaseline induced lesions of the iris in 2 out of 3 tested animals with a score equal to 1. Therefore, the test item has to be considered as eye irritant at a concentration of 70%.
Other effects:
Neither mortalities nor significant clinical signs of toxicity were observed (table 2).

Table 2: Clinical signs of toxicity

 

 

Time after application

Systemic findings

Local findings

animal 1

1 – 72 h

no specific findings

mild discharge

4 – 6 days

no specific findings

slight discharge

7 – 9 days

no specific findings

no specific findings

animal 2

1 h

no specific findings

mild discharge

24 h

no specific findings

slight discharge

48 h – 6 days

no specific findings

no specific findings

animal 3

1 h – 24 h

no specific findings

mild discharge

48 h

no specific findings

severe discharge

72 h

no specific findings

slight discharge

4 – 5 days

no specific findings

no specific findings

6 and 8 days

no specific findings

slight discharge

9 – 11 days

no specific findings

no specific findings

Table 3: Absolute body weight (kg)

 

 

animal 1

animal 2

animal 3

start of study

4.4

4.6

3.5

72 h post application

4.6

4.7

3.4

end of observation period

4.5

4.6

3.5

Interpretation of results:
other: Eye Cat. 2, H319 at a concentration of 70% according to Regulation (EC) No 1272/2008
Conclusions:
CLP: Eye irritation, Cat. 2, H319 at a concentration of 70%
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin

In vivo

Skin irritation after application of octanoic acid was investigated in a GLP-study performed according to OECD guideline 404. 0.5 mL of 100% octanoic acid was applied to the clipped skin of three New Zealand White rabbits under semi-occlusive conditions for 4 hours (1984). The resulting mean scores over 24, 48 and 72 hours after application were 3.0 and 1.8 for erythema and edema, respectively. The also observed light-brown staining of the skin proved to indicate skin necrosis, since a crust had formed 48 h after exposure. In each of the animals the hairs failed to grow on day 7 after treatment, showing that the dermis was affected in the deep. After the formation and loosening of the crust, the skin had almost returned to normal 14 days after exposure in the two animals, while the third animal showed a rather scurfy skin and only partial restoration of hair growth. Based on the findings, octanoic acid has to be considered as corrosive.

To determine the level of primary skin irritation of octanoic acid under occluded conditions, 0.8 mL of octanoic acid at concentrations of 30%, 50%, 60%, 70% in PEG200/H2O and 100% was applied to the clipped skin of 6 New Zealand White rabbits under occlusive conditions for 3 hours (1981a). While the mean scores for 24 and 48 hour readings were both 0 for erythema and edema after application of 30%, 50%, 60%, 70% octanoic acid, respectively, the scores were 3.3 for erythema and 3.2 for edema for 100% octanoic acid, respectively.

In another closed patch test by the same author, octanoic acid at concentrations of 4%, 7.5%, 10%, 15% and 100% was tested by applying 0.4 mL to the clipped skin of 6 white rabbits under occlusion for 3 hours (1981b). The resulting mean scores for erythema and edema were all 0 for the dilutions of octanoic acid. At 100%, the resulting mean scores were 3.3 and 2.5 for erythema and edema, respectively.

The irritation after repeated administration was investigated in a study, where five New Zealand White rabbits received applications of 0.8 mL octanoic at concentration of 55%, 60% 65% and 80% to the clipped skin under occlusion for 3 hours/day on 7 consecutive days (1981c). Based on the scores for erythema and edema the primary irritation index was calculated with the combined scores for 30 min and 21-hour post-treatment readings. The scores were 0.03, 0.03, 0.7, and >0.3 for 55%, 60%, 65% and 80% octanoic acid, respectively.

In vitro

Possible corrosive properties were evaluated in a GLP - in vitro test, where discs of freshly prepared rat skin were exposed to 150 µL of octanoic acid for 24 hours followed by a measurement of the transcutaneous electrical resistance (TER) (1994). Based on the significant reduction in the measured mean resistance of the skin, the authors concluded that octanoic acid displays properties characteristic of those substances which may be corrosive to animal skin in vivo.

Whittle et al. published results of two in vitro tests on rat and human skin (1996). The experiments with rat skin were performed similar to OECD guideline 430. 150 µL of octanoic acid was added to the epidermis of each freshly prepared rat skin disc for 24 hours. After washing, the resistance measurements were conducted and resulted in a TER of 2.5 kΩ. Since the TER decreased below 5 kΩ, octanoic acid is considered to be corrosive to rat skin.

In the experiments with human skin, human skin samples (waste material obtained from mammary cosmetic surgery, 9 donors) were also exposed to 150 µL of octanoic acid for 24 hours. Tissue treated with distilled water served as concurrent control. For none of the nine donors the TER was decreased below the threshold value of 11 kΩ. According to these results, octanoic acid is considered to be non-corrosive to human skin.

In summary the available data indicate that octanoic acid has to be regarded as corrosive to skin, while concentrations <=70% did not lead to any skin irritation.

 

Eye

In a published study performed according to national guidelines, octanoic acid was instilled into the eyes of six rabbits and considered as eye irritant. Corneal opacity and moderate conjunctivitis did not subside in 72 h (Briggs et al., 1976). Due to the limited information, this study does not provide sufficient data for hazard assessment.

The eye irritation potential by octanoic acid at a concentration of 70% was examined in a GLP study according to OECD guideline 405. 0.1 mL of 70% octanoic acid in vaseline was instilled into one eye each of 3 female New Zealand White rabbits (2011). The untreated left eye of each animal served as control. After 24 h the eyes were rinsed. The eye reactions were examined 24, 48 and 72 h after application and every 24 h thereafter for up to 11 days. Under the conditions of the test, a single ocular application produced irritant effects in the rabbits, which were fully reversible within 6-11 days. The mean scores for corneal opacity, iris, conjunctival redness and chemosis were 0.78, 0.66, 1.6 and 1 respectively. Since, in 2 out of 3 tested animals lesions of the iris with a score equal to 1 were induced, octanoic acid has to be considered as eye irritant at a concentration of 70%.

Based on the fact, that corrosion of the skin was found, octanoic acid has to be regarded as serious eye damaging according to the Guidance on CLP criteria, although the available studies rather indicate an eye irritation potential.

Justification for classification or non-classification

The available data on skin irritation/corrosion of octanoic acid meet the criteria for classfication as Skin Corr. 1C, H314 according to Regulation (EC) 1272/2008.

Data (1981a) revealed, that at and below a concentration of 70% no irrating properties are present. However, RAC does not support a specific concentration limit of 70% for skin corrosion, as the available data do not allow for their determination (RAC Opinion for octanoic acid, June 2013).

Based on the fact, that corrosion of the skin was found, octanoic acid has to be regarded as serious eye damaging according to the Guidance on CLP criteria.

Harmonised classification for octanoic acid (7th ATP; Index: 607-708-00-4): Skin Corr. 1C, H314