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Administrative data

Description of key information

Skin irritation:

One read-across study is available (Beutler, 1991). The test substance is slightly irritating to rabbit skin with a 24-hour semiocclusive application.

Eye irritation:

One read-across study is available (Beutler, 1991). The test substance is slightly irritating to rabbit eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
During June of 1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study run to a method comparable with current guidelines and to GLP
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
The only differences were that the compound was evaluated on both intact and abraded skin following a 24-hour exposure, rather than only on intact skin followiing a 4-hour exposure as directed in the OECD Guidelines.
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source:
- Age at study initiation:
- Weight at study initiation: 2.71 to 3.11 kg
- Housing:
- Diet (e.g. ad libitum):
- Water (e.g. ad libitum):
- Acclimation period:
Type of coverage:
occlusive
Preparation of test site:
other: one intacted and one abraded
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
Duration of treatment / exposure:
24 hours
Observation period:
72 hours
Number of animals:
2 males, 1 female
Details on study design:
TEST SITE
- Area of exposure: approximately two inches square
- % coverage: The compound was covered with a 2x2 gauze patch that was also premoistened with deionized water.
- Type of wrap if used:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The test sites were gently wiped with a soft cloth and deionized water.
- Time after start of exposure: 24 h
SCORING SYSTEM: Draize, J.H., Woodard, G., and Calvery, H.O.: J. Pharmacol. exptl. Therap., 82:377-390,1944.
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: mean of 24, 48 and 72 hours
Score:
ca. 0.22
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Intact skin, one fully reversed within 72 hours, the other two did not appear erythema.
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: mean of 24, 48 and 72 hours
Score:
ca. 0.44
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Abraded skin, two fully reversed within 72 hours, the other one did not appear erythema.
Irritation parameter:
edema score
Basis:
mean
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
0
Remarks on result:
other: Intact skin
Irritation parameter:
edema score
Basis:
mean
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
0
Remarks on result:
other: Abraded skin
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: mean of 24 and 72 hours
Score:
0.25
Remarks on result:
other: mean of score in intact and abraded skin
Irritant / corrosive response data:
Following a 24-hour exposure to the compound, very slight (score =1), non-confluent erythema was apparent at both the intavt and the abraded site of one animal and at the abraded site of a second rabbit. No erythema was evident at either site in the third rabbit, and there was no edema at any of the application sites. There was no obvious change at any of the sites at 48 hours post dose. However, by 72 hours post dose, the erythema had subsided completely, and the skin at each intact and abraded site appeared essentially normal.
Other effects:
Throughout the 72-hour observation period, all animals remained alert and active, but the food consumption of one rabbit was reduced. The final body weight of each rabbit was essentially comparable to the animal's pre-test weight.

Individual Skin Reactions Following 24-Hour Exposure

Condition of skin

Observation

period

(hours)

Rabbit No.

1

2

3

Erythema

Edema

Erythema

Edema

Erythema

Edema

Intact

24

1

0

0

0

0

0

48

1

0

0

0

0

0

72

0

0

0

0

0

0

Abraded

24

1

0

0

0

1

0

48

1

0

0

0

1

0

72

0

0

0

0

0

0

Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The results of this reveal that the Primary Irritation Score is 0.25, indicating that the test substance produced only negligible irritation on rabbit skin and is therefore not a primary skin irritant.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
During June of 1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study run to a method comparable with current guidelines and to GLP
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.79 to 2.96 kg
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): a dose (18.8 mg) equivalent to a volume of 0.1 mL
- Concentration (if solution):

VEHICLE
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution):
- Lot/batch no. (if required):
- Purity:
Duration of treatment / exposure:
72 hours
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
2 males, 1 female
Details on study design:
A dose of 18.8 mg (the amount of compound equivalent to a volume of 0.1 mL) of the test substance was instilled into the conjunctivasl sac of the left of each the three rabbits (2 males, 1 female); the right eye of each animal served as an untreated control. The eyes were not rinsed after dosing.
All animals were observed 3 days. on the day of dosing (day 1), the eyes were evaluated wuth minimal manipulation and without the use of fluorescein.
The scoring system used was that of Draize.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
mean
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
1
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: One animal appeared at 1 hour but fully reversible within 24 hours.
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: mean of 24, 48 and 72 hours
Score:
ca. 0.11
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Two animals appeared, one fully reversible within 24 hours, the other one fully reversible within 48 hours.
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: mean of 24, 48 and 72 hours
Score:
0
Max. score:
1
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: Two animals appeared at 1 hour but fully reversible within 24 hours.
Irritant / corrosive response data:
Immediately after dosing, each rabbit blinked and rubbed the treated eye; however, none of the rabbits exhibited sign of obvious pain or discomfort. Within 1 hour of dosing, slight circumcorneal reddening was apperent in the treated eye of each rabbit. Slight comjuctival reddening and chemosis was also evident in two of the rabbits, and iritis was apperent in the treated eye of one of these animals. By 6 hours post dose, the ocular changes were subsiding, and at 24 hours, the only changes noted were slight circumcorneal reddening in one rabbit and slight reddening of the conjuctivae in another animal. By 48 hours post dose, the treated eye of each rabbit appeared normal.
Other effects:
All rabbits were asymptomatic throughout the 72-hour test period, and they all gained weight.

Individual Scores and Individual Total Scores for Ocular Irritation

Rabbit Number

Time after

application

Cornea opacity

Iris

Conjunctivae

Redness

Chemosis

1

1 hour

24 hours

48 hours

72 hours

0

0

0

0

0

0

0

0

1

1

0

0

1

0

0

0

2

1 hour

24 hours

48 hours

72 hours

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3

1 hour

24 hours

48 hours

72 hours

0

0

0

0

1

0

0

0

1

0

0

0

1

0

0

0

Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test indicated that the test substance is not an ocular irritant in rabbits because a positive irritating effect was not apperent in any of the treated eyes at 24, 48, or 72 hours post dose.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin irritation:

One read-across study is available which was conducted according to OECD Guideline 404 under GLP (Beutler, 1991). The test substance is slightly irritating to rabbit skin with a 24-hour semiocclusive application. See read-across justification document attached in section 13.

Eye irritation:

One read-across study is available which was conducted according to OECD Guideline 405 under GLP (Beutler, 1991). The test substance is slightly irritating to rabbit eyes. See read-across justification document attached in section 13.

Justification for selection of skin irritation / corrosion endpoint:

Read-across study run to a method comparable with current guidelines and to GLP

Justification for selection of eye irritation endpoint:

Read-across study run to a method comparable with current guidelines and to GLP

Effects on skin irritation/corrosion: slightly irritating

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

Classification conducted based on read-across data:

Skin irritation/corrosion: Mean scores at 24, 48 and 72 hours for erythema were < 2.3 (actual value 0.44) and for edema were < 2.3 (actual value 0).

Serious eye damage/eye irritation: Mean scores at 24, 48 and 72 hours for corneal opacity were < 1 (actual value 0), for iris were < 1 (actual value 0), for conjunctival redness were < 2 (actual value ca.0.11) and for chemosis were < 1 (actual value 0).

Therefore in accordance with Regulation (EC) No. 1272/2008 Table 3.2.2 & 3.3.2, this substance should not be classified for skin irritation/corrosion and serious eye damage/eye irritation endpoints.

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