Registration Dossier

Administrative data

Description of key information

The test substance 2-ethylanthraquinone is neither irritating nor corrosive to the skin and the eyes. Information on respiratory irritation is lacking. 

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
Study period:
1990-09-27 to 1991-01-30
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline-conform study under GLP without deviations
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, UK
- Age at study initiation: approximately 12 to 16 weeks
- Weight at study initiation: 2.26 - 2.54 kg
- Housing: individually housed in suspended metal cages
- Diet (e.g. ad libitum): ad libitum (Rabbit Diet, Preston Farmers Limited, New Leake, Boston, Lincolnshire, U.K.)
- Water (e.g. ad libitum): ad libitum (mains drinking water)
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22. On one occasion, the temperature was outside the upper limit specified in the protocol (21°C).
- Humidity (%): 49-65
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 27.9.1990 To: 30.9.1990
Type of coverage:
semiocclusive
Preparation of test site:
other: clipped free from fur
Vehicle:
water
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g moistened with water

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
2 females, 2 males
Details on study design:
TEST SITE
- Area of exposure: dorsal/ flank area
- Type of wrap if used: 2.5 cm x 2.5 cm gauze patch placed in position on the shorn skin. The patch was secured in position with a strip of surgical adhesive tape (BLENDERM: approximate size 2.5 cm x 4.0 cm). To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset (TUBIGRIP).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): gentle swabbing with cotton wool soaked in distilled water
- Time after start of exposure: 4 hours

SCORING SYSTEM:
Erythema and Eschar Formation
No erythema: 0
Very slight erythema (barely perceptible): 1
Well-defined erythema: 2
Moderate t o severe erythema: 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth): 4

Oedema Formation
No oedema: 0
Very slight oedema (barely perceptible): 1
Slight oedema (edges of area well- defined by definite raising ): 2
Moderate oedema (raised approximately 1 millimetre ): 3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure): 4

Primary Irritation Index
The scores for erythema and oedema a t the 24 and 72-hour readings were totalled for the three test rabbits (12 values) and this total was divided
by 6 to give the primary irritation index of the test material. The test material was classified according to the following scheme:
Primary irritation index = 0 : Non-irritant
Primary irritation index > 0 - 2: Mild irritant
Primary irritation index > 2 - 5: Moderate irritant
Primary irritation index > 5 - 8: Severe irritant
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: mean of scores at 24 and 72 hours
Score:
0.3
Max. score:
8
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation

Erythema/Eschar Formation

Reading (hours)

Individual Scores – Rabbit Number and Sex

(bodyweight kg)

86 female

(2.26)

89 male

(2.54)

92 female

(2.37)

1

1

0

1

24

1

0

1

48

0

0

0

72

0

0

0

Total of 24, 48 and 72 hours

1

0

1

Mean Score of 24, 48 and 72 hours

0.3

0.0

0.3

 

Oedema Formation

Reading (hours)

Individual Scores – Rabbit Number and Sex

(bodyweight kg)

86 female

(2.26)

89 male

(2.54)

92 female

(2.37)

1

1

0

0

24

0

0

0

48

0

0

0

72

0

0

0

Total of 24, 48 and 72 hours

0

0

0

Mean Score of 24, 48 and 72 hours

0.0

0.0

0.0

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material was classified as a mild irritant to rabbit skin. No corrosive effects were noted. The test material can be classified as non-irritant according to Regulation (EC) No 1272/2008 (CLP).
Executive summary:

A GLP-study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method used followed that described in the OECD TG No. 404.

A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced incidents of very slight erythema and an isolated incident of very slight oedema. The test material produced a primary irritation index of 0.3 (out of 8) and was classified as a mild irritant to rabbit skin. No corrosive effects were noted.

The test material can be classified as non-irritant according to Regulation (EC) No 1272/2008 (CLP).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 1990-10-03 to 1991-01-30
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline-conform study under GLP without deviations
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: 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
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, UK
- Age at study initiation: 12-16 weeks
- Weight at study initiation: 2.64 - 3.12 kg
- Housing: individually housed in suspended metal cages
- Diet (e.g. ad libitum): ad libitum (Rabbit Diet, Preston Farmers Limited, New Leake, Boston, Lincolnshire, U.K.)
- Water (e.g. ad libitum): ad libitum (mains drinking water)
- Acclimation period: 5 days in minimum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 21
- Humidity (%): 52 - 65
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 1990-10-03 To: 1990-10-10
Vehicle:
unchanged (no vehicle)
Controls:
other: The left eye of the rabbits remained untreated and was used for control purposes.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL corresponding to approximately 70 mg
Duration of treatment / exposure:
one single application
Observation period (in vivo):
Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment. An additional observation was made in one animal on day 7 to assess the reversibility of the ocular effects.
Number of animals or in vitro replicates:
1 male, 2 females (1 initially treated, 2 treated after consideration of the ocular responses produced in the first treated animal)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): not done

SCORING SYSTEM:

Initial local pain reaction:
No response: 0
A few blinks only, normal within one or two minutes: 1
Rabbit blinks and tries to open eye, but reflex closes it: 2
Rabbit holds eye shut and puts pressure on lids, may rub eye with paw: 3
Rabbit holds eye shut vigorously, may squeal: 4
Rabbit holds eye shut vigorously, may squeal, claw at eye, jump and try to escape: 5

The Draize scale was used for numerical scoring of the ocular irritation. Using the numerical data obtained, a modified version of the system described by Kay J.H. and Calandra J.C., J. Soc. Cosmet. Chem., 1962 13 281-289 was used to classify the ocular irritancy potential of the test material.

TOOL USED TO ASSESS SCORE: Examination of the eye was facilitated by use of the light source from a standard ophthalmoscope.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0.22
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0.11
Max. score:
2
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
24/48/72 h
Score:
0.78
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0.44
Max. score:
4
Reversibility:
fully reversible within: 72 hours

Individual and mean scores for cornea, iris and conjunctivae

Rabbit Number and Sex (Bodyweigh in kg)

Time after treatment

Corneal Opacity

Iridial Inflammation

Conjunctival Redness

Conjunctival Chemosis

125 Male (2.64)

24 hours

1

1

2

2

48 hours

1

0

1

1

72 hours

0

0

1

0

Total

2

1

4

3

Mean

0.7

0.3

1.3

1.0

92 Female (3.12)

24 hours

0

0

1

1

48 hours

0

0

1

0

72 hours

0

0

0

0

Total

0

0

2

1

Mean

0.0

0.0

0.7

0.3

100 Female (3.01)

24 hours

0

0

1

0

48 hours

0

0

0

0

72 hours

0

0

0

0

Total

0

0

1

0

Mean

0.0

0.0

0.3

0.0

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material 2-ethylanthraquinone was classified as a mild irritant to the rabbit eye according to a modified Kay and Calandra classification system. The test material is classified as non-irritant to the rabbit eye according to Regulation (EC) No 1272/2008 (CLP).
Executive summary:

A study was performed to assess the irritancy potential of the test material 2-ethylanthraquinone to the eye o f the New Zealand White rabbit. The method used followed that described in the OECD TG 405.

A single application o f the test material to the non-irrigated eye of three rabbits produced minimal to moderate conjunctival irritation. Diffuse corneal opacity and iridial inflammation was confined to one treated eye. All treated eyes appeared normal 72 hours after treatment or on day 7.

The test material was classified as a mild irritant to the rabbit eye according to a modified Kay and Calandra classification system. The test material is classified as non-irritant to the rabbit eye according to Regulation (EC) No 1272/2008 (CLP).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Two studies on the irritation potential of the test material to the skin and eye are available each.

One skin irritation study was performed under GLP and followed OECD TG No. 404 (Jones 1991). The other study was performed according to the method of Draize (Lewis 1987). In both studies, very slight erythema were observed which were fully reversible within 48 or 72 hours. In the OECD study, an isolated incident of very slight oedema was produced which was fully reversible within 24 hours.

One eye irritation study was performed under GLP and followed OECD TG No. 405 (Jones 1991). Diffuse corneal opacity and iridial inflammation was confined to one treated eye. All treated eyes appeared normal 72 hours after treatment or on day 7. The other eye irritation study followed the method of Draize (Lewis 1987). One rabbit showed slight redness of the conjunctivae and slight swelling of the chemosis on day 1. From day 2 on, no effects were observed in any of the treated rabbits.


Justification for selection of skin irritation / corrosion endpoint:
The study selected as the key study was performed under GLP and in accordance with OECD TG 404. One supporting study is availble which followed no guideline and was not performed under GLP.

Justification for selection of eye irritation endpoint:
The study selected as the key study was performed under GLP and in accordance with OECD TG 405. One supporting study is availble which followed no guideline and was not performed under GLP.

Justification for classification or non-classification

In the skin irritation studies, the observed mean scores erythema/eschar and oedema that were obtained from ratings at 24, 48 and 72 hours after treatment were not exceeding 0.3 in all animals and thus were well below 2.3. All effects were fully reversible within 72 hours. The substance has therefore not to be classified as irritating to the skin according to Regulation (EC) No 1272/2008 (CLP).

In the eye irritation studies, the observed mean scores for 24, 48 and 72 hours were below 1 (corneal opacity, iritis) or 2 (conjuntival redness, chemosis) and all effects were fully reversible within 7 days. The substance has therefore not to be classified as irritating to the eye according to Regulation (EC) No 1272/2008 (CLP).