Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Skin irritation:

A skin irritation/ corrosion study was performed in rabbits according to the OECD 404 principles leading to an irritation response in compliance with the CLP-criteria for Skin Irrit 2, H315.

Eye irritation:

An OECD 405 study was conducted in three New Zealand White female rabbits using conjunctival exposure to 0.1 ml of the test substance . According to scoring for eye irritation in this study the substance should according to the CLP-criteria be classified as Eye Irrit 2, H319

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1991
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to OECD 404 and conducted according to GLP of the US EPA, CFR Part 792
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
small deviations
Principles of method if other than guideline:
no step-wise approach used, 6 animals used
exposed skin area 10 cm2 instead of 6 cm2
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Six healthy New Zeland Albino rabbits ( 3 males and 3 females ) 2.0 -2,.4 kg bw were individually caged with a light/dark cycle of 12 hours under temperture controlled conditions.
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 ml of the test article was applied.
Duration of treatment / exposure:
4 hrs
Observation period:
14 days;
Observation points: > 1hrs , 24 hrs, 48 hrs, 72 hrs, 7 d, 14d
Number of animals:
6: 3 males and 3 females
Details on study design:
similar to OECD 404
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 30 min to 1 hrs
Score:
1
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 hrs
Score:
0.83
Max. score:
1
Remarks on result:
other: 1/6 brown areas on the skin
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 48 hrs
Score:
1.67
Max. score:
2
Remarks on result:
other: 1/6 brown areas on the skin
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 hrs
Score:
1.67
Max. score:
2
Remarks on result:
other: 1/6 brown areas on the skin
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 7 days
Score:
2.5
Max. score:
4
Remarks on result:
other: 5/6 flaking skin
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: day 14
Score:
0.5
Max. score:
1
Remarks on result:
other: 1/6 poor hair regrowth, 2/6 flaking skin
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 30 min to 1 hr
Score:
3.33
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 hrs
Score:
2.83
Max. score:
3
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 48 hrs
Score:
2.17
Max. score:
3
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72 hrs
Score:
1.83
Max. score:
2
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 7 d
Score:
1.66
Max. score:
2
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 14 d
Score:
0.5
Max. score:
1
Interpretation of results:
Category 2 (irritant)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:

Under the conclusion of this study, the test article is an irritant but not corrosive and thus fulfill the CLP-classification criteria as Skin Irrit 2, H315.
Executive summary:

Six healthy New Zeland Albino rabbits ( 3 males and 3 females ) were dosed dermally with SR 256 HXF 0946. 0.5 ml of test article was applied under semi-occlusive conditions on intact clipped skin. The test article was kept in contact with the skin for 4 hours. Draize scoring was performed after ½-1, 24, 48, 72 hours and 7 and 14 days. The scoring indicated the substance to be a moderate to severe irriatant but not a corrosive as irreversible damage and necrosis was not observed.

According to the CLP-criteria the substance should be classified as Skin Irrit 2, H315.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
one week year: 1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Exposure period and observation period are varies compare to the applicable test guideline.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
Substance is indicated but not documented..
Principles of method if other than guideline:
24 hours exposure period. Occlusive dressing used.
First observation was performed after the removal of the test material, while the second reading was 48 hours later (72 hours after application).
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Healthy adults
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
not specified
Controls:
not specified
Amount / concentration applied:
Just the dosing indicated:
Duration of treatment / exposure:
24 hours
Observation period:
7 days
Number of animals:
12
Details on study design:
Animals were groupped according to the skin surface into two groups : intact skin surface group and abraded skin group.
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 hours
Score:
4
Max. score:
4
Reversibility:
no data
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 hours
Score:
3.2
Max. score:
4
Reversibility:
no data
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 hours
Score:
4
Max. score:
4
Reversibility:
no data
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72 hours
Score:
2.5
Max. score:
3
Reversibility:
no data
Irritant / corrosive response data:
Primary Irritation Index: 6.7
After one week, the application sites both on intact and on abraded skin still showed necrosis
Interpretation of results:
highly irritating
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
A primary Irritation Index of 6.7 was calculated.
After one week, the application sites both on intact and on abraded skin still showed necrosis.
From this it was concluded that the test material was severely irritating.
Executive summary:

In an acute dermal irritation test six rabits (New Zealand White Rabbit) were exposed to 0.5 ml of ethyldiglycol acrylate

on clipped intact skin for 24 hours under occlusive dressing. Furter six rabits were dosed similarly on abraded skin. Draize scoring was performed 24 and 72 hours after start of exposure and the animals wer observed for a total of 7 days.

From the data a primary Irritation Index of 6.7 was calculated. Also, after one week, the application sites both on intact and on abraded skin still showed necrosis. From this it was concluded that the test material was severely irritating.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
26-08-1991 and 17-10-1991
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: test material only defined as code number. Deviations from current OECD 404 guideline
Guideline:
other: 16CFR 1500.41 Method of Testing Primary Irritant Substances
Principles of method if other than guideline:
Deviations from OECD 404
Both intact and abraded skin areas used.
24 hrs exposure period
occlusive dressing used
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
-Supplier: Hazleton Research Product Inc., Denver, Pennsylvania
- Number: Six (three/ sex)
- Age at study initiation: Adults, at least 8 weeks old at study initiation
- Weight at study initiation: 2.0-4.0 kg
- Housing: Individually housed, randomly assigned to cages
- Diet (e.g. ad libitum): Lab Rabbit Chow HF (Purina #5326)
- Water (e.g. ad libitum): automatic ad libitum watering system
- Acclimation period: 49 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): monitored and reconder twice daily
- Humidity (%): monitored and recorded daily
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark

IN-LIFE DATES: From October 14, 1991 to October 17, 1991
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin surface
Amount / concentration applied:
Five-tenths of a milliliter (0.5 mls) of the test material was applied beneath a 1X1 gauze square, placed direclty on the test site and held in place with an occlusive dressing.
Duration of treatment / exposure:
24 hrs.
Observation period:
30 min after removal of the patch, and 72 hours after the initial administration of the test substance.
Number of animals:
6 animals
3 females, 3 males
Details on study design:
TEST SITE
There were two test sited on the back of each animals, one on either side of the spinal column. After placing the test material on gauze pads, the animals were wrapped in an impervious plastic sleeve, which was secured with tape. This sleeve was designed to contain the test material without leakage or under pressure (occlusive dressing). Elizabethan collars were placed on all animals prior to or at the time of dosing to prevent disruption of the wrappings and test sites.

ABRAISON
Abrasions were made (on the left side) just prior to dosing using a hypodermic needle with point filed off. Thie skin was abraded longitudinally every 0.5 and 1.0 centimeters over the area of exposure. Abraisons were deep enough to penetrate the straum corneum but no so deep as to penetrate the dermis or produce bleeding.

REMOVAL OF TEST SUBSTANCE
Following approximately 24 hrs of exposure, the wrappings and gauze squares were removed and the test sites gently wiped free of excess material with water and gauze.
Irritation parameter:
erythema score
Basis:
mean
Remarks:
Intact Site
Time point:
other: 24 Hours
Score:
3.3
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Remarks:
Intact Site
Time point:
other: 24 Hours
Score:
1.7
Max. score:
2
Irritation parameter:
erythema score
Basis:
mean
Remarks:
Abraded Site
Time point:
other: 24 Hours
Score:
3.5
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Remarks:
Abraded Site
Time point:
other: 24 Hours
Score:
1.7
Max. score:
2
Irritation parameter:
erythema score
Basis:
mean
Remarks:
Intact SIte
Time point:
other: 72 Hours
Score:
3.7
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Remarks:
Intact Site
Time point:
other: 72 Hours
Score:
1.5
Max. score:
2
Irritation parameter:
erythema score
Basis:
mean
Remarks:
Abraded Site
Time point:
other: 72 Hours
Score:
3.7
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Remarks:
Abraded Site
Time point:
other: 72 Hours
Score:
1.5
Max. score:
2
Irritant / corrosive response data:
Mean Total Score = 20.6
Primary Irritation Index (Total Score /4) = 5.2
Interpretation of results:
corrosive
Remarks:
Migrated information Criteria used for interpretation of results: other: 16 CFR 1500.3(c)
Conclusions:
48 hours after exposure has stopped tissue damage was noted in five og six animals. However, this reponse was found after 24 hours of exposure using occlusive dressing. According to current OECD guidline used for classification an exposure duration of 4 hours and semiacclusive dressing should be used. Thus from the study it cannot be concluded whether the substance according to the CLP criteria should be classificed as a corrosive or as a skin irritant.
Executive summary:

An acute skin irritation test was conducted with six New Zealand White rabits. Intact and abraded skin was exposed to Sartomer 256 during 24 hours using occlusive dressing.

Two of the six animals treated with Sartomer 256 had tissue demage (subepidermal necrosis) with edema at the intact site, at 24 hours; three animals had moderate to severe erythema with edema; one animal had only very mild erythema. By 72 hours, five of the six animals had tissue damage at the intact site; one animal had only slight edema. The Primary Irritation Index of Sartomer 256 was calculated to 5.2.

According to the current OECD 404 guidline used for classification an exposure duration of 4 hours and semi-occlusive dressing should be used. Thus from the availbe study it cannot be concluded whether the substance according to the CLP criteria should be classificed as a corrosive or as a skin irritant.

Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: According to OECD 405 (1987).
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
New Zeland White rabbits were received from Ace Animals, Boyertown, PA and quarantined for at least 5 days. Only animals in apparent good health were made available for study assignment. Prior to being selected for this study, both eyes of each animals were examined according to the Draize technique for any evidence for irritation or abnormalities of the cornea, iris and /or conjuciva.
The animals weer hused 1/ cage in suspended cages. Bedding was palced beneath the cages and changed at least three times /week. Fresh purina Rabbit Chow was provided daily. Water was availabel ad libitum. The animal room, reserved exclusively for rabbits on acute test, was temperature controlled, had a 12 hour light/dark cycle and was kept clean and vermin free.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Duration of treatment / exposure:
-
Observation period (in vivo):
14 days
Number of animals or in vitro replicates:
3
Details on study design:

DOSING:
- One eyee of each rabbit was dosed. the contralateral eye served as a control. the test articel (0.1ml)was placed by syringe into the conjuctival sac, which was formed by gently pulling the lower eyelid away from the eye. After instillation, the lids were held together for approximately one second to insure adequate distribution of the test substance.

TYPE and FREQUENCY of OBSERVATIONS:
Using a hand-held auxillary source of illumination, the treated eye on each rabbit was examined for irritation of the cornea, iri and conjuctiva at 1, 24, 48, 72 hours post dose and on day 7. Ocular reactions were graded accordingly to the numerical Draize technique.

ANALYSIS of DATA:
The primary eye irritation score of each rabbit was calculated from the weighted Draize scale. Mean total scores for each time period were also calculated.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: hour 1
Score:
3.33
Max. score:
10
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: hour 24
Score:
20
Max. score:
30
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: hour 48
Score:
13.3
Max. score:
20
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: hour 72
Score:
3.33
Max. score:
10
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: day 7
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
mean
Time point:
other: hour 1
Score:
1.67
Max. score:
5
Irritation parameter:
iris score
Basis:
mean
Time point:
other: hour 24
Score:
5
Max. score:
5
Irritation parameter:
iris score
Basis:
mean
Time point:
other: hour 48
Score:
3.33
Max. score:
5
Irritation parameter:
iris score
Basis:
mean
Time point:
other: hour 72
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
mean
Time point:
other: day 7
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: hour 1
Score:
12
Max. score:
12
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: hour 24
Score:
13.3
Max. score:
14
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: hour 48
Score:
12
Max. score:
12
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: hour 72
Score:
4
Max. score:
6
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: day 7
Score:
0
Max. score:
0
Irritant / corrosive response data:
Corneal opacity and conjuctival irritation, noted in 3/3 eyes, cleared by day 7. Iritis, noted in 3/3 eyes, cleared by day 3.
Interpretation of results:
Category 2A (irritating to eyes)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
According to scoring for eye irritation in this study the substance should according to the CLP-criteria be classified as Eye Irrit 2, H319
Executive summary:

An OECD 405 study was conducted in three New Zealand White female rabbits using conjunctival exposure to 0.1 ml of the substance SR 256 . Draize scoring was performed at 1, 24, 48, and 72 hours post dosing and the mean total scores were calculated. Corneal opacity and iritis occurred in all rabbits but cleared by day 7 and day 3, respectively.

According to scoring for eye irritation in this study the substance should according to the CLP-criteria be classified as Eye Irrit 2, H319

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
Aug-78
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Testing performed comparable to OECD 405. Substance ID not further described.
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
NA
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:

no data
Vehicle:
not specified
Controls:
other: The untreated eye in each inimal case.
Amount / concentration applied:
0.1 ml
Duration of treatment / exposure:
-
Observation period (in vivo):
1h, 24h, 48h, 72h, 7 days
Number of animals or in vitro replicates:
6
Details on study design:
Comparable to OECD 405
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 1 hr
Score:
8.94
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24 hrs
Score:
20
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 48 hrs
Score:
22.21
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 72 hrs
Score:
26.25
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 7 day
Score:
2.24
Max. score:
2
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 1 hr
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24 hrs
Score:
5
Max. score:
1
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 48 hrs
Score:
5
Max. score:
1
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 72 hrs
Score:
4.15
Max. score:
1
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 7 day
Score:
0.8
Max. score:
1
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 1 hr
Score:
12.3
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24 hrs
Score:
14.3
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 48 hrs
Score:
12.6
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 72 hrs
Score:
9
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 7 day
Score:
2
Max. score:
2

An overall eye irritation score of 40 was calculated.

During the first day slight corneal opacity, slight iritis and moderate to severe lesions of the conjunctivae were observed. In the course of the seven-day observation period some recovery occurred. At the end of this period moderate corneal opacity and slight or moderat lesions of the conjunctivae were still observed in two rabbits while another rabbit showed slight irritation.

The subtances was concluded to be moderately irritating to the eyes.

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the study observations and the CLP-criteria the substance should be classified as Eye Irr 2; H319
Executive summary:

An eye irritation test comparble to an OECD 405 study was conducted with 0.1 ml of ethyldiglycolacrylate in three New Zealand White rabbits. Draize scoring was performed at 1, 24, 48, and 72 hours post dosing. An overall eye irritation score of 40 was calculated.

During the first day slight corneal opacity, slight iritis and moderate to severe lesions of the conjunctivae were observed. In the course of the seven-day observation period some recovery occurred. At the end of this period moderate corneal opacity and slight or moderat lesions of the conjunctivae were still observed in two rabbits while another rabbit showed slight irritation.

The subtances was concluded to be moderately irritating to the eyes.

According to scoring for eye irritation in this study the substance should according to the CLP-criteria be classified as Eye Irrit 2, H319

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

A skin irritation/ corrosion study was performedin rabbits according to the OECD 404 principles leading to an irritation response in compliance with the CLP-criteria for Skin Irrit 2, H315.

An OECD 405 study was conducted in three New Zealand White female rabbits.

According to scoring for eye irritation in this study the substance should according to the CLP-criteria be classified as Eye Irrit 2, H319


Justification for selection of skin irritation / corrosion endpoint:
Among the three study reports which are all considered valid studies this study is the study most comparable with the OECD 404 test guideline as the study uses 4 hrs exposure and semi-occlusive dressing (resulting in skin irritation) , whereas the other two studies used 24 hrs exposure and occlusive dressing (resulting in skin corrosion).

Justification for selection of eye irritation endpoint:
Performed according to OECD 405, high reliability score

Effects on skin irritation/corrosion: highly irritating

Effects on eye irritation: moderately irritating

Justification for classification or non-classification

Skin irritation:

A skin irritation/ corrosion study was performed in rabbits according to the OECD 404 principles leading to an irritation response in compliance with the CLP-criteria for Skin Irrit 2, H315.

Eye irritation:

An OECD 405 study was conducted in three New Zealand White female rabbits using conjunctival exposure to 0.1 ml of the test substance . According to scoring for eye irritation in this study the substance should according to the CLP-criteria be classified as Eye Irrit 2, H319