Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Data are available from in vivo skin and eye irritation studies conducted using a diluted form of the registered substance. These studies were conducted prior to the adoption of the relevant OECD Guidelines and have some differences in design compared to current Guidelines. However, the studies are well documented and considered sufficient for assessment.

In the skin irritation study in rabbits, at the 24-hour time point well-defined erythema to severe erythema was observed at both intact and abraded test sites, as well as edema ranging from moderate to severe. At the 72 -hour time point, no edema was noted but erythema ranged from well-defined to severe.

In the eye irritation study, positive reactions were noted in the treated eyes of all six rabbits at the 24, 48 and 72 hour readings. Some of the effects (cornea, iris) were reversible within 72 hours in some animals. However, the conjunctiva effects (erythema, chemosis, discharge) were not reversible within this time period.

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:
29/10/1980 to 1/11/1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
This primary dermal irritation study was conducted prior to the adoption of OECD Guideline 404 (original adopted in 1981). However, the study was conducted in accordance with the test facility protocol and US FHSA guidelines available at the time. Study methods and results are well documented in the study report and summarised here.
GLP compliance:
yes (incl. QA statement)
Specific details on test material used for the study:
Test material is 65% of the registered substance diluted in 35% non-hazardous mineral oil. Described in the study reports as a thick, brown oily liquid.
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: B&D Commercial Rabbitry, Malvern, Arkansas
- Age at study initiation: At least 8 weeks old
- Weight at study initiation: 2507-2866 g
- Housing: Individually housed in stainless steel cages, which are elevated above the droppings, in an environmentally controlled room. Rooms and cages maintained in accordance with the standards of the American Association for Accredication of Laboratory Animal Care (AAALAC).
- Diet: Wayne Feeds Rabbit Ration available ad libitum
- Water: Tap water available ad libitum
- Acclimation period: 21 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not reported
- Humidity (%): Not reported
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light

IN-LIFE DATES: From: To: 29/10/1980 to 1/11/1980
Type of coverage:
semiocclusive
Preparation of test site:
other: Fur was clipped from the dorsal area of the test animnals at least 24 hours prior to application. Two test sites were used per animal; one site was abraded using a hypodermic needle immediately prior to dosing. The skin of the other site was left intact.
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml per test site
Duration of treatment / exposure:
24 hours
Observation period:
72 hours
Number of animals:
Six; 3 females and 3 males
Details on study design:
TEST SITE
- Area of exposure: 3 cm2 per test site
- % coverage: Not reported
- Type of wrap if used:
Each dose was introduced under a square patch of surgical gauze measuring 1 inch by 1 inch and two single layers thick. Patches secured in place with Coban elastic bandage and Johnson and Johnson Zonas porous adhesive tape. The entire trunk of each animal was then wrapped with an impervious non-reactive material (such as plastic, 2 mils thick) and sealed at both ends to retard evaporation of volatile substances and to prevent the ingestion of the test material. A white cotton towel (15cm x 45cm) was then wrapped over the plastic and secured with Johnson and Johnson Zonas porous tape.

REMOVAL OF TEST SUBSTANCE
After the 24-hour exposure, the patches were removed and the skin was wiped, but not washed (unless necessary to observe the skin) to remove any test substance still remaining.

OBSERVATION TIME POINTS
A 30-minute period was allowed following removal of the test substance for pressure and hydration effects to subside. The animals were then scored for dermal reactions. Test sites were scored again after an additional 48 hours (i.e. 24 and 72-hour time points).

SCORING SYSTEM:
Irritation potential was scored according to the method of Draize (1944), as outlined in the Federal Hazardous Substances Act Grading Code at 16 CFR 1500.41. Primary irritation score was calculated as the total of the average scores for erythema / eschar formation and edema formation at 24- and 72-hours in either intact or abraded skin (8 values) divided by 4.
Irritation parameter:
overall irritation score
Basis:
other: Primary Irritation score = Total of average scores / 4
Time point:
other: 24/72 hr
Score:
5.38
Reversibility:
not specified
Remarks on result:
other: Primary dermal irritant
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24 h
Score:
4
Reversibility:
not specified
Remarks on result:
other: Severe erythema to slight eschar formation
Remarks:
Intact skin
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
72 h
Score:
3
Reversibility:
not specified
Remarks on result:
other: Moderate to severe erythema
Remarks:
Intact skin
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24 h
Score:
2
Reversibility:
not specified
Remarks on result:
other: Well-defined erythema
Remarks:
Intact skin
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
72 h
Score:
2
Reversibility:
not specified
Remarks on result:
other: Well-defined erythema
Remarks:
Intact skin
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24 h
Score:
4
Reversibility:
not specified
Remarks on result:
other: Severe erythema to slight eschar formation
Remarks:
Intact skin
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
72 h
Score:
3
Reversibility:
not specified
Remarks on result:
other: Moderate to severe erythema
Remarks:
Intact skin
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24 h
Score:
4
Reversibility:
not specified
Remarks on result:
other: Severe erythema to slight eschar formation
Remarks:
Intact skin
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
72 h
Score:
3
Reversibility:
not specified
Remarks on result:
other: Moderate to severe erythema
Remarks:
Intact skin
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24 h
Score:
4
Reversibility:
not specified
Remarks on result:
other: Severe erythema to slight eschar formation
Remarks:
Intact skin
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
72 h
Score:
3
Reversibility:
not specified
Remarks on result:
other: Moderate to severe erythema
Remarks:
Intact skin
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24 h
Score:
4
Reversibility:
not specified
Remarks on result:
other: Severe erythema to slight eschar formation
Remarks:
Intact skin
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
72 h
Score:
3
Reversibility:
not specified
Remarks on result:
other: Moderate to severe erythema
Remarks:
Intact skin
Irritation parameter:
erythema score
Basis:
mean
Time point:
24 h
Score:
3.67
Max. score:
4
Reversibility:
not specified
Remarks on result:
probability of severe irritation
Remarks:
Intact skin
Irritation parameter:
erythema score
Basis:
mean
Time point:
72 h
Score:
2.83
Max. score:
3
Reversibility:
not specified
Remarks on result:
probability of severe irritation
Remarks:
Intact skin
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24 h
Score:
4
Reversibility:
not specified
Remarks on result:
other: Severe erythema to slight eschar formation
Remarks:
Abraded skin
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
72 h
Score:
4
Reversibility:
not specified
Remarks on result:
other: Severe erythema to slight eschar formation
Remarks:
Abraded skin
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24 h
Score:
2
Reversibility:
not specified
Remarks on result:
other: Well-defined erythema
Remarks:
Abraded skin
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
72 h
Score:
2
Reversibility:
not specified
Remarks on result:
other: Well-defined erythema
Remarks:
Abraded skin
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24 h
Score:
4
Reversibility:
not specified
Remarks on result:
other: Severe erythema to slight eschar formation
Remarks:
Abraded skin
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
72 h
Score:
4
Reversibility:
not specified
Remarks on result:
other: Severe erythema to slight eschar formation
Remarks:
Abraded skin
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24 h
Score:
4
Reversibility:
not specified
Remarks on result:
other: Severe erythema to slight eschar formation
Remarks:
Abraded skin
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
72 h
Score:
4
Reversibility:
not specified
Remarks on result:
other: Severe erythema to slight eschar formation
Remarks:
Abraded skin
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24 h
Score:
4
Reversibility:
not specified
Remarks on result:
other: Severe erythema to slight eschar formation
Remarks:
Abraded skin
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
72 h
Score:
4
Reversibility:
not specified
Remarks on result:
other: Severe erythema to slight eschar formation
Remarks:
Abraded skin
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24 h
Score:
4
Reversibility:
not specified
Remarks on result:
other: Severe erythema to slight eschar formation
Remarks:
Abraded skin
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
72 h
Score:
4
Reversibility:
not specified
Remarks on result:
other: Severe erythema to slight eschar formation
Remarks:
Abraded skin
Irritation parameter:
erythema score
Basis:
mean
Time point:
24 h
Score:
3.67
Max. score:
4
Reversibility:
not specified
Remarks on result:
probability of severe irritation
Remarks:
Abraded skin
Irritation parameter:
erythema score
Basis:
mean
Time point:
72 h
Score:
3.67
Max. score:
4
Reversibility:
not specified
Remarks on result:
probability of severe irritation
Remarks:
Abraded skin
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24 h
Score:
4
Reversibility:
fully reversible within: 72 hours (no 48-hour scoring)
Remarks on result:
other: Severe edema
Remarks:
Intact skin
Irritation parameter:
edema score
Basis:
animal #1
Time point:
72 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Remarks:
Intact skin
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24 h
Score:
3
Reversibility:
fully reversible within: 72 hours (no 48-hour scoring)
Remarks on result:
other: Moderate edema
Remarks:
Intact skin
Irritation parameter:
edema score
Basis:
animal #2
Time point:
72 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Remarks:
Intact skin
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24 h
Score:
4
Reversibility:
fully reversible within: 72 hours (no 48-hour scoring)
Remarks on result:
other: Severe edema
Remarks:
Intact skin
Irritation parameter:
edema score
Basis:
animal #3
Time point:
72 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Remarks:
Intact skin
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24 h
Score:
4
Reversibility:
fully reversible within: 72 hours (no 48-hour scoring)
Remarks on result:
other: Severe edema
Remarks:
Intact skin
Irritation parameter:
edema score
Basis:
animal #4
Time point:
72 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Remarks:
Intact skin
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24 h
Score:
4
Reversibility:
fully reversible within: 72 hours (no 48-hour scoring)
Remarks on result:
other: Severe edema
Remarks:
Intact skin
Irritation parameter:
edema score
Basis:
animal #5
Time point:
72 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Remarks:
Intact skin
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24 h
Score:
4
Reversibility:
fully reversible within: 72 hours (no 48-hour scoring)
Remarks on result:
other: Severe edema
Remarks:
Intact skin
Irritation parameter:
edema score
Basis:
animal #6
Time point:
72 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Remarks:
Intact skin
Irritation parameter:
edema score
Basis:
mean
Time point:
24 h
Score:
3.83
Max. score:
4
Reversibility:
fully reversible within: 72 hours (no 48-hour scoring)
Remarks on result:
probability of severe irritation
Remarks:
Intact skin
Irritation parameter:
edema score
Basis:
mean
Time point:
72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Remarks:
Intact skin
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24 h
Score:
4
Reversibility:
fully reversible within: 72 hours (no 48-hour scoring)
Remarks on result:
other: Severe edema
Remarks:
Abraded skin
Irritation parameter:
edema score
Basis:
animal #1
Time point:
72 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Remarks:
Abraded skin
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24 h
Score:
3
Reversibility:
fully reversible within: 72 hours (no 48-hour scoring)
Remarks on result:
other: Moderate edema
Remarks:
Abraded skin
Irritation parameter:
edema score
Basis:
animal #2
Time point:
72 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Remarks:
Abraded skin
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24 h
Score:
4
Reversibility:
fully reversible within: 72 hours (no 48-hour scoring)
Remarks on result:
other: Severe edema
Remarks:
Abraded skin
Irritation parameter:
edema score
Basis:
animal #3
Time point:
72 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Remarks:
Abraded skin
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24 h
Score:
4
Reversibility:
fully reversible within: 72 hours (no 48-hour scoring)
Remarks on result:
other: Severe edema
Remarks:
Abraded skin
Irritation parameter:
edema score
Basis:
animal #4
Time point:
72 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Remarks:
Abraded skin
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24 h
Score:
4
Reversibility:
fully reversible within: 72 hours (no 48-hour scoring)
Remarks on result:
other: Severe edema
Remarks:
Abraded skin
Irritation parameter:
edema score
Basis:
animal #5
Time point:
72 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Remarks:
Abraded skin
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24 h
Score:
4
Reversibility:
fully reversible within: 72 hours (no 48-hour scoring)
Remarks on result:
other: Severe edema
Remarks:
Abraded skin
Irritation parameter:
edema score
Basis:
animal #6
Time point:
72 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Remarks:
Abraded skin
Irritation parameter:
edema score
Basis:
mean
Time point:
24 h
Score:
3.83
Max. score:
4
Reversibility:
fully reversible within: 72 hours (no 48-hour scoring)
Remarks on result:
probability of severe irritation
Remarks:
Abraded skin
Irritation parameter:
edema score
Basis:
mean
Time point:
72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Remarks:
Abraded skin
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
48 h
Reversibility:
not specified
Remarks on result:
not measured/tested
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
48 h
Reversibility:
not specified
Remarks on result:
not measured/tested
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
48 h
Reversibility:
not specified
Remarks on result:
not measured/tested
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
48 h
Reversibility:
not specified
Remarks on result:
not measured/tested
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
48 h
Reversibility:
not specified
Remarks on result:
not measured/tested
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
48 h
Reversibility:
not specified
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Basis:
animal #1
Time point:
48 h
Reversibility:
not specified
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Basis:
animal #2
Time point:
48 h
Reversibility:
not specified
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Basis:
animal #3
Time point:
48 h
Reversibility:
not specified
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Basis:
animal #4
Time point:
48 h
Reversibility:
not specified
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Basis:
animal #5
Time point:
48 h
Reversibility:
not specified
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Basis:
animal #6
Time point:
48 h
Reversibility:
not specified
Remarks on result:
not measured/tested
Other effects:
No abnormal behaviour was noted in any animal during the conduct of this study.

Primary irritation scores in six rabbits following a 24 -hour exposure:

Skin condition

Time (hr)

Animal number / sex

Total score

Average score

 

1/M

2/M

3/M

4/F

5/F

6/F

Erythema and Eschar formation

Intact

24

4

2

4

4

4

4

22

3.67

Intact

72

3

2

3

3

3

3

17

2.83

Abraded

24

4

2

4

4

4

4

22

3.67

Abraded

72

4

2

4

4

4

4

22

3.67

Edema formation

Intact

24

4

3

4

4

4

4

23

3.83

Intact

72

0

0

0

0

0

0

0

0

Abraded

24

4

3

4

4

4

4

23

3.83

Abraded

72

0

0

0

0

0

0

0

0
Interpretation of results:
Category 1 (corrosive) based on GHS criteria
Conclusions:
A primary irritation score of 5.38 was calculated. The test substance was therefore considered to be a primary dermal irritant according to the FHSA Regulations at 16 CFR 1500.3, as referenced in the study report. Severe erythema was observed at both the 24- and 72-hour timepoints in intact and abraded skin. Severe edema was noted at the 24-hour time point but was reversible within 72-hours. Due to the lack of 14-day observation period in this study, it is unclear whether the erythema would be reversible after a longer period of time. Therefore, as a worst case, the test substance is classified as Category 1 for skin corrosion/irritation under GHS and CLP. There is insufficient information to subcategorise.

Executive summary:

A study was conducted in order to evaluate the dermal irritation potential of the test substance in six New Zealand White rabbits (3/sex). The test sites were prepared by clipping the fur (dorsal trunk area) 24 hours prior to treatment. Two test sites (each approximately 3 cm2) were prepared within the clipped area per animal; one to the left of the spinal column and one to the right, with at least 3 cm of separation between test sites. On one site the skin was abraded immediately prior to treatment and on the other the skin was left intact. A dose of 0.5 ml test substance was applied to each site under semi-occlusive conditions for 24 hours. Following the exposure period, the test area was wiped and a 30 -minute period allowed for pressure and hydration effects to subside. The test areas were then scored for dermal reactions (erythema and edema). The animals were observed for an additional 48 hours (72 hours total) and the dermal reactions were then scored again. At the 24-hour time point, well-defined erythema to severe erythema was observed at both the intact and abraded test sites, as well as edema ranging from moderate to severe. At the 72 -hour time point, erythema ranged from well-defined to severe but no edema was noted. Due to the lack of 14-day observation period in this study, it is unclear whether the erythema would be reversible after a longer period of time. Therefore, as a worst case, the test substance is classified as Category 1 for skin corrosion/irritation under GHS and CLP. There is insufficient information to subcategorise.

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:
key study
Study period:
29 Oct 1980 to 1 Nov 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
This acute eye irritation study was conducted prior to the adoption of OECD Guideline 405 (original adopted in 1981). However, the study was conducted in accordance with the test facility protocol and US FHSA guidelines available at the time. Study methods and results are well documented in the study report and summarised here.
GLP compliance:
yes (incl. QA statement)
Specific details on test material used for the study:
Test material is 65% of the registered substance diluted in 35% non-hazardous mineral oil. Described in the study reports as a thick, brown oily liquid.
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: B and D Commercial Rabbitry, Malvern, Arkansas
- Age at study initiation: Young adults, at least 8 weeks old
- Weight at study initiation: 2424 -2843 g
- Housing: Individual housing in stainless steel cages, which were elevated above the droppings, in an environmentally controlled room. Rooms and cages maintained in accordance with the standards of the American Association for Accredication of Laboratory Animal Care (AAALAC). Sawdust, wood chips and other extraneous materials that might produce eye irritation were excluded from the animal facilities.
- Diet (e.g. ad libitum): Wayne Feeds Rabbit Ration available ad libitum
- Water (e.g. ad libitum): Tap water available ad libitum
- Acclimation period: 21 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not reported
- Humidity (%): Not reported
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light

IN-LIFE DATES: From: 29 Oct 1980 To: 1 Nov 1980
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml of undiluted test material
Duration of treatment / exposure:
Single instillation into the conjunctival sac of the right eye. The lid was held together for one second to insure adequate distribution of the test material. Observations for eye irritation were made after 24, 48 and 72 hours. Left eye remained untreated and served as the control.
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
Six; 3 females and 3 males
Details on study design:
REMOVAL OF TEST SUBSTANCE
The treated eye was not irrigated.

SCORING SYSTEM: Method of Draize

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope /
In addition to regular eye examination, the treated eyes of all animals were examined after application of sodium fluorescein 72 hours post treatment. The reading of reactions was facilitated by ophthalmoscopy.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24 h
Score:
1
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Scattered or diffuse areas, details of iris clearly visible
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
48 h
Score:
1
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Scattered or diffuse areas, details of iris clearly visible
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
72 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24 h
Score:
1
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Scattered or diffuse areas, details of iris clearly visible
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
48 h
Score:
1
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Scattered or diffuse areas, details of iris clearly visible
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
72 h
Score:
2
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Easily discernible translucent areas, details of iris slightly obscured
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24 h
Score:
0
Reversibility:
other: Not applicable (no effects)
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
48 h
Score:
0
Reversibility:
other: Not applicable (no effects)
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
72 h
Score:
0
Reversibility:
other: Not applicable (no effects)
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
24 h
Score:
0
Reversibility:
other: Not applicable (no effects)
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
48 h
Score:
1
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Scattered or diffuse areas, details of iris clearly visible
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
72 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
24 h
Score:
0
Reversibility:
other: Not applicable (no effects)
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
48 h
Score:
0
Reversibility:
other: Not applicable (no effects)
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
72 h
Score:
0
Reversibility:
other: Not applicable (no effects)
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
24 h
Score:
0
Reversibility:
other: Not applicable (no effects)
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
48 h
Score:
1
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Scattered or diffuse areas, details of iris clearly visible
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
72 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24 h
Score:
1
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Folds above normal, congestion, swelling, circumcorneal injection (any or all of these combinations of any thereof), iris still reacting to light (sluggish reaction is positive)
Irritation parameter:
iris score
Basis:
animal #1
Time point:
48 h
Score:
1
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Folds above normal, congestion, swelling, circumcorneal injection (any or all of these combinations of any thereof), iris still reacting to light (sluggish reaction is positive)
Irritation parameter:
iris score
Basis:
animal #1
Time point:
72 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24 h
Score:
1
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Folds above normal, congestion, swelling, circumcorneal injection (any or all of these combinations of any thereof), iris still reacting to light (sluggish reaction is positive)
Irritation parameter:
iris score
Basis:
animal #2
Time point:
48 h
Score:
1
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Folds above normal, congestion, swelling, circumcorneal injection (any or all of these combinations of any thereof), iris still reacting to light (sluggish reaction is positive)
Irritation parameter:
iris score
Basis:
animal #2
Time point:
72 h
Score:
1
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Folds above normal, congestion, swelling, circumcorneal injection (any or all of these combinations of any thereof), iris still reacting to light (sluggish reaction is positive)
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24 h
Score:
1
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Folds above normal, congestion, swelling, circumcorneal injection (any or all of these combinations of any thereof), iris still reacting to light (sluggish reaction is positive)
Irritation parameter:
iris score
Basis:
animal #3
Time point:
48 h
Score:
1
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Folds above normal, congestion, swelling, circumcorneal injection (any or all of these combinations of any thereof), iris still reacting to light (sluggish reaction is positive)
Irritation parameter:
iris score
Basis:
animal #3
Time point:
72 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #4
Time point:
24 h
Score:
1
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Folds above normal, congestion, swelling, circumcorneal injection (any or all of these combinations of any thereof), iris still reacting to light (sluggish reaction is positive)
Irritation parameter:
iris score
Basis:
animal #4
Time point:
48 h
Score:
1
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Folds above normal, congestion, swelling, circumcorneal injection (any or all of these combinations of any thereof), iris still reacting to light (sluggish reaction is positive)
Irritation parameter:
iris score
Basis:
animal #4
Time point:
72 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #5
Time point:
24 h
Score:
1
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Folds above normal, congestion, swelling, circumcorneal injection (any or all of these combinations of any thereof), iris still reacting to light (sluggish reaction is positive)
Irritation parameter:
iris score
Basis:
animal #5
Time point:
48 h
Score:
1
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Folds above normal, congestion, swelling, circumcorneal injection (any or all of these combinations of any thereof), iris still reacting to light (sluggish reaction is positive)
Irritation parameter:
iris score
Basis:
animal #5
Time point:
72 h
Score:
1
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Folds above normal, congestion, swelling, circumcorneal injection (any or all of these combinations of any thereof), iris still reacting to light (sluggish reaction is positive)
Irritation parameter:
iris score
Basis:
animal #6
Time point:
24 h
Score:
1
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Folds above normal, congestion, swelling, circumcorneal injection (any or all of these combinations of any thereof), iris still reacting to light (sluggish reaction is positive)
Irritation parameter:
iris score
Basis:
animal #6
Time point:
48 h
Score:
1
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Folds above normal, congestion, swelling, circumcorneal injection (any or all of these combinations of any thereof), iris still reacting to light (sluggish reaction is positive)
Irritation parameter:
iris score
Basis:
animal #6
Time point:
72 h
Score:
1
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Folds above normal, congestion, swelling, circumcorneal injection (any or all of these combinations of any thereof), iris still reacting to light (sluggish reaction is positive)
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24 h
Score:
2
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
More diffuse, deeper crimson red, individual vessels not easily discernible
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
48 h
Score:
2
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
More diffuse, deeper crimson red, individual vessels not easily discernible
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
72 h
Score:
2
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
More diffuse, deeper crimson red, individual vessels not easily discernible
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24 h
Score:
2
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
More diffuse, deeper crimson red, individual vessels not easily discernible
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
48 h
Score:
2
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
More diffuse, deeper crimson red, individual vessels not easily discernible
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
72 h
Score:
2
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
More diffuse, deeper crimson red, individual vessels not easily discernible
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24 h
Score:
1
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Vessels definitely injected above normal
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
48 h
Score:
1
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Vessels definitely injected above normal
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
72 h
Score:
1
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Vessels definitely injected above normal
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
24 h
Score:
1
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Vessels definitely injected above normal
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
48 h
Score:
1
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Vessels definitely injected above normal
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
72 h
Score:
1
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Vessels definitely injected above normal
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
24 h
Score:
1
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Vessels definitely injected above normal
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
48 h
Score:
1
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Vessels definitely injected above normal
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
72 h
Score:
1
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Vessels definitely injected above normal
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
24 h
Score:
1
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Vessels definitely injected above normal
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
48 h
Score:
1
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Vessels definitely injected above normal
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
72 h
Score:
1
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Vessels definitely injected above normal
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24 h
Score:
4
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Swelling with lids about half closed to completely closed
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
48 h
Score:
3
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Obvious swelling with lids about half closed
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
72 h
Score:
3
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Obvious swelling with lids about half closed
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24 h
Score:
4
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Swelling with lids about half closed to completely closed
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
48 h
Score:
3
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Obvious swelling with lids about half closed
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
72 h
Score:
3
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Obvious swelling with lids about half closed
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24 h
Score:
2
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Obvious swelling with partial eversion of lids
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
48 h
Score:
2
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Obvious swelling with partial eversion of lids
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
72 h
Score:
3
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Obvious swelling with lids about half closed
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24 h
Score:
2
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Obvious swelling with partial eversion of lids
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
48 h
Score:
2
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Obvious swelling with partial eversion of lids
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
72 h
Score:
2
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Obvious swelling with partial eversion of lids
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
24 h
Score:
2
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Obvious swelling with partial eversion of lids
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
48 h
Score:
2
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Obvious swelling with partial eversion of lids
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
72 h
Score:
2
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Obvious swelling with partial eversion of lids
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
24 h
Score:
2
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Obvious swelling with partial eversion of lids
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
48 h
Score:
2
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Obvious swelling with partial eversion of lids
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
72 h
Score:
2
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
Obvious swelling with partial eversion of lids
Irritation parameter:
overall irritation score
Basis:
animal #1
Time point:
24 h
Score:
38
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
probability of moderate irritation
Irritation parameter:
overall irritation score
Basis:
animal #1
Time point:
48 h
Score:
31
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
probability of moderate irritation
Irritation parameter:
overall irritation score
Basis:
animal #1
Time point:
72 h
Score:
16
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
probability of mild irritation
Irritation parameter:
overall irritation score
Basis:
animal #2
Time point:
24 h
Score:
33
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
probability of moderate irritation
Irritation parameter:
overall irritation score
Basis:
animal #2
Time point:
48 h
Score:
31
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
probability of moderate irritation
Irritation parameter:
overall irritation score
Basis:
animal #2
Time point:
72 h
Score:
41
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
probability of moderate irritation
Irritation parameter:
overall irritation score
Basis:
animal #3
Time point:
24 h
Score:
19
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
probability of mild irritation
Irritation parameter:
overall irritation score
Basis:
animal #3
Time point:
48 h
Score:
19
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
probability of mild irritation
Irritation parameter:
overall irritation score
Basis:
animal #3
Time point:
72 h
Score:
14
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
probability of weak irritation
Irritation parameter:
overall irritation score
Basis:
animal #4
Time point:
24 h
Score:
17
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
probability of mild irritation
Irritation parameter:
overall irritation score
Basis:
animal #4
Time point:
48 h
Score:
22
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
probability of mild irritation
Irritation parameter:
overall irritation score
Basis:
animal #4
Time point:
72 h
Score:
12
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
probability of weak irritation
Irritation parameter:
overall irritation score
Basis:
animal #5
Time point:
24 h
Score:
17
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
probability of mild irritation
Irritation parameter:
overall irritation score
Basis:
animal #5
Time point:
48 h
Score:
17
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
probability of mild irritation
Irritation parameter:
overall irritation score
Basis:
animal #5
Time point:
72 h
Score:
17
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
probability of mild irritation
Irritation parameter:
overall irritation score
Basis:
animal #6
Time point:
24 h
Score:
19
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
probability of mild irritation
Irritation parameter:
overall irritation score
Basis:
animal #6
Time point:
48 h
Score:
22
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
probability of mild irritation
Irritation parameter:
overall irritation score
Basis:
animal #6
Time point:
72 h
Score:
17
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
probability of mild irritation
Irritant / corrosive response data:
Positive reactions were noted in the treated eyes of all six rabbits at the 24, 48 and 72 hour readings. In some animals, the cornea and iris effects were reversible within 72 hours, but this was not the case with the conjunctiva effects (erythema, chemosis, discharge) in any animal.
Other effects:
No abnormal appearance or behaviour was noted during the conduct of this study.

Rabbit

Time (hours)

Cornea

Iris

Conjunction

Total score

Opacity

Area

Iritis

Erythema

Chemosis

Discharge

1

24

1

3

1

2

4

3

38

48

1

2

1

2

3

3

31

72

0

0

0

2

3

3

16

2

24

1

2

1

2

4

3

33

48

1

2

1

2

3

3

31

72

2

2

1

2

3

3

41

3

24

0

0

1

1

2

4

19

48

0

0

1

1

2

4

19

72

0

0

0

1

3

3

14

4

24

0

0

1

1

2

3

17

48

1

1

1

1

2

3

22

72

0

0

0

1

2

3

12

5

24

0

0

1

1

2

3

17

48

0

0

1

1

2

3

17

72

0

0

1

1

2

3

17

6

24

0

0

1

1

2

4

19

48

1

1

1

1

2

3

22

72

0

0

1

1

2

3

17

 

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Positive reactions were noted in the treated eyes of all six rabbits at the 24, 48 and 72 hour readings. Therefore, when instilled into the eyes of albino rabbits the test substance was considered to be a primary irritant as defined in the FHSA Regulations at 16 CFR 1500.3, as referenced in the study report. Some of the effects (cornea, iris) were reversible within 72 hours in some animals. However, the conjunctiva effects (erythema, chemosis, discharge) were not reversible within this time period. Since a 21-day observation period (as recommended by the current OECD Guideline) was not included in this study, it is unclear whether the remaining irritation effects would be reversible after a longer period of time. Therefore, as a worst case, the test substance is classified as Category 1 for effects on the eye under GHS and CLP.
Executive summary:

A study was conducted in order to evaluate the eye irritation potential of the test substance in six New Zealand White rabbits (3/sex). The test substance was instilled into the conjunctival sac of the right eye of each animal. The lid was held together for one second to insure adequate distribution of the test material. Observations for eye irritation were made after 24, 48 and 72 hours. Positive reactions were noted in the treated eyes of all six rabbits at the 24, 48 and 72 hour readings. Some of the effects (cornea, iris) were reversible within 72 hours in some animals. However, the conjunctiva effects (erythema, chemosis, discharge) were not reversible within this time period. Since a 21-day observation period (as recommended by the current OECD Guideline) was not included in this study, it is unclear whether the remaining irritation effects would be reversible after a longer period of time. Therefore, as a worst case, the test substance is classified as Category 1 for irreversible effects on the eye under GHS and CLP.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Since 14 -day and 21 -day observation periods were not included in the skin and eye irritation studies, respectively, as recommended by current OECD Guidelines, it is unclear whether the irritation effects observed would be reversible after a longer period of time. Therefore, as a worst case, classifications of Category 1 for skin corrosion/irritation and for irreversible effects on the eye are appropriate under Regulation (EC) No 1272/2008 on the classification, labelling and packaging of substances and mixtures. There is insufficient information to subcategorise for skin corrosion/irritation