Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Skin Irritation:
The test substance was found not to be irritating to the skin of rabbits.
Eye Irritation:
The test substance was found not to be irritating to the eyes of rabbits.

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:
1 August 1984 - 3 September 1984
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Strain: Albino New Zealand
- Sex: males
- Age at study initiation: no data
- Weight at study initiation: 2.5 ± 0.2 kg
- Housing: individual housing, in polystyrene cages, of internal dimensions 540 x 360 x 315 mm, with a perforated floor
- Diet: ad libitum, 150 g of complete maintenance food per rabbit per day
- Water: ad libitum
- Acclimation period: at least 8 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 3 °C
- Humidity: 30 - 70 %
- Air changes: 12 to 14 times per hour (pre-filtered air : 5 - 10 µl)
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 1 August 1984 To: data not available
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
Concentration: 0.5 g of the test material was applied as a paste with 0.16 mL of water
Duration of treatment / exposure:
4 hours
Observation period:
14 days
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: a surface of about 6 cm²
- % coverage: no data
- Type of wrap: semiocclusive dressing: covered with a Codex hydrophilic eight layer gauze pad 2.5 cm per side, followed by 10 cm wide adhesive perforated tape (Peloplast: M.S.R.) applied on a crimped gauze bandage (Creplux-Molinier) covering more particularly the whole clipped surface (to avoid possible orthoergic reactions) and wrapped around the animal (without blocking the respiratory and abdominal movements).


REMOVAL OF TEST SUBSTANCE
- Washing: the bandages were removed and if necessary excess test material, which had not penetrated, was wiped away with a gauze pad moistened with 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 to severe erythema 3
Severe erythema (beet redness) or eschar formation (injuries in depth) preventing erythema reading 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 (edges raised approximately 1 millimetre) 3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure) 4
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Not applicable
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Not applicable
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Not applicable
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Not applicable
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Not applicable
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Not applicable
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Not applicable
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Not applicable
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Not applicable
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Not applicable
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Not applicable
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Not applicable
Irritant / corrosive response data:
No irritation observed.
Other effects:
No data available.

Table 1 Summary of Erythema Scores

Animal Number

Mean Score over 24, 48 and 72 hours

1

0

2

0

3

0

4

0

5

0

6

0

Mean

0

 

Table 2 Summary of Oedema Scores

Animal Number

Mean Score over 24, 48 and 72 hours

1

0

2

0

3

0

4

0

5

0

6

0

Mean

0
Interpretation of results:
not irritating
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
According to this study, the test material is not classified as a dermal irritant.
Executive summary:

A dermal irritation study was conducted in accordance with the standardised guideline OECD 404.

Six male New Zealand White rabbits were dermally exposed to 0.5 g of the test material moistened with 0.16 mL of water to form a paste. Test sites were covered with a semi-occlusive dressing for 4 hours, followed by observation of the animals for 14 days. Irritation was evaluated based on erythema and oedema reactions observed 1, 24, 48 and 72 hours after the end of application.

No skin reactions were observed during the study. The mean score for the readings at 24, 48 and 72 hours for both erythema and oedema was equal to 0.

Under the conditions of this study, the test material is not classified for dermal irritation.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
data not available
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in accordance with generally accepted scientific principles, with incomplete reporting or methodological deficiencies. This reference does not provide a full report with regard to the methods used in this study. However, as most basic key information is reported, the study can be judged as scientifically acceptable.
Qualifier:
equivalent or similar to guideline
Guideline:
other: FHSA 16 CFR 1500.41
Deviations:
not specified
Principles of method if other than guideline:
no data
GLP compliance:
not specified
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, Housing, Diet, Water, Acclimation period: data not available

ENVIRONMENTAL CONDITIONS:
- Temperature, Humidity, Air changes, Photoperiod: data not available

IN-LIFE DATES: data not available
Type of coverage:
occlusive
Preparation of test site:
other: one intact and one abraded skin site
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
undiluted / 0.5 g
Duration of treatment / exposure:
24 hours
Observation period:
72 hours; the sites were evaluated 24 and 72 hours after the initial exposure.
Number of animals:
6
Details on study design:
TEST SITE:
- Area of exposure: ca. 2.5 cm²
- % coverage: data not available
- Type of wrap if used: data not available

REMOVAL OF TEST SUBSTANCE:
- Washing: yes (the test sites were wiped)
- Time after start of exposure: 24 hours

SCORING SYSTEM: according to Draize:

Erythema and eschar formation:

No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) or eschar formation (injuries in depth) preventing erythema reading 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 (edges raised approximately 1 millimetre) 3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure) 4
Irritation parameter:
primary dermal irritation index (PDII)
Score:
0.13
Reversibility:
no data
Irritant / corrosive response data:
There were no signs of dermal irritation.
Interpretation of results:
not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The test material was not irritating under the conditions of this test and is not classified in accordance with EU criteria.
Executive summary:

In a primary dermal irritation study that broadly followed the FHSA 16 CFR 1500.41 guideline, six New Zealand White rabbits were dermally exposed to 0.5 g of the test material on one intact and one abraded skin site. Test sites were covered with an occlusive dressing for 24 hours and the animals were observed for the following 72 hours. Irritation was scored by the method of Draize 24 and 72 hours after the initial exposure.

There were no signs of dermal irritation and the Primary Dermal Irritation Index = 0.13.

Under the conditions of this study, the test material is not a dermal irritant and does not require classification in accordance with EU criteria.

Endpoint:
skin corrosion: 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:
no adverse effect observed (not 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
Study period:
8 August 1984 - 3 September 1984
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Strain: Albino New Zealand
- Sex: males
- Age at study initiation: no data
- Weight at study initiation: 2.5 ± 0.2 kg
- Housing: individual housing, in polystyrene cages, of internal dimensions 540 x 360 x 315 mm, with a perforated floor
- Diet: ad libitum, 150 g of complete maintenance food per rabbit per day
- Water: ad libitum
- Acclimation period: at least 8 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 3 °C
- Humidity: 30 - 70 %
- Air changes: 12 to 14 times per hour (pre-filtered air: 5 - 10 µl)
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 8 August 1984 To: data not available
Vehicle:
unchanged (no vehicle)
Remarks:
no
Controls:
other: the left eye remained untreated and served as control
Amount / concentration applied:
Amount applied: 0.1 g in the right eye.
Duration of treatment / exposure:
The upper and lower eyelid are held together for 10 seconds to avoid loss of test substance.
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
6 males
Details on study design:
REMOVAL OF TEST SUBSTANCE
no washing

TOOL USED TO ASSESS SCORE: Heine's ophthalmoscope / fluorescein

SCORING SYSTEM:

1. CONJUNCTIVAE

Redness (refers to palpebral and bulbar conjunctivae excluding cornea and iris)
Vessels normal............................................................................................................................................0
Vessels definitely injected above normal................................................................................................1
More diffuse, deeper crimson red, individual vessels not easily discernible....................................2
Diffuse beefy red.........................................................................................................................................3

Chemosis
No swelling..................................................................................................................................................0
Any swelling above normal (includes nictitating membrane).............................................................1
Obvious swelling with partial eversion of lids.......................................................................................2
Swelling with lids about half closed.........................................................................................................3
Swelling with lids half closed to completely closed...............................................................................4


IRIS

Values
Normal.........................................................................................................................................................0
Folds above normal, congestion, swelling, circumcorneal injection (any or all
of these or combination of any thereof) iris still reacting to light
(sluggish reaction is positive).................................................................................................................1
No reaction to light, haemorrhage, gross destruction (any or all of these)....................................2

CORNEA

Degree of Opacity (most dense area used)
No opacity...................................................................................................................................................0
Scattered or diffuse areas, details of iris clearly visible......................................................................1
Easily discernible translucent areas, details of iris slightly obscured..............................................2
Opalescent areas, no details of iris visible, size of pupil barely discernible....................................3
Opaque, iris not discernible through the opacity................................................................................4

Area of Cornea Involved
One quarter (or less) but not zero..........................................................................................................1
Greater than one quarter but less than half...........................................................................................2
Greater than half but less than three quarters......................................................................................3
Greater than three quarters, up to whole area.......................................................................................4

ULCERATION
No ulceration.................................................................................................................................................0
Presence of ulceration.................................................................................................................................U
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.667
Max. score:
2
Reversibility:
fully reversible within: 72 h
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
3
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
Slight iris irritation observed in one rabbit at 24 and 48 hour time points. No other effects observed in any rabbit.
Other effects:
No data available.

Table 1 Individual Results

Timepoint

(hours)

Rabbit Number

Conjunctiva

Iris

Congestion

Cornea

Chemosis

Redness

Degree of Opacity

Area

Ulceration

 

 

 

24

892

0

0

0

0

0

0

893

0

0

1*

0

0

0

894

0

0

0

0

0

0

895

0

0

0

0

0

0

896

0

0

0

0

0

0

897

0

0

0

0

0

0

Mean

0

0

0.17

0

 0

0 

 

 

 

48

892

0

0

0

0

0

0

893

0

0

1*

0

0

0

894

0

0

0

0

0

0

895

0

0

0

0

0

0

896

0

0

0

0

0

0

897

0

0

0

0

0

0

Mean

0

0

0.17

0

 0

0 

 

 

 

72

892

0

0

0

0

0

0

893

0

0

0

0

0

0

894

0

0

0

0

0

0

895

0

0

0

0

0

0

896

0

0

0

0

0

0

897

0

0

0

0

0

0

Mean

0

0

0

0

 0

0

 *Circumcorneal injection

Interpretation of results:
not irritating
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
According to this study, the test material is not classified as an eye irritant.
Executive summary:

An eye irritation study was conducted in accordance with the standardised guideline OECD 405. 0.1 g of the test material was instilled into the conjunctival sac of the right eye of six male New Zealand white rabbits.

Animals were observed for 21 days. Ocular irritation was scored based on chemosis and changes to the iris, cornea and conjunctivae at 24, 48 and 72 h.

The mean scores for the 6 rabbits across all timepoints were 0 for corneal opacity, 0.66 for iritis, 0 for redness and 0 for chemosis of the conjunctivae.

In this study, the test material was seen to be not irritating to the eye, requiring no classification.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
31 October 1990 - 3 November 1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in accordance with generally accepted scientific principles, possibly with incomplete reporting or methodological deficiencies, which do not affect the quality of the relevant results. Irritation effects in animals only observed for 72 hours. Signs of conjunctival irritation still in evidence at 72 hour point in 3/6 rabbits, therefore observation period should have been extended.
Qualifier:
according to guideline
Guideline:
other: FHSA 16 CFR 1500.42
Deviations:
no
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Housing: Individually housed in suspended stainless steel caging with mesh floors
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum tap water supplied by automatic watering system
- Acclimation period: 6 - 10 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 20 °C

IN-LIFE DATES: From: To: 31 October 1990 - 3 November 1990
Vehicle:
unchanged (no vehicle)
Controls:
other: the right eye of each rabbit remained untreated and served as control
Amount / concentration applied:
undiluted
Amount applied: 0.1 g
Duration of treatment / exposure:
The upper and lower lids were gently held together for 1 second post-installation to prevent loss of the test material.

Three of the treated eyes were rinsed 30 seconds post-installation.
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3 males, 3 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): three of the treated eyes were rinsed with saline.
- Time after start of exposure: 30 seconds post-exposure.

- Scoring system: according to the method of Draize. Ocular lesions were evaluated at 24, 48 and 72 hours post installation. Fluorescein was used at the 24 hour evaluation.

Draize Scale for Scoring Ocular Irritation

1. CONJUNCTIVAE

(A) Redness (refers to palpebral and bulbar conjunctivae excluding cornea and iris)
Vessels normal............................................................................................................................................0
Vessels definitely injected above normal................................................................................................1
More diffuse, deeper crimson red, individual vessels not easily discernible....................................2
Diffuse beefy red.........................................................................................................................................3

(B) Chemosis
No swelling..................................................................................................................................................0
Any swelling above normal (includes nictitating membrane).............................................................1
Obvious swelling with partial eversion of lids.......................................................................................2
Swelling with lids about half closed.........................................................................................................3
Swelling with lids half closed to completely closed...............................................................................4

(C) Discharge
No discharge...............................................................................................................................................0
Any amount different from normal (does not include small amounts observed in inner
canthus of normal animals)......................................................................................................................1
Discharge with moistening of the lids and hairs just adjacent to lids...............................................2
Discharge with moistening of the lids and hairs a considerable area around the eye...................3

THE TOTAL SCORE = (A + B + C) x 2 MAXIMUM TOTAL = 20

2. IRIS

(D) Values
Normal.........................................................................................................................................................0
Folds above normal, congestion, swelling, circumcorneal injection (any or all
of these or combination of any thereof) iris still reacting to light
(sluggish reaction is positive).................................................................................................................1
No reaction to light, haemorrhage, gross destruction (any or all of these)....................................2

THE TOTAL SCORE = D x 5 MAXIMUM TOTAL = 10

3. CORNEA

(E) Degree of Opacity (most dense area used)
No opacity...................................................................................................................................................0
Scattered or diffuse areas, details of iris clearly visible......................................................................1
Easily discernible translucent areas, details of iris slightly obscured..............................................2
Opalescent areas, no details of iris visible, size of pupil barely discernible....................................3
Opaque, iris not discernible through the opacity................................................................................4

(F) Area of Cornea Involved
One quarter (or less) but not zero..........................................................................................................1
Greater than one quarter but less than half...........................................................................................2
Greater than half but less than three quarters......................................................................................3
Greater than three quarters, up to whole area.......................................................................................4

THE TOTAL SCORE = (E x F) x 5 MAXIMUM TOTAL = 80

MAXIMUM TOTAL SCORE POSSIBLE = 110
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: n/a
Remarks on result:
other: Unwashed
Irritation parameter:
iris score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0.11
Max. score:
2
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Unwashed
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean of 24, 48 and 72 hours
Score:
1.11
Max. score:
3
Reversibility:
other: 1 animal still exhibited a hyperemia score of 1 at 72 hours
Remarks on result:
other: Unwashed
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0.78
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Unwashed
Irritation parameter:
other: Discharge
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0.56
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Unwashed
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: n/a
Remarks on result:
other: Washed
Irritation parameter:
iris score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0
Max. score:
2
Reversibility:
other: n/a
Remarks on result:
other: Washed
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0.78
Max. score:
3
Reversibility:
other: 2 animals still exhibited a hyperemia score of 1 at 72 hours
Remarks on result:
other: Washed
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0.44
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Washed
Irritation parameter:
other: Discharge
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Washed
Irritant / corrosive response data:
-No corneal opacity was noted in any of the treated eyes.
-Iritis was noted in one unwashed eye 24 hours post installation; this cleared by the 48 hour observation.
-Conjunctival irritation was noted in all eyes 24 hours after administration. This remained in one unwashed and two washed eyes after 72 hours.
Other effects:
All animals appeared active and healthy. No signs of gross toxicity, adverse pharmacologic effects or abnormal behaviour were observed.

Table 1 Individual Results

Time Point (hours)

Rabbit Number

Cornea

Iris

Conjunctivae

Chemosis

Discharge

 

 

24

7686

7687

7688

7689

7690

7691

0

0

0

0

0

0

0

1

0

0

0

0

2

2

2

1

1

1

1

2

1

1

1

1

1

2

1

1

1

1

 

 

48

7686

7687

7688

7689

7690

7691

0

0

0

0

0

0

0

0

0

0

0

0

1

1

1

1

1

0

1

1

1

1

0

0

0

1

0

0

0

0

 

 

72

7686

7687

7688

7689

7690

7691

0

0

0

0

0

0

0

0

0

0

0

0

1

0

0

1

1

0

0

0

0

0

0

0

0

0

0

0

0

0

Rabbits 7689, 7690 and 7691 had the treated eye rinsed with 30 cc of saline solution 30 seconds post-installation

Interpretation of results:
not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The test material produced minimal irritation to both the unwashed and washed eyes; no classification is required under the conditions of this study.
Executive summary:

A primary eye irritation study was conducted in accordance with FHSA guideline16 CFR 1500.42.

0.1 g of the test material was instilled into the left eye of six New Zealand white rabbits, with three of the treated eyes being rinsed after 30 seconds with saline. The animals were observed for three days and the eyes examined at 24, 48 and 72 hours. Irritation was scored according to the method of Draize.

 

The test material produced minimal irritation to both the unwashed and washed eyes and no classification is required under the conditions of this study in accordance with EU criteria.

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:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin Irritation

The key study was conducted in accordance with the standardised guideline OECD 404.

Six male New Zealand White rabbits were dermally exposed to 0.5 g of the test material moistened with 0.16 mL of water to form a paste. Test sites were covered with a semi-occlusive dressing for 4 hours, followed by observation of the animals for up to 14 days. Irritation was evaluated based on erythema and oedema reactions observed 1, 24, 48 and 72 hours after the end of application.

No skin reactions were observed during the study. The mean score for the readings at 24, 48 and 72 hours for both erythema and oedema was equal to 0.

Under the conditions of this study, the test material is not classified.

 

Supporting information is provided in the form of a second study that broadly followed the FHSA 16 CFR 1500.41 guideline. This study was awarded a reliability score of 2 in accordance with the criteria of Klimisch (1997).

Six New Zealand White rabbits were dermally exposed to 0.5 g of the test material on one intact and one abraded skin site. Test sites were covered with an occlusive dressing for 24 hours and the animals were observed for the following 3 days. Irritation was scored by the method of Draize.

There were no signs of dermal irritation and the Primary Dermal Irritation Index = 0.13.

In this study the test material is not a dermal irritant and does not require classification.

 

Eye Irritation

The key eye irritation study was conducted in accordance with the standardised guideline OECD 405. 0.1 g of the test material was instilled into the conjunctival sac of the right eye of six male New Zealand white rabbits.

Animals were observed for 21 days. Ocular irritation was scored based on chemosis and changes to the iris, cornea and conjunctivae at 24, 48 and 72 hours.

The mean scores for the 6 rabbits across all time points were 0 for corneal opacity, 0.66 for iritis, 0 for redness and 0 for chemosis of the conjunctivae.

In this study, the test material was seen to be not irritating to the eye, requiring no classification.

 

Supporting information is provided in the form of second study conducted in accordance with FHSA guideline 16 CFR 1500.42. This study was awarded a reliability score of 2 in accordance with the criteria of Klimisch (1997).

0.1 g of the test material was instilled into the left eye of six New Zealand white rabbits, with three of the treated eyes being rinsed after 30 seconds with saline. The animals were observed for three days and the eyes examined at 24, 48 and 72 hours. Irritation was scored according to the method of Draize.

The test material produced minor irritation to both the unwashed and washed eyes, but not sufficient for classification under the conditions of this study.


Justification for selection of skin irritation / corrosion endpoint:
The key study was conducted in accordance with the standardised guideline OECD 404. It was well reported and adhered to sound scientific principles. It was awarded a reliability score of 1 in accordance with the criteria of Klimisch (1997).

Justification for selection of eye irritation endpoint:
The key study was conducted in accordance with the standardised guideline OECD 405. It was well reported and adhered to sound scientific principles. It was awarded a reliability score of 1 in accordance with the criteria of Klimisch (1997).

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No. 1272/2008, the test material does not require classification for irritation or corrosion to either the skin or eye.