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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 
Not irritant
EYE IRRITATION: 
Not irritant

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:
From June 32 to July 25, 1975
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
other: method given in the "Hazardous Substances Regulations" under the U.S. Federal Hazardous . Substances Labelling Act Sect. 191.11 (February 1965).
GLP compliance:
no
Remarks:
Pre GLP.
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS- Number of animals: 6 (3 male; 3 female)- Age at study initiation: 9 -14 weeks- Weight at study initiation: 2.15 (male); 2.75 (female)- Housing: singly caged- Diet : commercial irradiated diet (Syles Oxoid), ad libitum- Water : ad libitum for all test durationENVIRONMENTAL CONDITIONS- Temperature (°C): 21°C ± 2°- Relative humidity: 50-70 %- Photoperiod (hrs dark / hrs light): 10 hours of light (8:00-18:00)
Type of coverage:
occlusive
Preparation of test site:
abraded
Vehicle:
water
Controls:
other: non abraded part of the skin area considered
Amount / concentration applied:
10g. of the test compound was mixed with 10ml of water to make a solution of 15ml. 0.75ml of which was applied to each test site on a 2.5 cm square gauze pad.
Number of animals:
6 (3 male and 3 female)
Details on study design:
TEST SITE24 hours prior to the dermal application, the backs of the rabbits were shaved over an area consisting of at least 10 %of the total body surface. Two test sites lateral to the mid line of the back were used on each rabbit. Immediately before the application of the test compound, the right hand site was abraded with the point of a sterile hypodermic needle. The abrasions weresufficiently deep to penetrate the stratum corneum but not to damage the dermis. The left hand sits remained intact.These were covered with aluminium foil secured with "Sleek" adhesive tape. The test sites were then enclosed by a 6 " wide "Coban" self adhesive bandage the edges of which were fixed to the skin by strips of "Sleek" in order to retain the test substance in close contact with the skin.REMOVAL OF TEST SUBSTANCEAfter 24 hours the dressing was removed and the intact and abraded application sites were assessed for oedema and erythema.A further assessment was made at 72 hours.SCORE SYSTEMThe assessment of the macroscopic skin reaction was made according to the Draize et al. 3. Pharmac. Exp. Ther. 82 377 1944.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
4
Remarks on result:
no indication of irritation
Remarks:
48th hour data is not available. The value of the 24th hour was taken to be more conservative. See attached table of results.
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
4
Remarks on result:
no indication of irritation
Remarks:
48th hour data is not available. The value of the 24th hour was taken to be more conservative. See attached table of results.
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
4
Remarks on result:
no indication of irritation
Remarks:
48th hour data is not available. The value of the 24th hour was taken to be more conservative. See attached table of results.
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
4
Remarks on result:
no indication of irritation
Remarks:
48th hour data is not available. The value of the 24th hour was taken to be more conservative. See attached table of results.
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
4
Remarks on result:
no indication of irritation
Remarks:
48th hour data is not available. The value of the 24th hour was taken to be more conservative. See attached table of results.
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
4
Remarks on result:
no indication of irritation
Remarks:
48th hour data is not available. The value of the 24th hour was taken to be more conservative. See attached table of results.
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 1.33
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: 48th hour data is not available. The value of the 24th hour was taken to be more conservative. See attached table of results.
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 1.33
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: 48th hour data is not available. The value of the 24th hour was taken to be more conservative. See attached table of results.
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 1.33
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: 48th hour data is not available. The value of the 24th hour was taken to be more conservative. See attached table of results.
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
ca. 1.33
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: 48th hour data is not available. The value of the 24th hour was taken to be more conservative. See attached table of results.
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
ca. 1.33
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: 48th hour data is not available. The value of the 24th hour was taken to be more conservative. See attached table of results.
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
ca. 1.33
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: 48th hour data is not available. The value of the 24th hour was taken to be more conservative. See attached table of results.
Irritant / corrosive response data:
Slight erythema was seen on 2/6 abraded sites and slight to moderate oedema was seen on all sites, 24 hours after application of the compound. All sites were normal by 72 hours.See table for further details.
Interpretation of results:
other: CLP criteria not met
Conclusions:
Not skin irritant
Executive summary:

The determination of skin irritation was determined in an a Primary Skin Irritation test. No guideline is available and the test was not performed in GLP. The test substance was tested in albino rats for 72 h. Erythema and oedema formation were observed.

No erythema was observed on intact skin. Slight erythema was seen on 2/6 abraded sites and slight to moderate oedema was seen on all sites, 24 hours after application of the compound. All sites were normal by 72 hours. The primary irritation score was 1.2

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

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 10 to 25 of July 1975
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study following official guideline not in GLP
Qualifier:
according to guideline
Guideline:
other: method given in the "Hazardous Substances Regulations" under the U.S. Federal Hazardous . Substances Labelling Act Sect. 191.12 (February 1965) with slight modification.
GLP compliance:
no
Remarks:
Pre GLP.
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Number of animals: 6 (3 male; 3 female)
- Age at study initiation: 9 -14 weeks
- Weight at study initiation: 2.15 (male); 2.57 (female)
- Housing: singly caged
- Diet : commercial irradiated diet (Syles Oxoid), ad libitum
- Water : sterile water, ad libitum for all test duration

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21°C ± 2°
- Relative humidity: 50-70 %
- Photoperiod (hrs dark / hrs light): 10 hours of light (8:00-18:00)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
100 mg of the test compound
Duration of treatment / exposure:
1 second
Observation period (in vivo):
1, 24, 48, 72 h after application and for any further period considered necessary (6 and 10 days)
Number of animals or in vitro replicates:
6 (3 male and 3 female)
Details on study design:
TEST SITE
The eyes of the experimental animals were examined and found normal prior to the test.

REMOVAL OF TEST SUBSTANCE
After 30 seconds the compound was, as far as possible, flushed out of the eye of three of the rabbits with warm water For 1 minute.

SCORE SYSYEM
The ocular reactions were scored by the method described in "Appraisal of the Safety of Chemicals in Food Drugs and Cosmetics" page 51, published by the Association of Food and Drug Officials of the U.S.A.
Irritation parameter:
cornea opacity score
Basis:
animal: 15, 16
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
cornea opacity score
Basis:
animal: 14
Time point:
24/48/72 h
Score:
0.66
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
other: 15, 16
Time point:
24/48/72 h
Score:
1.66
Max. score:
3
Reversibility:
fully reversible within: 6 days
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal: 14
Time point:
24/48/72 h
Score:
1.33
Max. score:
3
Reversibility:
fully reversible within: 6 days
Irritation parameter:
chemosis score
Basis:
animal: 15
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 6 days
Irritation parameter:
chemosis score
Basis:
animal: 14, 16
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 6 days
Irritant / corrosive response data:
CONJUNTIVAL REACTION:
A mild to moderate reaction was seen in all treated eyes one hour after application of the compound.
This had subsided very slightly by 24 hours and thereafter continued to do so until all eyes had returned to normal by day 6 (1/3 unwashed, 3/3 washed) and 10 (2/3 unwashed). Staining of the conjunctivae by the compound was seen in the unwashed eyes at 24 hours.

CORNEAL REACTION:
Slight opacity and damage to the surface epithelium was seen in all treated eyes at one hour. This was still present at 24 hours. These returned to normal by 48 hours (2/3 washed), 72 hours (1/3 washed) and 6 days (3/3 unwashed).

IRIS:
Increased folding of the iris was seen in 2/3 unwashed eyes, (no. 11) at 24 hours and (no. 13) at 40 hours only.
Interpretation of results:
other: Not clasified according to CLP Regulation (EC) No. 1907/2006.
Conclusions:
According to CLP criteria the substance is not classified as eye irritant.
Based on the evaluation of the overall score of the eye reaction on Cornea, Iris and Conjunctivae, the substance can be considered slightly irritant under the conditions of the study.
Executive summary:

The determination of the eye irritation was determined in an eye irritation test. No guideline is available and the test was not performed on GLP. The reaction on the test substance was observed in albino rats for 10 days after the instillation. Reactions on Cornea, Conjunctivae and Iris were evaluated.

CONJUNTIVAL REACTION: a mild to moderate reaction was seen in all treated eyes one hour after application of the compound.

This had subsided very slightly by 24 hours and thereafter continued to do so until all eyes had returned to normal by day 6 (1/3 unwashed, 3/3 washed) and 10 (2/3 unwashed). Staining of the conjunctivae by the compound was seen in the unwashed eyes at 24 hours.

CORNEAL REACTION: slight opacity and damage to the surface epithelium was seen in all treated eyes at one hour. This was still present at 24 hours. These returned to normal by 48 hours (2/3 washed), 72 hours (1/3 washed) and 6 days (3/3 unwashed).

IRIS: increased folding of the iris was seen in 2/3 unwashed eyes, (no. 11) at 24 hours and (no. 13) at 40 hours only. Based on the evaluation of the overall score of the eye reactions of Cornea, Iris and Conjunctivae, the substance can be considered slightly irritant under the conditions of the study.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

The determination of skin irritation was determined in an a Primary Skin Irritation test. No guideline is available and the test was not performed on GLP. The test substance was tested in albino rats for 72 h. Erythema and oedema formation were observed.

Slight erythema was seen on 2/6 abraded sites and slight to moderate oedema was seen on all sites, 24 hours after application of the compound. All sites were normal by 72 hours. The primary irritation score was 1.2. Eye irritation

An Eye Irritation test was performed on the substance. No guideline is available and the test was not performed on GLP. The reaction on the test substance was observed in albino rats for 10 days after the instillation. Reactions on Cornea, Conjunctivae and Iris were evaluated.

The mean score of Corneal opacity of the washed eyes were all <1. No Iris reaction was observed in any of the washed eyes. The mean score of Conjuctival redness and chemosis of the washed eyes were all <2.

Conjunctival reaction: a mild to moderate reaction was seen in all treated eyes one hour after application of the compound.

This had subsided very slightly by 24 hours and thereafter continued to do so until all eyes had returned to normal by day 6 (1/3 unwashed, 3/3 washed) and 10 (2/3 unwashed). Staining of the conjunctivae by the compound was seen in the unwashed eyes at 24 hours.

Corneal reaction: slight opacity and damage to the surface epithelium was seen in all treated eyes at one hour. This was still present at 24 hours. These returned to normal by 48 hours (2/3 washed), 72 hours (1/3 washed) and 6 days (3/3 unwashed).

IRIS: increased folding of the iris was seen in 2/3 unwashed eyes, (no. 11) at 24 hours and (no. 13) at 40 hours only.

Justification for classification or non-classification

SKIN IRRITATION

According to the CLP Regulation 1272/2008/EC, 3.2 section, table 3.2.2:

(1) Mean value of ≥ 2,3 - ≤ 4,0 for erythema/eschar or for oedema in at least 2 of 3 tested animals from gradings at 24, 48 and 72 hours after patch removal or, if reactions are delayed, from grades on 3 consecutive days after the onset of skin reactions; or

(2) Inflammation that persists to the end of the observation period normally 14 days in at least 2 animals, particularly taking into account alopecia (limited area), hyperkeratosis, hyperplasia, and scaling; or

(3) In some cases where there is pronounced variability of response among animals, with very definite positive effects related to chemical exposure in a single animal but less than the criteria above.

Reversibility of skin lesions is the other decisive factor in evaluating responses in the animal test.

The study performed on the substance to be registered involved 6 rabbits instead 3. In this case the classification as skin irritation is considered if at least 4 out of 6 rabbits show a mean score per animal of ≥ 2.3 ≤ 4.0 for erythema/eschar or for oedema.

The scores recorded during the primary skin Irritation test on the substance to be registered less than 2.3 and the reactions was fully reversible after 72 hours.

Therefore, according to the paragraph 3.2. of the CLP Regulation n. 1272/2008, the substance shall be non classified as a skin irritant.

EYE CORROSION/IRRITATION

According to the CLP Regulation 1272/2008/EC, 3.3 section, table 3.3.1: 

Category for irreversible eye effects

Irreversible effects on the eye (Category 1) If, when applied to the eye of an animal, a substance produces:

- at least in one animal effects on the cornea, iris or conjunctiva that are not expected to reverse or have not fully reversed within an observation period of normally 21 days; and/ or

- at least in 2 of 3 tested animals, a positive response of: corneal opacity ≥ 3 and/or iritis > 1,5 calculated as the mean scores following grading at 24, 48 and 72 hours after installation of the test material.

Category for eye irritation

Irritating to eyes (Category 2) if, when applied to the eye of an animal, a substance produces:

- at least in 2 of 3 tested animals, a positive response of: corneal opacity ≥ 1 and/or iritis ≥ 1, and/or conjunctival redness ≥ 2 and/or conjunctival oedema (chemosis) ≥ 2

- calculated as the mean scores following grading at 24, 48 and 72 hours after installation of the test material, and which fully reverses within an observation period of 21 days.

The study performed on the substance to be registered involved 6 rabbits instead 3.

In case of 6 rabbits the following applies:

Category for irreversible eye effects

a. Classification as serious eye damage – Category 1 if:

i. at least in one animal effects on the cornea, iris or conjunctiva that are not expected to reverse or have not fully reversed within an observation period of normally 21 days; and/or

(ii) at least 4 out of 6 rabbits show a mean score per animal of ≥ 3 for corneal opacity and/or > 1.5 for iritis

Category for eye irritation

b. Classification as eye irritation – Category 2 if at least 4 out of 6 rabbits show a mean score per animal of:

i. ≥ 1 for corneal opacity and/or

ii. ≥ 1 for iritis and/or

iii. ≥ 2 conjunctival erythema (redness) and/or

iv. ≥ 2 conjunctival oedema (swelling) (chemosis)

and which fully reverses within an observation period of normally 21 days.

Detailed results were evaluated in order tho define the classification and for every point no more than 4 rabbits fullfilled the requirement for the irritation (Category 2):

Corneal opacity: 3 of 6 animals =1 (everage of 24,48,72 h), fully reversible after 10 days;

Iris: 2 of 6 animals =1 (everage 24,48,72 h), fully reversible after 10 days;

Redness Conjuntivae: 3 of 6 animals =2 (everage 24,48,72 h), fully reversible after 10 days;

Chemosis Conjuntivae: 1 su 6 animals =2 (everage 24,48,72 h), fully reversible after 10 days.

According to the paragraph 3.3. of the CLP Regulation n. 1272/2008, the substance shall be non classified as an eye corrosive or irritant.