Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Eye irritation: Not irritant


Skin 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:
May 26, 1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
according to guideline
Guideline:
other: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics (1959), the US Association of Food and Drug Officials (AFDO).
Deviations:
not specified
Principles of method if other than guideline:
Test method similar to OECD 404.
GLP compliance:
no
Remarks:
pre GLP
Species:
rabbit
Strain:
other: russian breed
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 1.6 to 2.0 Kg.
- Housing: individually in metal cages.
- Diet: standard rabbit food - NAFAG Gossau SG - ad libitum.
- Water: ad libitum.
- Acclimation period: for a minimum of 8 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 1°C.
- Humidity (%): 55 ± 5%
- Photoperiod (hrs dark/hrs light): 14 hours light cycle day.
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
not specified
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
Duration of treatment / exposure:
24 hours
Observation period:
7 days
Number of animals:
6 (3 males and 3 females)
Details on study design:
TEST SITE:
- Area of exposure: 2.5 x 2.5 cm.
- Type of wrap if used: gauze patches.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Remarks:
intact skin
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Remarks:
intact skin
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: intact skin
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Remarks:
intact skin
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0.66
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: intact skin
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0.66
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: intact skin
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Remarks:
intact skin
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Remarks:
intact skin
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: intact skin
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Remarks:
intact skin
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0.66
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: intact skin
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0.66
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: intact skin
Interpretation of results:
GHS criteria not met
Conclusions:
Not irritant
Executive summary:

Method:


The skin irritation was determined in an irritation test on rabbits according to Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics (1959), the US Association of Food and Drug Officials (AFDO), similar to OECD guideline 404.


 


Result:


Not irritant.

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:
April 11, 1975
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
according to guideline
Guideline:
other: "Hazardous Substances Regulations" under the U.S.A. Federal Hazardous Substances Labelling Act Sect. 191.12 (February 1965)
Deviations:
yes
Remarks:
no informations
Principles of method if other than guideline:
Similar to OECD guideline 405
GLP compliance:
no
Remarks:
pre GLP
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: bred on the premises.
- Age at study initiation: 9-13 weeks.
- Weight at study initiation: 2.19 Kg to 2.28 Kg.
- Housing: singly in an experimental room.
- Diet: Styles-Oxoid ad libitum.
- Water: sterile filtered water available at all times.
- Acclimation period: one week prior to the start of the trial.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C (±1°C).
- Humidity (%): 50-70%
- Photoperiod (hrs dark / hrs light): animals exposed to artificial light for 10 hours daily from 08.00 - 18.00 hours.
Vehicle:
not specified
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 100 mg
Duration of treatment / exposure:
30 sec
Observation period (in vivo):
14 days
Number of animals or in vitro replicates:
6 (3 males and 3 females)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: flushed out with warm water for 1 minute.
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 10 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.66
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 6 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #4
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #5
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 6 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #6
Time point:
24/48/72 h
Score:
1.66
Max. score:
3
Reversibility:
fully reversible within: 6 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24 h
Score:
1
Max. score:
2
Reversibility:
not specified
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #4
Time point:
24 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #5
Time point:
24 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #6
Time point:
24 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 6 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Interpretation of results:
GHS criteria not met
Conclusions:
Not irritant
Executive summary:

Method:


The eye irritation was determined in an irritation test on rabbits according to the "Hazardous Substances Regulations" under the U.S.A. Federal Hazardous Substances Labelling Act Sect. 191.12 (February 1965), similar to OECD guideline 405.


 


Observation:


A slight to mild conjunctival reaction was seen in all treated eyes from 1 hour after application of the compound. The washed eyes were slightly less severe and returned to normal by day 6.


 


Result:


Not irritant.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin Irritation


The test substance was evaluated in the key study for its skin irritation potential according to the Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics (1959), the US Association of Food and Drug Officials (AFDO), similar to OECD guideline 404.


0.5 g of the test substance was applied on the skin of six rabbits using gauze patches, then covered by impermeable material. After 24 hours the gauzes were removed and the skin observed for 7 days.


The mean score of observed values of irritation/corrosion , calculated for each rabbit, after 24, 48, 72 hours, were always under the limit for irritation potential set out in the OECD guideline, therefore the substance is considered as not irritant.


This result is in line with that achieved by other tests, with reliability = 4, due to the low purity of the active ingredient.


 


Eye Irritation


The test substance was evaluated in the key study for its eye irritation potential according to the "Hazardous Substances Regulations" under the U.S.A. Federal Hazardous Substances Labelling Act Sect. 191.12 (February 1965), similar to OECD guideline 405.


100 mg of the test substance were instilled into the conjunctival sac of the left eye, of six rabbits. The eyelids were then held closed for 1 second. The right eye served as a control. The eyes of the animals were observed for 14 days.


The mean score of observed values of irritation/corrosion, calculated for each rabbit, after 24, 48, 72 hours, were always under the limit for irritation potential set out in the OECD guideline, therefore the test substance does not show any eye irritation potential.


This result is in line with that achieved by other tests, with reliability = 4, due to the low purity of the active ingredient.

Justification for classification or non-classification

SKIN IRRITATION/CORROSION


A corrosive substance is a substance that produces destruction of skin tissues, namely, visible necrosis through the epidermis and into the dermis, in at least 1 tested animal after exposure up to 4 hours duration.


Three subcategories are provided within the Corrosive category 1:


Subcategory 1A where responses are noted following up to 3 minutes exposure and up to 1 hour observation;


Subcategory 1B where responses are described following exposure between 3 minutes and 1 hour and observations up to 14 days;


Subcategory 1C where responses occur after exposures between 1 hour and 4 hours and observations up to 14 days


To classify a substance as irritant, the major criterion is that at least 2 of 3 tested animals have a mean score of ≥ 2.3 - ≤ 4.0.


Category 2:


- 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


- 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


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


The substance is not classified as skin irritant because in the performed tests it doesn't meet the classification criteria of the CLP regulation n. 1272/2008.


 


EYE IRRITATION


Serious eye damage means the production of tissue damage in the eye, or serious physical decay of vision, following application of a test substance to the anterior surface of the eye, which is not fully reversible within 21 days of application.


Eye irritation means the production of changes in the eye following the application of test substance to the anterior surface of the eye, which are fully reversible within 21 days of application.


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.


These observations include animals with grade 4 cornea lesions and other severe reactions (e.g., destruction of cornea) observed at any time during the test, as well as persistent corneal opacity, discoloration of the cornea by a dye substance, adhesion, pannus, and interference with the function of the iris or other effects that impair sight. In this context, persistent lesions are considered those which are not fully reversible within an observation period of normally 21 days. Substances are also classified in Category 1 if they fulfil the criteria of corneal opacity ≥ 3 or iritis > 1.5 detected in a Draize eye test with rabbits, recognising that such severe lesions usually do not reverse within a 21-day observation period.


The substance does not meet the requirements to be classified in Category 1.


Irritating to eyes (Category 2):


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 test substance does not meet the requirements to be classified in Category 2, therefore it is not classified.