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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:
other: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
From December 17 to January 9, 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
The test was conducted by means of Read Across approach. The reliability of the source study report is 2. Further information was attached at section 13
Qualifier:
according to
Guideline:
EPA OPP 81-5 (Acute Dermal Irritation)
Deviations:
no
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: IVANOVAS
- Age at study initiation: 2-3 kg
- Weight at study initiation:
- Housing: metal cage
- Diet: standard rabbit food - NAFAG ad libitum
- Water: ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2 °C
- Humidity (%): 55 ± 10 %
- Photoperiod : 10 hours light cycle dark/light

Type of coverage:
occlusive
Preparation of test site:
other: shaved and scarified
Vehicle:
other: propylene glycol + saline (70 : 30 parts)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 g of the test material
- Concentration: 50 %

Duration of treatment / exposure:
24 hour
Observation period:
7 days
Number of animals:
3 male and 3 female
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used:The patches were covered with an impermeable material and were fastened to the body of the rabbit with adhesive tape.



Irritation parameter:
erythema score
Basis:
animal: 164, 169
Time point:
24/48/72 h
Score:
ca. 0.33
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal: 165, 166, 167, 168
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
0
Reversibility:
other: No signs of irritation
Irritation parameter:
edema score
Basis:
animal: 164, 169
Time point:
24/48/72 h
Score:
ca. 0.33
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal: 165, 166, 167, 168
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
0
Reversibility:
other: No signs of irritation

Due to intensive staining by the test compound erythema was not assessable. For the purpose of calculating the primary irritation index erythema was assumed to be equal to edema based on the correlation existing (Marzulli and Maibach, Fol. Cosm. Tox. 13, 355, 1975).

Evaluation of the skin reactions

TIME After 24 h After 49 h After 72 h
SEX MALE FEMALE MALE FEMALE MALE FEMALE
Animal N° 164 165 166 167 168 169 164 165 166 167 168 169 164 165 166 167 168 169
Erythema a 1 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0
b 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Edema a 1 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0
b 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Total a 2 0 0 0 0 2 0 0 0 0 0 0 0 0 0 0 0 0
b 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Mean a 0.6 0.6 0 0 0 0
b 0 0 0 0 0 0
Group mean a 0.6 0 0
b 0 0 0
TIME After 4 days After 7 days
SEX MALE FEMALE MALE FEMALE
Animal N° 164 165 166 167 168 169 164 165 166 167 168 169
Erythema a 0 0 0 0 0 0 0 0 0 0 0 0
b 0 0 0 0 0 0 0 0 0 0 0 0
Edema a 0 0 0 0 0 0 0 0 0 0 0 0
b 0 0 0 0 0 0 0 0 0 0 0 0
Total a 0 0 0 0 0 0 0 0 0 0 0 0
b 0 0 0 0 0 0 0 0 0 0 0 0
Mean a 0 0 0 0
b 0 0 0 0
Group mean a 0 0
b 0 0

mean reaction score
time after exposure erythema edema
intact
skin
abraded
skin
intact
skin
abraded
skin
24 0.3 0 0.3 0
72 0 0 0 0
total 0.3 0 0.3 0 0.6
Interpretation of results:
other: CLP criteria not met
Conclusions:
Non irritant
Executive summary:

The substance has been tested According to EPA OPP 81 -5 guideline. Under the conditions of the present experiment the test item was found to cause no irritation when applied to intact and abraded rabbit skin according to the Regulation EC n. 1272/2008.

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:
other: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
October 3, 1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
The test was conducted by means of Read Across approach. The reliability of the source study report is 2. Further information was attached at section 13
Qualifier:
according to
Guideline:
EPA OPP 81-4 (Acute Eye Irritation)
Deviations:
not specified
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
- Source: IVANOVAS
- Weight at study initiation: 2-3 kg
- Housing:individually in metal cages
- Diet: rabbit food - NAFAG, No. 814, Gossau SG ad libitum.
- Water: Sterile filtered water was available at all times.
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1°C
- Humidity (%): 50 ± 10 %
- Photoperiod (hrs dark / hrs light): 10 hour light cycle day.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.1 g

After 30 seconds the compound was, as far as possible, flushed out of the eyes of three of the rabbits with approximately 10 ml. of physiological saline
Duration of treatment / exposure:
After 30 seconds the compound was, as far as possible, flushed out of the eyes of three of the rabbits with approximately 10 ml. of physiological saline
Observation period (in vivo):
The rabbits were examined 1, 24, 48, 72 hours and 7 days
Number of animals or in vitro replicates:
The test was performed on 3 male and 3 female adult rabbits
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: yes

TOOL USED TO ASSESS SCORE:
The eye irritation was appraised with a slit-lamp on day 1, 2, 3, 4 and 7
Irritation parameter:
cornea opacity score
Basis:
animal: 167, 168, 169
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
0
Reversibility:
other: no signs of irritation
Irritation parameter:
iris score
Basis:
animal: 167, 168, 169
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
0
Reversibility:
other: no signs of irritation
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal: 167
Time point:
24/48/72 h
Score:
ca. 0.33
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal: 168, 169
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
0
Reversibility:
other: no signs of irritation
Irritation parameter:
chemosis score
Basis:
animal: 167, 168, 169
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
0
Reversibility:
other: no signs of irritation
Interpretation of results:
other: CLP criteria not met
Conclusions:
Non irritant
Executive summary:

The substance has been tested for eye irritation according to (EPA) § 163.81-4 "Primary eye irritation study". According to the Regulation EC n. 1272/2008 the test material was found to cause no irritation when applied to the rabbit eye mucosa.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

SKIN IRRITATION/CORROSION

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

 

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.

Based on the results obtained in the skin and eye irritation studies, the test substance does not need to be classified for skin and eye irritation according to the CLP Regulation (EC) No. 1272/2008.