Registration Dossier

Administrative data

Description of key information

The test substance was not irritating to skin and eyes.

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 May. 14, 1979 to Jun. 5, 1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
EPA OPP 81-5 (Acute Dermal Irritation)
Deviations:
not specified
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
-non-GLP study with non-OECD 404 testing protocol: 24h occlusive wrapping
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: IVANOVAS, 7964 Kisslegg/Allgäu, Germany and MADOERIN AG, 4414 Füllinsdorf, Switzerland
- Age at study initiation: Not reported
- Weight at study initiation: 2 to 3 kg
- Housing: Housed individually in metal cages
- Diet: Standard rabbit food, NAFAG, No. 814, Gossau SG, ad libitum
- Water: ad libitum
- Acclimation period: Minimum of 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 14 hrs dark/10 hrs light
Type of coverage:
occlusive
Preparation of test site:
other: shaved with or without abrasion
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
Single exposure for 24 hours
Observation period:
7 days
Number of animals:
3 males and 3 females
Details on study design:
TEST SITE
- Area of exposure: abraded and intact skin (back and flank)
- % coverage: 2.5 x 2.5 cm
- Type of wrap if used: Gauze patches (with the test material) were covered with an impermeable material and were fastened to the body of the rabbit with adhesive tape.
the shaven skin on one side was slightly scarified with the help of a "Schropfschnapper", Aesculap, Switzerland.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not reported
- Time after start of exposure: Dressings were removed 24 hours after application.

SCORING SYSTEM: Same as the scale provided in the OECD guideline.
Calculation of the primary skin irritation index: The scores read after 24 and 72 hours for erythema and edema for the intact as well as for the abraded skin were summed up and divided by 4.

Assessment of Irritation:
0 = none
>0 – 1 = minimal
>1 – 2 = slight
>2 – 4 = moderate
>4 – 6 = marked
>6 – 8 = extreme
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
mean
Time point:
24/48/72 h
Score:
0.44
Max. score:
1
Reversibility:
fully reversible within: 3 days
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
mean
Time point:
24/48/72 h
Score:
0.05
Max. score:
1
Reversibility:
fully reversible within: 3 days
Irritation parameter:
erythema score
Remarks:
abraded skin
Basis:
mean
Time point:
24/48/72 h
Score:
0.44
Max. score:
1
Reversibility:
fully reversible within: 3 days
Irritation parameter:
edema score
Remarks:
abraded skin
Basis:
mean
Time point:
24/48/72 h
Score:
0.11
Max. score:
1
Reversibility:
fully reversible within: 3 days
Irritant / corrosive response data:
The calculated primary irritation index was 0.47. Test substance was found to cause a minimal irritation when applied to intact and abraded rabbit skin. The mean group score for erythema was 0.66, 0.66 and 0 for intact skin after 24, 48 and 72 hours, respectively. The mean group score for edema was 0.17, 0 and 0 for intact skin after 24, 48 and 72 hours, respectively.
Interpretation of results:
GHS criteria not met
Conclusions:
The test item was found to be not irritant to the skin under the test conditions applied.
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 May. 14, 1979 to June 5, 1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
EPA OPP 81-4 (Acute Eye Irritation)
Deviations:
not specified
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
treated eye was rinsed with physiological saline in 3 of the 6 rabbits
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: IVANOVAS, 7964 Kisslegg/Allgäu, Germany and MADOERIN AG, 4414 Füllinsdorf, Switzerland
- Age at study initiation: Not reported
- Weight at study initiation: 2 to 3 kg
- Housing: Housed individually in metal cages
- Diet: Standard rabbit food, NAFAG, No. 814, Gossau SG, ad libitum
- Water: ad libitum
- Acclimation period: Minimum of 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 14 hrs dark/10 hrs light
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
Duration of treatment / exposure:
Single exposure: 30 seconds for rinsed eyes, substance not removed at all for unrinsed eyes
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3 males and 3 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): In 3 of the 6 rabbits, the treated eye was flushed with 10 mL of physiological saline
- Time after start of exposure: Approximately 30 seconds after treatment (for 3 of the 6 rabbits)

SCORING SYSTEM: Irritation reactions were assessed according to the same scale provided in the OECD guideline, with the exception of 1 criteria (additional changes to discharge were included in addition to the other parameters).

TOOL USED TO ASSESS SCORE: Eye irritation was appraised with a slit lamp on day 1, 2, 3, 4, and 7 for each individual rabbit.

Calculation of the primary eye irritation index:
The mean reaction scores for cornea, iris, and conjunctiva observed after 1, 2, 3, 4, and 7 days were summed up and the sum divided by 5. This procedure was carried out separately for unrinsed and rinsed eyes, respectively. The conjunctivae score includes observations for redness, chemosis, and discharge.

Index:
0 - 10 = minimal
11 - 25 = slight
26 - 55 = moderate
56 - 84 = marked
above 84 = extreme
Irritation parameter:
cornea opacity score
Remarks:
unrinsed or rinsed eyes
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
iris score
Remarks:
unrinsed or rinsed eyes
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Remarks:
unrinsed or rinsed eyes
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
chemosis score
Remarks:
unrinsed or rinsed eyes
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritant / corrosive response data:
All scores recorded for all animals at all tim points were zero. The primary irritation index for unrinsed or rinsed eyes was equal to 0.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this experiment 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 adverse effect observed (not irritating)

Additional information

Skin Irritation

The available studies for skin irritation were performed with a design that is more stringent compared to OECD testing guideline 404. In the key study, the undiluted test item was applied by topical occlusive application to the back of three male and three female adult New Zealand White rabbits. One side of the shaven back was slightly scarified and Gauze patches of 2.5 x 2.5 cm laden with 0.5 ml of the test material were applied for an exposure period of 24 hours. Following removal of the dressing the skin reactions were appraised at 24, 48 and 72 h and after 4 and 7 days according to the Draize scoring scheme. The mean group score for erythema was 0.7, 0.7 and 0 for intact skin after 24, 48 and 72 hours, respectively. The mean group score for edema was 0.2, 0 and 0 for intact skin after 24, 48 and 72 hours, respectively. This result is confirmed by a supporting study performed following the same protocol. Here, the mean group score for erythema was 1.8, 1.8 and 1.7 for intact skin after 24, 48 and 72 hours, respectively. The mean group score for edema was 0.8, 0.8 and 0.5 for intact skin after 24, 48 and 72 hours, respectively. A third study is available which received a Klimisch code of 3, as a consequence of discrepancies in the conduct of the study. In this study, the skin reactions were more severe, however still below the threshold triggering classification. The observation period was too short to assess reversibility appropriately. Overall, the test article is considered to be not irritating to the skin.

Eye Irritation

Two studies are available investigating the irritation potential of the test item. In the key study the test substance was tested according to a guideline from the Environmental Protection Agency from 1978. 0.1 ml of the test item were inserted into the conjunctival sac of the left eye of the rabbits and the lids were gently closed for a few seconds. The right eye was not treated and served as an untreated control. In 3 of the 6 rabbits approximately 30 seconds after treatment the treated eye was flushed with 10 ml of physiological saline. The eye irritation was appraised with a slit-lamp on day 1, 2, 3, 4 and 7 and was scored for each individual rabbit. No findings regarding cornea, iris, conjunctival redness or chemosis were observed within the whole study period in all animals. In a supporting study the test substance was tested following the same method. Here, slight conjunctival reactions below the classification threshold were observed. No reactions of the cornea and the iris were reported. Slight efects were still reported after the observation period of 7 days, but a trend to reversilbility is given. Overall, the test item is considered to be not irritating to the eye.

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for the purpose of classification under Regulation (EC) No.1272/2008. Based on the present data, classification for irritation is not warranted under Regulation (EC) No.1272/2008.

The studies for skin irritation were performed according to the method given in the "Hazardous-Substances Regulations" under the U.S. Federal Hazardous Substances Labelling Act Sect. 191.11 (February 1965). This method is more stringent than the OECD testing guideline 404. In cases like this where findings were reversible or showed at least a trend to reversibility within the observation period, hazard assessment based on EU regulations can be applied.

None of the average score on the relevant timepoints (24, 48, 72 hours) exceeded the threshold limit for classification in the studies relevant for classification. Therefore, the test substance is considered as not irritating to the skin in relation to the EU classification criteria as well as GHS regulations. The same conclusion applies to eye irritation.