Registration Dossier

Administrative data

Description of key information

Skin: not corrosive and not irritating (OECD 439 and 431 combined report)
Eyes: not irritating (OECD 405)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vitro / ex vivo
Remarks:
a skin corrosion test was included in the test design
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP- and guideline compliant
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
Qualifier:
according to guideline
Guideline:
other: OECD 431 Commission Regulation (EC) No 440/2008 OECD Draft for corrosion test
GLP compliance:
yes (incl. QA statement)
Test system:
human skin model
Cell type:
non-transformed keratinocytes
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 50 µL (corrosion test), 30 µL (irritation test)
- Concentration (if solution): 100%
Duration of treatment / exposure:
1 hour
Observation period:
2 days
Number of animals:
not applicable
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
corrosion 3 min exposure
Value:
101
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
no indication of irritation
Remarks:
no indication of corrosion
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
corrosion 1 hour exposure
Value:
86
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
no indication of irritation
Remarks:
no indication of corrosion
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
irritation 1 hour exposure
Value:
110
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
no indication of irritation

1. Corrosion test


 



























































































             Exposure: 3 min          Exposure: 1 hour
 Test article     tissue 1   tissue 2 KC mean
 NC  mean OD570 1.7627 1.7522 0.2267 1.7574 1.7657 1.6962 0.1762 1.7309
  viability[% of NC] 100.3 99.7 - 100 102.0 98.0 - 100
 ASA  mean OD570 1.8112 1.7222 0.2012 1.7667 1.3892 1.6027 0.1867 1.4959
  viability[% of NC] 103.1 98.0 - 101 80.3 92.6 - 86
 PC  mean OD570 0.4438 0.3498 - 0.39680.1597   0.1867 - 0.1732
  viability[% of NC] 25.3 19.9 - 23 9.2 10.8 - 10

 


Due to the ability of the test substance to reduce MTT directly, a KC was applied in parallel.


However, the result of the KC did not indicate an increased MTT reduction (difference to KC


of NC is not greater than 0.1; see section 3.6.4). Thus the KC was not used for viability


calculation.


 


2. Irritation test


 




































































 Test article  tissue 1 tissue 2 tissue 3 mean SD
 NC  mean OD570 1.6795 1.6125 1.5725 1.6215 
   viability[% of NC] 103.6 99.4 97.0 100 3.33
 ASA mean OD570 1.7575 1.7070 1.8980 1.7875 
    viability[% of NC] 108.4 105.3 117.1 110 6.10
 PC  mean OD570 0.1165 0.13200.1215  0.1233 
   viability[% of NC] 7.2 8.1 7.5 8 0.49
Interpretation of results:
GHS criteria not met
Remarks:
substance is not corrosive and not irritating to the skin
Conclusions:
Based on the observed results and applying the evaluation criteria it is concluded, that substance does not show a skin irritation potential in the EpiDerm ™ skin corrosion/irritation test under the test conditions chosen.
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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP- and guideline compliant
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Stolzenseeweg 32 – 36, 88353 Kisslegg
- Age at study initiation: 9 weeks
- Weight at study initiation: 2.1 kg – 2.2 kg
- Housing:Single housing; Terulan cages, Ehret GmbH, A-3430 Tulln, 73 cm x 73 cm bottom area, 50 cm height.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period:for at least 5 days before application


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C +/- 3 °C
- Humidity (%): 30 – 70%
- Air changes (per hr): 12 per hour
- Photoperiod (hrs dark / hrs light): 12/12


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
- Concentration (if solution): undiluted

Duration of treatment / exposure:
24 hours
Observation period (in vivo):
Approx. 1, 24, 48 and 72 h after application.
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): About 24 hours after application of the test item the treated eye of the animal(s) was rinsed with 3 to 6 mL of hand warm tap water for 1 to 2 minutes using a syringe with a blunt probe
- Time after start of exposure: About 24 hours after application of the test item


SCORING SYSTEM: Draize


Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 48 h
Score:
0.3
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
0
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Irritant / corrosive response data:
The cornea and the iris were not affected in any animal at any examination term. Slight conjunctival redness (grade 1) was noted in one animal only 1 hour after application, in one animal 1 and 24 hours after application. In the third animal no conjunctival redness was observed.
Slight conjunctival chemosis was noted in all three animals only 1 hour after application. Slight discharge (grade 1) was noted in two animals only 1 h our after application.
Interpretation of results:
GHS criteria not met
Conclusions:
Considering the described ocular reactions as well as the average score for irritation, ASA is not irritating to eyes under the test conditions chosen.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The potential of the substance to cause dermal corrosion/irritation was assessed by a single topical application of 50 μL (corrosion test) or 30 μL (irritation test) of the test substance to a reconstructed three dimensional human epidermis model (EpiDerm™) in accordance with OECD 431 and GLP. Based on the observed results it was concluded, that the substance does not show a skin irritation potential.


Eye irritation was evaluated in study in accordance with OECD 405 and GLP, where 0.1mL of the substance was instilled into the eyes of three New Zealand rabbits. The only observed effects were slight conjunctival effects noted after 48 h, so that it was concluded that substance is not irritating to eyes.


 


The potential of the substance to cause serious damage to the eyes/mucous membranes was assessed by a single topical application of 0.3 mL of the undiluted test substance and 0.3 mL of a 10% test-substance solution in olive oil to the chorioallantoic membrane of fertilized and incubated hen eggs. Based on the absence of haemorrhagia and coagulation, after the 90 or 160 sec observation period, the substance was not found to produce changes indicative for serious eye damage.



Justification for selection of skin irritation / corrosion endpoint:
Guideline study according to GLP

Justification for selection of eye irritation endpoint:
Guideline study according to GLP

Justification for classification or non-classification

The available data are conclusive but not sufficient data for classification with regard to irritation / corrosion in accordance with the CLP Regulation (EC) No 1272/2008.