Registration Dossier

Administrative data

Description of key information

No skin and eye irritation was observed by the test item.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study according to GLP.
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland
- Age at study initiation: Ca. 9 weeks.
- Weight at study initiation: 2.6, 1.9 and 1.9 kg
- Housing: Individual metal wire caging
- Diet: Ssniff K-H ad libitum
- Water): tap water via automatic watering system - ad libitum
- Acclimation period: at least 12 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Mean 19.3 to 20.0 °C
- Humidity (%): average of 62.4 to 65.7 %
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Controls:
not required
Amount / concentration applied:
Amount applied: 0.5 g test substance moistend with 1 mL deionised water, applied to an area of 25 x 25 mm.
Duration of treatment / exposure:
4 hours.
Observation period:
Rabbits observed at 1, 24, 48 and 72 hours after dressing removal. termination on Day 4
Number of animals:
3 females.
Details on study design:
Stepwise procedure:
First the test substance was administered to one animal. As no corrosive effect was observed, the test substance was administered
to two additional animals one week later.

Test site:
Area of exposure: 25 x 25 mm. Samples of the test substance were placed on gauze patches. They were held in place by fixing them marginally with non irritating tapes. The application sites were covered semi-occlusively by a dressing. Access by the animals to the application sites was prevented by a plastic collar.

Skin examinations:
The skins of the animals were examined for local alterations one day before the administration of the test substance (after clipping of the hair) and immediately before the administration. The treated areas of the animals were examined for erythema/eschar and oedema as well as for other local alterations (such as hyperplasia, scaling, discolouration, fissures, scabs and alopecia) approximately 1, 24, 48 and 72 hours after patch removal.

General examinations:
The animals were examined once daily for other than local changes of the skin.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritant / corrosive response data:
All areas treated with the test substance and all control areas were normal before the application and at each observation time.
Other effects:
General signs of toxicity:
No signs of systemic toxicity were observed in the animals during the test period and no mortality occurred.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
All areas treated with the test substance and all control areas were normal before the application and at each observation time.
Executive summary:

A skin irritation test was performed according to OECD and EU test methods. Three female rabbits were exposed to MPI-ACA for 4 hours.

All areas treated with the test substance and all control areas were normal before the application and at each observation time. The test.substance is not a skin 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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: A study according to the EU and OECD methods, including GLP.
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River Germany
- Age at study initiation: ca. 9 weeks.
- Weight at study initiation: 2.3 - 2.4
- Housing: single caging
- Diet: SNIFF K-H ad libitum
- Water: Tap water ad libitum
- Acclimation period: >= 12 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): average of 19.2
- Humidity (%): average of 61.7
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
Equivalent to 0.1 mL: 16 to 18 mg.
Duration of treatment / exposure:
Once.
Observation period (in vivo):
1, 24, 48, 72 h and 7 d p.a.
Number of animals or in vitro replicates:
3.
Details on study design:
Prior to starting the eye irritation/corrosion study the pH-value of the test substance was determined. Substances with a pH < 2.0 and pH > 11.5 need not to be tested for acute eye irritation/corrosion.
The test substance was administered first to one animal. As no evidence for a serious damage to the eye of this animal was found during the initial 72 hour observation period (no corrosive effect), the test substance was administered to the other two animals subsequently.

The approximate equivalent of 0.1 mL of the test substance was administered per animal into the conjunctival sacs of the right eyes by gently pulling the lower lids away from the eyeballs for instillation. The eyes were held closed for about one second to prevent a loss of test substance. The left eyes remained untreated and served as a control.
The whole eyes, especially the corneae, the irises and the conjunctivae were examined, using an otoscope lamp.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritant / corrosive response data:
The untreated eyes ("control eyes") were normal at each observation time.
The eyes, treated with the test substance ("test eyes") were normal before the instillation. After the instillation of the test substance, the following findings were made:
Corneae: Not affected at any examination term.
Irises: Not affected at any examination term.
Conjunctivae, redness: A score of "1" in all animals from 1 h p.a. until a maximum of 24 h p.a.
Conjunctivae, chemosis: A score of "1" in 2/3 animals only 1 h p.a.
Other effects:
No signs of systemic toxicity were observed in the animals during the test period and no mortality occurred.
The untreated eyes ("control eyes") were normal at each observation time.

For details of the results see the attachment.

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Only slight irritations of the conjunctivae were observed at 1 and 24 h p.a. The substance is not classified as irritant.
Executive summary:

Eye irritation was investigated according to the EU- and OECD-methods. The equivalent of 0.1 mL of the test substance was instilled into the conjunctival sac of one eye of each of 3 New Zealand White rabbits. Results:

Corneae and irises: Not affected at any observation point.

Conjunctivae, redness and chemosis: slight irritations were observed at 1 and 24 h p.a, returning to normal afterwards. The substance is not classified as irritant.

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

Additional information

Justification for selection of skin irritation / corrosion endpoint:
An in vivo guideline study.

Justification for selection of eye irritation endpoint:
An in vivo guideline study.

Justification for classification or non-classification

No results were obtained that would justify a classification of the substance.