Registration Dossier

Administrative data

Description of key information

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:
2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
During the test, the animals (males) weighed 1.92 kg and 2.47 kg. At the beginning of the test, the animals were 10-11 weeks old.

Each animal was kept in an individual box installed in conventional air conditioned animal husbanding.
The temperature and relative humidity of the main test were controlled to remain within target ranges of 17 to 23°C and 30 to 70%, respectively.
The rate of air exchange was approximately thirteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (07.00 to 19.00) and twelve hours darkness.
Drinking water and foodstuff were supplied freely.
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: On the opposite flank an untreated area was served as the control.
Amount / concentration applied:
The test item C.A.E. Code: 8500010 was applied, as supplied, at the dose of 0.5 mL.
Duration of treatment / exposure:
The undamaged skin area of one flank of each animal was exposed during 4 hours.
Observation period:
The skin reactions were appreciated 1 hour and then 24, 48 and 72 hours after removal of the patch.
If no reaction is observed 72 hours after treatment the study is terminated. In case of persistent reactions, additional observations can be carried out from D7 to D14 in order to determine the reversible character of the lesions observed.
Number of animals:
3 animals were treated sequentially.
Initially, a single animal was treated. After considerations of the cutaneous responses produced in the first animal on day 14, two additional animals were treated during 4 hours in the same experimental conditions.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 1.7
Max. score:
2
Reversibility:
fully reversible
Remarks on result:
other:
Remarks:
see conclusions
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 1
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
other:
Remarks:
see conclusions
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 1
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
other:
Remarks:
see conclusions
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 1.3
Max. score:
2
Reversibility:
fully reversible
Remarks on result:
other:
Remarks:
see conclusions
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 0.3
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
other:
Remarks:
see conclusions
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 0.3
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
other:
Remarks:
see conclusions
Irritant / corrosive response data:
A well defined erythema was noted on the treated area, 1 hour after the patch removal, and was totally reversible on day 7. A slight oedema was noted on the treated area, 1 hour after the patch removal, and was totally reversible between days 3 and 7.
On the cutaneous structure, dryness of the skin was noted from day 3 in one animal and from day 7 in two animals. The skin recovered a normal aspect on day 14 in two animals but the dryness of the skin was still noted on day 14 in one rabbit (end of the observations).
Other effects:
None.

 OBSERVATIONS

          INDIVIDUAL DATA

 Skin reactions  Observation time  Animal 1  Animal 2  Animal 3
 Erythema and eschar        24 hours  2  1  1
 48 hours  2  1  1
 72 hours  1  1  1
 MEAN     1.7  1.0  1.0
 Oedema        24 hours
48 hours 
72 hours   1  0
 MEAN     1.3 0.3   0.3

 

Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
The results obtained, in these experimental conditions, enable to conclude that the test item C.A.E. Code: 8500010 must not be classified, according to the criteria for classification, packaging and labelling of dangerous substances and preparations in compliance with the E.E.C. Directives 67/548, 2001/59 and 1999/45. No symbol or risk phrase is required.

In accordance with the Regulation (EC) No.1272/2008, the test item must not be classified. No signal word or hazard statement is required.
Executive summary:

The test item C.A.E. Code: 8500010 was applied, as supplied, at the dose of 0.5 mL, under semi-occlusive dressing during 4 hours on an undamaged skin area of three New Zealand rabbits. The experimental protocol was established according to the OECD guideline No.404 dated April 24th, 2002 and the test method B.4 of the Council regulation No.440/2008 of 30 May 2008.

 

A well defined erythema was noted on the treated area, 1 hour after the patch removal, and was totally reversible on day 7. A slight oedema was noted on the treated area, 1 hour after the patch removal, and was totally reversible between days 3 and 7.

On the cutaneous structure, dryness of the skin was noted from day 3 in one animal and from day 7 in two animals. The skin recovered a normal aspect on day 14 in two animals but the dryness of the skin was still noted on day 14 in one rabbit (end of the observations).

 

The results obtained, in these experimental conditions, enable to conclude that the test item C.A.E. Code: 8500010 must not be classified, according to the criteria for classification, packaging and labelling of dangerous substances and preparations in compliance with the E.E.C. Directives 67/548, 2001/59 and 1999/45. No symbol or risk phrase is required.

 

In accordance with the Regulation (EC) No.1272/2008, the test item must not be classified. No signal word or hazard statement is required.

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:
2014
Reliability:
1 (reliable without restriction)
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
During the test, the animals (females) weighed between 1.93 kg and 2.56 kg. At the beginning of the test, the animals were 10-12 weeks old.

Each animal was kept in an individual box installed in conventional air conditioned animal husbanding.
The temperature and relative humidity of the main test were controlled to remain within target ranges of 17 to 23 °C and 30 to 70 %, respectively.
The rate of air exchange was approximately thirteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (07.00 to 19.00) and twelve hours darkness.
Drinking water and foodstuff were supplied freely.
Vehicle:
unchanged (no vehicle)
Controls:
other: The other eye remained untreated serving as control.
Amount / concentration applied:
0.1 mL of the test item was instilled as supplied.
Duration of treatment / exposure:
24 hours of exposure.
Observation period (in vivo):
Ocular examinations were performed on both right and left eyes 1 hour, 24, 48 and 72 hours following treatment.
If no reaction is observed 72 hours after instillation, the study is terminated. In case of persistent reactions, additional observations can be carried out from D7 to D21 in order to determine the reversible character of the lesions observed.

Number of animals or in vitro replicates:
Three female albino New Zealand rabbits were treated sequentially.
After consideration of the responses produced on day 3 in the first animal, two additional animals were treated, in the same experimental conditions.
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 0
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 1
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 0
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 0
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 1
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 1.7
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 0
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 0.7
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 1.3
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 1.7
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 0
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 0.7
Irritant / corrosive response data:
The ocular reactions observed during the study have been slight to important and totally reversible:
- at the conjunctivae level: a moderate to important redness noted 1 hour after the test item instillation and totally reversible between days 3 and 14, associated with a slight to moderate chemosis noted 1 hour after the test item instillation and totally reversible between days 1 and 7;
- at the iris level : a congestion, noted 1 hour after the test item instillation in two animals and totally reversible between days 1 and 2.
- at the corneal level : a moderate opacity, noted 24 hours after the test item instillation in two animals and totally reversible between days 2 and 3.
Other effects:
None.

 Animal No.     Time after treatment        CONJUNCTIVAE  IRIS  CORNEA
 Chemosis (A)  Redness (C)  Lesion (D)  Opacity (E)
1           24 hours  0  2  0  0
 48 hours  0  1  0  0
 72 hours  0  0  0  0
 Mean  0.0  1.0  0.0  0.0
2  24 hours  1  2  1  2
48 hours   1  2  0  2
72 hours   1  1  0  0
Mean   1.0  1.7  0.3  1.3
3 24 hours   2  2  0  2
48 hours   1  2  0  0
72 hours   1  1  0  0
 Mean  1.3  1.7  0.0  0.7
Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
The results obtained, under these experimental conditions, enable to conclude that the test item C.A.E. Code: 8500010 must not be classified, according to the criteria for classification, packaging and labelling of dangerous substances and preparations in compliance with the E.E.C. Directives 67/548, 2001/59 and 1999/45. No symbol or risk phrase is required.

In accordance with the Regulation (EC) No.1272/2008 on classification, labelling and packaging of substances and mixtures, the test item must not be classified. No signal word or hazard statement is required.
Executive summary:

The test item C.A.E. Code: 8500010 was instilled as supplied into the eye of three New Zealand rabbits at the dose of 0.1 mL. The experimental protocol was established according to the OECD guideline No.405 dated April 24th, 2002 and the test method B.5 ohe council regulation No.440/2008.

 

The ocular reactions observed during the study have been slight to important and totally reversible:

-  at the conjunctivae level: a moderate to important redness noted 1 hour after the test item instillation and totally reversible between days 3 and 14, associated with a slight to moderate chemosis noted 1 hour after the test item instillation and totally reversible between days 1 and 7;

-  at the iris level : a congestion, noted 1 hour after the test item instillation in two animals and totally reversible between days 1 and 2.

-  at the corneal level : a moderate opacity, noted 24 hours after the test item instillation in two animals and totally reversible between days 2 and 3.

 

In conclusion, the results obtained, under these experimental conditions, enable to conclude that the test item C.A.E. Code: 8500010 must not be classified, according to the criteria for classification, packaging and labelling of dangerous substances and preparations in compliance with the E.E.C. Directives 67/548, 2001/59 and 1999/45. No symbol or risk phrase is required.

 

In accordance with the Regulation (EC) No.1272/2008 on classification, labelling and packaging of substances and mixtures, the test item must not be classified.No signal word or hazard statement is required.

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