Registration Dossier

Administrative data

Description of key information

Skin: The skin of one rabbit was exposed to undiluted Dermalcare MAP L-213/K or  Dermalcare MAP L-210 under a semiocclusive dressing for 4 hrs or 3 min, 1 hr and 4 hrs, respectively. Dermalcare MAP L-213/K induced well-defined erythema but this effect was fully reversible by day 7. The scores obtained for erythema induced the classification of Dermalcare MAP L-213/K as Xi, R38 according to the criteria of the Directive 67/548/EEC. The scores obtained for erythema do not allow to classify according to the CLP criteria but as the cutaneous effect was significant and by precaution, Dermalcare MAP L-213/K is also classified as skin irr. 2 (H315) according to Regulation (EC) 1272/2008.
Dermalcare MAP L-210 induced stronger irritant effects particularly after an exposure of 1 hr. Severe erythema was observed from 4 hours to 7 days after removal of the dressing and a moderate edema was also observed. Necrotic areas were observed from 24 hrs to 7 days. On day 14, desquamation and scabs were persisting. Following a 4 hr exposure, a severe erythema at 4 hours after the removal of the dressing reducing to a moderate erythema to 72 hours, and a slight edema were observed. However no necrotic areas were observed. The only effect persisiting to the 14 day observation period was desquamation. Therefore Dermalcare MAP L-210 was considered to be irritating to the skin (Skin irr. 2 (H315)) according to the Regulation (EC) 1272/2008 (CLP) and as Xi, R38 according to the Directive 67/548/EEC) and not corrosive due to the results obtained following the 4 hr exposure time.
Eye: The eye of one rabbit was exposed to undiluted Dermalcare MAP L-213/K without rinsing. The test substance induced irreversible damage on the cornea and on the iris of the rabbit eye (21 days of observation). Dermalcare MAP L-213/K is classified as Eye Dam. 1 (H318) according to the Regulation (EC) 1272/2008 (CLP) and as Xi, R41 according to the Directive 67/548/EEC.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
From 28 February 2000 to 27 October 2003
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study is a screening test but followed international guidance requirements with acceptable restrictions.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
: screening study, only one tested animal, no certificate of analysis included
Principles of method if other than guideline:
Not applicable
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River Italia S.p.A
- Age at study initiation: no data
- Weight at study initiation: 2.8 kg
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: From: To: no data
Vehicle:
unchanged (no vehicle)
Controls:
other: the left eye remained untreated
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): not applicable

VEHICLE
not applicable
Duration of treatment / exposure:
the eye was not rinsed after administration of test item
Observation period (in vivo):
Ocular reactions were observed approximately 1 hour, 24, 48 and 72 hours after the instillation and then at days 7, 14 and 21.
Number of animals or in vitro replicates:
1
Details on study design:
REMOVAL OF TEST SUBSTANCE
not applicable

SCORING SYSTEM: Draize scale

TOOL USED TO ASSESS SCORE: no data
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not reversible
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Irritant / corrosive response data:
Corneal opacity was observed at 24 and 48 hours (grade 1) and persisted with grade 2 from 72 hours until the end of the study period (day 21). Iris inflammation (grade 1) was observed from the 24-hour observation until the end of the study. The mean scores calculated over the 24-48-72 hours period were 1.33 for corneal opacity, and 1.0 for iris inflammation.
Conjunctival reactions, redness (grade 2) and chemosis (grade 2 or 3) were observed between 1 and 72 hours, and then cleared by day 21. The mean scores (24-48-72 hours) were 2.0 for conjunctival redness, and 3.0 for chemosis. In addition, discharge was observed between 1 and 72 hours following administration (see details in Table 7.3.2/1).
Other effects:
none

Table 7.3.2/1: Irritant/corrosive response data at each observation time up to removal of animal from the test (21 days)

Score at time point / Reversibility

Cornea

Iris

Conjunctivae

Chemosis

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

60 min

0

0

2

2

24 h

1

1

2

3

48 h

1

1

2

3

72 h

2

1

2

3

7 days

2

1

1

1

14 days

2

1

1

1

21 days

2

1

0

0

Average 24h, 48h, 72h

1.3

1.0

2.0

3.0

Reversibility*)

n

n

c

c

Average time (day) for reversion

-

-

21

21

*) Reversibility: c. = completely reversible;n.c.= not completely reversible; n. = not reversible

OP: Scoring masked by marked corneal opacity

Interpretation of results:
Category 1 (irreversible effects on the eye)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, Dermalcare MAP L-213/K induced irreversible eye damage (persistent corneal and iridal effects on day 21) and is therefore classified as Eye Dam. 1 (H318) according to the criteria of the Regulation (EC) 1272/2008 (CLP) or to the criteria of the Directive 67/548/EEC.
Executive summary:

In an eye irritation screening study performed similarly to the OECD No. 405 guideline, 0.1 mL of undiluted Dermalcare MAP L-213/K was instilled into the conjunctival sac of right eye of one male New Zealand White Rabbit. After the instillation the substance was not rinsed off. The animal was then observed for 21 days for eye edema and erythema of the conjunctivae, corneal opacity and iris lesion. Eye irritation was assessed and scored according to the Draize scale at 1,24, 48 and 72 hrs, 7, 14 and 21 days after the instillation of the substance. The mean individual scores were calculated within 3 scoring times (24, 48 and 72 hrs).

The mean score was 1.3 for corneal opacity, 1.0 for the iris lesion, 3.0 for chemosis and 2.0 for conjunctival erythema. While the effects on the conjunctivae (redness and chemosis) were fully reversible within 21 days, effects on the cornea and on the iris were irreversible over the 21 -day observation period.

 

Therefore, under the test conditions, Dermalcare MAP L-213/K induced irreversible damage to the rabbit eye and is classified as Eye Dam. 1 (H318) according to the criteria of the Regulation (EC) 1272/2008 (CLP) and as Xi, R41according to the criteria of the Directive 67/548/EEC.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The data available on two structural analogs of Dermalcare MAP L-213/S satisfy the irritation / corrosion endpoint requirements for an Annex VII dossier. The studies are screening tests but are scientifically acceptable and of good quality.


Justification for selection of skin irritation / corrosion endpoint:
No study selected because a weight of evidence approach was used based on data available for structural analogs of Dermalcare MAP L213/S (for justification of read-across between Dermalcare MAP L213S and its analogues, please refer to corresponding assessment report in Section 13).

Justification for selection of eye irritation endpoint:
Only one study available

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: corrosive

Justification for classification or non-classification

Harmonized classification:

No harmonized classification is available according to the Regulation (EC) No 1272/2008 including ATP2.

Self classification:

Dermalcare MAP L213/S is classified as Skin irr. 2 (H315) according to Regulation (EC) 1272/2008 (CLP) and as Xi; R38 according to Directive 67/548/EEC.

Dermalcare MAP L213/S is classified as Eye Dam. 1 (H318) according to Regulation (EC) 1272/2008 (CLP) and as Xi; R41 according to Directive 67/548/EEC.