Registration Dossier

Toxicological information

Skin irritation / corrosion

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Administrative data

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, GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report date:
2005

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
2004
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
2002
Deviations:
no
GLP compliance:
yes (incl. QA statement)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material: DOPA-Glycinate

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Elevage Scientific des Dombes, Chatillon sur Chalaronne, France
- Age at study initiation: 14–15 weeks (male), 12–13 weeks (females)
- Weight at study initiation: 2229 – 2309 g
- Housing: individually
- Diet (e.g. ad libitum): pelleted diet, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: not stated

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
Duration of treatment / exposure:
4 h
Observation period:
14 d
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 16 cm² (4.0 cm x 4.0 cm) on a flank

REMOVAL OF TEST SUBSTANCE
- Washing (if done): tap water
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize scale

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: score of this animal was not assessable after 48 and 72 hours due to deep necrosis
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: mean 24, 48, 72 h
Score:
2
Max. score:
4
Reversibility:
other: not expected to be reversible
Remarks on result:
other: this animal was killed for ethical reasons after the 72-hour reading due to the deep necrosis observed
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: mean 24, 48, 72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: mean 24, 48, 72
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: mean 24, 48, 72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks on result:
other: scaling was observed on days 7 and 10 (reversible within 14 d)
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: mean 24, 48, 72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritant / corrosive response data:
One hour after patch removal slight erythema, well-defined erythema, severe erythema were observed in all animals and slight swelling oedema and moderate swelling oedema were observed in two animals. After 24 hours one animal showed no erythema and no oedema. The well-defined erythema persisted until 72 hours, decreased to slight erythema 7 days after patch removal and was gone on day 14. In animal no.9 the oedema decreased from slight swelling after 24 hours to very slight swelling after 48 hours and 7 days after patch removal the oedema was gone. The severe erythema of animal no.7 persisted until 24 hour reading; it was noted with dry skin from the 24- to the 72-hour reading and was not assessable due to deep necrosis at 48 and 72 hour evaluation. The oedema decreased from moderate swelling after 24 hours to slight swelling after 48 hours and very slight swelling after 72 hours, then animal no. 7 was killed for ethical reasons.
The cutaneous reactions were reversible in one animal after 24 hours, in another animal within 14 days after removal of the patch. The third animal was sacrificed after the 72 hour reading for ethical reasons.
No staining produced by the test item of the treated skin was observed.
Other effects:
No clinical signs of systemic toxicity were observed in the animals during the study. One animal was sacrificed for ethical reasons after the 72-hour reading.
In one animal (no.9) on day 7 and day 10 scaling was present.
The body weights of all rabbits were considered to be within the normal range of variability.

Any other information on results incl. tables

 

animal

observation

erythema

edema

scaling

#1

#2

#3

1 h

4

1

2

3

0

2

0

0

0

#1

#2

#3

24 h

4

0

2

3

0

2

0

0

0

#1

#2

#3

48 h

n.a.

0

2

2

0

1

0

0

0

#1

#2

#3

72 h

n.a.

0

2

1

0

1

0

0

0

#1

#2

#3

7 d

-**

0

1

-**

0

0

-**

0

x

#1

#2

#3

10 d

-**

0

1

-**

0

0

-**

0

x

#1

#2

#3

14 d

-**

0

0

-**

0

0

-**

0

0

 

n.a. : score of this animal was not assessable after 48 and 72 hours due to deep necrosis

-**: this animal was killed for ethical reasons after the 72-hour reading due to the deep necrosis observed

x: scaling present

Applicant's summary and conclusion

Interpretation of results:
Category 1C (corrosive)
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)
Conclusions:
In this skin irritation test in rabbit, DOPA-Glycinate caused full thickness destruction of the skin tissue at the application site in one animal. Thus, the test substance has to be classified as corrosive.
Executive summary:

The acute dermal irritation of DOPA-Glycinate (99.4% a.i.) was tested in 3 New Zealand white rabbits, according to EC method B.4 (2004/73/EEC) and OECD guideline 404 (2002).Rabbits were applied a dose of 0.5 g on the shaved intact skin for a period of 4 hours (semi-occlusive).

The application of the test item to the skin resulted in mild to severe and early-onset signs of irritation such as erythema, oedema and scaling. These effects were reversible and were no longer evident in the two surviving animals 14 days after treatment, the end of the observation period for all animals. One animal was noted with dry skin from the 24- to the 72-hour reading as well as with deep necrosis (full thickness destruction of the skin tissue) at the 48- and 72-hour reading. Thereafter, it was sacrificed for ethical reasons.

According to the requirements specified by Regulation (EC) 1272/2008 and subsequent regulations, DOPA-Glycinate requires classification for skin corrosion/irritation with classification category 1C, signal word “danger” and the hazard phrase “H314: Causes severe skin burns and eye damage” according to the classification criteria of Regulation 1272/2008.