1H-Isoindole-1,3(2H)-dione, 2-[(2R)-2-hydroxy-3-[[4-(3-oxo-4-morpholinyl)phenyl]amino]propyl]-

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Oct 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

2002

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

1H-Isoindole-1,3(2H)-dione, 2-[(2R)-2-hydroxy-3-[[4-(3-oxo-4-morpholinyl)phenyl]amino]propyl]-

IUPAC Name:

1H-Isoindole-1,3(2H)-dione, 2-[(2R)-2-hydroxy-3-[[4-(3-oxo-4-morpholinyl)phenyl]amino]propyl]-

Constituent 2

Reference substance name:

2-[(2R)-2-hydroxy-3-{[4-(3-oxomorpholin-4-yl)phenyl]amino}propyl]-1H-isoindole-1,3(2H)-dione

EC Number:

610-200-5

Cas Number:

446292-07-5

Molecular formula:

C21 H21 N3 O5

IUPAC Name:

2-[(2R)-2-hydroxy-3-{[4-(3-oxomorpholin-4-yl)phenyl]amino}propyl]-1H-isoindole-1,3(2H)-dione

Specific details on test material used for the study:

purity: 98.2%

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, 88353 Kißlegg, Germany, 69592
- Age at study initiation: young adult animals
- Weight at study initiation: 2.2 kg — 2.4 kg
- Housing: The animals were housed individually in cage units Metall/Noryl by EBECO. Excrement trays below the cages contained low dust wood granulate bedding (J. Rettenmaier & Söhne, 73494 Rosenberg, Germany).
- Diet (e.g. ad libitum): The animals received the standard diet “SsniffK-Z” 4mm (manufacturer: Ssniff Spezialdiäten GmbH, 59494 Soest, Germany), approximately 100 g per animal per day
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±3
- Humidity (%): 50±25
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Remarks:

pulverized test item moistened with water

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):0.5 g

Duration of treatment / exposure:

one animal: first patch removed after 3 minutes, second patch (because no serious skin reactions were observed after the first patch) removed after 1 hour and third patch removed after 4 hours
two more animals: exposed for 4 hours

Observation period:

72 hours

Number of animals:

3 females

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: 0.5 g of the pulverized test substance moistened with Aqua p.i. (to ensure good contact with the skin) was applied to the skin of the animal under a gauze patch. The patch was placed on the dorso-lateral areas of the trunk of each animal and was held in place with non-irritating tape for the duration of the exposure period.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The exposed skin area was carefully washed with water without altering the existing response, or the integrity of the epidermis.
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
(indicate if minutes, hours or days): 1, 24, 48, 72 h

SCORING SYSTEM: The degree of erythema/eschar formation and oedema formation was recorded as specified by DRAIZE

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Other effects:

There were no systemic intolerance reactions.

Any other information on results incl. tables

Results of the study:

	Irritant Effects (Scores)
	24 h		48 h		72 h		Mean scores
animal	erythema	edema	erythema	edema	erythema	edema	erythema	edema
1	0	0	0	0	0	0	0	0
2	0	0	0	0	0	0	0	0
3	0	0	0	0	0	0	0	0

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

the test item is not irritating to skin

Executive summary:

500 mg of the test substance was semi-occlusively applied to the shaved intact skin of 3 female rabbits for an exposure period of 4 h. Evaluation of skin irritation was made according to Draize.

In this skin irritation study Hydroxyaminophthalimid was not irritating to the skin.