Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
08 April 2003 to 18 April 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report Date:
2003

Materials and methods

Test guidelineopen allclose all
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
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Identification: HSY-2701
Description: Red powder
Batch: 03A-20
Purity: > 99.9 %
Test substance storage: At room temperature protected from light
Stability under storage conditions: Stable
Expiry date: 07 August 2003 (6 months from the date of receipt).

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Kisslegg, Germany
- Age at study initiation: At least 6 weeks old
- Weight at study initiation: At least 1.0 kg
- Housing: Housed individually in labelled cages with perforated floors (Scanbur, Denmark, dimensions 65 x 44 x 37.5 cm)
- Diet (e.g. ad libitum): Standard laboratory rabbit diet (Charles River Breeding and Maintenance Diet for Rabbits, Altromin, Lage, Germany) approx 100 g per day. In addition, pressed hay (BMI, Helmond, the Netherlands) was provided twice a week.
- Water (e.g. ad libitum): Free access to tap-water.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16.8-22.2 °C
- Humidity (%): 58.10 to 79.58 %
- Air changes (per hr):15 per hour
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: watery ethanol (50 % v/v)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

VEHICLE
- Amount(s) applied (volume or weight with unit): 1 mL
Duration of treatment / exposure:
4 hours
Observation period:
7 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2 x 3 cm (dorsal)
- Type of wrap if used: Test material was applied to the skin of one flank, using a metalline patch of 2 x 3 cm. The patch was mounted on Micropore tape; which was wrapped around the abdomen and secured with Coban elastic bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Four hours after the application, the dressing was removed and the skin cleaned of residual test substance using water, ethanol and acetone.
- Time after start of exposure: 4 hours

SCORING SYSTEM:
ERYTHEMA AND ESCHAR FORMATION
No erythema 0
Very slight erythema (barely perceptible) 1
Well defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) 4
* Where signs of necrosis or corrosion (injuries in depth) prevent erythema scoring, the maximum grade for erythema (= 4) is given.

OEDEMA FORMATION
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by definite raising) 2
Moderate oedema (raised approximately 1 millimeter) 3
Severe oedema (raised more than 1 millimeter and extending beyond the area of exposure) 4

Results and discussion

In vivo

Results
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24
Score:
0
Max. score:
8
Reversibility:
fully reversible
Remarks:
1 animal noted with very slight oedema at 1 hour, which had fully reversed by 24 hours
Irritant / corrosive response data:
Four hours exposure to 0.5 g of HSY-2701 resulted in very slight oedema in the treated skin-area of one rabbit.
The skin irritation had resolved within 24 hours after exposure.
There was no evidence of a corrosive effect on the skin
Other effects:
Yellow/orange staining of the treated skin by the test substance was observed throughout the observation period, which did not hamper the scoring of the skin reactions.
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Any other information on results incl. tables

Table 1: Individual Skin Irritation Scores

Following exposure, yellow/orange staining of the treated skin-area was noted after removal of the test substance

Animal #

227 (sentinel)

219

270

Time after exposure

Erythema

Oedema

Comments

Erythema

Oedema

Comments

Erythema

Oedema

Comments

1 hour

0

1

a

0

0

a

0

0

a

24 hours

0

0

a

0

0

a

0

0

a

48 hours

0

0

a

0

0

a

0

0

a

72 hours

0

0

a

0

0

a

0

0

a

Comments:

a. Yellow/orange staining of the skin by the test substance.

Table 2: Mean Value Irritation Scores

Animal #

Mean 24-72 hours

Erythema

Oedema

227

0

0

219

0

0

270

0

0

 

# Animal specifications:

Animal no.

Sex

Age at start (weeks)

Body weights (grams)

Prior to application

At termination

227

Male

11-13

2216

2325

219

Male

10 -12

2441

2601

270

Male

7-9

1671

1770

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
HSY-2701 was found to be non-corrosive and non-irritating in New Zealand White rabbits.
Executive summary:

In an OECD guideline study (404) performed in compliance with GLP, the irritation potential of HSY-2701 was determined in three male New Zealand White Rabbits. After four hours of exposure, very slight oedema was noted in 1 animal at 1 hour, however this was fully reversible within 24 hours. Yellow/orange staining of the test site was noted in all animals. HSY-2701 was determined to be non-corrosive and non-irritating to rabbit skin.