1H-Purine-2,6-dione, 8-bromo-7-(2-butyn-1-yl)-3,7-dihydro-3-methyl-

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19 Aug 2003 - 12 Sep 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

8-bromo-7-(but-2-yn-1-yl)-3-methyl-2,3,6,7-tetrahydro-1H-purine-2,6-dione

EC Number:

613-975-8

Cas Number:

666816-98-4

Molecular formula:

C10-H9-Br-N4-O2

IUPAC Name:

8-bromo-7-(but-2-yn-1-yl)-3-methyl-2,3,6,7-tetrahydro-1H-purine-2,6-dione

Test material form:

solid: particulate/powder

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Biological Laboratory Service of Boehringer Ingelheim
Pharma GmbH & Co. KG
- Age at study initiation: approximately 4 months
- Weight at study initiation: 3.3 - 3.6 kg (day of application)
- Housing: Rabbits were housed individually in solid wire cages.Housing in room 33, application in room 40 (building N81)
-Dry food and municipal drinking water were supplied ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 45 - 75%
- Air changes (per hr): approximately 10 air changes per hour
- Light/darkness cycle: 12/12 h, with light cycle from 6.00 h to 18.00 h

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Amount / concentration applied:

Approximately 0.5 g

Duration of treatment / exposure:

4h

Observation period:

1h, 24, 48h and 72h

Number of animals:

3 female rabbits

Details on study design:

TEST SITE
- Area of exposure: dermal skin
- The area to be treated is about 6 cm2
- occluded by muslin
- The shaved and marked skin areas were treated with the test item and occluded by muslin
tissue and fixed by a non-skin-irritating plaster.

REMOVAL OF TEST SUBSTANCE
- At the end of the indicated exposure times, the respective skin area was washed with
demineralized water to remove the test item.
- According to the test strategy described in OECD Guideline 404, only one animal was treated
initially (Group 1, initial test). Sequentially, the test item was administered to three skin sites
for 3 min (area 1), 1 h (area 2), and 4 h (area 3), respectively. Administration to the next skin
area was only performed in the absence of serious skin alterations in the previous one. When
no serious skin alterations occurred subsequent to 4 h of exposure on the first rabbit, the test
item was administered to two more animals (Group 2, confirmatory test) on the following day
for 4 h at a single site only.

OBSERVATION TIME POINTS
- 1 h, 24 h, 48 h, and 72 h

SCORING SYSTEM:
- They were evaluated according to the criteria given in OECD Guideline 404

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 1H/24H/48H/72H

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 24H

Remarks on result:

other: In summary, BI 1344 BZ/CD 164 had no corrosive, but a very slight, transient irritating effect. Minimal, barely perceptible erythema, but no edema, was seen in one out of three animals exclusively at 1 h only following exposure for either 1 h or 4 h and

Results 2

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 1h/24h/48h/72h

Score:

0

Max. score:

4

Results 3

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 1h/24h/48h/72h

Score:

0

Max. score:

4

Results 4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 1h/24h/48h/72h

Score:

0

Max. score:

4

Results 5

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 1h/24h/48h/72h

Score:

0

Max. score:

4

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: 1h/24h/48h/72h

Score:

0

Max. score:

4

Applicant's summary and conclusion

Interpretation of results:

other: not classified acc. CLP

Conclusions:

Under the conditions of the present study, BI 1344 BZ/CD 164 had no corrosive, but a very
slight, transient irritating effect. Minimal, barely perceptible erythema, but no edema, was
seen in one out of three animals exclusively at 1 h only following exposure for either 1 h or 4
h and returning to normal within 24 h. There were no signs of systemic side effects or of skin
alterations beyond the area of exposure. Thus, according to the Globally Harmonized Hazard
Classification and Labeling Scheme (GHS), the test item BI 1344 BZ/CD 164 is not
classified.