3-(2-hydroxyethyl)-1H,3H-quinazoline-2,4-dione

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2006-07-19 to 2006-07-28

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Comparable to guideline study. Study was conducted according to OECD Guideline 404 "Acute Dermal Irritation/Corrosion" and Commission Directive 2004/73/EC B.4 "Acute Toxicity: Dermal Irritation/Corrosion".

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

The testing facility reported the following deviation from the protocol: the test substance was put on a surgical gauze patch of approximately 4 cm x 4cm instead of 6 cm x 6 cm.

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

The testing facility reported the following deviation from the protocol: the test substance was put on a surgical gauze patch of approximately 4 cm x 4cm instead of 6 cm x 6 cm.

GLP compliance:

yes (incl. QA statement)

Remarks:

Swiss Agency for Therapeutic Products and the Swiss Agency for the Environment, Forests and Landscape

Test material

Test material information

Constituent 1

Reference substance name:

3-(2-hydroxyethyl)-1H,3H-quinazoline-2,4-dione

EC Number:

214-897-3

EC Name:

3-(2-hydroxyethyl)-1H,3H-quinazoline-2,4-dione

Cas Number:

1207-75-6

Molecular formula:

C10H10N2O3

IUPAC Name:

3-(2-hydroxyethyl)-1,2,3,4-tetrahydroquinazoline-2,4-dione

Test material form:

solid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 00495665 RT001200G1A291
- Expiration date of the lot/batch: 2011-11-09
- Purity test date: no data

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature (range of 20 +/- 5°C), light protected
- Stability under test conditions: no data

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: 0.5 g (per animal) of T001200 was weighed as delivered by the sponsor and then moistened with approximately 0.5 mL of purified water before application

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: 3 New Zealand White rabbit; Harlan Netherlands BV, Kreuzelweg 53, 5961 NM Horst, The Netherlands
- Age at study initiation: 14-15 weeks (male), 10-11 weeks (females)
- Weight at study initiation: 2354 grams (male), 1808 and 1547 grams (females)
- Housing: standard laboratory conditions; Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Woodblocks (RCC Ltd, Füllinsdorf) and haysticks 4642 (batch no. 77/05, Provimi Kliba AG) were provided for gnawing.
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 24/06).
- Water (e.g. ad libitum): Community tap water from Füllinsdorf, ad libitum.
- Acclimation period: 5 days for one female; 6 days for one female and one male, under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (deg C): 17-23
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12, music was played during the daytime light period


IN-LIFE DATES: From: 2006-07-24 To: 2006-07-28

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
- Concentration (if solution): not applicable


VEHICLE
- Amount(s) applied (volume or weight with unit): not applicable. However, approximately 0.5 mL of purified water was used to moisten the test material before application.
- Concentration (if solution): not applicable
- Lot/batch no. (if required): not applicable
- Purity:not applicable

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3 (one male and two females)

Details on study design:

TEST SITE
- Area of exposure: left flank (or both flanks)
- % coverage: no data
- Type of wrap if used: semi-occlusive
- On the day of treatment, 0.5 g of T001200 was placed on a surgical gauze patch (ca. 4 cm x 4 cm). This gauze patch was applied to the intact skin of the clipped area. The patch was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the skin was flushed with lukewarm tap water
- Time after start of exposure: 4-hours

OBSERVATION TIME POINTS
- viability/mortality, clinical signs: daily from acclimatization of the animals to the termination of test
- body weights: at start of acclimatization, on the day of application and at termination of observation
- skin reactions: at approximately 1, 24, 48 and 72 hours after exposure (removal of gauze patch and test item)


SCORING SYSTEM:
- The skin reaction was assessed according to the numerical scoring system listed in the Commission Directive 2004/73/EC, April 29, 2004. Scaling from 0 to 4 for erythema and eschar formation, and 0 to 4 for edemal formation.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Remarks:

mean of 3 animals

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: not applicable

Results 2

Irritation parameter:

edema score

Remarks:

mean of 3 animals

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: not applicable

Irritant / corrosive response data:

The test item did not elicit any skin reactions at the application site of any animal at any of the observation times (all scores 0). The individual mean score for erythema/eschar and oedema for each of the three animals was therefore 0.
Neither alterations of the treated skin were observed nor were corrosive effects evident on the skin.

Other effects:

No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.
No staining of the treated skin was produced by the test item.
One animal showed a loss of body weight (10%) during the acclimatization period and recovered at the end of the study. The body weights of the other rabbits were considered to be within the normal range of variability.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the referred classification criteria (Commission Directive 2001/59/EC of August 2001), T001200 is considered to be "not irritating" to rabbit skin.