2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

05-Dec-2007 to 13-DEC-2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

not specified

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

2,4-dichloro-7H-pyrrolo[2,3-d]pyrimidine

EC Number:

618-507-6

Cas Number:

90213-66-4

Molecular formula:

C6H3Cl2N3

IUPAC Name:

2,4-dichloro-7H-pyrrolo[2,3-d]pyrimidine

Test material form:

solid

Details on test material:

White to yellow tan colour

Specific details on test material used for the study:

Identification: CP-902684
Description: Solid; tan
Batch Number: E010005632 or 166-TNN-73
Purity: 98%
Stability of Test Item: Stable under storage conditions.
Expiry Date: 21-MAR-2009
Storage Conditions: At room temperature (range of 20 ± 5 °C, provided by RCC), light protected.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Animals: Young Adult New Zealand White Rabbit, SPF
Rationale: Recognized by international guidelines as a recommended test system.
Breeder: Harlan Netherlands BV, Kreuzelweg 53, NL-5961 NM Horst / The Netherlands, Postbus 6174, NL-5960, AD Horst / The Netherlands
Number of Animals per Test: 3 (Animals of both sexes were used)
Age when treated: 12 weeks (male), 12 weeks (females)
Identification: By unique cage number and corresponding ear number.
Acclimatization: Under laboratory conditions after health examination, Only animals without any visual signs of illness were used for the study.
Allocation: Male No. 70, Female Nos. 71,72
Conditions: Standard Laboratory Conditions. Air-conditioned with 10-15 air changes per hour, and continuously monitored environment with ranges for room temperature 17-23 °C and for relative humidity between 30-70 % (values above 70 % during cleaning process possible), automatically controlled light cycle of 12 hours light and 12 hours dark, music during the daytime light period.
Accommodation: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks (RCC Ltd, Ftillinsdorf) and haysticks 4642 (batch no. 36/07, Provimi Kliba AG) were provided for gnawing.
Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 61/07) provided by Provimi Kliba AG, CH-4303 Kaiseraugst.
Water: Community tap water from Füllinsdorf ad libitum.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

other: 0.5 g (per animal) of CP-902684 was weighed as delivered by the Sponsor and then moistened with approximately 0.5 mL of purified water before application.

Controls:

not specified

Amount / concentration applied:

0.5 g (per animal) of CP-902684 was weighed as delivered by the Sponsor and then moistened with approximately 0.5 mL of purified water before application.

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

1 male/2 females

Details on study design:

TEST SITE
- Area of exposure: intact left flank
- % coverage: 100 cm2 (10cm x 10 cm)
- Type of wrap if used: On the day of treatment, 0.5 g of CP-902684 was placed on a surgical gauze patch (ca. 2.5 cm x 2.5 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): After 4 hours, the dressing was removed and the skin was flushed with lukewarm tap water to clean the application site so that any reactions (erythema) were clearly visible at that time.

OBSERVATION TIME POINTS
Skin observation time points: 1, 24, 48 and 72 hours after exposure

SCORING SYSTEM:
- Method of calculation: The mean score was calculated across 3 scoring times (24, 48 and 72 hours after patch removal) for each animal for erythemaJeschar grades and for oedema grades, separately. An animal is positive when the mean score is 2 or greater. The test is positive for irritation when at least 2
animals are positive for the same endpoint (erythema/eschar or oedema). The Cumulative Scores for the Skin Irritation Scores were calculated too and represent the sum of all numerical scores for each animal at each time point. The resulting Mean Cumulative Skin Irritation Score was calculated for all animals at each time point. The Primary Irritation Index (P.I.I.) was calculated by totaling the mean cumulative scores at 24, 48 and 72 hours and then dividing by the number of available figures.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 1, 24, 48 and 72 hours

Max. score:

0

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 1, 24, 48 and 72 hours

Score:

0

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Irritation: The mean score was calculated across 3 scoring times (24, 48 and 72 hours after patch removal) for each animal for erythema/eschar grades and for oedema grades, separately. 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.
Corrosion: Neither alterations of the treated skin were observed nor were corrosive effects evident on the skin.

Other effects:

Viability / Mortality / Clinical Signs: No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.
Coloration: No staining produced by the test item of the treated skin was observed.
Body Weights: there were no body weigh losses observed

Any other information on results incl. tables

The animals were not sacrificed. No signs of irritation were observed on the treated skin following the application of the test item.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based upon the referred classification criteria (Commission Directive 2001/59/EC of August 2001), CP-902684 is considered to be "not irritating" to rabbit skin. According to Draize classification criteria CP-902684 is considered to be "not irritant" to rabbit skin (P.I.I. = 0.00).

Executive summary:

The primary skin irritation potential of CP-902684 was investigated according to OECD test guideline no. 404. The test item was applied by topical semi-occlusive application of 0.5 g to the intact left flank of each of three young adult New Zealand White rabbits. The duration of treatment was four hours. The scoring of skin reactions was performed 1, 24, 48 and 72 hours after removal of the dressing. The mean score was calculated across 3 scoring times (24, 48 and 72 hours after patch removal) for each animal for erythema/eschar grades and for oedema grades, separately. 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. The primary irritation index was calculated by totaling the mean cumulative scores at 24, 48 and 72 hours and then dividing by the number of data points. The primary irritation index was 0.00 (max. 8.0). The test item caused no staining of the treated skin. No corrosive effects were noted on the treated skin of any animal at any of the measuring intervals and no clinical signs were observed. Thus, the test item did not induce significant or irreversible damage to the skin. Based upon the referred classification criteria (Commission Directive 2001/59/EC of August 2001), CP-902684 is considered to be "not irritating" to rabbit skin. According to Draize classification criteria CP-902684 is considered to be "not irritant" to rabbit skin (P.1.1. = 0.00).