2-(4-fluorophenyl)-5-(5-iodo-2-methylbenzyl)thiophene

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2009-03-23 to 2009-03-26

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Well documented GLP study according to OECD guideline 404 en EU Method B.4.

Justification for type of information:

The study was performed in 2009 to investigate further the results obtained in the in vitro test. The report was finalized in 2015.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-(4-fluorophenyl)-5-(5-iodo-2-methylbenzyl)thiophene

EC Number:

618-312-6

Cas Number:

898566-17-1

Molecular formula:

C18H14FIS

IUPAC Name:

2-(4-fluorophenyl)-5-(5-iodo-2-methylbenzyl)thiophene

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material (as cited in study reports): JNJ-39453193-AAA (T003063)
- Physical state: solid (powder)
- Appearance: white to almost white powder

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 507652
- Expiration date of the lot/batch: 2009-04-03 (retest date)
- Purity test date: no data

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

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: the test item was used as delivered by the sponsor and was 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: young adult New Zealand White rabbits, SPF; from Harlan Laboratories B.V., Kreuzelweg 53, 5961 NM Horst, The Nertherlands
- Age when treated: 15 weeks (male), 15 weeks (females)
- Weight when treated: 2631 grams (male), 2831 - 2852 grams (females)
- Housing: Standard Laboratory Conditions; individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks (Harlan Laboratories Ltd., Füllinsdorf) and haysticks 4642 (batch no. 69/08, Provimi Kliba AG) were provided for gnawing.
- Diet (e.g. ad libitum): pelleted standard Provimi Kliba 3418 rabbit maintenance diet, ad libitum
- Water (e.g. ad libitum): Community tap water from Füllinsdorf, ad libitum
- Acclimation period: 5 days (from 2009-03-18 to 2009-03-22) under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23 °C
- Humidity (%): 30 - 70% (values above 70% during cleaning process possible)
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12, automatically controlled light cycle, music during the daytime light period

IN-LIFE DATES: From: 2009-09323 To: 2009-03-26

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Remarks:

purified

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g/animal, as delivered by the sponsor
- The pH of the test item was measured before the study initiation date in a 1 % (w/w) solution in purified water and was found to be 5.

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

1 male and 2 females

Details on study design:

TEST SITE
- Area of exposure: left flank, 100 cm² (10 cm x 10 cm)
- % coverage: no data, ca. 2.5 cm x 2.5 cm
- Type of wrap if used: 0.5g of T003063 on a surgical gauze patch was held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restrainer bandage wrapped around the abdomen.

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

SCORING SYSTEM:
- The skin reaction was assessed according to the numerical scoring system listed in the Commission Regulation (EC) No. 440/2008, B.4, at approximately 1, 24, 48 and 72 hours after exposure (removal of the dressing, gauze patch and test item).

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Remarks:

male 60

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

edema score

Basis:

mean

Remarks:

male 60

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 3

Irritation parameter:

other: scaling

Basis:

mean

Remarks:

male 60

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 4

Irritation parameter:

erythema score

Basis:

mean

Remarks:

female 61

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 5

Irritation parameter:

edema score

Basis:

mean

Remarks:

female 61

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 6

Irritation parameter:

other: scaling

Basis:

mean

Remarks:

female 61

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 7

Irritation parameter:

erythema score

Basis:

mean

Remarks:

female 62

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 8

Irritation parameter:

edema score

Basis:

mean

Remarks:

female 62

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 9

Irritation parameter:

other: scaling

Basis:

mean

Remarks:

female 62

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Irritation:
- 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).

Corrosion:
- Neither alterations of the treated skin were observed nor were corrosive effects evident on the skin.

Other effects:

Mortality/Viability:
- No mortality occurred.

Clinical signs:
- No clinical signs were observed during the course of the study.

Body Weights:
- The body weights of all rabbits were considered to be within the normal range of variability.

Pathology:
- Macroscopic findings: no necropsy was performed at the end of the study.

Coloration:
- No staining produced by the test item of the treated skin was observed.

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), T003063 is considered to be “not irritating” to rabbit skin. According to the CLP classification, the test item should not be classified.