4-Quinazolinamine, N-(3-chloro-4-fluorophenyl)-6-nitro-7-(phenylsulfonyl)-

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2003 - 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted in GLP compliance and according to an OECD guideline.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Principles of method if other than guideline:

The following deviations from the standardized study plan occurred which were considered to have no impact on the integrity of the study:
- Deviations from the specified range for relative humidity (45 – 75 %) were observed intermittently: for short periods of time during cleaning in the morning, relative humidity rose up to approximately 95 %.
- Due to their high body weight, food for rabbits was restricted to 120 g per day per animal (instead of ad libitum feeding).

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

7-(benzenesulfonyl)-N-(3-chloro-4-fluorophenyl)-6-nitroquinazolin-4-amine

EC Number:

620-069-6

Cas Number:

945553-94-6

Molecular formula:

C20 H12 Cl F N4 O4 S

IUPAC Name:

7-(benzenesulfonyl)-N-(3-chloro-4-fluorophenyl)-6-nitroquinazolin-4-amine

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

Test item: BIBW 2992 Sulfon (intermediate in the chemical synthesis of BIBW 2992 MA2)
Appearance: yellow - crystalline powder
Batch number: V12SRE00198
Purity: 99.7 area % (HPLC method: AF10_LC3_BIBWSulfon_LM_MS)
Certificate of analysis: dated 13 June 2005
Stability: guaranteed until May 2006
Manufacturer: Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany
Storage conditions: at room temperature, protected from light

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- 3 female rabbits, strain: Chbb:NZW (New Zealand White)
- Age (day of application): approximately 9 – 10 months
- Body weight (day of application): 4.0 – 4.7 kg
- Supplier/Source: Biological Laboratory Service of Boehringer Ingelheim Pharma GmbH & Co. KG
- Housing: individually in solid wire cages
- Diet (e.g. ad libitum): dry food (Kliba No. 3413.0.25, Provimi Kliba SA, CH-4303 Kaiseraugst, Switzerland) was restricted to 120 g per animal and day
- Water (e.g. ad libitum): municipal drinking water ad libitum
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Room number: housing and application in room 40 (building N81)
- Temperature (°C): 22 +/- 2
- Humidity (%): 45 - 75
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12:12 hrs, illumination period: 6:00 - 18:00, average illumination: approximately 60 lx (depending on the cage position; during work in the room the intensity is raised to approximately 450 lx)

Test system

Type of coverage:

other: occluded by muslin tissue and fixed by a non-skin-irritating plaster

Preparation of test site:

shaved

Vehicle:

water

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g per site/rabbit

Duration of treatment / exposure:

pretest period
- one animal was treated initially
- sequentiall exposure on three skin areas of about 6 cm2 for 3 min, 1 hr and 4 hr (Application to the next skin area was only performed in the absence of serious skin alterations in the previous one.)
- at the end of the exposure, residual test item was removed by using demineralized water

main test
- 4 hours
- at the end of the exposure, residual test item was removed by using demineralized water

Observation period:

immediately after the end of exposure, 1, 24, 48 and 72 hours after patch removal

Number of animals:

3 female rabbits

Details on study design:

TEST SITE
- Area of exposure: 6cm²
- % coverage: 100
- Type of wrap if used: muslin tissue / non-irritating tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): washed with demineralized water
- Time after start of exposure: 4 hrs

SCORING SYSTEM: as described in OECD 404 guideline

- general appearance of the rabbits was inspected twice daily
- The animals were killed at the end of study with an intravenous overdose of ketamine / xylazine.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal: all

Time point:

other: all time points up to 72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Results 2

Irritation parameter:

edema score

Basis:

animal: all

Time point:

other: all time points up to 72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Other effects:

none

Any other information on results incl. tables

In summary, BIBW 2992 Sulfon had no irritating or corrosive effect on rabbit skin subsequent to dermal application.

No alterations of the rabbits' general appearance were observed subsequent to local application of the test item. In addition, no skin reaction beyond the area of exposure was observed.

Application of BIBW 2992 Sulfon did not result in any effect on body weight development.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

There were no macroscopic signs of irritation or corrosion. In addition, there were no signs of systemic side effects or of skin alterations beyond the area of exposure.
The test item was determined to be not irritating.