1H-Indole-6-carboxylic acid, 2,3-dihydro-2-oxo-, methyl ester

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

15 February - 01 March 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

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:

methyl 2-oxo-2,3-dihydro-1H-indole-6-carboxylate

EC Number:

604-263-8

Cas Number:

14192-26-8

Molecular formula:

C10 H9 N O3

IUPAC Name:

methyl 2-oxo-2,3-dihydro-1H-indole-6-carboxylate

Test material form:

solid: particulate/powder

Test animals

Species:

rabbit

Strain:

other: Chbb:NZW (SPF) and Crl:KBL (NZW), (SPF)

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Chbb:NZW (SPF): Biological Labaratory Service, Boehringer Ingelheim Pharma KG, Biberach
Crl:KBL (NZW), (SPF): Charles River Deutschland, Kißlegg, Germany
- Age at study initiation: Initial animals: 11-24 weeks, additional animals: 1.5-2 kg
- Weight at study initiation: Initial animals: 2-5 kg, additional animals: 56 days
- Housing: rabbit cages
- Diet (e.g. ad libitum): pelleted food ad libitum
- Water (e.g. ad libitum): municipal drinking water ad libitum
- Acclimation period: 3 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C ± 3°C
- Humidity (%): 45-75%
- Air changes (per hr): approximately 12 air changes per hour
- Photoperiod (hrs dark / hrs light): 9/15 hours, Illumination period: 07:00 to 16:00

IN-LIFE DATES: End: 01 March 2002.

Test system

Type of coverage:

other: gauze patch

Preparation of test site:

shaved

Vehicle:

water

Controls:

no

Amount / concentration applied:

500mg/6cm²

Duration of treatment / exposure:

3min, 1h and 4h

Observation period:

1h, 24h, 48h and 72 hours
General clinical appearance was checked twice daily ( once daily during pretest phase and non-working days)

Number of animals:

7

Details on study design:

Dose formulation:
A total amount of 5 g of the test article was moistened with the smallest amount of vehicle needed to ensure good skin contact. An amount of 500 mg(or slightly more) of the moistened test article was used for each application site.
Due to fur density, hair clipping was not satisfactory, which raised doubts whether the skin of animals No. 151-154 was sufficiently exposed. Therefore it was decided to extend the study using additional animals. Because OECD Guideline No. 404 recommends rabbits, but does not specify a strain, it was decided to use Crl:KBL (NZW) rabbits, which - according to experience - are more easy to clip.
The supplier of the Crl:KBL (NZW) rabbits did not disclose the age ofthe animals in the delivery documents. The age has been estimated based on the growth curve for this strain provided by the supplier (On arrival the animals weighed 1.5-2 kg corresponding to an age of approximately 56 days). This procedure was considered acceptable, because knowledge ofthe exact age is not crucial in this type of study.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 1, 24, 48, 72 hours

Score:

0

Max. score:

4

Results 2

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 1, 24, 48, 72 hours

Score:

0

Max. score:

4

Any other information on results incl. tables

General clinical appearance:

Except for animal No. 154, the general clinical appearance of all animals was normal during the entire study. Animal No. 154 exhibited paralysis of the hind limbs after release from the restraint cage, where it was placed during the administration period. Therefore, it was killed for humane reasons.

Clinical evaluation ofthe skin:

All animals had anormal clinical appearance ofthe skin during the entire study. No erythema or edema were observed for any animal at any time point.

Applicant's summary and conclusion

Interpretation of results:

other: not classified acc. CLP

Conclusions:

Dermal exposure of Chbb:NZW or Crl:KBL (NZW) rabbits to approximately 500mg BIBF 1120 Indol on 6 cm² skin for up to 4 hours did not cause
erythema or edema in any animal at any point. Therefore, the test substance is considered non-irritating and non-corrosive.