4-methyloxazole-5-carbonitrile

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: according to OECD test guideline No. 404 (2002) and Commission Regulation (EC) No. 440/2008, B.4.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

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:

4-methyloxazole-5-carbonitrile

EC Number:

213-709-7

EC Name:

4-methyloxazole-5-carbonitrile

Cas Number:

1003-52-7

Molecular formula:

C5H4N2O

IUPAC Name:

4-methyl-1,3-oxazole-5-carbonitrile

Details on test material:

Name of test item (as cited in the report): CMO
Physical state: liquid
Purity: 99.9% (m/m)
Batch Number: 485
CAS Number: 1003-52-7
Expiry Date: 04-Dec-2010
Storage Conditions: In the refrigerator (range of 5 ± 3 °C, provided by Harlan Laboratories Ltd.), light and humidity protected, under inert gas (nitrogen).

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH, Stolzenseeweg 32-36, 88353 Kisslegg / Germany
- Age at treatment start: males: 11 weeks, females 11 and 19 weeks
- Weight at streatment start: male: 3064 g, females 2860g and 3406 g
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls.
- Diet (e.g. ad libitum): Pelleted standard Kliba Nafag 3418 rodent maintenance diet (batch nos. 65/09 and 05/10 provided by Provimi Kliba AG, 4303 Kaiseraugst / Switzerland) available ad libitum. Results of analyses for contaminants are archived at Harlan Laboratories Ltd.
- Water (e.g. ad libitum):Community tap water from Füllinsdorf ad libitum.
- Acclimation period: 17-Mar-2010 to 21-Mar-2010 (one female) and 17-Mar-2010 to 22-Mar-2010 (the male and the second female)


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 °C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark


IN-LIFE DATES: From: 22-Mar-2010 To: 26-Mar-2010

Test system

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped with an electric clipper

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL/animal

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: approx. 6.25 cm2
- coverage: approximately 0.4% of the surface area
- Type of wrap if used: adhesive hypoallergenic aerated semi-occlusive dressing and a restrainer bandage wrapped around the abdomen


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


SCORING SYSTEM: 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).
Data were summarized in tabular form, showing for each individual animal the irritation scores for erythema and oedema at all measurement intervals. Any lesions were described, including the degree and nature of irritation, corrosion or any other toxic effects observed, and their reversibility.
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. 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).

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

other: mean score for animal numbers 29, 30 and 31

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: No skin reaction

Remarks on result:

other: individual mean scores: 0 -0 -0

Results 2

Irritation parameter:

edema score

Basis:

other: mean score for animal numbers 29, 30 and 31

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: No skin reaction

Remarks on result:

other: individual mean scores: 0 - 0 - 0

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.

Other effects:

No staining produced by the test item of the treated skin was observed.
Neither were alterations of the treated skin observed nor were corrosive effects evident on the skin.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based upon the Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008, CMO does not have to be classified with respect to skin irritation in rabbits.

Executive summary:

The primary skin irritation potential of CMO was investigated according to OECD test guideline No. 404 (2002) and Commission Regulation (EC) No. 440/2008, B.4. The test item was applied by topical semi-occlusive application of 0.5 mL 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 and flushing the application site with lukewarm water. 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 erythema/eschar and oedema score for each of the three animals was therefore 0. The test item did not cause any staining of the treated skin.

Based upon the Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008, CMO does not have to be classified with respect to skin irritation in rabbits.