Propanoic acid, 2-cyano-2-methyl-, methyl ester

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2005-01-11 to 2005-06-23

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

April 24, 2002

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

June 16, 2004

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Version / remarks:

August 1998

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: MAFF Testing Guideline of 12 Nousan No. 8147, November 24, 2000 as this is in line with OECD 404

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

2-cyano-2-methyl-propanoic acid methyl ester

EC Number:

615-749-4

Cas Number:

72291-30-6

Molecular formula:

C6 H9 N O2

IUPAC Name:

2-cyano-2-methyl-propanoic acid methyl ester

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Animal identification via ear tattoo. Age at the beginning of the study was 7 - 8 months, body weight range at day 0 3.68 - 3.9 kg. The rabbits were housed in fully air-conditioned rooms with a temperature in the range of 20 - 24°C and a relative humidity ranging vom 30 - 70%. The day/night rhythm was 12 h dark and 12 h light. They were single housed in stainless steel wire mesh cages with grating (floor area 3000 cm²). A standardized animal laboratory diet (about 130 g/animal/day) and tap water ad libitum were offered.
TEST ANIMALS
- Source: Lago S.A., 01540 Vonnas, France
- Age at study initiation: 7 - 8 months
- Weight at study initiation: 3.68 kg - 3 .90 kg
- Housing: Single housing, stainless steel wire mesh cages with grating, floor area: 3000 cm²
- Diet: (Kaninchen & Meerschweinchenhaltung "GLP"), Provimi Kliba SA, Kaiseraugst, Basel, Switzerland (about 130 g/animal per day)
- Water: Tap water ad libitum
- Acclimation period: At least 5 days before the beginning of the study .

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Air changes (per hr): No data
- Photoperiod: 12 h light (6.00 a.m. - 6 .00 p .m.); 12 h darkness (6.00 p .m. - 6 .00 a.m .)

IN-LIFE DATES: From: August 24, 2004 To: January 17, 2005

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

4 hour

Observation period:

14 d

Number of animals:

3

Details on study design:

Clipping of the fur: at least 24 hours before start of the studay (clipping of the dorsolateral part of the trunk of the animal)
Body weight determination: just before application and after the last reading
Application: The test substance was applied in a single dose to the intact intreated skin. The test patch was secured in position with a semiocclusive dressing. The test substance was removed at the end of the exposure period with Lutrol and Lutrol/water (1:1).
Application area: 2.5 x 2.5 cm
Application site: flank
Readings: immediately after removal of the patches, then ca. 1, 24, 48 and 72 h after removal of the patches, thereafter in weekly intervals maximally up to day 14.
Check for dead or moribund animals: twice each working day and once on Saturdays, Sundays and public holidays

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 24, 48. 72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 24,48, 72 h

Score:

0

Max. score:

4

Results 4

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0.1

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 5

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Results 6

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Results 7

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Results 8

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Slight erythema (grade 1) was observed in all animals immediately after removal of the patch and persisted in two animals up to 1 hour and in one animal up to 24 hours.
No other cutaneous reactions were observed during the study.
The cutaneous reactions were reversible in two animals within 24 hours and in one animal within 48 hours after removal of the patch.