[No public or meaningful name is available]

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 26 September 2007 to 08 January 2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was performed according to international test guidelines and to GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

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:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Test material form:

other: liquid

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:
Harlan Netherlands BV
Kreuzelweg 53, NL-5961 NM Horst/The Netherlands
Postbus 6174, NL-5960 AD Horst/The Netherlands
- Age at study initiation: 13 weeks for the male; 12 weeks for the females
- Weight at study initiation: 2604 to 2850 g
- Housing: individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks (RCC Ltd, Füllinsdorf) and haysticks 4642 (batch no. 08/07, Provimi Kliba AG) were provided for gnawing.
- Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet, batch no. 31/07 (Provimi Kliba AG, CH-4303 Kaiseraugst/Switzerland) ad libitum. Results of analysis for contaminants are archived at RCC Ltd.
- Water: Community tap water from Füllinsdorf ad libitum. Results of bacteriological, chemical and contaminant analyses are archived at RCC Ltd.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23° C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12 (music during the daytime light period)

IN-LIFE DATES: From: 01 Oct 2007 to 11 Oct 2007

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
- Concentration (if solution): 100%

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48 and 72 hours as well as 7 and 10 days after exposure (removal of the dressing, gauze patch and test material)

Number of animals:

1 male, 2 females

Details on study design:

TEST SITE
- Area of exposure: approximately 6.25 cm2 (left flank)
- % coverage: approximately 0.4% of the surface area
- Type of wrap if used: The semi-occlusive dressing was wrapped around the abdomen and anchored with tape.

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

SCORING SYSTEM: numerical scoring system listed in the Commission Directive 2004/73/EC, April 29, 2004.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.67

Max. score:

1

Reversibility:

fully reversible within: 72 hours

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 10 days

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 48 hours

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 48 hours

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

The test material did not induce significant or irreversible damage to the skin.

The erythema (grade 1) was observed from the initial evaluation time point, i.e. 1 hour following removal of the patch.
The oedema (grade 1) was observed only at the 24-hour observation time-point.

Other effects:

No other local signs and no staining observed. No clinical signs and body weights were within the normal range.

Any other information on results incl. tables

Table of results:

Score at time point / Reversibility	Erythema	Edema
	Max. score: 4	Max. score: 4
60 min	1/1/1	0/0/0
24 h	1/1/1	0/1/0
48 h	1/1/0	0/0/0
72 h	0/1/0	0/0/0
Average 24h, 48h, 72h	0.67/1/033	0/0.33/0
7 days	0/1/0	0/0/0
10 days	0/0/0	0/0/0
Reversibility	Yes within 10 days	Yes within 48 hours

 

 

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based upon the referred classification criteria (commission Directive 2001/59/EC of August 2001), dimethyl 2-methylglutarate is considered to be "not irritating" to rabbit skin.

Executive summary:

In a skin irritation study, 3 New Zealand White rabbits were treated by a topical semi-occlusive application of 0.5 mL of undiluted Dimethyl 2-methyl glutarate for 4 hours and were observed 1, 24, 48 and 72 hours as well as 7 and 10 days after exposure.

 

The application of the test material to the skin resulted in mild signs of irritation, including erythema and oedema (maximum mean score of 1 and 0.33, respectively). These effects were reversible and no longer evident 48- or 72 hours and 10 days after treatment, respectively.

 

No other local signs and no staining were observed. There were no clinical signs and body weights were within the normal range.

 

This skin irritation study is classified as acceptable. It does satisfy the guideline requirement for an acute dermal irritation/corrosion study (OECD 404) in the rabbit.