Butanedioic acid, 1-[2-[(1-oxo-2-propen-1-yl)oxy]ethyl] ester

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was performed between 11 May 2006 and 31 May 2006.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

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 (incl. QA statement)

Remarks:

Date of Inspection: 30th August 2005. Date of signature: 21 November 2005

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

478-130-6

EC Name:

-

Cas Number:

50940-49-3

Molecular formula:

C9H12O6

IUPAC Name:

2-(acryloyloxy)ethyl hydrogen succinate

Details on test material:

- Name of test material (as cited in study report): MAES
- Substance type : Organic
- Physical state : Colourless turbid liquid
- Lot/batch No. : J41 7708-A
- Storage condition of test material : Room temperature in the dark

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:
New Zealand White rabbits were supplied by David Percival Ltd, Moston, Sandbach, Cheshire, UK.
- Age at study initiation: Twelve to twenty weeks old.
- Weight at study initiation: At the start of the study the animals were in the weight range of 2.0 to 3.5 kg.
- Housing: The animals were individually housed in suspended cages.
- Diet (e.g. ad libitum): Certified Rabbit Diet (Code 5322) supplied by BCM IPS Limited, London, UK.
- Water (e.g. ad libitum): Free access to mains drinking water
- Acclimation period: At least five days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23°C
- Humidity (%): 30 to 70%
- Air changes (per hr): The rate of air exchange was at least fifteen changes per hour.
- Photoperiod (hrs dark / hrs light): The lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped free of fur from the dorsal/flank area using veterinary clippers.

Vehicle:

unchanged (no vehicle)

Remarks:

test material was used as supplied.

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Concentration (if solution): Not applicable.

VEHICLE
- Amount(s) applied (volume or weight with unit): Not applicable
- Concentration (if solution): Not applicable.
- Lot/batch no. (if required): J41 7708-A

Duration of treatment / exposure:

3 minutes, 1 hour and 4 hours

Observation period:

Approximately one hour following the removal of the patches, and 24, 48 and 72 hours later

Number of animals:

1

Details on study design:

TEST SITE
- Area of exposure: On the day of the test three suitable sites were selected on the back of the rabbit
- % coverage: Not given in study report.
- Type of wrap if used: Test material was introduced under a 2.5 cm x 2.5 cm cotton gauze patch and placed in position on the shorn skin.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Any residual test material removed by gentle swabbing with cotton wool soaked in distilled water.
- Time after start of exposure: 3 minutes, 1 hour and 4 hours.

SCORING SYSTEM:
Approximately one hour following the removal of the patches, and 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored according to the following scale (table below).

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal: 215 Male

Time point:

24/48/72 h

Score:

2.67

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: CORROSIVE

Results 2

Irritation parameter:

edema score

Basis:

animal: 215 Male

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: CORROSIVE

Irritant / corrosive response data:

RESULTS

4-Hour Exposure Period
The scores for erythema/eschar and edema are given in attachment 1.
Well-defined erythema was noted at the treated skin site one hour after patch removal and at the 24-hour observation with moderate to severe erythema noted at the 48 and 72-hour observations and well-defined erythema noted at the 7-day observation. The erythematous reaction extended up to 5 cm beyond the treatment site. Severe edema was noted at the treated skin site one hour after patch removal and at the 24, 48 and 72-hour observations with slight oedema noted at the 7-day observation. The oedema extended approximately 5 cm ventrally below the treatment site. Crust formation and reduced regrowth of fur were noted at the treated skin site at the 7-day observation. Glossy skin, reduced regrowth of fur and areas of scar tissue (up to 5 rom x 5 rom), scattered over and around the edges of the treatment site, were noted at the 14-day observation. The reactions noted at the 14-day observation were considered to be indicative of dermal corrosion.

1-Hour Exposure Period
Well-defined erythema was noted at the treated skin site at the 24, 48 and 72-hour observations with very slight erythema noted at the 7-day observation. The erythematous reaction extended up to 5 cm beyond the treatment site. Moderate to severe oedema was noted at the treated skin site at the 24-hour observation with slight oedema at the 48 and 72-hour observations and very slight oedema at the 7-day observation. The oedema extended approximately 5 cm ventrally below the treatment site. Crust formation was noted at the treated skin site at the 7-day observation. The treated skin site appeared normal at the 14-day observation.

3-Minute Exposure Period
Very slight erythema was noted at the treated skin site at the 24, 48 and 72-hour observations. Very slight oedema was noted at the treated skin site at the 24-hour observation. The treated skin site appeared normal at the 7-day observation.

CONCLUSION
The test material should be considered as CORROSIVE to rabbit skin.

Applicant's summary and conclusion

Interpretation of results:

corrosive

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material was classified as CORROSIVE to rabbit skin.

Executive summary:

Introduction: The study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method was designed to meet the requirements of the following:

- OECD Guidelines for the Testing of Chemicals No. 404 "Acute Dennal Irritation/Corrosion" (adopted 24 April 2002)

- Method B4 Acute Toxicity (Skin Irritation) of Commission Directive 2004/73/EC

Initial considerations. Available information indicated that the test material had the potential to produce severe irritation/corrosion and to confirm this initial assessment an ex vivo pre-screen test, the Transcutaneous Electrical Resistance Assay (TER), was performed. The results of the pre-screen test indicated that the test material was considered not to be corrosive to the skin and the in vivo test was performed.

Results: A single 4-hour, semi-occluded application of the test material to the intact skin of one rabbit produced corrosive effects. Moderate to severe erythema, severe oedema, crust formation, reduced regrowth of fur, glossy skin and areas of scar tissue (up to 5 mm x 5 mm), scattered over and around edges of the treatment site, were also noted. The erythematous reaction extended approximately 5 cm beyond the treatment site and the oedema extended ventrally approximately 5 cm below the treatment site.

3-minute and 1-hour semi-occluded applications of the test material to the intact skin of one rabbit produced no corrosive effects.

Conclusion: The test material was classified as CORROSIVE to rabbit skin.