Propanoic acid, 2-[(ethoxythioxomethyl)thio]-, methyl ester

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

The relative humidity and temperature of the animal room exceeded the limits mentioned in the guidelines. the body weight range ordered was 2000-2500 g instead of 1500-1900 g. These deviations had no impact on the study.

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

The relative humidity and temperature of the animal room exceeded the limits mentioned in the guidelines. the body weight range ordered was 2000-2500 g instead of 1500-1900 g. These deviations had no impact on the study.

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Test material form:

liquid

Test animals

Species:

rabbit

Strain:

New Zealand White

Remarks:

SPF bred

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Centre Lagro, France
- Age at study initiation: young adult
- Weight at study initiation: 2950-3363 g
- Housing: individually in stainless steel cages with perforated floor
- Diet (e.g. ad libitum): standard laboratory rabbit diet ad libitum. Each batch of this diet is analyzed by the supplier (SDS Special Diets services, Whitham, England) for the nutrients and contaminants and the results are available upon request.
- Water (e.g. ad libitum): Tap water (N.V. Waterleidingbedrijf Midden-Nederland) ad libitum. Results of routine physical, chemical and microbiological examination of drinking water as conducted by the supplier are available upon request.
- Acclimation period: 49 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3°C. (On 13 June, the temperature was up to 26.2°C for a very short period of time due to a malfunction).
- Humidity (%): 56-99.9 % (incidentally the upper limit was higher !han 70%, because of wet cleaning of the animal room and/or meteorological circumstances).
- Air changes (per hr): ca 10 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 h light/12 h dark cycle

OTHERS
Upon arrival, the rabbits were checked for overt signs of ill health and anomalies. Three days prior to the start of the study, the hair was removed from the back and flanks of the animals using electric clippers in a way as to avoid abrasions. The clipping was repeated if considered necessary.

IN-LIFE DATES: From: 25 April 2000 To: 4 July 2000

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml of the test substance

VEHICLE
No

NEGATIVE CONTROL
No

POSITIVE CONTROL
No

Duration of treatment / exposure:

4 hours

Observation period:

24, 48, 72 h and at 7, 14, and 21 days

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- % coverage: Just prior to application. a skin site suitable for application was selected on the clipped back and flanks of the animal.
- Type of wrap if used: The patch loaded with the test substance was fixed to the selected application site by means of adhesive tape (Leukopor, BDF, Germany). Subsequently, the entire trunk of the rabbit was wrapped with a self-adhesive-gauze (F1Xomull, BDF, Germany) to maintain the patch in position and to retard evaporation of volatile substances. The gauze was additionally fastened with two strips of tape (Leukoflex, BDF, Germany).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes
- Time after start of exposure: After a 4-hour exposure period, the test substance and patch were removed and the test site was cleaned with a tissue moistened with water.

OBSERVATION TIME POINTS
One hour after treatment, the resulting skin reactions were evaluated by the method of Draize et al. (J. Pharmacol. Exp. Ther. 82 (1944) 377-390). Further skin readings were made at approximately 24, 48, 72 h, and at 7, 14 and 21 days after treatment.

SCORING SYSTEM:
- Method of calculation: Grading system by Draize et al.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

fully reversible within: 21 days

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

fully reversible within: 21 days

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

fully reversible within: 21 days

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

fully reversible within: 21 days

Irritant / corrosive response data:

At l h after treatment, the dermal effects observed in the three rabbits consisted of well-defined erythema and moderate oedema. At 24, 48 and 72 h after treatment, the dermal effects observed in the three rabbits consisted of moderate or severe erythema and moderate or severe oedema. In addition, the three rabbits showed slight ischemic necrosis. At 7 days after treatment, the dermal effects observed in the three rabbits consisted of moderate or severe erythema and moderate oedema. ln addition, two rabbits showed slight incrustation and one rabbit severe scaliness. At 14 days after treatment, the dermal effects had cleared in one rabbit, while the two remaining rabbits showed well-defined erythema, moderate scaliness and slight oedema. At 21 days after treatment, no signs of dermal irritation were observed in any of the three rabbits.

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

Based on the results of the study, RHODIXAN A-1 was considered to be irritant to the skin.

Executive summary:

RHODIXAN A-1 was tested for primary dermal irritation in 3 male New Zealand White rabbits, according to O.E.C.D. guideline Nb.404/EEC Method B.4, and in compliance with Good Laboratory Practice. The test article, a liquid, was applied in a single dermal dose of 0.5 ml on a 2.5 x 2.5 cm2 clipped areas of intact skin, under a semi-occlusive dressing for a 4-hour exposure period. The cutaneous examinations were performed 24, 48, and 72 hours after removal of the dressing, then daily until day 21 for reversibility.

 

At 1 hour after treatment, well-defined erythema and moderate oedema were observed in the 3 rabbits. At 24, 48, and 72 hours, and at day 7, dermal effects observed in the 3 rabbits consisted of moderate or severe erythema, or severe oedema. In addition, the 3 rabbits showed slight ischemic necrosis at 48 and 72 hours, and at day 7, 2 rabbits showed slight incrustation and one rabbit severe scaliness. At day 14, dermal effects had cleared in one rabbit, while the two remaining animals showed well-defined erythema, moderate scaliness and slight oedema. The mean scores (24-48-72 hours) calculated for each animal were 4.0 - 4.0 and 4.0 for erythema and 3.0 - 4.0 and 3.7 for oedema.

 

Based on theses results, RHODIXAN A-1 is classified Skin irrit. 2, H315, irritant to the skin according to CLP and GHS criteria.