Oxazolidine, diheptyl~

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

September - October 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

2002

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2004

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Version / remarks:

1998

GLP compliance:

yes

Test material

Test material information

Constituent 1

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

ANIMALS
- Species: Albino rabbit, New Zealand White, (SPF-Quality). Recognised by international guidelines as the recommended test system (e.g. EC, OECD). Source: Harlan, Horst, The Netherlands.
- Number of animals: 3 males
- Age and body weight: Animals used within the study were at least 6 weeks old and body weights were at least 1.0 kg.
- Identification: Earmark.
- Health inspection: A health inspection was performed prior to the commencement of treatment, to ensure that the animals were in a good state of health. Special attention was paid to the skin to be treated, which was intact and free from abnormalities.

HUSBANDRY
- Conditions: Animals were housed in a controlled environment, in which optimal conditions were considered to be approximately 15 air changes per hour, a temperature of 21.0 ± 3.0 °C (actual range: 21.3 - 23.1 °C), a relative humidity of 30-70% (actual range: 39 - 64%) and 12 hours artificial fluorescent light and 12 hours darkness per day.
- Accommodation: Individually in labelled cages with perforated floors (Scanbur, Denmark, dimensions 56x44x37.5 cm). Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.
- Diet: Pelleted diet for rabbits (K-H from SSNIFF® Spezialdiäten GmbH, Soest, Germany) approximately 100 grams per day. Hay (TecniLab-SMI SV, Someren, The Netherlands) was provided at least three times a week.
- Water: Free access to tap water.
Results of analysis for each batch of diet (nutrients and contaminants), hay and water were assessed and did not reveal any findings that were considered to have affected the study integrity. All certificates and results of analysis are retained in the NOTOX archives.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

4 h

Observation period:

7 d

Number of animals:

3

Details on study design:

The study was performed in a stepwise manner and was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner 3 weeks later, after considering the degree of skin irritation observed in the first animal.

Approximately 24 hours before treatment, the dorsal fur was clipped with electric clippers, exposing an area of approximately 150 square centimeters (10x15 cm). To facilitate scoring, treated skin areas were re-clipped at least 3 hours before the observations.
Each animal was treated by dermal application of 0.5 mL of the test substance. The test substance was applied to the skin of one flank, using a metalline patch of 2x3 cm. The patch was mounted on Micropore tape, which was wrapped around the abdomen and secured with Coban elastic bandage.
Four hours after the application, the dressing was removed and the skin cleaned of residual test substance using tap water.
After the final observation, the animals were sacrificed by intra-venous injection of pentobarbital Euthesate® (Ceva Sante Animale SV, Naaldwijk, The Netherlands).

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal: 520

Time point:

24/48/72 h

Score:

2

Reversibility:

fully reversible within: 7 d

Results 2

Irritation parameter:

erythema score

Basis:

animal: 563

Time point:

24/48/72 h

Score:

2.3

Reversibility:

fully reversible within: 7 d

Results 3

Irritation parameter:

erythema score

Basis:

animal: 564

Time point:

24/48/72 h

Score:

2.3

Reversibility:

fully reversible within: 7 d

Results 4

Irritation parameter:

edema score

Basis:

animal: 520

Time point:

24/48/72 h

Score:

1.3

Reversibility:

fully reversible within: 7 d

Results 5

Irritation parameter:

edema score

Basis:

animal: 563

Time point:

24/48/72 h

Score:

1.7

Reversibility:

fully reversible within: 7 d

Results 6

Irritation parameter:

edema score

Basis:

animal: 564

Time point:

24/48/72 h

Score:

1.7

Reversibility:

fully reversible within: 7 d

Irritant / corrosive response data:

Four hours exposure to 0.5 mL of the test substance resulted in well defined or moderate to severe erythema and slight oedema in the treated skin-areas of the three rabbits. The skin irritation had
resolved within 7 days after exposure in all animals. There was no evidence of a corrosive effect on the skin.

Other effects:

Sticky and dry remnants of the test substance were present on the skin on Day 1.
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

According to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2003) the test substance should be classified as: skin irritant (Category 2).

Executive summary:

Primary skin irritation/corrosion study with the test substance in the rabbit (4-hour semi-occlusive application)"

The study was carried out based on the guidelines described in:

OECD No 404, "Acute Dermal lrritation/Corrosion" (2002)

EC, Council Directive 67/548/EEC, An.V, BA (2004), "Acute Toxicity: Dermal Irritation/ Corrosion"

US EPA, OPPTS 870"2500 (1998), Acute Dermal Irritation

JMAFF Guidelines (2000) including the most recent partial revisions"

Three rabbits were exposed to 0.5 mL of the test substance by application onto clipped skin for 4 hours using a semi-occlusive dressing. Skin reactions were assessed 1, 24, 48 and 72 hours and 7 days after exposure.

Exposure to test substance resulted in well defined or moderate to severe erythema and slight oedema in the treated skin-areas of the three rabbits. The skin irritation had resolved within 7 days after exposure in all animals. Sticky and dry remnants of the test substance were present on the skin on Day 1.

Based on these results:

- according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2003) the test substance should be classified as: skin irritant (Category 2).

- according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC), the test substance should be

labelled as: irritating to skin (R 38).