1,4-dioxane-2,5-dione

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vitro

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the available information indicates that the substance should be classified for respiratory sensitisation or corrosivity

Cross-reference

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1998-10-12 to 1998-10-15

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

(adopted 1992-07-17)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(dated 1992-07-31)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: young adult
- Weight at study initiation: 1646-1822 g
- Housing :individually in stainless steel cages with perforated floor
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 47.5-57.5
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 /12

IN-LIFE DATES: From: To: 1998-10-12 to 1998-10-15

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g in 0.3 mL water
- Purity: 99.5%

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.3 mL water

Duration of treatment / exposure:

4 h

Observation period:

72 h
Reading time points: 1, 24, 48 and 72 h

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm²
- Type of wrap if used: self-adhesive gauze (Fixomull, BDF, Germany)
REMOVAL OF TEST SUBSTANCE
- Washing (if done): site was cleaned with a moistened tissue
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize et al. 1944

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: ischemic necrosis and incrustation

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: ischemic necrosis and haemorrhages, open wounds and incrustations

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: ischemic necrosis and haemorrhages, open wounds and incrustations

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: ischemic necrosis and incrustation

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.3

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: ischemic necrosis and haemorrhages, open wounds and incrustations

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: ischemic necrosis and haemorrhages, open wounds and incrustations

Irritant / corrosive response data:

After treatment with 1,4-dioxane-2,5-dione severe effects, such as ischemic necosis, haemorrhages and (open) wounds were observed. Because the skin effects were considered to result in irreversible damage, it was decided for ethical reasons to kill the animals after the 72-hour reading. At 24 hours after treatment, the skin effects observed in the three rabbits consisted of well-defined or moderate erythema and very slight or moderate oedema.In addition, one rabbit showed ischemic necrosis, while rabbit 2 and 3 showed (open) wounds. At 48 and 72 hours after treatment, the skin effects observed in the three rabbits were generally the same as observed after 24 hours. Additionally, incrustation was observed.

Interpretation of results:

Category 1C (corrosive) based on GHS criteria

Conclusions:

A sample of Glycolide (1,4-dioxane-2,5-dione, 99.5% a.i.) was tested for acute dermal irritating properties in an experiment according to OECD guideline 404 (adopted 17 July 1992) with three albino rabbits. The dermal exposure period was 4 hours under semi-occlusive conditions.
Glycolide caused well-defined or moderate erythema, ischemic necrosis, haemorrhages, wounds and very slight or moderate oedema in the three rabbits. For ethical reasons, it was decided to kill the animals after the 72-hour reading.
The individual mean values for erythema/oedema from gradings at 24, 48 and 72h were 4.0/1.0, 4.0/2.3 and 4.0/3.0 in animals 1, 2 and 3, respectively. Therefore, the test material fulfils the criteria for classification as skin corrosive Category 1C according to Regulation (EC) No 1272/2008 (CLP) and the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).