1,5,2,4-dioxadithiane 2,2,4,4-tetraoxide

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

15 December - 24 December, 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

(2002)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(2008)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Version / remarks:

(1998)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, April 2011, including the most recent partial revisions.

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

1,5,2,4-dioxadithiane 2,2,4,4-tetraoxide

EC Number:

700-464-0

Cas Number:

99591-74-9

Molecular formula:

C2H4O6S2

IUPAC Name:

1,5,2,4-dioxadithiane 2,2,4,4-tetraoxide

Details on test material:

- Name of test material (as cited in study report): MMDS
- Physical state: White powder
- Storage condition of test material: In refrigerator (2-8°C) in the dark under nitrogen
- Hygroscopic Yes, store in well-sealed container
- Volatile: No
- Test substance handling: Handle in nitrogen environment in glovebox

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

- Source: Charles River France, L’Arbresle Cedex, France
- Age at study initiation: at least 6 weeks old
- Weight at study initiation: at least 1.0 kg
- Housing: Animals were individually housed in labeled cages with perforated floors (Ebeco, Germany, dimensions 67 x 62 x 55 cm) and shelters (Ebeco, Germany, dimensions 40 x 32 x 23 cm).
- Diet: Free access to pelleted diet for rabbits (Global Diet 2030 from Harlan Teklad, Italy). Hay and wooden sticks were abailable during the study period.
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 ± 3.0
- Humidity (%): 40 - 70
- Air changes (per hr): approx 15
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

other: dehydrated corn oil

Controls:

other: Adjacent areas of the untreated skin of each animal served as controls.

Amount / concentration applied:

TEST MATERIAL - Amount(s) applied: 0.5 grams

VEHICLE - The test substance was mixed with 0.3 mL dehydrated corn oil

Duration of treatment / exposure:

Single application.

Observation period:

14 days.

Number of animals:

3 males.

Details on study design:

STUDY DESIGN
The study was performed in a stepwise manner and started with the treatment of one animal (sentinel) with a stepwise exposure regime. The two other animals were exposed to the substance for four hours only and in a similar manner 6 days later, after considering the degree of skin irritation observed in the first animal.

TEST SUBSTANCE PREPARATION
The powdery test substance was mixed with dehydrated corn oil, specific gravity 0.92 (Fagron, Nieuwerkerk a/d IJssel, The Netherlands), immediately before application, to ensure close contact with the animal's skin.

TEST SITE
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.

The study was initiated by treatment of one rabbit.
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. The dressing was removed 3 minutes after application.
Since no signs of severe skin reactions (i.e. necrosis or corrosion) were observed and it was considered that exposure could be continued humanely, two samples of 0.5 grams of the test substance mixed with 0.3 mL of the vehicle were then applied to separate skin-sites on the intact, clipped skin of the same animal, using an identical procedure and one sample per dressing. One of the dressings was removed after a 1-hour exposure.
After similar considerations (i.e. no severe skin reactions, necrosis or corrosion), the other dressing was removed after a 4-hour exposure.

Since no signs of severe skin reactions (i.e. necrosis or corrosion) were observed after 4 hours exposure and the irritation was considered reversible in the first animal, two further animals were treated at a later stage. These animals received single samples of 0.5 grams of the test substance mixed with 0.3 mL of the vehicle on the intact, clipped skin of one flank applied in a similar manner as in the first animal. Four hours after the application, the dressing was removed and the skin cleaned of residual test substance using vehicle.

REMOVAL OF TEST SUBSTANCE
After each removal of a dressing, the treated skin was cleaned of residual test substance using dehydrated corn oil.

OBSERVATIONS
- Mortality/Viability: Twice daily.
- Toxicity: At least once daily.
- Body Weight: Day of treatment (prior to application) and after the final observation.
- Necropsy: No necropsy was performed.
- Irritation:
In the initially treated animal, the skin reactions of all visible treated sites were assessed immediately after removal of a dressing and approximately 1, 24, 48, 72 hours after the removal of the last dressing and test substance. After the 4 hours exposure in two further animals, the skin reactions were assessed approximately 1, 24, 48, 72 hours after the removal of the dressing and test substance.
The irritation scores and a description of all other (local) effects were recorded. Adjacent areas of untreated skin of each animal serve as controls.

SCORING SYSTEM:
The irritation was assessed according to the numerical scoring system according to OECD 404.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal #1, #2 and #3

Time point:

other: 24, 48 and 72 hours.

Score:

0

Max. score:

4

Results 2

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #1, #2 and #3

Time point:

other: 24, 48 and 72 hours.

Score:

0

Max. score:

4

Irritant / corrosive response data:

No skin irritation was caused by 0.5 g of MMDS after exposure periods of 3 minutes, 1 hour and 4 hours.
There was no evidence of a corrosive effect on the skin.

Other effects:

No staining of the treated skin by the test substance was observed and no test substance remnants were seen.
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:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In an skin irritation study with rabbits, performed according to OECD/EC test guidelines, no irritation was observed.

Executive summary:

Primary skin irritation/corrosion study with MMDS in the rabbit (semi-occlusive application).

Initially, one rabbit was exposed to three samples of 0.5 grams of MMDS mixed with dehydrated corn oil applied to separate skin-sites on intact, clipped skin using a semi-occlusive dressing. The exposure periods were 3 minutes, 1 hour and 4 hours, respectively. Based on the absence of severe skin reactions, two further animals exposed for 4 hours to MMDS at a later stage.

No skin irritation was caused by MMDS after exposure periods of 3 minutes, 1 hour and 4 hours.