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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

25 January - 08 February, 2012

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 402 (Acute Dermal Toxicity)

Version / remarks:

(1987)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

(2008)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

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 type:

standard acute method

Limit test:

yes

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:

rat

Strain:

other: Wistar strain, Crl:WI (Han)

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Young adult animals (approx. 11 weeks old)
- Weight at study initiation: Body weight variation was within +/- 20% of the sex mean.
- Housing: Individually housed in labeled Makrolon cages (MIII type, height 18 cm.)
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- 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

Temporary deviations from the minimum level of relative humidity occurred. Evaluation: Laboratory historical data do not indicate an effect of the deviations. The study integrity was not adversely affected by the deviation.

Administration / exposure

Type of coverage:

occlusive

Vehicle:

corn oil

Details on dermal exposure:

One day before exposure (Day -1) an area of approximately 5x7 cm on the back of the animal was clipped.

The test substance formulation was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females. The test substance formulation was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D), successively covered with aluminum foil and Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.

Frequency: Single dosage, on Day 1.

Washing: Following application, dressings were removed and the skin cleaned of residual test substance using tap water.

Duration of exposure:

24 hours.

Doses:

2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

VEHICLE
- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed at NOTOX and on test substance data supplied by the sponsor.

Dose volume: 10 mL/kg body weight

DOSAGE PREPARATION: The formulation (w/w) was prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level. Adjustment was made for specific gravity of the vehicle. No correction was made for purity of the test substance.

Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily.
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
- Other examinations performed: none.

Statistics:

None.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

Chromodacryorrhoea (snout) was observed for three males and two females on Day 1 only.
All animals showed a combination of the following findings in the treated skin-area during the observation period: general erythema, necrosis, scales, scabs and/or a yellow appearance.

Body weight:

The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.

Gross pathology:

No internal macroscopic abnormalities were found at post mortem examination of the animals.

Other findings:

None.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In an acute dermal toxicity study with rats, performed according to OECD/EC test guidelines, an LD50 >2000 mg/kg bw was determined.

Executive summary:

MMDS was administered to five Wistar rats of each sex by a single dermal application at 2000 mg/kg body weight for 24 hours.

No mortality occurred. Chromodacryorrhoea (snout) was observed for three males and two females on Day 1 only. All animals showed a combination of the following findings in the treated skin-area during the observation period: general erythema, necrosis, scales, scabs and/or a yellow appearance. The mean body weight gain during the observation period was within the range expected for rats used in this type of study. No internal macroscopic abnormalities were found at post mortem examination of the animals. The dermal LD50 value of MMDS in Wistar rats was established to exceed 2000 mg/kg body weight.