5H-1,2-oxathiole 2,2-dioxide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

04. 09. 2019 - 07.11.2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

5H-1,2λ⁶-oxathiole-2,2-dione

EC Number:

606-834-7

Cas Number:

21806-61-1

Molecular formula:

C3H4O3S

IUPAC Name:

5H-1,2λ⁶-oxathiole-2,2-dione

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Shijiazhuang Suntec-chem Co., Ltd; 190403
- Expiration date of the lot/batch: Apr 10, 2020
- Purity:99.92%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Store in cool place. Keep container tightly closed in a dry and well-ventilated place. Containers which are opened must be carefully resealed.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test item does not make a homogenous suspension with water or olive oil, due to our experiences in other experiments, DMSO (dimethylsulphoxide) was used. Immediately before application the test item was weighed, mixed with vehicle DMSO and resulting suspension was administered by gavage. All prepared suspensions of the test item in DMSO were mixed by magnetic stirrer during administration.

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: SPF breeding, VELAZ s.r.o., Lysolajské údolí 15/53, 165 00 Prague 6, Czech Republic, RČH CZ 11760500
- Females (if applicable) nulliparous and non-pregnant: Yes
- Weight at study initiation: 202.58 to 231.96 g
- Fasting period before study: About twenty hours before oral administration the animals were fasted
- Housing: Individual labelling of cages and labelling of the animals, three animals per cage; Monitored conditions, microbiologically defined background.
- Diet: Pelleted standard diet for experimental animals ad libitum (Altromin International, Altromin Spezialfutter GmbH & Co. KG, Germany) ad libitum
- Water: Drinking tap water ad libitum
- Acclimation period: 18 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30 – 70 %
- Photoperiod (hrs dark / hrs light): 12 hours light/dark

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

DMSO

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 1 mL/100 g of animal body weight
- Justification for choice of vehicle: The test item does not make a homogenous suspension with water or olive oil, due to the lab's experiences in other experiments, DMSO (dimethylsulphoxide) was used.
- Lot/batch no. (if required): 2103180316
- Purity: 99.0%

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The starting dose was 300 mg/kg bw, according the test guideline, because there is no information about toxicity from sponsor.

Doses:

Step 1: 300 mg/kw bw
Step 2: 300 mg/kw bw
Step 3: 50 mg/kg bw
Step 4: 50 mg/kg bw

No. of animals per sex per dose:

3 females per dose per step.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were daily observation and weighed before application, at the 8th day of study and at the 15th day.
- Necropsy of survivors performed: yes
- Other examinations performed:
1. Clinical signs: After application the animals were observed individually: the first day: twice (30 minutes and 3 hours after application) and the second day: twice (in the morning and in the afternoon) and daily thereafter for 14 days. Observations included changes in skin and fur, eyes, visible mucous membranes, behaviour of animals, somatomotor activity, reactions to stimuli, and presence of lacrimation, salivation and discharge from nostrils, function of respiratory, digestive and urogenital system. The results of the observations were recorded on special data sheets.

2. Pathological examination: All test animals that survived to the end of study were sacrificed on the 15th day and gross necropsy was carried out. Animals that died during the study were also examined. Nutritious status, body surface, body foramina, thoracic, abdominal and cranial cavity were evaluated. All gross macroscopic changes of organs and tissues were recorded

Statistics:

Average body weight in a group was calculated from individual body weights (mean and SD)

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 50 - < 300 mg/kg bw

Mortality:

At the dose level 300 mg/kg bw (group No. 1 and 2), Female No. 1 was found dead on the morning of the second day (Table 5). Female No. 4 died five hours after application. Female No. 6 was found dead on the morning of the second day (Table 6). The dose of 50 mg/kg bw (group No. 3 and 4) did not cause any deaths.

Clinical signs:

other: At the dose level 300 mg/kg bw (group No. 1 and 2), no clinical signs of intoxication were observed 30 minutes after application in all 6 females. The following symptoms were observed 3 hours after application at 300 mg/kg bw: piloerection, anemia of visi

Gross pathology:

At 300 mg/kg bw, the following pathological macroscopic changes were found in animals that died before the end of the study: hyperemia of stomach mucous membrane in females No. 1, 4 and 6, and erosions of stomach mucous membrane in female No. 6. No pathological macroscopic changes were found in females No. 2, 3 and 5 (Tables 9, 10).

No pathological macroscopic changes were diagnosed during examination of animals dosed at 50 mg/kg bw in group No. 3 and No. 4 (Tables 11, 12).

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

In an acute oral toxicity study in female Wistar Crl: WI(Han) rats, the LD50 was > 50 mg/kg to 300 mg/kg bw.

Executive summary:

In an acute oral toxicity test (152-19-1), 4 groups of female Wistar Crl: WI(Han) rats (3/group) were administered 1,3 Propene Sultone (99.92%) in DMSO by oral gavage at 300 mg/kg bw (2 steps) and 50 mg/kg bw (2 steps). Animals were observed for 14 days.

The LD50 was > 50 mg/kg - 300 mg/ kg bw.

No clinical signs of intoxication were observed 30 minutes after application in all 6 females at 300 mg/kg bw. The following symptoms were observed 3 hours after application at 300 mg/kg bw: piloerection, anemia of visible mucous membranes, abdominal position, ataxia, decrease response to stimuli, bradypnea in two females, abdominal position in four females. On the morning of the second day, piloerection was observed in females No 2 and 3. From the afternoon of the second day to the fourteenth day, no clinical signs of intoxication were observed in surviving females. Weight increments were adequate to species, sex and age of animals during the experiment. The test item administered at the dose of 300 mg/kg bw caused the death of 3 of 6 animals. Two females were found dead on the morning of the second day after application of the test item. One female died five hours after application. The following pathological macroscopic changes were found in animals that died before the end of the study: hyperemia of stomach mucous membrane in females No. 1, 4 and 6, and erosions of stomach mucous membrane in female No. 6. No pathological macroscopic changes were found in surviving females.

The test item administered at the dose of 50 mg/kg bw caused no death of any animal. No serious clinical signs of intoxication were detected at this dose during the whole study. Weight increments were adequate to species, sex and age of animals during the experiment. No macroscopic changes were diagnosed during the pathological examination.