3-methyltetrahydrothiophene 1,1-dioxide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

25 Aug 2017 - 11 Oct 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

17 Dec 01

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3-methyltetrahydrothiophene 1,1-dioxide

EC Number:

212-833-9

EC Name:

3-methyltetrahydrothiophene 1,1-dioxide

Cas Number:

872-93-5

Molecular formula:

C5H10O2S

IUPAC Name:

3-methyl-1λ⁶-thiolane-1,1-dione

Test material form:

liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Texas Animal Specialties; Humble, TX
- Females (if applicable) nulliparous and non-pregnant: Yes
- Weight at study initiation: 190 - 238 g
- Fasting: 16 hours
- Housing: 1/cage in polycarbonate box with bedding; hutches provided as enrichment
- Diet (e.g. ad libitum): Teklad Global Diets® #2018; available ad libitum except for ~16 hours
before dosing
- Water (e.g. ad libitum): Municipal water supply analyzed by TCEQ Water Utilities Division;
available ad libitum from automatic water system
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): ∙ 22 +/- 3°C
- Humidity (%): 30 - 70% target humidity
- Air changes (per hr): 10+ air changes per hour
- Photoperiod (hrs dark / hrs light): 12-hr light/12-hr dark cycle

IN-LIFE DATES: From - To
- 2000 mg/kg bw: 01 Jul 17 - 31 Aug 17
- 300 mg/kg bw: 01 Jul 17 - 14 Sep 17
- 300 mg/kg bw:01 Jul 17 - 31 Aug 17
- 300 mg/kg bw: 01 Jul 17 - 01 Sep 17
- 50 mg/kg bw: 01 Jul 17 - 19 Sep 17
- 50 mg/kg bw: 01 Jul 17 - 21 Sep 17

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 1.68 mL/kg bw at the 2000 mg/kg level

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: 2000 mg/kg bw is the limit dose specified in regulation guideline for test items for which no information regarding toxicity is available.

Doses:

2000 mg/kg bw
300 mg/kg bw
50 mg/kg bw

No. of animals per sex per dose:

2000 mg/kg bw: 1 female animal
300 mg/kg bw: 3 female animals
50 mg/kg bw: 6 female animals

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 3 times on the day of dosing, once daily for 14 days. Individual body weights were recorded
just prior to dosing and on Days 7 and 14, or at time of discovery after death.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights

Results and discussion

Preliminary study:

The first animal dosed at 2000 mg/kg immediately convulsed and died; therefore, per protocol amendment, the starting limit dose was changed to 300 mg/kg.

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 50 - < 300 mg/kg bw

Based on:

test mat.

Mortality:

The first (and only) animal dosed at 2000 mg/kg died almost immediately after being dosed. Two of the three animals dosed at 300 mg/kg died during the study. There was no mortality in either group of animals dosed at 50 mg/kg. The acute oral LDso, as indicated by the data, was determined to be greater than 50 mg/kg bw but less than 300 mg/kg bw.

Clinical signs:

other: Clinical signs in survivors included hunched posture and piloerection, on the day of dosing only. One animal that died during test exhibited activity decrease and piloerection.

Gross pathology:

Abnormal necropsy findings in one animal dying during test pertained to eye closure/discharge. Gross necropsy on animals surviving to study termination revealed no observable abn01malities.

Applicant's summary and conclusion

Interpretation of results:

other: Acute toxic (Category 3)

Remarks:

in accordance with Annex I of 1272/2008/EC (CLP)

Conclusions:

The acute oral LD50 for 3-Methyl Sulfolane is determined to be greater than 50 mg/kg bw but less than 300 mg/kg bw in female albino rats; the test substance therefore needs to be classified as Category 3 acute toxicant according to the classification criteria outlined in Annex I of 1272/2008/EC (CLP).

Executive summary:

3 Methyl Sulfolane was evaluated for its acute oral toxicity potential in female albino Sprague-Dawley rats when administered as a gavage dose in a OECD 423 method, performed under GLP. The first animal dosed at 2000 mg/kg immediately convulsed and died; therefore, per protocol amendment, the starting limit dose was changed to 300 mg/kg. Two of three animals dosed at 300 mg/kg died, so no further animals were dosed at that level. No mortality occurred in the six animals thereafter dosed at 50 mg/kg. The study was terminated following stopping rules of this procedure. Clinical signs in survivors included hunched posture and piloerection, on the day of dosing only; one animal that died exhibited activity decrease and piloerection. Animals surviving to termination exhibited weekly weight gain, except for three that lost or failed to gain weight between Days 7 and 14. Abnormal necropsy findings occurred only in one animal dying during test, and pertained to eye closure/discharge. The acute oral LD50 was determined to be greater than 50 mg/kg bw but less than 300 mg/kg bw.